GARST ANDREW (US)
LIPSCOMB TANYA ELIZABETH (US)
BASSALO MARCELO (US)
ZEITOUN RAMSEY (US)
INSCRIPTA INC (US)
CLAIMS WHAT IS CLAIMED IS: 1. A composition comprising: i) a first donor nucleic acid comprising: a) a modified first target nucleic acid sequence; b) a first protospacer adjacent motif (PAM) mutation; and c) a first guide nucleic acid sequence comprising a first spacer region complementary to a portion of the first target nucleic acid; and ii) a second donor nucleic acid comprising: a) a barcode corresponding to the modified first target nucleic acid sequence; and b) a second guide nucleic acid sequence comprising a second spacer region complementary to a portion of a second target nucleic acid. 2. The composition of claim 1, wherein the modified first target nucleic acid sequence comprises at least one inserted, deleted, or substituted nucleic acid compared to a corresponding un-modified first target nucleic acid. 3. The composition of claim 1, wherein the first guide nucleic acid and second guide nucleic acid are compatible with a nucleic acid-guided nuclease. 4. The composition of claim 3, wherein the nucleic acid-guided nuclease is a Type II or Type V Cas protein. 5. The composition of claim 3, wherein the nucleic acid-guided nuclease is a Cas9 homologue or a Cpfl homologue. 6. The composition of claim 1, wherein the second donor nucleic acid comprises a second PAM mutation. 7. The composition of claim 1, wherein the second donor nucleic acid sequence comprises a regulatory sequence or a mutation to turn a screenable or selectable marker on or off. 8. The composition of claim 1, wherein the second donor nucleic acid sequence targets a unique landing site. 9. A method of genome engineering, the method comprising: a) contacting a population of cells with a polynucleotide, wherein each cell comprises a first target nucleic acid, a second target nucleic acid, and a nucleic acid-guided nuclease, wherein the polynucleotide comprises 1) an editing cassette comprising: i) a modified first target nucleic acid sequence; ii) a first protospacer adjacent motif (PAM) mutation; iii) a first guide nucleic acid sequence comprising a spacer region complementary to a portion of the first target nucleic acid and compatible with the nucleic acid-guided nuclease; and 2) a recorder cassette comprising i) a barcode corresponding to the modified first target nucleic acid sequence; and ii) a second guide nucleic acid sequence comprising a second spacer region complementary to a portion of the second target nucleic acid and compatible with the nucleic acid-guided nuclease; b) allowing the first guide nucleic acid sequence, the second guide nucleic acid sequence, and the nucleic acid-guided nuclease to create a genome edit within the first target nucleic acid and the second target nucleic acid. 10. The method of claim 9, further comprising c) sequencing a portion of the barcode, thereby identifying the modified first target nucleic acid that was inserted within the first target nucleic acid in step a). 11. The method of claim 9, wherein the nucleic acid-guided nuclease is a CRISPR nuclease. 12. The method of claim 9, wherein the PAM mutation is not recognized by the nucleic acid- guided nuclease. 13. The method of claim 9, wherein the nucleic acid-guided nuclease is a Type II or Type V Cas protein. 14. The method of claim 9, wherein the nucleic acid-guided nuclease is a Cas9 homologue or a Cpfl homologue. 15. The method of claim 9, wherein the recorder cassette further comprises a second PAM mutation that is not recognized by the nucleic acid-guided nuclease. 16. A method of selectable recursive genetic engineering comprising a) contacting cells comprising a nucleic acid-guided nuclease with a polynucleotide comprising a recorder cassette, said recorder cassette comprising i) a nucleic acid sequence that recombines into a unique landing site incorporated during a previous round of engineering, wherein the nucleic acid sequence comprises a unique barcode; and ii) a guide RNA compatible with the nucleic acid-guided nuclease that targets the unique landing site; and b) allowing the nucleic acid-guided nuclease to edit the unique landing site, thereby incorporating the unique barcode into the unique landing site. 17. The method of claim 16, wherein the nucleic acid sequence further comprises a regulatory sequence that turns transcription of a screenable or selectable marker on or off. 18. The method of claim 16, wherein the nucleic acid sequence further comprises a PAM mutation that is not compatible with the nucleic acid-guided nuclease. 19. The method of claim 16, wherein the nucleic acid sequence further comprises a second unique landing site for subsequent engineering rounds. 20. The method of claim 16, wherein the polynucleotide further comprises an editing cassette comprising a) a modified first target nucleic acid sequence; b) a first protospacer adjacent motif (PAM) mutation; and c) a first guide nucleic acid sequence comprising a first spacer region complementary to a portion of the first target nucleic acid, wherein the unique barcode corresponds to the modified first target nucleic acid such that the modified target nucleic acid can be identified by the unique barcode. |
CROSS-REFERENCE
[0001] The present application claims priority to U.S. Provisional Application Serial No. 62/354,516, filed June 24, 2016; U.S. Provisional Application Serial No. 62/367,386, filed July 27, 2016; and U.S. Provisional Application Serial No. 62/483,930, filed April 10, 2017, the contents of each being hereby incorporated by reference in their entirety.
STATEMENT AS TO FEDERALLY SPONSORED RESEARCH
[0002] This disclosure was made with the support of the United States government under Contract number DE-SC0008812 by the Department of Energy.
SEQUENCE LISTING
[0003] This application contains a sequence list in Table 5.
BACKGROUND OF THE DISCLOSURE
[0004] Understanding the relationship between a protein's amino acid structure and its overall function continues to be of great practical, clinical, and scientific significance for biologists and engineers. Directed evolution can be a powerful engineering and discovery tool, but the random and often combinatorial nature of mutations makes their individual impacts difficult to quantify and thus challenges further engineering. More systematic analysis of contributions of individual residues or saturation mutagenesis remains labor- and time-intensive for entire proteins and simply is not possible on reasonable timescales for editing of multiple proteins in parallel, such as metabolic pathways or multi-protein complexes, using standard methods.
SUMMARY OF THE DISCLOSURE
[0005] Disclosed herein are compositions comprising: i) a first donor nucleic acid comprising: a) a modified first target nucleic acid sequence; b) a first protospacer adjacent motif (PAM) mutation; and c) a first guide nucleic acid sequence comprising a first spacer region complementary to a portion of the first target nucleic acid; and ii) a second donor nucleic acid comprising: a) a barcode corresponding to the modified first target nucleic acid sequence; and b) a second guide nucleic acid sequence comprising a second spacer region complementary to a portion of a second target nucleic acid. Further disclosed are compositions wherein the modified first target nucleic acid sequence comprises at least one inserted, deleted, or substituted nucleic acid compared to a corresponding un-modified first target nucleic acid. Further disclosed are compositions wherein the first guide nucleic acid and second guide nucleic acid are compatible with a nucleic acid-guided nuclease. Further disclosed are compositions wherein the nucleic acid-guided nuclease is a Type II or Type V Cas protein. Further disclosed are compositions wherein the nucleic acid-guided nuclease is a Cas9 homologue or a Cpfl homologue. Further disclosed are compositions wherein the second donor nucleic acid comprises a second PAM mutation. Further disclosed are compositions wherein the second donor nucleic acid sequence comprises a regulatory sequence or a mutation to turn a screenable or selectable marker on or off. Further disclosed are compositions wherein the second donor nucleic acid sequence targets a unique landing site.
[0006] Disclosed herein are methods of genome engineering, the method comprising: a) contacting a population of cells with a polynucleotide, wherein each cell comprises a first target nucleic acid, a second target nucleic acid, and a nucleic acid-guided nuclease, wherein the polynucleotide comprises 1) an editing cassette comprising: i) a modified first target nucleic acid sequence; ii) a first protospacer adjacent motif (PAM) mutation; iii) a first guide nucleic acid sequence comprising a spacer region complementary to a portion of the first target nucleic acid and compatible with the nucleic acid-guided nuclease; and 2) a recorder cassette comprising i) a barcode corresponding to the modified first target nucleic acid sequence; and ii) a second guide nucleic acid sequence comprising a second spacer region complementary to a portion of the second target nucleic acid and compatible with the nucleic acid-guided nuclease; b) allowing the first guide nucleic acid sequence, the second guide nucleic acid sequence, and the nucleic acid- guided nuclease to create a genome edit within the first target nucleic acid and the second target nucleic acid. Further disclosed are methods further comprising c) sequencing a portion of the barcode, thereby identifying the modified first target nucleic acid that was inserted within the first target nucleic acid in step a). Further disclosed are methods wherein the nucleic acid-guided nuclease is a CRISPR nuclease. Further disclosed are methods wherein the PAM mutation is not recognized by the nucleic acid-guided nuclease. Further disclosed are methods wherein the nucleic acid-guided nuclease is a Type II or Type V Cas protein. Further disclosed are methods wherein the nucleic acid-guided nuclease is a Cas9 homologue or a Cpfl homologue. Further disclosed are methods wherein the recorder cassette further comprises a second PAM mutation that is not recognized by the nucleic acid-guided nuclease.
[0007] Disclosed herein are methods of selectable recursive genetic engineering comprising a) contacting cells comprising a nucleic acid-guided nuclease with a polynucleotide comprising a recorder cassette, said recorder cassette comprising i) a nucleic acid sequence that recombines into a unique landing site incorporated during a previous round of engineering, wherein the nucleic acid sequence comprises a unique barcode; and ii) a guide RNA compatible with the nucleic acid-guided nuclease that targets the unique landing site; and b) allowing the nucleic acid-guided nuclease to edit the unique landing site, thereby incorporating the unique barcode into the unique landing site. Further disclosed are methods wherein the nucleic acid sequence further comprises a regulatory sequence that turns transcription of a screenable or selectable marker on or off. Further disclosed are methods wherein the nucleic acid sequence further comprises a PAM mutation that is not compatible with the nucleic acid-guided nuclease. Further disclosed are methods wherein the nucleic acid sequence further comprises a second unique landing site for subsequent engineering rounds. Further disclosed are methods wherein the polynucleotide further comprises an editing cassette comprising a) a modified first target nucleic acid sequence; b) a first protospacer adjacent motif (PAM) mutation; and c) a first guide nucleic acid sequence comprising a first spacer region complementary to a portion of the first target nucleic acid, wherein the unique barcode corresponds to the modified first target nucleic acid such that the modified target nucleic acid can be identified by the unique barcode.
[0008] Provided herein are compositions comprising i) a first donor nucleic acid comprising: a) a modified first target nucleic acid sequence; b) a mutant protospacer adjacent motif (PAM) sequence; and c) a first guide nucleic acid sequence comprising a first spacer region complementary to a portion of the first target nucleic acid; and ii) a second donor nucleic acid comprising: a) a recorder sequence; and b) a second guide nucleic acid sequence comprising a second spacer region complementary to a portion of the second target nucleic acid. In some aspects, the first donor nucleic acid and the second donor nucleic acid are covalently linked or comprised on a single nucleic acid molecule. Further provided are compositions wherein the modified first target nucleic acid comprises a 5' homology are and a 3 ' homology arm. Further provided are compositions wherein the 5' homology arm and the 3' homology arm are homologous to nucleic acid sequence flanking a protospacer complementary to the first spacer region. Further provided are compositions wherein the modified first target nucleic acid sequence comprises at least one inserted, deleted, or substituted nucleic acid compared to a corresponding un-modified first target nucleic acid. Further provided are compositions wherein the first gRNA is compatible with a nucleic acid-guided nuclease, thereby facilitating nuclease- mediate cleavage of the first target nucleic acid. Further provided are compositions wherein the nucleic acid-guided nuclease is a Cas protein, such as a Type II or Type V Cas protein. Further provided are compositions wherein the nucleic acid-guided nuclease is Cas9 or Cpfl . Further provided are compositions wherein the nucleic acid-guided nuclease is MAD2 or MAD7. Further provided are compositions wherein the nucleic acid-guided nuclease is an engineered or non- natural enzyme. Further provided are compositions wherein the nucleic acid-guided nuclease is a engineered or non-natural enzyme derived from Cas9 or Cpfl . Further provided are compositions wherein the nucleic acid-guided nuclease is an engineered or non-natural enzyme that has less than 80% homology to either Cas9 or Cpfl . Further provided are compositions wherein the mutant PAM sequence is not recognized by the nucleic acid-guided nuclease. Further provided are compositions wherein the recorder sequence comprises a barcode. Further provided are compositions wherein the recorder sequence comprises a fragment of a screenable or selectable marker. Further provided are compositions wherein the recorder sequence comprises a unique sequence by which the modified first target nucleic acid sequence is specifically identified. Further provided are compositions wherein the recorder sequence comprises a unique sequence by which the edited cells may be selected or enriched. A first donor nucleic acid can be a cassette, such as an editing cassette as disclosed herein. A second donor nucleic acid can be a cassette, such as a recording cassette as disclosed herein. A first donor nucleic acid and a second donor nucleic acid can be comprised on a single cassette. A first donor nucleic acid and a second donor nucleic acid can be covalently linked. In any of these examples, the elements of the cassette or donor nucleic acids can be contiguous or non-contiguous.
[0009] Provided herein are cells comprising an engineered chromosome or polynucleic acid comprising: a first modified sequence; a first mutant protospacer adjacent motif (PAM); a first recorder sequence, the sequence of which uniquely identifies the first modified sequence, wherein the first modified sequence and the first recorder sequence are separated by at least lbp. Further provided are cells wherein the first modified sequence and the first recorder sequence are separated by at least lOObp. Further provided are cells wherein the first modified sequence and the first recorder sequence are separated by at least 500bp. Further provided are cells wherein the first modified sequence and the first recorder sequence are separated by at least lkbp. Further provided are cells wherein the first recorder sequence is a barcode. Further provided are cells wherein the first modified sequence is within a coding sequence. Further provided are cells wherein the first modified sequence comprises at least one inserted, deleted, or substituted nucleotide compared to an unmodified sequence. Further provided are cells further comprising: a second modified sequence; a second mutant PAM; and a second recorder sequence, the sequence of which uniquely identifies the second modified sequence, wherein the second modified sequence and the second recorder sequence are separated by at least 1 kb. Further provided are cells wherein the first recorder sequence and the second recorder sequence are separated by less than 100 bp. Further provided are cells wherein the second recorder sequence is a barcode. Further provided are cells wherein the second modified sequence is within a coding sequence. Further provided are cells wherein the second modified sequence comprises at least one inserted, deleted, or substituted nucleotide compared to an unmodified sequence. Further provided are cells wherein the first recorder sequence and the second recorder sequence are immediately adjacent to each other or overlapping, thereby generating a combined recorder sequence. Further provided are cells wherein the combined recorder sequence comprises a selectable or screenable marker. Further provided are cells wherein the combined recorder sequence comprises a selectable or screenable marker by which the cells may be enriched or selected. [0010] Provided herein are methods of genome engineering, the method comprising: a) introducing into a population of cells a plurality of polynucleotides, wherein each cell comprises a first target nucleic acid, a second target nucleic acid, and a targetable nuclease, wherein each polynucleotide comprises: i) a modified first target nucleic acid sequence; ii) a mutant protospacer adjacent motif (PAM) sequence; iii) a first guide nucleic acid sequence comprising a guide sequence complementary to a portion of the first target nucleic acid; and (iv) a recorder sequence; b) inserting the modified first target nucleic acid sequence within the first target nucleic acid; c) inserting the recorder sequence within the second target nucleic acid; d) cleaving the first target nucleic acid by the targetable nuclease in cells that do not comprise the mutant
PAM sequence, thereby enriching for cells comprising the inserted modified first target nucleic acid sequence. Further provided are methods wherein the recorder sequence is linked to the modified first target nucleic acid. Further provided are methods wherein each polynucleotide further comprises a second mutant PAM sequence. Further provided are methods wherein each polynucleotide further comprises a second guide nucleic acid sequence comprising a guide sequence complementary to a portion of the second target nucleic acid. Further provided are methods wherein the recorder sequence comprises a unique sequence by which the modified first target nucleic acid is specifically identified upon sequencing the recorder sequence. Further provided are methods further comprising e) sequencing the recorder sequence, thereby identifying the modified first target nucleic acid that was inserted within the first target nucleic acid in step b). Further provided are methods wherein inserting the modified first target nucleic acid sequence comprises cleaving the first target nucleic acid by the nuclease complexed with the transcription product of the first guide nucleic acid sequence. Further provided are methods wherein inserting the modified first target nucleic acid sequence further comprises homology- directed repair. Further provided are methods wherein inserting the modified first target nucleic acid sequence further comprises homologous recombination. Further provided are methods wherein the polynucleotide further comprises a second guide nucleic acid sequence comprising a spacer region complementary to a portion of the second target nucleic acid. Further provided are methods wherein inserting the recorder sequence comprises cleaving the second target nucleic acid by the nuclease complexed with the transcription product of the second guide nucleic acid sequence. Further provided are methods wherein inserting the modified first target nucleic acid sequence further comprises homology-directed repair. Further provided are methods wherein inserting the modified first target nucleic acid sequence further comprises homologous recombination. Further provided are methods wherein the targetable nuclease is a Cas protein.
Further provided are methods wherein the Cas protein is a Type II or Type V Cas protein.
Further provided are methods wherein the Cas protein is Cas9 or Cpfl . Further provided are methods wherein the targetable nuclease is a nucleic acid-guided nuclease. Further provided are methods wherein the targetable nuclease is MAD2 or MAD7. Further provided are methods wherein the mutant PAM sequence is not recognized by the targetable nuclease. Further provided are methods wherein the targetable nuclease is an engineered targetable nuclease. Further provided are methods wherein the mutant PAM sequence is not recognized by the engineered targetable nuclease. Further provided are methods further comprising introducing a second plurality of polynucleotides into a second population of cells comprising the enriched cells from step d), wherein each cell within the second population of cells comprises a third nucleic acid, a fourth target nucleic acid, and a targetable nuclease. Further provided are methods wherein each of the second polynucleotides comprises: i) a modified third target nucleic acid sequence; ii) a third mutant protospacer adjacent motif (PAM) sequence; iii) a third guide nucleic acid sequence comprising a spacer region complementary to a portion of the third target nucleic acid; and (iv) a second recorder sequence. Further provided are methods wherein each second polynucleotide further comprises a fourth mutant PAM sequence. Further provided are methods wherein each second polynucleotide further comprises a fourth guide nucleic acid sequence comprising a guide sequence complementary to a portion of the fourth target nucleic acid. Further provided are methods further comprising: a) inserting the modified third target nucleic acid sequence within the third target nucleic acid; b) inserting the second recorder sequence within the fourth target nucleic acid; c) cleaving the third target nucleic acid by the nuclease in cells that do not comprise the second mutant PAM sequence, thereby enriching for cells comprising the inserted modified third target nucleic acid sequence. Further provided are methods wherein the fourth target nucleic acid is adjacent to the second target nucleic acid. Further provided are methods wherein the inserted first recorder sequence is adjacent to the second recorder sequence, such that sequencing information can be obtained for the first and second recorder sequence from a single sequencing read. Further provided are methods further comprising obtaining sequence information from the first and second recorder sequences within a single sequence read, thereby identifying the modified first and third target nucleic acid sequences inserted into the first and third target nucleic acids respectively.
[0011] Provided herein are methods of identifying engineered cells, the method comprising: a) providing cells, wherein each cell comprises a first target nucleic acid, a second target nucleic acid, and a targetable nuclease, b) introducing into the cells a polynucleotide comprising: 1) a first donor nucleic acid comprising i) a modified target nucleic acid sequence; ii) a mutant protospacer adjacent motif (PAM) sequence; and iii) a first guide nucleic acid sequence comprising a first guide sequence complementary to a portion of the first target nucleic acid; and 2) a second donor nucleic acid comprising i) a recorder sequence corresponding to the modified target nucleic acid sequence; and ii) a second guide nucleic acid sequence comprising a second guide sequence complementary to a portion of the second target nucleic acid, c) cleaving the first target nucleic acid by the nuclease in cells that do not comprise the mutant PAM sequence, thereby enriching for cells comprising the modified target nucleic acid sequence, d) repeating steps a) - c) at least one time using the cells enriched for in step c) as the cells for step a) of the following round, wherein the recorder sequence from each round is incorporated adjacent to the recorder sequence from the previous round, thereby generating a record sequence array comprising a plurality of traceable barcodes, and e) sequencing the record sequence, thereby identifying engineered cells comprising a desired combination of modified target nucleic acids. Further provided are methods wherein the second donor nucleic acid further comprises a second mutant PAM sequence. Further provided are methods wherein sequencing the record sequence array comprises obtaining sequence information for each of the plurality of recorder sequences within a single sequencing read. Further provided are methods wherein steps a) - c) are repeated at least once. Further provided are methods wherein steps a) - c) are repeated at least twice. Further provided are methods wherein the recorder sequence is a barcode. Further provided are methods where the first donor nucleic acid and the second donor nucleic acid are covalently linked. A first donor nucleic acid can be a cassette, such as an editing cassette as disclosed herein. A second donor nucleic acid can be a cassette, such as a recording cassette as disclosed herein. A first donor nucleic acid and a second donor nucleic acid can be comprised on a single cassette. A first donor nucleic acid and a second donor nucleic acid can be covalently linked. In any of these examples, the elements of the cassette or donor nucleic acids can be contiguous or non-contiguous.
[0012] Provided herein are methods of identifying engineered cells, the method comprising: a) providing cells, wherein each cell comprises a first target nucleic acid, a second target nucleic acid, and a targetable nuclease, b) introducing into the cells a polynucleotide comprising: 1) a first donor nucleic acid comprising i) a modified target nucleic acid sequence; ii) a mutant protospacer adjacent motif (PAM) sequence; and iii) a first guide nucleic acid sequence comprising a first guide sequence complementary to a portion of the first target nucleic acid; and 2) a second donor nucleic acid comprising i) a marker fragment corresponding to the modified target nucleic acid sequence; and ii) a second guide nucleic acid sequence comprising a second guide sequence complementary to a portion of the second target nucleic acid, c) cleaving the first target nucleic acid by the nuclease in cells that do not comprise the mutant PAM sequence, thereby enriching for cells comprising the modified target nucleic acid sequence, d) repeating steps a) - c) at least one time using the cells enriched for in step c) as the cells for step a) of the following round, wherein the marker fragment from each round is incorporated adjacent to the marker fragment from the previous round, thereby generating a complete marker, and e) identifying cells comprising the complete marker, thereby identifying engineered cells comprising a desired combination of modified target nucleic acids. Further provided are methods wherein the second donor nucleic acid further comprises a second mutant PAM sequence. Further provided are methods wherein the complete marker comprises a selectable marker. Further provided are methods wherein the selectable marker comprises an antibiotic resistance marker or an auxotrophic marker. Further provided are methods wherein the complete marker comprises a screenable reporter. Further provided are methods wherein the screenable reporter comprises a fluorescent reporter. Further provided are methods wherein the screenable reporter comprises a gene. Further provided are methods wherein the screenable reporter comprises a promotor or regulatory element. Further provided are methods wherein the promoter or regulatory element turns on or off transcription of a screenable or selectable element. Further provided are methods wherein the screenable reporter comprises a screenable or selectable element which alters a characteristic of a colony comprising the element compared to a colony that does not comprise the element. A first donor nucleic acid can be a cassette, such as an editing cassette as disclosed herein. A second donor nucleic acid can be a cassette, such as a recording cassette as disclosed herein. A first donor nucleic acid and a second donor nucleic acid can be comprised on a single cassette. A first donor nucleic acid and a second donor nucleic acid can be covalently linked. In any of these examples, the elements of the cassette or donor nucleic acids can be contiguous or non-contiguous.
[0013] Provided herein are methods of genome engineering, the method comprising: a) introducing into a population of cells a polynucleotide, wherein each cell comprises a first target nucleic acid, a second target nucleic acid, and a targetable nuclease, wherein the polynucleotide comprises: i) a modified first target nucleic acid sequence; ii) a mutant nuclease recognition sequence; iii) a recorder sequence; b) inserting the modified first target nucleic acid sequence within the first target nucleic acid; c) inserting the recorder sequence within the second target nucleic acid; and d) selecting for a phenotype of interest. Further provided are methods wherein the polynucleotide further comprises a second mutant nuclease recognition site. Further provided are methods wherein selecting for a phenotype of interest comprises cleaving the first target nucleic acid by the nuclease in cells that do not comprise the mutant nuclease recognition sequence, thereby enriching for cells comprising the inserted modified first target nucleic acid sequence. Further provided are methods wherein selecting for a phenotype of interest comprises cleaving the second target nucleic acid by the nuclease in cells that do not comprise the second mutant nuclease recognition sequence, thereby enriching for cells comprising the inserted modified first target nucleic acid sequence. Further provided are methods wherein the recorder sequence is linked to the modified first target nucleic acid. Further provided are methods wherein the recorder sequence comprises a unique sequence by which the modified first target nucleic acid is specifically identified upon sequencing the recorder sequence. Further provided are methods further comprising e) sequencing the recorder sequence, thereby identifying the modified first target nucleic acid that was inserted within the first target nucleic acid in step b). Further provided are methods wherein inserting the modified first target nucleic acid sequence comprises homology-directed repair. Further provided are methods wherein inserting the modified first target nucleic acid sequence comprises homologous recombination. Further provided are methods wherein the nuclease is a Cas protein. Further provided are methods wherein the polynucleotide further comprises a first guide nucleic acid sequence comprising a guide sequence complementary to a portion of the first target nucleic acid. Further provided are methods wherein inserting the modified first target nucleic acid sequence comprises cleaving the first target nucleic acid by the nuclease complexed with the transcription product of the first guide nucleic acid sequence. Further provided are methods wherein the polynucleotide further comprises a second guide nucleic acid sequence comprising a guide sequence complementary to a portion of the second target nucleic acid. Further provided are methods wherein inserting the recorder sequence comprises cleaving the second target nucleic acid by the nuclease complexed with the transcription product of the second guide nucleic acid sequence. Further provided are methods wherein inserting the modified first target nucleic acid sequence or the recorder sequence comprises homology-directed repair. Further provided are methods wherein inserting the modified first target nucleic acid sequence or the recorder sequence comprises homologous recombination. Further provided are methods wherein the mutant nuclease recognition sequence comprises a mutant PAM sequence not recognized by the targetable nuclease. Further provided are methods wherein the Cas protein is a Type II or Type V Cas protein. Further provided are methods wherein the targetable nuclease is MAD2. Further provided are methods wherein the mutant PAM sequence is not recognized by MAD2. Further provided are methods wherein the targetable nuclease is MAD7. Further provided are methods wherein the mutant PAM sequence is not recognized by MAD7. Further provided are methods wherein the Cas protein is Cas9. Further provided are methods wherein the mutant PAM sequence is not recognized by Cas9. Further provided are methods wherein the Cas protein is Cpfl . Further provided are methods wherein the mutant PAM sequence is not recognized by Cpfl . Further provided are methods wherein the nuclease is an Argonaute nuclease. Further provided are methods further comprising introducing guide DNA oligonucleotides comprising a guide sequence complementary to a portion of the first target nucleic acid prior to selecting for a phenotype. Further provided are methods wherein the mutant nuclease recognition sequence comprises a mutant target flanking sequence not recognized by the Argonaute nuclease. Further provided are methods wherein the nuclease is a zinc finger nuclease. Further provided are methods wherein the mutant nuclease recognition sequence is not recognized by the zinc finger nuclease. Further provided are methods wherein the nuclease is a transcription activator-like effector nuclease (TALEN). Further provided are methods wherein the mutant nuclease recognition sequence is not recognized by the TALEN.
INCORPORATION BY REFERENCE
[0014] All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] Figures 1A-1C depict an example genetic engineering workflow including target design, plasmid design, and plasmid library generation.
[0016] Figures 2A-2D depicts validation data for an example experiment using a disclosed engineering method.
[0017] Figures 3A-3C depict an example trackable genetic engineering workflow, including a plasmid comprising an editing cassette and a recording cassette, and downstream sequencing of barcodes in order to identify the incorporated edit or mutation.
[0018] Figures 3D-3E depict an example trackable genetic engineering workflow, including iterative rounds of engineering with a different editing cassette and recorder cassette with unique barcode (BC) at each round, followed by selection and tracking to confirm the successful engineering step at each round..
[0019] Figures 4A-4B depict an example of incorporation of a target mutation and PAM mutation using a plasmid comprising an editing cassette.
[0020] Figures 5A-5B depict an example of a plasmid comprising an editing cassette, designed to incorporate a target mutation and a PAM mutation into a first target sequence, and a recording cassette, designed to incorporate a barcode sequence into a second target sequence. Figure 5B depicts example data validating incorporation of the editing cassette and recorder cassette and selection of the engineered bacterial cells.
[0021] Figure 6 depicts an example recursive engineering workflow.
[0022] Figures 7A-7B depict an example plasmid curing workflow for combinatorial engineering and validation of an example experiment using said workflow.
[0023] Figures 8A-8B depict an example genetic engineering workflow including target design, plasmid design, and plasmid library generation.
[0024] Figures 9A-9D depicts validation data for an example genetic engineering experiment. [0025] Figures 10A-10F depict an example data set from a genetic engineering experiment.
[0026] Figures 11A-11C depict an example design and data set from a genetic engineering experiment.
[0027] Figures 12A-12F depict an example design for a genetic engineering experiment.
[0028] Figures 13A-13D depict example designed edits to be made by a genetic engineering.
[0029] Figures 14A-14B depict an example design for a genetic engineering experiment.
[0030] Figures 15A-15D depict an example of Cas9 editing efficiency controls.
[0031] Figures 16A-16E depict an examples of toxicity of dsDNA cleavage in E. coli.
[0032] Figure 16F-16H depict an example of a transformation and survival assay, and editing and recording efficiencies, with low and high copy plasmids expressing Cas9.
[0033] Figures 17A-17D depict an example of genetic engineering strategy for gene deletion.
[0034] Figures 18A-18B depicts an example of editing efficiency controls by cotransformation of guide nucleic acid and linear dsDNA cassettes.
[0035] Figures 19A-19D depict an example of library cloning analysis and statistics.
[0036] Figures 20A-20B depict an example of precision of editing cassette tracking of recombineered populations.
[0037] Figure 21 depicts an example of growth characteristics of folA mutations in M9 minimal media
[0038] Figures 22A-22C depicts an example of enrichment profiles for folA editing cassettes in minimal media.
[0039] Figures 23A-23F depict an example of validation of identified acrB mutations for improved solvent and antibiotic tolerance.
[0040] Figures 24A-24D depict an example mutant variant assessment analysis.
[0041] Figure 25 depicts an example of reconstruction of mutations identified by erythromycin selection.
[0042] Figures 26A-26B depict an example of validation of Crp S28P mutation for furfural or thermal tolerance.
[0043] Figures 27A-27C depict an example of edit and barcode correlation studies.
[0044] Figure 28 depicts an example of a selectable recording strategy.
[0045] Figure 29 depicts an example of a selectable recording strategy.
[0046] Figures 30A-30B depict data from a selectable recording experiment.
[0047] Figures 31A-31B depict editing and transformation efficiencies from various nucleic acid-guided nucleases from an example experiment.
[0048] Figure 32 depict editing efficiencies of the MAD2 nuclease with various guide nucleic acids. [0049] Figure 33 depict editing efficiencies of the MAD7 nuclease with various guide nucleic acids.
DETAILED DESCRIPTION OF THE DISCLOSURE
[0050] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention.
[0051] Methods and compositions for enabling sophisticated combinatorial engineering strategies to optimize and explore complex phenotypes are provided herein. Many phenotypes of interest to basic research and biotechnology are the result of combinations of mutations that occur at distal loci. For example, cancer is often linked to mutations that influence multiple hallmark gene functions rather than a single chromosomal edit. Likewise, many metabolic and regulatory processes that are the target of continuing engineering efforts require the activities of many proteins acting in concert to produce the phenotypic output of interest. Methods and compositions disclosed herein can provide ways of rapid engineering and prototyping of such functions since they can provide rapid construction and accurate reporting on the mutational effects at many sites in parallel.
[0052] The methods and compositions described herein can be carried out or used in any type of cell in which a nucleic acid-guided nuclease system, such as CRISPR or Argonaute, or other targetable nuclease systems, such as TALEN, ZFN, or meganuclease can function (e.g., target and cleave DNA), including prokaryotic, eukaryotic, or archaeal cells. The cell can be a bacterial cell, such as Escherichia spp. (e.g., E. coli). The cell can be a fungal cell, such as a yeast cell, e.g., Saccharomyces spp. The cell can be a human cell. The cell can be an algal cell, a plant cell, an insect cell, or a mammalian cell, including a human cell. Additionally or alternatively, the methods described herein can be carried out in vitro or in cell-free systems in which a nucleic acid guided nuclease system, such as CRISPR or Argonaute, or other nuclease systems, such as TALEN, ZFN, or meganuclease can function (e.g., target and cleave DNA).
[0053] Disclosed herein are compositions and methods for genetic engineering. Disclosed are methods and compositions suitable for trackable or recursive genetic engineering. Disclosed method and compositions can use massively multiplexed oligonucleotide synthesis and cloning to enable high fidelity, trackable, multiplexed genome editing at single nucleotide resolution on a whole genome scale. Trackable plasmids
[0054] Methods and compositions can be used to perform high-fidelity trackable editing, for example, at single-nucleotide resolution and can be used to perform editing at a whole genome scale or on episomal nucleic acid molecules. Massively multiplexed oligonucleotide synthesis and/or cloning can be used in combination with a targetable nuclease system, such as a CRISPR system, MAD2 system, MAD7 system, or other nucleic acid-guided nuclease system, for editing.
[0055] As used herein, "cassette" often refers to a single molecule polynucleotide. A cassette can comprise DNA. A cassette can comprise RNA. A cassette can comprise a combination of DNA and RNA. A cassette can comprise non-naturally occurring nucleotides or modified nucleotides. A cassette can be single stranded. A cassette can be double stranded. A cassette can be synthesized as a single molecule. A cassette can be assembled from other cassettes, oligonucleotides, or other nucleic acid molecules. A cassette can comprise one or more elements. Such elements can include, as non-limiting examples, one or more of any of editing sequences, recorder sequences, guide nucleic acids, promoters, regulatory elements, mutant PAM sequences, homology arms, primer sites, linker regions, unique landing sites, a cassette, and any other element disclosed herein. Such elements can be in any order or combination. Any two or more elements can be contiguous or non-contiguous. A cassette can be comprised within a larger polynucleic acid. Such a larger polynucleic acid can be linear or circular, such as a plasmid or viral vector. A cassette can be a synthesized cassette. A cassette can be a trackable cassette.
[0056] A cassette can be designed to be used in any method or composition disclosed herein, including multiplex engineering methods and trackable engineering methods. An exemplary cassette can couple two or more elements, such as 1) a guide nucleic acid (e.g. gRNAs or gDNAs) designed for targeting a user specified target sequence in the genome and 2) an editing sequence and/or recorder sequence as disclosed herein (e.g. Figure IB and Figure 5A). A cassette comprising an editing sequence and guide nucleic acid can be referred to as an editing cassette. A cassette comprising an editing sequence can be referred to as an editing cassette. A cassette comprising a recorder sequence and a guide nucleic acid can be referred to as a recorder cassette. A cassette comprising a recorder sequence can be referred to as a recorder cassette. In a preferred embodiment, an editing cassette and a recorder cassette are delivered into the cell at the same time. Further, an editing cassette and a recorder cassette may be covalently linked. Further, these elements may be synthesized together by multiplexed oligonucleotide synthesis.
[0057] A cassette can comprise one or more guide nucleic acids and editing cassette as a contiguous polynucleotide. In other examples, one or more guide nucleic acids and editing cassette are contiguous. In other examples, one or more guide nucleic acids and editing cassette are non-contiguous. In other examples, two or more guide nucleic acids and editing cassette are non-contiguous.
[0058] A cassette can comprise one or more guide nucleic acids, an editing cassette, and a recorder cassette as a contiguous polynucleotide. In other examples, one or more guide nucleic acids, editing cassette, and recorder cassette are contiguous. In other examples, two or more guide nucleic acids, editing cassette, and recorder cassette are contiguous. In other examples, one or more guide nucleic acids, editing cassette, and recorder cassette are non-contiguous. In other examples, two or more guide nucleic acids, editing cassette, and recorder cassette are noncontiguous.
[0059] A cassette can comprise one or more guide nucleic acids, one or more editing cassettes, and one or more recorder cassettes as a contiguous polynucleotide. In other examples, one or more guide nucleic acids, one or more editing cassettes, and one or more recorder cassettes are contiguous. In other examples, two or more guide nucleic acids, two or more editing cassettes, and two or more recorder cassettes are contiguous. In other examples, one or more guide nucleic acids, one or more editing cassettes, and one or more recorder cassettes are non-contiguous. In other examples, two or more guide nucleic acids, two or more editing cassettes, and two or more recorder cassettes are non-contiguous.
[0060] A cassette can comprise one or more guide nucleic acids and editing sequence as a contiguous polynucleotide. In other examples, one or more guide nucleic acids and editing sequence are contiguous. In other examples, one or more guide nucleic acids and editing sequence are non-contiguous. In other examples, two or more guide nucleic acids and editing sequence are non-contiguous.
[0061] A cassette can comprise one or more guide nucleic acids, an editing sequence, and a recorder sequence as a contiguous polynucleotide. In other examples, one or more guide nucleic acids, editing sequence, and recorder sequence are contiguous. In other examples, two or more guide nucleic acids, editing sequence, and recorder sequence are contiguous. In other examples, one or more guide nucleic acids, editing sequence, and recorder sequence are non-contiguous. In other examples, two or more guide nucleic acids, editing sequence, and recorder sequence are non-contiguous.
[0062] A cassette can comprise one or more guide nucleic acids, one or more editing sequences, and one or more recorder sequences as a contiguous polynucleotide. In other examples, one or more guide nucleic acids, one or more editing sequences, and one or more recorder sequences are contiguous. In other examples, two or more guide nucleic acids, two or more editing sequences, and two or more recorder sequences are contiguous. In other examples, one or more guide nucleic acids, one or more editing sequences, and one or more recorder sequences are non-contiguous. In other examples, two or more guide nucleic acids, two or more editing sequences, and two or more recorder sequences are non-contiguous.
[0063] An editing cassette can comprise an editing sequence. An editing sequence can comprise a mutation, such as a synonymous or non-synonymous mutation, and homology arms (HAs). An editing sequence can comprise a mutation, such as a synonymous or non-synonymous mutation, and homology arms (HAs) designed to undergo homologous recombination with the target sequence at the site of nucleic acid-guided nuclease-mediated double strand break (e.g. Figure IB).
[0064] A recorder cassette can comprise a recorder sequence. A recorder sequence can comprise a trackable sequence, such as a barcode or marker, and homology arms (HAs). A recorder sequence can comprise a trackable sequence, such as a barcode or marker, and homology arms (HAs) designed to undergo homologous recombination with the chromosome at the site of nucleic acid-guided nuclease-mediated double strand break (e.g. Figure IB).
[0065] A cassette can encode machinery (e.g. targetable nuclease, guide nucleic acid, editing cassette, and/or recorder cassette as disclosed herein) necessary to induce strand breakage as well as designed repair that can be selectively enriched and/or tracked in cells. A cell can be any cell such as eukaryotic cell, archaeal cell, prokaryotic cell, or microorganisms such as E. coli (e.g. Figure 2A-2D).
[0066] A cassette can comprise an editing cassette. A cassette can comprise a recorder cassette. A cassette can comprise a guide nucleic acid and an editing cassette. A cassette can comprise a guide nucleic acid and a recorder cassette. A cassette can comprise a guide nucleic acid, an editing cassette, and a recorder cassette. A cassette can comprise two guide nucleic acids, an editing cassette, and a recorder cassette. A cassette can comprise more than two guide nucleic acids, one or more editing cassettes, and one or more recorder cassettes. These elements of a cassette can be linked covalently. These elements of a cassette can be contiguous. These elements of a cassette can be contiguous.
[0067] A cassette can comprise an editing sequence. A cassette can comprise a recorder sequence. A cassette can comprise a guide nucleic acid and an editing sequence. A cassette can comprise a guide nucleic acid and a recorder sequence. A cassette can comprise a guide nucleic acid, an editing sequence, and a recorder sequence. A cassette can comprise two guide nucleic acids, an editing sequence, and a recorder sequence. A cassette can comprise more than two guide nucleic acids, one or more editing sequences, and one or more recorder sequences. These elements of a cassette can be linked covalently. These elements of a cassette can be contiguous. These elements of a cassette can be contiguous. [0068] Single genome edits can be tracked using sequencing technologies, e.g. short read sequencing technologies (e.g. Figure 1C), long read sequencing technologies, or any other sequencing technologies known in the art.
[0069] In some embodiments, upon transformation, each editing cassette generates the designed genetic modification within the transformed cell. In some examples, the editng cassette can act in trans as a barcode of the genetic mutation introduced by the editing cassette and can enable the tracking of this mutation frequency in a complex population over time and across many different growth conditions (e.g. Figure 2A-2D and Figure 1C).
[0070] In some examples, a recording cassette inserts the designed trackable sequence, such as a marker or barcode sequence, within the transformed cell. In some examples, the recorder cassette can act in cis as a barcode of the chromosomal mutation and can enable the tracking of this mutation frequency in a complex population over time and across many different growth conditions.
[0071] By providing cis and/or trans tracking of designed genomic mutations, the methods provided herein simplify sample preparation and depth of coverage for mapping diversity genome wide, and provide powerful tools for engineering on a genome scale (e.g. Figure 1C).
[0072] A plurality of cassettes can be pooled into a library of cassettes. A library of cassettes can comprise at least 2 cassettes. A library of cassettes can comprise from 5 to a million cassettes. A library of cassettes can comprise at least a million cassettes. It should be understood, that a library of cassettes can comprise any number of cassettes.
[0073] A library of cassettes can comprise cassettes that have any combination of common elements and non-common or unique elements as compared to the other cassettes within the pool. For example, a library of cassettes can comprise common priming sites or common homology arms while also containing non-common or unique barcodes. Common elements can be shared by a plurality, majority, or all of the cassettes within a library of cassettes. Non- common elements can be shared by a plurality, minority, or sub-population of cassettes within the library of cassettes. Unique elements can be shared by a one, a few, or a sub-population of cassettes within the library of cassettes, such that it is able to identify or distinguish the one, few, or sub-population of cassettes from the other cassettes within the library of cassettes. Such combinations of common and non-common are advantageous for multiplexing techniques as disclosed herein.
[0074] Cassettes disclosed herein can generate the designed genetic modification or insert the designed marker or barcode sequence with high efficiency within a transformed cell. In many examples, the efficiency is greater than 50%. In some examples the efficiency is 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% (e.g., Figures 32A, 32B, and 33). [0075] In some examples, transformation, editing, and/or recording efficiency can be increased by modulating the expression of one or more components disclosed herein, such as a nucleic acid-guided nuclease. Methods for modulating components are disclosed herein and are known in the art. Such methods can include expressing a component, such as a nucleic acid- guided nuclease or CRISPR enzyme of a subject system on a low or high copy plasmid, depending on the experimental design.
[0076] Disclosed herein are methods and compositions for generating cassettes. A cassettes can comprise a cassettes as disclosed herein. For example, a cassette can comprise any combination of an editing cassette and/or recorder cassette disclosed herein. Such a cassette can be comprised on a larger polynucleic acid molecule. Such a larger polynucleic acid molecule can be linear or circular, such as a plasmid or viral vector.
[0077] An editing cassette can comprise a mutation relative to a target nucleic acid sequence. The editing cassette can comprise sequence homologous to the target sequence flanking the desired mutation or editing sequence. The editing cassette can comprise a region which recognizes, or hybridizes to, a target sequence of a nucleic acid in a cell or population of cells, is homologous to the target sequence of the nucleic acid of the cell and includes a mutation, or a desired mutation, of at least one nucleotide relative to the target sequence.
[0078] An editing cassette can comprise a first editing sequence comprising a first mutation relative to a target sequence. A first mutation can comprise a mutation such as an insertion, deletion, or substitution of at least one nucleotide compared to the non-editing target sequence. The mutation can be incorporated into a coding region or non-coding region.
[0079] An editing cassette can comprise a second editing sequence comprising a second mutation relative to a target sequence. The second mutation can be designed to mutate or otherwise silence a PAM sequence such that a corresponding nucleic acid guided nuclease or CRISPR nuclease is no longer able to cleave the target sequence. In such cases, this mutation or silencing of a PAM can serve as a method for selecting transformants in which the first editing sequence has been incorporated.
[0080] In some examples, an editing cassette comprises at least two mutations, wherein one mutation is a PAM mutation. In some examples, the PAM mutation can be in a second editing cassette. Such a second editing cassette can be covalently linked and can be continuous or noncontiguous to the other elements in the cassette.
[0081] An editing cassette can comprise a guide nucleic acid, such as a gRNA encoding gene, optionally operably linked to a promoter. The guide nucleic acid can be designed to hybridize with the targeted nucleic acid sequence in which the editing sequence will be incorporated. [0082] A recording cassette can comprise a recording sequence. A recorder sequence can comprise a barcoding sequence, or other screenable or selectable marker or fragment thereof. The recording sequence can be comprised within a recorder cassette. Recorder cassettes can comprise regions homologous to an insertion site within a target nucleic acid sequence such that the recording sequence is incorporated by homologous recombination or homology-driven repair systems. The site of incorporation of the recording cassette can be comprised on the same DNA molecule as the target nucleic acid to be edited by an editing cassette. The recorder sequence can comprise a barcode, unique DNA sequence, and/or a complete copy or fragment of a selectable or screenable element or marker.
[0083] A recorder cassette can comprise a mutation relative to the target sequence. The mutation can be designed to mutate or otherwise silence a PAM sequence such that a corresponding nucleic acid guided nuclease or CRISPR nuclease is no longer able to cleave the target sequence. In such cases, this mutation or silencing of a PAM site can serve as a method for selecting transformants in which the first recording sequence has been incorporated. A recorder cassette can comprise a PAM mutation. The PAM mutation can be designed to mutate or otherwise silence a PAM site such that a corresponding CRISPR nuclease is no longer able to cleave the target sequence. In such cases, this mutation or silencing of a PAM site can serve as a method for selecting transformants in which the recorder sequence has been incorporated.
[0084] A recorder cassette can comprise a guide nucleic acid, such as a gene encoding a gRNA. A promoter can be operably linked to a nucleic acid sequence encoding a guide nucleic acid capable of targeting a nucleic acid-guided nuclease to the desired target sequence. A guide nucleic acid can target a unique site within the target site. In some cases, the guide nucleic acid targets a unique landing site that was incorporated in a prior round of engineering. In some cases, the guide nucleic acid targets a unique landing site that was incorporated by a recorder cassette in a prior round of engineering.
[0085] A recorder cassette can comprise a barcode. A barcode can be a unique barcode or relatively unique such that the corresponding mutation can be identified based on the barcode. In some examples, the barcode is a non-naturally occurring sequence that is not found in nature. In most examples, the combination of the desired mutation and the barcode within the editing cassette is non-naturally occurring and not found in nature. A barcode can be any number of nucleotides in length. A barcode can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or more than 30 nucleotides in length. In some cases, the barcode is more than 30 nucleotides in length. A barcode can be generated by degenerate oligonucleotide synthesis. A barcode can be rationally designed or user-specified. [0086] A recorder cassette can comprise a landing site. A landing site can serve as a target site for a recorder cassette for a successive engineering round. A landing site can comprise a PAM. A landing site can be a unique sequence. A landing site can be at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50 nucleotides in length. In some cases, the landing site is greater than 50 nucleotides in length.
[0087] A recorder cassette can comprise a selectable or screenable marker, or a regulatory sequence or mutation that turns a selectable or screenable marker on or off. In such cases, the turning on or off of a selectable marker can be used of selection or counter-selection, respectively, of iterative rounds of engineering. An example regulatory sequence includes a ribosome-binding site (RBS), though other such regulatory sequences are envisioned. Mutations that turn a selectable or screenable marker on can include any possible start codon that is recognized by the host transcription machinery. A mutation that turns off a selectable or screenable marker includes a mutation that deletes a start codon or one that inserts a premature stop codon or a reading frame shift mutation.
[0088] A recorder cassette can comprise one or more of a guide nucleic acid targeting a target site into which the recorder sequence is to be incorporated, a PAM mutation to silence a PAM used by the guide RNA, a barcode corresponding to an editing cassette, a unique site to serve as a landing site for a recorder cassette of a subsequent rounds of engineering, a regulatory sequence or mutation that turns a screenable or selectable marker on or off, these one or more elements being flanked by homology arms that are designed to promote recombination of these one or more elements into the cleaved target site that is targeted by the guide RNA.
[0089] A recorder cassette can comprise a first homology arm, a PAM mutation, a barcode, a unique landing site, a regulatory sequence or mutation for a screenable or selectable marker, a second homology arm, and guide RNA. The first homology arm can be an upstream homology arm. The second homology arm can be a downstream homology arm. The homology arms can be homologous to sequences flanking a cleavage site that is targeted by the guide RNA.
[0090] A cassette can comprise two guide nucleic acids designed to target two distinct target nucleic acid sequences. In any case, the guide nucleic acid can comprise a single gRNA or chimeric gRNA consisting of a crRNA and trRNA sequences, or alternatively, the gRNA can comprise separated crRNA and trRNAs, or a guide nucleic acid can comprise a crRNA. In other examples, guide nucleic acid can be introduced simultaneously with a trackable polynucleic acid or plasmid comprising an editing cassette and/or recorder cassette. In these cases, the guide nucleic acid can be encoded on a separate plasmid or be delivered in RNA form via delivery methods well known in the art. [0091] A cassette can comprise a gene encoding a nucleic acid-guided nuclease, such as a CRISPR nuclease, functional with the chosen guide nucleic acid. A nucleic acid-guided nuclease or CRISPR nuclease gene can be provided on a separate plasmid. A nucleic acid-guided nuclease or CRISPR nuclease can be provided on the genome or episomal plasmid of a host organism to which a trackable polynucleic acid or plasmid will be introduced. In any of these examples, the nucleic acid-guided nuclease or CRISPR nuclease gene can be operably linked to a constitutive or inducible promotor. Examples of suitable constitutive and inducible promoters are well known in the art. A nucleic acid-guided nuclease or CRISPR nuclease can be provided as mRNA or polypeptide using delivery systems well known in the art. Such mRNA or polypeptide delivery systems can include, but are not limited to, nanoparticles, viral vectors, or other cell-permeable technologies.
[0092] A cassette can comprise a selectable or screenable marker, for example, such as that comprised within a recorder cassette. For example, the recorder cassette can comprise a barcode, such as trackable nucleic acid sequence which can be uniquely correlated with a genetic mutation of the corresponding editing cassette, or otherwise identifiably correlated with such a genetic mutation such that sequencing the barcode will allow identification of the corresponding genetic mutation introduced by the editing cassette. In other examples, recorder cassette can comprise a complete copy of or a fragment of a gene encoding an antibiotic resistance gene, auxotrophic marker, fluorescent protein, or other known selectable or screenable markers.
Trackable plasmid libraries
[0093] A trackable library can comprise a plurality of cassettes as disclosed herein. A trackable library can comprise a plurality of trackable polynucleic acids or plasmids comprising a cassette as disclosed herein. A cassette, polynucleotide, or plasmid comprising a recorder sequence or recorder cassette as disclosed herein can be referred to as a trackable cassette, polynucleotide, or plasmid. A cassette, polynucleotide, or plasmid comprising an editing sequence or editing cassette as disclosed herein can be referred to as a trackable cassette, polynucleotide, or plasmid.
[0094] In some cases, within the trackable library are distinct editing cassette and recorder cassette combinations that are sequenced to determine which editing sequence corresponds with a given marker or barcode sequence comprised within the recorder cassette. Therefore, when the editing and recorder sequences are incorporated into a target sequence, you can determine the edit that was incorporated by sequencing the recorder sequence. Sequence the recorder sequence or barcode can significantly cut down on sequencing time and cost.
[0095] Library size can depend on the experiment design. For example, if the aim is to edit each amino acid within a protein of interest, then the library size can depend on the number (N) of amino acids in a protein of interest, with a full saturation library (all 20 amino acids at each position or non-naturally occurring amino acids) scaling as 19 (or more)xN and an alanine- mapping library scaling as l xN. Thus, screening of even very large proteins of more than 1,000 amino acids can be tractable given current multiplex oligo synthesis capabilities (e.g. 120,000 oligos). In addition to or as an alternative to activity screens, more general properties with developed high-throughput screens and selections can be efficiently tested using the libraries disclosed herein. It should be readily understood that libraries can be designed to mutate any number of amino acids within a target protein, including 1, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc. up to the total number of amino acids within a target protein. Additionally, select amino acids can be targeted, such as catalytically active amino acids, or those involved in protein-protein interactions. Each amino acid that is targeted for mutation can be mutated into any number of alternate amino acids, such as any other natural or non-naturally occurring amino acid or amino acid analog. In some examples, all targeted amino acids are mutated to the same amino acid, such as alanine. In other cases, the targeted amino acids are independently mutated to any other amino acid in any combination or permutation.
[0096] Trackable libraries can comprise trackable mutations in individual residues or sequences of interest. Trackable libraries can be generated using custom-synthesized oligonucleotide arrays. Trackable plasmids can be generated using any cloning or assembly methods known in the art. For example, CREATE-Recorder plasmids can be generated by chemical synthesis, Gibson assembly, SLIC, CPEC, PCA, ligation-free cloning, other in vitro oligo assembly techniques, traditional ligation-based cloning, or any combination thereof.
[0097] Recorder sequences, such as barcodes, can be designed in silico via standard code with a degenerate mutation at the target codon. The degenerate mutation can comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or more than 30 nucleic acid residues. In some examples, the degenerate mutations can comprise 15 nucleic acid residues (N15).
[0098] Homology arms can be added to a recorder sequence and/or editing sequence to allow incorporation of the recorder and/or editing sequence into the desired location via homologous recombination or homology-driven repair. Homology arms can be added by synthesis, in vitro assembly, PCR, or other known methods in the art. For example, homology arms can be assembled via overlapping oligo extension, Gibson assembly, or any other method disclosed herein. A homology arm can be added to both ends of a recorder and/or editing sequence, thereby flanking the sequence with two distinct homology arms, for example, a 5' homology arm and a 3' homology arm. [0099] The same 5' and 3' homology arms can be added to a plurality of distinct recorder sequences, thereby generating a library of unique recorder sequences that each have the same spacer target or targeted insertion site. The same 5' and 3' homology arms can be added to a plurality of distinct editing sequences, thereby generating a library of unique editing sequences that each have the same spacer target or targeted insertion site. In alternative examples, different or a variety of 5' or 3' homology arms can be added to a plurality of recorder sequences or editing sequences.
[00100] A recorder sequence library comprising flanking homology arms can be cloned into a vector backbone. In some examples, the recorder sequence and homology arms are cloned into a recorder cassette. Recorder cassettes can, in some cases, further comprise a nucleic acid sequence encoding a guide nucleic acid or gRNA engineered to target the desired site of recorder sequence insertion. In many cases, the nucleic acid sequences flanking the CRISPR/Cas- mediated cleavage site are homologous or substantially homologous to the homology arms comprised within the recorder cassette.
[00101] An editing sequence library comprising flanking homology arms can be cloned into a vector backbone. In some examples, the editing sequence and homology arms are cloned into an editing cassette. Editing cassettes can, in some cases, further comprise a nucleic acid sequence encoding a guide nucleic acid or gRNA engineered to target the desired site of editing sequence insertion. In many cases, the nucleic acid sequences flanking the CRISPR/Cas-mediated cleavage site are homologous or substantially homologous to the homology arms comprised within the editing cassette.
[00102] Gene-wide or genome-wide editing libraries can be subcloned into a vector backbone. In some cases, the vector backbone comprises a recorder cassette as disclosed herein. The editing sequence library can be inserted or assembled into a second site to generate competent trackable plasmids that can embed the recording barcode at a fixed locus while integrating the editing libraries at a wide variety of user defined sites.
[00103] A recorder sequence and/or cassette can be assembled or inserted into a vector backbone first, followed by insertion of an editing sequence and/or cassette. In other cases, an editing sequence and/or cassette can be inserted or assembled into a vector backbone first, followed by insertion of a recorder sequence and/or cassette. In other cases, a recorder sequence and/or cassette and an editing sequence and/or cassette are simultaneous inserted or assembled into a vector. In other cases, a recorder sequence and/or cassette and an editing sequence and/or cassette are comprised on the same cassette prior to simultaneous insertion or assembly into a vector. In other cases, a recorder sequence and/or cassette and an editing sequence and/or cassette are linked prior to simultaneous insertion or assembly into a vector. In other cases, a recorder sequence and/or cassette and an editing sequence and/or cassette are covalently linked prior to simultaneous insertion or assembly into a vector. In any of these cases, trackable plasmids or plasmid libraries can be generated.
[00104] A cassette or nucleic acid molecule can be synthesized which comprises one or more elements disclosed herein. For example, a nucleic acid molecule can be synthesized that comprises an editing cassette and a guide nucleic acid. A nucleic acid molecule can be synthesized that comprises an editing cassette and a recorder cassette. A nucleic acid molecule can be synthesized that comprises an editing cassette, a guide nucleic acid, and a recorder cassette. A nucleic acid molecule can be synthesized that comprises an editing cassette, a recorder cassette, and two guide nucleic acids. A nucleic acid molecule can be synthesized that comprises a recorder cassette and a guide nucleic acid. A nucleic acid molecule can be synthesized that comprises a recorder cassette. A nucleic acid molecule can be synthesized that comprises an editing cassette. In any of these cases, the guide nucleic acid can optionally be operably linked to a promoter. In any of these cases, the nucleic acid molecule can further include one or more barcodes.
[00105] Synthesized cassettes or synthesized nucleic acid molecules can be synthesized using any oligonucleotide synthesis method known in the art. For example, cassettes can be synthesized by array based oligonucleotide synthesis. In such examples, following synthesis of the oligonucleotides, the oligonucleotides can be cleaved from the array. Cleavage of oligonucleotides from an array can create a pool of oligonucleotides.
[00106] Software and automation methods can be used for multiplex synthesis and generation. For example, software and automation can be used to create 10, 10 2 , 10 3 , 10 4 , 10 5 , 10 6 , or more cassettes, such as trackable cassettes. An automation method can generate trackable plasmids in rapid fashion. Trackable cassettes can be processed through a workflow with minimal steps to produce precisely defined genome-wide libraries.
[00107] Cassette libraries, such as trackable cassette libraries, can be generated which comprise two or more nucleic acid molecules or plasmids comprising any combination disclosed herein of recorder sequence, editing sequence, guide nucleic acid, and optional barcode, including combinations of one or more of any of the previously mentioned elements. For example, such a library can comprise at least 2, 3, 4, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500, 10 4 , 10 5 , 10 6 , 10 7 , 10 8 , 10 9 , 10 10 , or more nucleic acid molecules or plasmids of the present disclosure. It should be understood that such a library can include any number of nucleic acid molecules or plasmids, even if the specific number is not explicit listed above. [00108] Cassettes or cassette libraries can be sequenced in order to determine the recorder sequence and editing sequence pair that is comprised on each cassette. In other cases, a known recorder sequence is paired with a known editing sequence during the library generation process. Other methods of determining the association between a recorder sequence and editing sequence comprised on a common nucleic acid molecule or plasmid are envisioned such that the editing sequence can be identified by identification or sequencing of the recorder sequence.
[00109] Methods and compositions for tracking edited episomal libraries that are shuttled between E. coli and other organisms/cell lines are provided herein. The libraries can be comprised on plasmids, Bacterial artificial chromosomes (BACs), Yeast artificial chromosomes (YACs), synthetic chromosomes, or viral or phage genomes. These methods and compositions can be used to generate portable barcoded libraries in host organisms, such as E. coli. Library generation in such organisms can offer the advantage of established techniques for performing homologous recombination. Barcoded plasmid libraries can be deep-sequenced at one site to track mutational diversity targeted across the remaining portions of the plasmid allowing dramatic improvements in the depth of library coverage (e.g. Figure 3 A).
Trackable engineering methods
[00110] An example of trackable engineering workflow is depicted in Figure 3 A. Each plasmid can encode a recorder cassette designed to edit a site in the target DNA (e.g. Figure 3A, black cassette). Sites to be targeted can be functionally neutral sites, or they can be a screenable or selectable marker gene. The homology arm (HA) of the recorder cassette can contain a recorder sequence (e.g., Figure 3B) that is inserted into the recording site during recombineering. Recombineering can comprise DNA cleavage, such as nucleic acid-guided nuclease-mediated DNA cleavage, and repair via homologous recombination. The recorder sequence can comprise a barcode, unique DNA sequence, or a complete copy or fragment of a screenable or selectable marker. In some examples, the recorder sequence is 15 nucleotides. The recorder sequence can comprise less than 10, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 88, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more than 200 nucleotides.
[00111] Through a multiplexed cloning approach, the recorder cassette can be covalently coupled to at least one editing cassette in a plasmid (e.g., Figure 3A, green cassette) to generate trackable plasmid libraries that have a unique recorder and editing cassette combination. This trackable library can be sequenced to generate the recorder/edit mapping and used to track editing libraries across large segments of the target DNA (e.g., Figure 3C). Recorder and editing sequences can be comprised on the same polynucleotide, in which case they are both incorporated into the target nucleic acid sequence, such as a genome or plasmid, by the same recombination event. In other examples, the recorder and editing sequences can be comprised on separate cassettes within the same trackable plasmid, in which case the recorder and editing sequences are incorporated into the target nucleic acid sequence by separate recombination events, either simultaneously or sequentially.
[00112] Methods are provided herein for combining multiplex oligonucleotide synthesis with recombineering, to create libraries of specifically designed and trackable mutations. Screens and/or selections followed by high-throughput sequencing and/or barcode microarray methods can allow for rapid mapping of mutations leading to a phenotype of interest.
[00113] Methods and compositions disclosed herein can be used to simultaneously engineer and track engineering events in a target nucleic acid sequence.
[00114] Trackable plasmids can be generated using in vitro assembly or cloning techniques. For example, the CREATE-Recorder plasmids can be generated using chemical synthesis, Gibson assembly, SLIC, CPEC, PCA, ligation-free cloning, other in vitro oligo assembly techniques, traditional ligation-based cloning, or any combination thereof.
[00115] Trackable plasmids can comprise at least one recording sequence, such as a barcode, and at least one editing sequence. In most cases, the recording sequence is used to record and track engineering events. Each editing sequence can be used to incorporate a desired edit into a target nucleic acid sequence. The desired edit can include insertion, deletion, substitution, or alteration of the target nucleic acid sequence. In some examples, the one or more recording sequence and editing sequences are comprised on a single cassette comprised within the trackable plasmid such that they are incorporated into the target nucleic acid sequence by the same engineering event. In other examples, the recording and editing sequences are comprised on separate cassettes within the trackable plasmid such that they are each incorporated into the target nucleic acid by distinct engineering events. In some examples, the trackable plasmid comprises two or more editing sequences. For example, one editing sequence can be used to alter or silence a PAM sequence while a second editing sequence can be used to incorporate a mutation into a distinct sequence.
[00116] Recorder sequences can be inserted into a site separated from the editing sequence insertion site. The inserted recorder sequence can be separated from the editing sequence by lbp or any number of base pairs. For example, the separation distance can be about lbp, lObp, 50bp, lOObp, 500bp, lkp, 2kb, 5kb, lOkb, or greater. The separation distance can be any discrete integer of base pairs. It should be readily understood that there the limit of the number of base pairs separating the two insertion sites can be limited by the size of the genome, chromosome, or polynucleotide into which the insertions are being made. In some examples, the maximum distance of separation depends on the size of the target nucleic acid or genome. [00117] Recorder sequences can be inserted adjacent to editing sequences, or within proximity to the editing sequence. For example, the recorder sequence can be inserted outside of the open reading frame within which the editing sequence is inserted. Recorder sequence can be inserted into an untranslated region adjacent to an open reading frame within which an editing sequence has been inserted. The recorder sequence can be inserted into a functionally neutral or nonfunctional site. The recorder sequence can be inserted into a screenable or selectable marker gene.
[00118] In some examples, the target nucleic acid sequence is comprised within a genome, artificial chromosome, synthetic chromosome, or episomal plasmid. In various examples, the target nucleic acid sequence can be in vitro or in vivo. When the target nucleic acid sequence is in vivo, the CREATE-Recorder plasmid can be introduced into the host organisms by transformation, transfection, conjugation, biolistics, nanoparticles, cell-permeable technologies, or other known methods for DNA delivery, or any combination thereof. In such examples, the host organism can be a eukaryote, prokaryote, bacterium, archaea, yeast, or other fungi.
[00119] The engineering event can comprise recombineering, non-homologous end joining, homologous recombination, or homology-driven repair. In some examples, the engineering event is performed in vitro or in vivo.
[00120] The methods described herein can be carried out in any type of cell in which a nucleic acid-guided nuclease system can function (e.g., target and cleave DNA), including prokaryotic and eukaryotic cells or in vitro. In some embodiments the cell is a bacterial cell, such as Escherichia spp. (e.g., E. coli). In other embodiments, the cell is a fungal cell, such as a yeast cell, e.g., Saccharomyces spp. In other embodiments, the cell is an algal cell, a plant cell, an insect cell, or a mammalian cell, including a human cell.
[00121] In some examples, a cell is a recombinant organism. For example, the cell can comprise a non-native nucleic acid-guided nuclease system. Additionally or alternatively, the cell can comprise recombination system machinery. Such recombination systems can include lambda red recombination system, Cre/Lox, attB/attP, or other integrase systems. Where appropriate, the trackable plasmid can have the complementary components or machinery required for the selected recombination system to work correctly and efficiently.
[00122] A method for genome editing can comprise: (a) introducing a vector that encodes at least one editing cassette and at least one guide nucleic acid into a first population of cells, thereby producing a second population of cells comprising the vector; (b) maintaining the second population of cells under conditions in which a nucleic acid-guided nuclease is expressed or maintained, wherein the nucleic acid-guided nuclease is encoded on the vector, a second vector, on the genome of cells of the second population of cells, or otherwise introduced into the cell, resulting in DNA cleavage and incorporation of the editing cassette; (c) obtaining viable cells. Such a method can optionally further comprise (d) sequencing the target DNA molecule in at least one cell of the second population of cells to identify the mutation of at least one codon.
[00123] A method for genome editing can comprise: (a) introducing a vector that encodes at least one editing cassette comprising a PAM mutation as disclosed herein and at least one guide nucleic acid into a first population of cells, thereby producing a second population of cells comprising the vector; (b) maintaining the second population of cells under conditions in which nucleic acid-guided nuclease is expressed or maintained, wherein the nucleic acid-guided nuclease is encoded on the vector, a second vector, on the genome of cells of the second population of cells, or otherwise introduced into the cell, resulting in DNA cleavage, incorporation of the editing cassette, and death of cells of the second population of cells that do not comprise the PAM mutation, whereas cells of the second population of cells that comprise the PAM mutation are viable; (c) obtaining viable cells. Such a method can optionally further comprise (d) sequencing the target DNA in at least one cell of the second population of cells to identify the mutation of at least one codon.
[00124] Method for trackable genome editing can comprise: (a) introducing a vector that encodes at least one editing cassette, at least one recorder cassette, and at least two gRNA into a first population of cells, thereby producing a second population of cells comprising the vector; (b) maintaining the second population of cells under conditions in which a nucleic acid-guided nuclease is expressed or maintained, wherein the nucleic acid-guided nuclease is encoded on the vector, a second vector, on the genome of cells of the second population of cells, or otherwise introduced into the cell, resulting in DNA cleavage and incorporation of the editing and recorder cassettes; (c) obtaining viable cells. Such a method can optionally further comprise (d) sequencing the recorder sequence of the target DNA molecule in at least one cell of the second population of cells to identify the mutation of at least one codon.
[00125] In some examples where the trackable plasmid comprises an editing cassette designed to silence a PAM site, a method for trackable genome editing can comprise: (a) introducing a vector that encodes at least one editing cassette, a recorder cassette, and at least two gRNA into a first population of cells, thereby producing a second population of cells comprising the vector; (b) maintaining the second population of cells under conditions in which a nucleic acid-guided nuclease is expressed or maintained, wherein the nucleic acid-guided nuclease is encoded on the vector, a second vector, on the genome of cells of the second population of cells, or otherwise introduced into the cell, resulting in DNA cleavage, incorporation of the editing cassette and recorder cassette, and death of cells of the second population of cells that do not comprise the PAM mutation, whereas cells of the second population of cells that comprise the PAM mutation are viable; and (c) obtaining viable cells. Such a method can optionally further comprise (d) sequencing the recorder sequence of the target DNA in at least one cell of the second population of cells to identify the mutation of at least one codon. Such methods can also further comprise a recorder cassette comprising a second PAM mutation, such that both PAMs must be silences by the editing cassette PAM mutation and recorder cassette PAM mutation in order to escape cell death.
[00126] In some examples transformation efficiency is determined by using a non-targeting guide nucleic acid control, which allows for validation of the recombineering procedure and CFU/ng calculations. In some cases, absolute efficient is obtained by counting the total number of colonies on each transformation plate, for example, by counting both red and white colonies from a galK control. In some examples, relative efficiency is calculated by the total number of successful transformants (for example, white colonies) out of all colonies from a control (for example, galK control).
[00127] The methods of the disclosure can provide, for example, greater than lOOOx improvements in the efficiency, scale, cost of generating a combinatorial library, and/or precision of such library generation.
[00128] The methods of the disclosure can provide, for example, greater than: lOx, 50x, lOOx, 200x, 300x, 400x, 500x, 600x, 700x, 800x, 900x, lOOOx, l lOOx, 1200x, 1300x, 1400x, 1500x, 1600x, 1700x, 1800x, 1900x, 2000x, or greater improvements in the efficiency of generating genomic or combinatorial libraries.
[00129] The methods of the disclosure can provide, for example, greater than: lOx, 50x, lOOx, 200x, 300x, 400x, 500x, 600x, 700x, 800x, 900x, lOOOx, l lOOx, 1200x, 1300x, 1400x, 1500x, 1600x, 1700x, 1800x, 1900x, 2000x, or greater improvements in the scale of generating genomic or combinatorial libraries.
[00130] The methods of the disclosure can provide, for example, greater than: lOx, 50x, lOOx, 200x, 300x, 400x, 500x, 600x, 700x, 800x, 900x, lOOOx, l lOOx, 1200x, 1300x, 1400x, 1500x, 1600x, 1700x, 1800x, 1900x, 2000x, or greater decrease in the cost of generating genomic or combinatorial libraries.
[00131] The methods of the disclosure can provide, for example, greater than: lOx, 50x, lOOx, 200x, 300x, 400x, 500x, 600x, 700x, 800x, 900x, lOOOx, l lOOx, 1200x, 1300x, 1400x, 1500x, 1600x, 1700x, 1800x, 1900x, 2000x, or greater improvements in the precision of genomic or combinatorial library generation.
Recursive tracking for combinatorial engineering
[00132] Disclosed herein are methods and compositions for iterative rounds of engineering. Disclosed herein are recursive engineering strategies that allow implementation of trackable engineering at the single cell level through several serial engineering cycles (e.g., Figure 3D or Figure 6). These disclosed methods and compositions can enable search-based technologies that can effectively construct and explore complex genotypic space. The terms recursive and iterative can be used interchangeably.
[00133] Combinatorial engineering methods can comprise multiple rounds of engineering. Methods disclosed herein can comprise 2 or more rounds of engineering. For example, a method can comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, or more than 30 rounds of engineering.
[00134] In some examples, during each round of engineering a new recorder sequence, such as a barcode, is incorporated at the same or nearby locus in a target site (e.g., Figure 3D, green bars or Figure 6, black bars) such that following multiple engineering cycles to construct combinatorial diversity throughout the genome (e.g., Figure 3E, green bars or Figure 6, grey bars) a PCR, or similar reaction, of the recording locus can be used to reconstruct each combinatorial genotype or to confirm that the engineered edit from each round has been incorporated into the target site. .
[00135] Disclosed herein are methods for selecting for successive rounds of engineering. Selection can occur by a PAM mutation incorporated by an editing cassette. Selection can occur by a PAM mutation incorporated by a recorder cassette. Selection can occur using a screenable, selectable, or counter-selectable marker. Selection can occur by targeting a site for editing or recording that was incorporated by a prior round of engineering, thereby selecting for variants that successfully incorporated edits and recorder sequences from both rounds or all prior rounds of engineering.
[00136] Quantitation of these genotypes can be used for understanding combinatorial mutational effects on large populations and investigation of important biological phenomena such as epi stasis.
[00137] Serial editing and combinatorial tracking can be implemented using recursive vector systems as disclosed herein. These recursive vector systems can be used to move rapidly through the transformation procedure (e.g., Figure 7A). In some examples, these systems consist of two or more plasmids containing orthogonal replication origins, antibiotic markers, and gRNAs. The gRNA in each vector can be designed to target one of the other resistance markers for destruction by nucleic acid-guided nuclease-mediated cleavage. These systems can be used, in some examples, to perform transformations in which the antibiotic selection pressure is switched to remove the previous plasmid and drive enrichment of the next round of engineered genomes. Two or more passages through the transformation loop can be performed, or in other words, multiple rounds of engineering can be performed. Introducing the requisite recording cassettes and editing cassettes into recursive vectors as disclosed herein can be used for simultaneous genome editing and plasmid curing in each transformation step with high efficiencies.
[00138] In some examples, the recursive vector system disclosed herein comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 unique plasmids. In some examples, the recursive vector system can use a particular plasmid more than once as long as a distinct plasmid is used in the previous round and in the subsequent round.
[00139] Recursive methods and compositions disclosed herein can be used to restore function to a selectable or screenable element in a targeted genome or plasmid. The selectable or screenable element can include an antibiotic resistance gene, a fluorescent gene, a unique DNA sequence or watermark, or other known reporter, screenable, or selectable gene. In some examples, each successive round of engineering can incorporate a fragment of the selectable or screenable element, such that at the end of the engineering rounds, the entire selectable or screenable element has been incorporated into the target genome or plasmid. In such examples, only those genome or plasmids, which have successfully incorporated all of the fragments, and therefore all of the desired corresponding mutations, can be selected or screened for. In this way, the selected or screened cells will be enriched for those that have incorporated the edits from each and every iterative round of engineering.
[00140] Recursive methods can be used to switch a selectable or screenable marker between an on and an off position, or between an off and an on position, with each successive round of engineering. Using such a method allows conservation of available selectable or screenable markers by requiring, for example, the use of only one screenable or selectable marker. Furthermore, short regulatory sequence or start codon or non-start codons can be used to turn the screenable or selectable marker on and off. Such short sequences can easily fit within a cassette or polynucleotide, such as a synthesized cassette.
[00141] One or more rounds of engineering can be performed using the methods and compositions disclosed herein. In some examples, each round of engineering is used to incorporate an edit unique from that of previous rounds. Each round of engineering can incorporate a unique recording sequence. Each round of engineering can result in removal or curing of the CREATE plasmid used in the previous round of engineering. In some examples, successful incorporation of the recording sequence of each round of engineering results in a complete and functional screenable or selectable marker or unique sequence combination.
[00142] Unique recorder cassettes comprising recording sequences such as barcodes or screenable or selectable markers can be inserted with each round of engineering, thereby generating a recorder sequence that is indicative of the combination of edits or engineering steps performed. Successive recording sequences can be inserted adjacent to one another. Successive recording sequences can be inserted within proximity to one another. Successive sequences can be inserted at a distance from one another.
[00143] Successive sequences can be inserted at a distance from one another. For example, successive recorder sequences can be inserted and separated by 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 ,21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, or greater than 100 bp. In some examples, successive recorder sequences are separated by about 10, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1100, 1200, 1300, 1400, 1500, or greater than 1500bp.
[00144] Successive recorder sequences can be separated by any desired number of base pairs and can be dependent and limited on the number of successive recorder sequences to be inserted, the size of the target nucleic acid or target genomes, and/or the design of the desired final recorder sequence. For example, if the compiled recorder sequence is a functional screenable or selectable marker, than the successive recording sequences can be inserted within proximity and within the same reading frame from one another. If the compiled recorder sequence is a unique set of barcodes to be identified by sequencing and have no coding sequence element, then the successive recorder sequences can be inserted with any desired number of base pairs separating them. In these cases, the separation distance can be dependent on the sequencing technology to be used and the read length limit.
[00145] In some examples, a recorder cassette comprises a landing site to be used as a target site for the recorder cassette of the next round of engineering. By using such a method, successive rounds of recorder cassettes can only be introduced into the target site if the recorder cassette from the previous round was successfully incorporated, thereby providing the target site for the present engineering round (e.g., Figure 28).
Guide nucleic acid
[00146] A guide nucleic acid can complex with a compatible nucleic acid-guided nuclease and can hybridize with a target sequence, thereby directing the nuclease to the target sequence. A subject nucleic acid-guided nuclease capable of complexing with a guide nucleic acid can be referred to as a nucleic acid-guided nuclease that is compatible with the guide nucleic acid. Likewise, a guide nucleic acid capable of complexing with a nucleic acid-guided nuclease can be referred to as a guide nucleic acid that is compatible with the nucleic acid-guided nucleases.
[00147] A guide nucleic acid can be DNA. A guide nucleic acid can be RNA. A guide nucleic acid can comprise both DNA and RNA. A guide nucleic acid can comprise modified of non- naturally occurring nucleotides. In cases where the guide nucleic acid comprises RNA, the RNA guide nucleic acid can be encoded by a DNA sequence on a polynucleotide molecule such as a plasmid, linear construct, or editing cassette as disclosed herein.
[00148] A guide nucleic acid can comprise a guide sequence. A guide sequence is a polynucleotide sequence having sufficient complementarity with a target polynucleotide sequence to hybridize with the target sequence and direct sequence-specific binding of a complexed nucleic acid-guided nuclease to the target sequence. The degree of complementarity between a guide sequence and its corresponding target sequence, when optimally aligned using a suitable alignment algorithm, is about or more than about 50%, 60%, 75%, 80%, 85%, 90%, 95%), 97.5%), 99%), or more. Optimal alignment may be determined with the use of any suitable algorithm for aligning sequences. In some embodiments, a guide sequence is about or more than about 5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 75, or more nucleotides in length. In some embodiments, a guide sequence is less than about 75, 50, 45, 40, 35, 30, 25, 20 nucleotides in length. Preferably the guide sequence is 10-30 nucleotides long. The guide sequence can be 15-20 nucleotides in length. The guide sequence can be 15 nucleotides in length. The guide sequence can be 16 nucleotides in length. The guide sequence can be 17 nucleotides in length. The guide sequence can be 18 nucleotides in length. The guide sequence can be 19 nucleotides in length. The guide sequence can be 20 nucleotides in length.
[00149] A guide nucleic acid can comprise a scaffold sequence. In general, a "scaffold sequence" includes any sequence that has sufficient sequence to promote formation of a targetable nuclease complex, wherein the targetable nuclease complex comprises a nucleic acid- guided nuclease and a guide nucleic acid comprising a scaffold sequence and a guide sequence. Sufficient sequence within the scaffold sequence to promote formation of a targetable nuclease complex may include a degree of complementarity along the length of two sequence regions within the scaffold sequence, such as one or two sequence regions involved in forming a secondary structure. In some cases, the one or two sequence regions are comprised or encoded on the same polynucleotide. In some cases, the one or two sequence regions are comprised or encoded on separate polynucleotides. Optimal alignment may be determined by any suitable alignment algorithm, and may further account for secondary structures, such as self- complementarity within either the one or two sequence regions. In some embodiments, the degree of complementarity between the one or two sequence regions along the length of the shorter of the two when optimally aligned is about or more than about 25%, 30%>, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 97.5%, 99%, or higher. In some embodiments, at least one of the two sequence regions is about or more than about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,
19, 20, 25, 30, 40, 50, or more nucleotides in length.
[00150] A scaffold sequence of a subject guide nucleic acid can comprise a secondary structure. A secondary structure can comprise a pseudoknot region. In some example, the compatibility of a guide nucleic acid and nucleic acid-guided nuclease is at least partially determined by sequence within or adjacent to a pseudoknot region of the guide RNA. In some cases, binding kinetics of a guide nucleic acid to a nucleic acid-guided nuclease is determined in part by secondary structures within the scaffold sequence. In some cases, binding kinetics of a guide nucleic acid to a nucleic acid-guided nuclease is determined in part by nucleic acid sequence with the scaffold sequence.
[00151] In aspects of the invention the terms "guide nucleic acid" refers to a polynucleotide comprising 1) a guide sequence capable of hybridizing to a target sequence and 2) a scaffold sequence capable of interacting with or complexing with an nucleic acid-guided nuclease as described herein.
[00152] A guide nucleic acid can be compatible with a nucleic acid-guided nuclease when the two elements can form a functional targetable nuclease complex capable of cleaving a target sequence. Often, a compatible scaffold sequence for a compatible guide nucleic acid can be found by scanning sequences adjacent to a native nucleic acid-guided nuclease loci. In other words, native nucleic acid-guided nucleases can be encoded on a genome within proximity to a corresponding compatible guide nucleic acid or scaffold sequence.
[00153] Nucleic acid-guided nucleases can be compatible with guide nucleic acids that are not found within the nucleases endogenous host. Such orthogonal guide nucleic acids can be determined by empirical testing. Orthogonal guide nucleic acids can come from different bacterial species or be synthetic or otherwise engineered to be non-naturally occurring.
[00154] Orthogonal guide nucleic acids that are compatible with a common nucleic acid- guided nuclease can comprise one or more common features. Common features can include sequence outside a pseudoknot region. Common features can include a pseudoknot region. Common features can include a primary sequence or secondary structure.
[00155] A guide nucleic acid can be engineered to target a desired target sequence by altering the guide sequence such that the guide sequence is complementary to the target sequence, thereby allowing hybridization between the guide sequence and the target sequence. A guide nucleic acid with an engineered guide sequence can be referred to as an engineered guide nucleic acid. Engineered guide nucleic acids are often non-naturally occurring and are not found in nature. More methods
[00156] Disclosed herein are methods for genome engineering that employ a nuclease, such as a nucleic acid-guided nuclease to perform directed genome evolution/produce changes (deletions, substitutions, additions) in a target sequence, such as DNA or RNA, for example, genomic DNA or episomal DNA. Suitable nucleases can include, for example, RNA-guided nucleases such as Cas9, Cpfl, MAD2, or MAD7, DNA-guided nucleases such as Argonaute, or other nucleases such as zinc-finger nucleases, TALENs, or meganucleases. Nuclease genes can be obtained from any source, such as from a bacterium, archaea, prokaryote, eukaryote, or virus. For example, a Cas9 gene can be obtained from a bacterium harboring the corresponding Type II CRISPR system, such as the bacterium S. pyogenes (SEQ ID NO: 110). The nucleic acid sequence and/or amino acid sequence of the nuclease may be mutated, relative to the sequence of a naturally occurring nuclease. A mutation can be, for example, one or more insertions, deletions, substitutions or any combination of two or three of the foregoing. In some cases, the resulting mutated nuclease can have enhanced or reduced nuclease activity relative to the naturally occurring nuclease. In some cases, the resulting mutated nuclease can have no nuclease activity relative to the naturally occurring nuclease.
[00157] Methods for nucleic acid-guided nuclease-mediated genome editing are provided herein. Some disclosed methods can include a two-stage construction process which relies on generation of cassette libraries that incorporate directed mutations from an editing cassettes directly into a genome, episomal nucleic acid molecule, or isolated nucleic acid molecule. In some examples, during the first stage of cassette library construction, rationally designed editing cassettes can be cotransformed into cells with a guide nucleic acid (e.g., guide RNA) that hybridizes to or targets a target DNA sequence. In some examples, the guide nucleic acid is introduced as an RNA molecule, or encoded on a DNA molecule.
[00158] Editing cassettes can be designed such that they couple deletion or mutation of a PAM site with the mutation of one or more desired codons or nucleic acid residues in the adjacent nucleic acid sequence. The deleted or mutated PAM site, in some cases, can no longer be recognized by the chosen nucleic acid-guided nuclease. In some examples, at least one PAM or more than one PAM can be deleted or mutated, such as two, three, four, or more PAMs.
[00159] Methods disclosed herein can enable generation of an entire cassette library in a single transformation. The cassette library can be retrieved, in some cases, by amplification of the recombinant chromosomes, e.g. by a PCR reaction, using a synthetic feature or priming site from the editing cassettes. In some examples, a second PAM deletion or mutation is simultaneously incorporated. This approach can covalently couple the codon-targeted mutations directly to a PAM deletion. [00160] In some examples, there is a second stage to construction of cassette libraries. During the second stage the PCR amplified cassette libraries carrying the destination PAM deletion/mutation and the targeted mutations, such as a desired mutation of one or more nucleotides, such as one or more nucleotides in one or more codons, can be co-transformed into naive cells. The cells can be eukaryotic cell, archaeal cell, or prokaryotic cells. The cassette libraries can be co-transformed with a guide nucleic acid or plasmid encoding the same to generate a population of cells that express a rationally designed protein library. The libraries can be co-transformed with a guide nucleic acid such as a gRNA, chimeric gRNA, split gRNA, or a crRNA and trRNA set. The cassette library can comprise a plurality of cassettes wherein each cassette comprises an editing cassette and guide nucleic acid. The cassette library can comprise a plurality of cassettes wherein each cassette comprises an editing cassette, recorder cassettes and two guide nucleic acids.
[00161] In some targetable nuclease systems, the guide nucleic acid can guide selection of a target sequence. As used herein, a target sequence refers to any locus in vitro or in in vivo, or in the nucleic acid of a cell or population of cells in which a mutation of at least one nucleotide, such as a mutation of at least one nucleotide in at least one codon, is desired. The target sequence can be, for example, a genomic locus, target genomic sequence, or extrachromosomal locus. The guide nucleic acid can be expressed as a DNA molecule, referred to as a guide DNA, or as a RNA molecule, referred to as a guide RNA. A guide nucleic acid can comprise a guide sequence, that is complementary to a region of the target region. A guide nucleic acid can comprise a scaffold sequence that can interact with a compatible nucleic acid-guided nuclease, and can optionally form a secondary structure. A guide nucleic acid can functions to recruit a nucleic acid-guided nuclease to the target site. A guide sequence can be complementary to a region upstream of the target site. A guide sequence can be complementary to at least a portion of the target site. A guide sequence can be completely complementary (100% complementary) to the target site or include one or more mismatches, provided that it is sufficiently complementary to the target site to specifically hybridize/guide and recruit the nuclease. Suitable nucleic acid guided nuclease include, as non-limiting examples, CRISPR nucleases, Cas nucleases, such as Cas9 or Cpfl, MAD2, and MAD7.
[00162] In some CRISPR systems, the CRISPR RNA (crRNA or spacer-containing RNA) and trans-activating CRISPR RNA (tracrRNA or trRNA) can guide selection of a target sequence. As used herein, a target sequence refers to any locus in vitro or in in vivo, or in the nucleic acid of a cell or population of cells in which a mutation of at least one nucleotide, such as a mutation of at least one nucleotide in at least one codon, is desired. The target sequence can be, for example, a genomic locus, target genomic sequence, or extrachromosomal locus. The tracrRNA and crRNA can be expressed as a single, chimeric RNA molecule, referred to as a single-guide RNA, guide RNA, or gRNA. The nucleic acid sequence of the gRNA comprises a first nucleic acid sequence, also referred to as a first region, that is complementary to a region of the target region and a second nucleic acid sequence, also referred to a second region, that forms a stem loop structure and functions to recruit a CRISPR nuclease to the target region. The first region of the gRNA can be complementary to a region upstream of the target genomic sequence. The first region of the gRNA can be complementary to at least a portion of the target region. The first region of the gRNA can be completely complementary (100% complementary) to the target genomic sequence or include one or more mismatches, provided that it is sufficiently complementary to the target genomic sequence to specifically hybridize/guide and recruit a CRISPR nuclease, such as Cas9 or Cpf 1.
[00163] A guide sequence or first region of the gRNA can be at least 15, 16, 17, 18, 19,
20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or at least 30 nucleotides in length. The guide sequence or first region of the gRNA can be at least 20 nucleotides in length.
[00164] A stem loop structure that can be formed by the scaffold sequence or second nucleic acid sequence of a gRNA can be at least 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 7, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 nucleotides in length. A stem loop structure can be from 80 to 90 or 82 to 85 nucleotides in length. A scaffold sequence or second region of the gRNA that forms a stem loop structure can be 83 nucleotides in length.
[00165] A guide nucleic acid of a cassette that is introduced into a first cell using the methods disclosed herein can be the same as the guide nucleic acid of a second cassette that is introduced into a second cell. More than one guide nucleic acid can be introduced into the population of first cells and/or the population of second cells. The more than one guide nucleic acids can comprise guide sequences that are complementary to more than one target region.
[00166] Methods disclosed herein can comprise using oligonucleotides. Such oligonucleotides can be obtained or derived from many sources. For example, an oligonucleotide can be derived from a nucleic acid library that has been diversified by nonhomologous random recombination (NRR); such a library is referred to as an NRR library. An oligonucleotide can be synthesized, for example by array-based synthesis or other known chemical synthesis method. The length of an oligonucleotide can be dependent on the method used in obtaining the oligonucleotide. An oligonucleotide can be approximately 50-200 nucleotides, 75-150 nucleotides, or between 80- 120 nucleotides in length. An oligonucleotide can be about 10, 20, 30, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more nucleotides in length, including any integer, for example, 51, 52, 53, 54, 201, 202, etc. An oligonucleotide can be about 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1250, 1500, 1750, 2000, or more nucleotides in length, including any integer, for example, 101, 203, 1001, 2001, 2010, etc.
[00167] Oligonucleotides and/or other nucleic acid molecules can be combined or assembled to generate a cassette. Such a cassette can comprise (a) a region that is homologous to a target region of the nucleic acid of the cell and includes a desired mutation of at least one nucleotide or one codon relative to the target region, and (b) a protospacer adjacent motif (PAM) mutation. The PAM mutation can be any insertion, deletion or substitution of one or more nucleotides that mutates the sequence of the PAM such that it is no longer recognized by a nucleic acid-guided nuclease system or CRISPR nuclease system. A cell that comprises such a PAM mutation may be said to be "immune" to nuclease- mediated killing. The desired mutation relative to the sequence of the target region can be an insertion, deletion, and/or substitution of one or more nucleotides. In some examples, the insertion, deletion, and/or substitution of one or more nucleotides is in at least one codon of the target region. Alternatively, the cassette can be synthesized in a single synthesis, comprising (a) a region that is homologous to a target region of the nucleic acid of the cell and includes a desired mutation of at least one nucleotide or one codon relative to the target region, (b) a protospacer adjacent motif (PAM) mutation, and optionally (c) a region that is homologous to a second target region of the nucleic acid of the cell and includes a recorder sequence.
[00168] The methods disclosed herein can be applied to any target nucleic acid molecule of interest, from any prokaryote including bacteria and archaea, or any eukaryote, including yeast, mammalian, and human genes, or any viral particle. The nucleic acid module can be a non- coding nucleic acid sequence, gene, genome, chromosome, plasmid, episomal nucleic acid molecule, artificial chromosome, synthetic chromosome, or viral nucleic acid.
[00169] Methods for assessing recovery efficiency of donor strain libraries are disclosed herein. Recovery efficiency can be verified based on the presence of a PCR product or on changes in amplicon or PCR product sizes or sequence obtained with primers directed at the selected target locus. Primers can be designed to hybridize with endogenous sequences or heterologous sequences contained on the donor nucleic acid molecule. For example, the PCR primer can be designed to hybridize to a heterologous sequence such that PCR will only be possible if the donor nucleic acid is incorporated. Sequencing of PCR products from the recovered libraries indicates the heterologous sequence or synthetic priming site from the dsDNA cassettes or donor sequences can be incorporated with about 90-100% efficiency. In other examples, the efficiency can be about 5%, 10% 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100%. [00170] In some cases, the ability to improve final editing efficiencies of the methods disclosed herein can be assessed by carrying out cassette construction in gene deficient strains before transferring to a wild-type donor strain in an effort to prevent loss of mutations during the donor construction phase. Additionally or alternatively, efficiency of the disclosed methods can be assessed by targeting an essential gene. Essential genes can include any gene required for survival or replication of a viral particle, cell, or organism. In some examples, essential genes include dxs, metA, and folA. Essential genes have been effectively targeted using guide nucleic acid design strategies described. Other suitable essential genes are well known in the art.
[00171] Provided herein are method of increasing editing efficiencies by modulating the level of a nucleic acid-guided nuclease. This could be done by using copy control plasmids, such as high copy number plasmids or low copy number plasmids. Low copy number plasmids could be plasmids that can have about 20 or less copies per cell, as opposed to high copy number plasmids that can have about 1000 copies per cell. High copy number plasmids and low copy number plasmids are well known in the art and it is understood that an exact plasmid copy per cell does not need to be known in order to characterize a plasmid as either high or low copy number.
[00172] In some cases, the decreasing expression level of a nucleic acid-guided nuclease, such as Cas9, Cpfl, MAD2, or MAD7, can increase transformation, editing, and/or recording efficiencies. In some cases, decreasing expression level of the nucleic acid-guided nuclease is done by expressing the nucleic acid-guided nuclease on a low copy number plasmid.
[00173] In some cases, the increasing expression level of a nucleic acid-guided nuclease, such as Cas9, Cpfl, MAD2, or MAD7, can increase transformation, editing, and/or recording efficiencies. In some cases, increasing expression level of the nucleic acid-guided nuclease is done by expressing the nucleic acid-guided nuclease on a high copy number plasmid.
[00174] Other methods of modulating the expression level of a protein are also envisioned and are known in the art. Such methods include using a inducible or constitutive promoter, incorporating enhancers or other expression regulatory elements onto an expression plasmid, using RNAi, amiRNAi, or other RNA silencing techniques to modulate transcript level, fusing the protein of interest to a degradation domain, or any other method known in the art.
[00175] Provided herein are methods for generating mutant libraries. In some examples, the mutant library can be effectively constructed and retrieved within 1-3 hours post recombineering. In some examples, the mutant library is constructed within 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, or 24 hours post recombineering. In some examples, the mutant library can be retrieved within 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 36, or 48 hours post recombineering and/or post-constructing by recombineering. [00176] Some methods disclosed herein can be used for trackable, precision genome editing. In some examples, methods disclosed herein can achieve high efficiency editing/mutating using a single cassette that encodes both an editing cassette and guide nucleic acid, and optionally a recorder cassette and second guide nucleic acid. Alternatively, a single vector can encode an editing cassette while a guide nucleic acid is provided sequentially or concomitantly. When used with parallel DNA synthesis, such as array-based DNA synthesis, methods disclosed herein can provide single step generation of hundreds or thousands of precision edits/mutations. Mutations can be mapped by sequencing the editing cassette on the vector, rather than by sequencing of the genome or a section of the genome of the cell or organism.
[00177] The methods disclosed herein can have broad utility in protein and genome engineering applications, as well as for reconstruction of mutations, such as mutations identified in laboratory evolution experiments. In some examples, the methods and compositions disclosed here can combine an editing cassette, which could include a desired mutation and a PAM mutation, with a gene encoding a guide nucleic acid on a single vector.
[00178] In some examples, a trackable mutant library can be generated in a single transformation or single reaction.
[00179] Methods disclosed herein can comprise introducing a cassette comprising an editing cassette that includes the desired mutation and the PAM mutation into a cell or population of cells. In some embodiments, the cell into which the cassette or vector is introduced also comprises a nucleic acid-guided nuclease, such as Cas9, Cpfl, MAD2, or MAD7. In some embodiments, a gene or mRNA encoding the nucleic acid-guided nuclease is concomitantly, sequentially, or subsequently introduced into the cell or population of cells. Expression of a targetable nuclease system, including nucleic acid-guided nuclease and a guide nucleic acid, in the cell or cell population can be activated such that the guide nucleic acid recruits the nucleic acid-guided nuclease to the target region, where dsDNA cleavage occurs.
[00180] In some examples, without wishing to be bound by any particular theory, the homologous region of an editing cassette complementary to the target sequence mutates the PAM and the one or more codon of the target sequence. Cells of the population of cells that did not integrate the PAM mutation can undergo unedited cell death due to nucleic acid-guided nuclease mediated dsDNA cleavage. In some examples, cells of the population of cells that integrate the PAM mutation do not undergo cell death; they remain viable and are selectively enriched to high abundance. Viable cells can be obtained and can provide a library of trackable or targeted mutations.
[00181] In some examples, without wishing to be bound by any particular theory, the homologous region of a recorder cassette complementary to the target sequence mutates the PAM and introduces a barcode into a target sequence. Cells of the population of cells that did not integrate the PAM mutation can undergo unedited cell death due to nucleic acid-guided nuclease mediated dsDNA cleavage. In some examples, cells of the population of cells that integrate the PAM mutation do not undergo cell death; they remain viable and are selectively enriched to high abundance. Viable cells can be obtained and can provide a library of trackable mutations.
[00182] A separate vector or mRNA encoding a nucleic acid-guided nuclease can be introduced into the cell or population of cells. Introducing a vector or mRNA into a cell or population of cells can be performed using any method or technique known in the art. For example, vectors can be introduced by standard protocols, such as transformation including chemical transformation and electroporation, transduction and particle bombardment. Additionally or alternatively, mRNA can be introduced by standard protocols, such as transformation as disclosed herein, and/or by techniques involving cell permeable peptides or nanoparticles.
[00183] An editing cassette can include (a) a region, which recognizes (hybridizes to) a target region of a nucleic acid in a cell or population of cells, is homologous to the target region of the nucleic acid of the cell and includes a mutation, referred to a desired mutation, of at least one nucleotide that can be in at least one codon relative to the target region, and (b) a protospacer adjacent motif (PAM) mutation. In some examples, the editing cassette also comprises a barcode. The barcode can be a unique barcode or relatively unique such that the corresponding mutation can be identified based on the barcode. The PAM mutation may be any insertion, deletion or substitution of one or more nucleotides that mutates the sequence of the PAM such that the mutated PAM (PAM mutation) is not recognized by a chosen nucleic acid-guided nuclease system. A cell that comprises such as a PAM mutation may be said to be "immune" to nucleic acid-guided nuclease-mediated killing. The desired mutation relative to the sequence of the target region may be an insertion, deletion, and/or substitution of one or more nucleotides and may be at least one codon of the target region. In some embodiments, the distance between the PAM mutation and the desired mutation is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, or 100 nucleotides on the editing cassette In some embodiments, the PAM mutation is located at least 9 nucleotides from the end of the editing cassette. In some embodiments, the desired mutation is located at least 9 nucleotides from the end of the editing cassette.
[00184] A desired mutation can be an insertion of a nucleic acid sequence relative to the sequence of the target sequence. The nucleic acid sequence inserted into the target sequence can be of any length. In some embodiments, the nucleic acid sequence inserted is at least 1, 2, 3, 4, 5, 10, 20, 30, 40, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, or at least 2000 nucleotides in length. In embodiments in which a nucleic acid sequence is inserted into the target sequence, the editing cassette comprises a region that is at least 10, 15, 20, 25, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 51, 52, 53, 54, 55, 56, 57, 58, 59, or at least 60 nucleotides in length and homologous to the target sequence. The homology arms or homologous region can be about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more nucleotides in length, including any integer therein. The homology arms or homologous region can be over 200 nucleotides in length.
[00185] A barcode can be a unique barcode or relatively unique such that the corresponding mutation can be identified based on the barcode. In some examples, the barcode is a non- naturally occurring sequence that is not found in nature. In most examples, the combination of the desired mutation and the barcode within the editing cassette is non-naturally occurring and not found in nature. A barcode can be any number of nucleotides in length. A barcode can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or more than 30 nucleotides in length. In some cases, the barcode is more than 30 nucleotides in length.
[00186] An editing cassette or recorder cassette can comprise at least a portion of a gene encoding a guide nucleic acid, and optionally a promoter operable linked to the encoded guide nucleic acid. In some embodiments, the portion of the gene encoding the guide nucleic acid encodes the portion of the guide nucleic acid that is complementary to the target sequence. The portion of the guide nucleic acid that is complementary to the target sequence, or the guide sequence, can be at least 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or at least 30 nucleotides in length. In some embodiments, the guide sequence is 24 nucleotides in length. In some embodiments, the guide sequence is 18 nucleotides in length.
[00187] In some embodiments, the editing cassette or recorder cassette further comprises at least two priming sites. The priming sites may be used to amplify the cassette, for example by PCR. In some embodiments, the portion of the guide sequence is used as a priming site.
[00188] Editing cassettes or recorder cassettes for use in the described methods can be obtained or derived from many sources. For example, the cassettes can be synthesized, for example by array-based synthesis, multiplex synthesis, multi-parallel synthesis, PCR assembly, in vitro assembly, Gibson assembly, or any other synthesis method known in the art. In some embodiments, the editing cassette or recorder cassette is synthesized, for example by array-based synthesis, multiplex synthesis, multi-parallel synthesis, PCR assembly, -in vitro assembly, Gibson assembly, or any other synthesis method known in the art. The length of the editing cassette or recorder cassette may be dependent on the method used in obtaining said cassette. [00189] An editing cassette can be approximately 50-300 nucleotides, 75-200 nucleotides, or between 80-120 nucleotides in length. In some embodiments, the editing cassette can be any discrete length between 50 nucleotide and 1 Mb.
[00190] A recorder cassette can be approximately 50-300 nucleotides, 75-200 nucleotides, or between 80- 120 nucleotides in length. In some embodiments, the recorder cassette can be any discrete length between 50 nucleotide and 1 Mb.
[00191] Methods disclosed herein can also involve obtaining editing cassettes and recorder cassettes and constructing a trackable plasmid or vector. Methods of constructing a vector will be known to one ordinary skill in the art and may involve ligating the cassettes into a vector backbone. In some examples, plasmid construction occurs by in vitro DNA assembly methods, oligonucleotide assembly, PCR-based assembly, SLIC, CPEC, or other assembly methods well known in the art. In some embodiments, the cassettes or a subset (pool) of the cassettes can be amplified prior to construction of the vector, for example by PCR.
[00192] The cell or population of cells comprising a polynucleotide encoding a nucleic acid- guided nuclease can be maintained or cultured under conditions in which the nuclease is expressed. Nucleic acid-guided nuclease expression can be controlled or can be constitutively on. The methods described herein can involve maintaining cells under conditions in which nuclease expression is activated, resulting in production of the nuclease, for example, Cas9, Cpfl, MAD2, or MAD7. Specific conditions under which the nucleic acid-guided nuclease is expressed can depend on factors, such as the nature of the promoter used to regulate expression of the nuclease. Nucleic acid-guided nuclease expression can be induced in the presence of an inducer molecule, such as arabinose. When the cell or population of cells comprising nucleic acid-guided nuclease encoding DNA are in the presence of the inducer molecule, expression of the nuclease can occur. CRISPR-nuclease expression can be repressed in the presence of a repressor molecule. When the cell or population of cells comprising nucleic acid-guided nuclease encoding DNA are in the absence of a molecule that represses expression of the nuclease, expression of the nuclease can occur.
[00193] Cells or the population of cells that remain viable can be obtained or separated from the cells that undergo unedited cell death as a result of nucleic acid-guided nuclease -mediated killing; this can be done, for example, by spreading the population of cells on culture surface, allowing growth of the viable cells, which are then available for assessment.
[00194] Disclosed herein are methods for the identification of the mutation without the need to sequence the genome or large portions of the genome of the cell. The methods can involve sequencing of the editing cassette, recorder cassette, or barcode to identify the mutation of one of more codon. Sequencing of the editing cassette can be performed as a component of the vector or after its separation from the vector and, optionally, amplification. Sequencing can be performed using any sequencing method known in the art, such as by Sanger sequencing or next-generation sequencing methods.
[00195] Some methods described herein can be carried out in any type of cell in which a targetable nuclease system can function, or target and cleave DNA, including prokaryotic and eukaryotic cells. In some embodiments, the cell is a bacterial cell, such as Escherichia spp., e.g., E. coli. In other embodiments, the cell is a fungal cell, such as a yeast cell, e.g., Saccharomyces spp. In other embodiments, the cell is an algal cell, a plant cell, an insect cell, or a mammalian cell, including a human cell.
[00196] A "vector" is any of a variety of nucleic acids that comprise a desired sequence or sequences to be delivered to or expressed in a cell. A desired sequence can be included in a vector, such as by restriction and ligation or by recombination or assembly methods know in the art. Vectors are typically composed of DNA, although RNA vectors are also available. Vectors include, but are not limited to plasmids, fosmids, phagemids, virus genomes, artificial chromosomes, and synthetic nucleic acid molecules.
[00197] Vectors useful in the methods disclosed herein can comprise at least one editing cassette as described herein, at least one gene encoding a gRNA, and optionally a promoter and/or a barcode. More than one editing cassette can be included on the vector, for example 2, 3, 4, 5, 6, 7, 8, 9, 10 or more editing cassettes. The more than one editing cassettes can be designed to target different target regions, for example, there could be different editing cassettes, each of which contains at least one region homologous with a different target region. In other examples, each editing cassette target the same target region while each editing cassette comprises a different desired mutation relative to the target region. In other examples, the plurality of editing cassettes can comprise a combination of editing cassettes targeting the same target region and editing cassettes targeting different target regions. Each editing cassette can comprise an identifying barcode. Alternatively or additionally, the vector can include one or more genes encoding more than one gRNA, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10 or more gRNAs. The more than one gRNAs can contain regions that are complementary to a portion of different target regions, for example, if there are different gRNAs, each of which can be complementary to a portion of a different target region. In other examples, the more than one gRNA can each target the same target region. In other examples, the more than one gRNA can be a combination of gRNAs targeting the same and different target regions.
[00198] A cassette comprising a gene encoding a portion of a guide nucleic acid, can be ligated or assembled into a vector that encodes another portion of a guide nucleic acid. Upon ligation or assembly, the portion of the guide nucleic acid from the cassette and the other portion of the guide nucleic acid can form a functional guide nucleic acid. A promoter and a gene encoding a guide nucleic acid can be operably linked.
[00199] In some embodiments, the methods involve introduction of a second vector encoding a nucleic acid-guided nuclease, such as Cas9, Cpfl, MAD2, or MAD7. The vector may further comprise one or more promoters operably linked to a gene encoding the nucleic acid-guided nuclease.
[00200] As used herein, "operably" linked can mean the promoter affects or regulates transcription of the DNA encoding a gene, such as the gene encoding the gRNA or the gene encoding a CRISPR nuclease.
[00201] A promoter can be a native promoter such as a promoter present in the cell into which the vector is introduced. A promoter can be an inducible or repressible promoter, for example, the promoter can be regulated allowing for inducible or repressible transcription of a gene, such as the gene encoding the guide nucleic acid or the gene encoding a nucleic acid-guided nuclease. Such promoters that are regulated by the presence or absence of a molecule can be referred to as an inducer or a repressor, respectively. The nature of the promoter needed for expression of the guide nucleic acid or nucleic acid-guided nuclease can vary based on the species or cell type and can be recognized by one of ordinary skill in the art.
[00202] A separate vector encoding a nucleic acid-guided nuclease can be introduced into a cell or population of cells before or at the same time as introduction of a trackable plasmid as disclosed herein. The gene encoding a nucleic acid-guided nuclease can be integrated into the genome of the cell or population of cells, or the gene can be maintained episomally. The nucleic acid-guided nuclease-encoding DNA can be integrated into the cellular genome before introduction of the trackable plasmid, or after introduction of the trackable plasmid. In some examples, a nucleic acid molecule, such as DNA-encoding a nucleic acid-guided nuclease, can be expressed from DNA integrated into the genome. In some embodiments, a gene encoding Cas9, Cpfl, MAD2, or MAD7 is integrated into the genome of the cell.
[00203] Vectors or cassettes useful in the methods described herein can further comprise two or more priming sites. In some embodiments, the presence of flanking priming sites allows amplification of the vector or cassette.
[00204] In some embodiments, a cassette or vector encodes a nucleic acid-guided nuclease comprising one or more nuclear localization sequences (NLSs), such as about or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more NLSs. In some embodiments, the engineered nuclease comprises about or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more NLSs at or near the amino-terminus, about or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more NLSs at or near the carboxy-terminus, or a combination of these (e.g. one or more NLS at the amino-terminus and one or more NLS at the carboxy terminus). When more than one NLS is present, each may be selected independently of the others, such that a single NLS may be present in more than one copy and/or in combination with one or more other NLSs present in one or more copies. In a preferred embodiment of the invention, the engineered nuclease comprises at most 6 NLSs. In some embodiments, an NLS is considered near the N- or C-terminus when the nearest amino acid of the NLS is within about 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 40, 50, or more amino acids along the polypeptide chain from the N- or C-terminus. Non-limiting examples of NLSs include an NLS sequence derived from: the NLS of the SV40 virus large T-antigen, having the amino acid sequence PKKKRKV (SEQ ID NO: 111); the NLS from nucleoplasmin (e.g. the nucleoplasmin bipartite NLS with the sequence KRPAATKKAGQAKKKK (SEQ ID NO: 112)); the c-myc NLS having the amino acid sequence PAAKRVKLD (SEQ ID NO: 113) or RQRRNELKRSP (SEQ ID NO: 114); the hRNPAl M9 NLS having the sequence NQS SNFGPMKGGNFGGRS SGP YGGGGQYF AKPRNQGGY (SEQ ID NO: 115); the sequence RMRIZFKNKGKDTAELRRRRVEVSVELRKAKKDEQILKRRNV (SEQ ID NO: l 116) of the IBB domain from importin-alpha; the sequences VSRKRPRP (SEQ ID NO: 117) and PPKKARED (SEQ ID NO: 115) of the myoma T protein; the sequence PQPKKKPL (SEQ ID NO: 119) of human p53; the sequence SALIKKKKKMAP (SEQ ID NO: 120) of mouse c-abl IV; the sequences DRLRR (SEQ ID NO: 121) and PKQKKRK (SEQ ID NO: 122) of the influenza virus NS1; the sequence RKLKKKIKKL (SEQ ID NO: 123) of the Hepatitis virus delta antigen; the sequence REKKKFLKRR (SEQ ID NO: 124) of the mouse Mxl protein; the sequence KRKGDEVDGVDEVAKKKSKK (SEQ ID NO: 125) of the human poly(ADP-ribose) polymerase; and the sequence RKCLQAGMNLEARKTKK (SEQ ID NO: 126) of the steroid hormone receptors (human) glucocorticoid.
[00205] In general, the one or more NLSs are of sufficient strength to drive accumulation of the nucleic acid-guided nuclease in a detectable amount in the nucleus of a eukaryotic cell. In general, strength of nuclear localization activity may derive from the number of NLSs, the particular NLS(s) used, or a combination of these factors. Detection of accumulation in the nucleus may be performed by any suitable technique. For example, a detectable marker may be fused to the nucleic acid-guided nuclease, such that location within a cell may be visualized, such as in combination with a means for detecting the location of the nucleus (e.g. a stain specific for the nucleus such as DAPI). Cell nuclei may also be isolated from cells, the contents of which may then be analyzed by any suitable process for detecting protein, such as immunohistochemistry, Western blot, or enzyme activity assay. Accumulation in the nucleus may also be determined indirectly, such as by an assay for the effect of the nucleic acid-guided nuclease complex formation (e.g. assay for DNA cleavage or mutation at the target sequence, or assay for altered gene expression activity affected by targetable nuclease complex formation and/or nucleic acid-guided nuclease activity), as compared to a control not exposed to the nucleic acid-guided nuclease or targetable nuclease complex, or exposed to a nucleic acid-guided nuclease lacking the one or more LSs.
ProSAR
[00206] Methods disclosed herein are capable of engineering a few to hundreds of genetic sequence or proteins simultaneously. These methods can permit one to map in a single experiment many or all possible residue changes over a collection of desired proteins onto a trait of interest, as part of individual proteins of interest or as part of a pathway. This approach can be used at least for the following by mapping i) any number of residue changes for any number of proteins of interest in a specific biochemical pathway or that catalyze similar reactions or ii) any number of residues in the regulatory sites of any number of proteins or interest with a specific regulon or iii) any number of residues of a biological agent used to treat a health condition.
[00207] In some embodiments, methods described herein include identifying genetic variations of one or more target genes that affect any number or residues, such as one or more, or all residues of one or more target proteins. In accordance with these embodiments, compositions and methods disclosed herein permit parallel analysis of two or more target proteins or proteins that contribute to a trait. Parallel analysis of multiple proteins by a single experiment described can facilitate identification, modification and design of superior systems for example for producing a eukaryotic or prokaryotic byproduct, producing a eukaryotic byproduct, for example, a biological agent such as a growth factor or antibody, in a prokaryotic organism and the like. Relevant biologies used in analysis and treatment of disease can be produced in these genetically engineered environments that could reduce production time, increase quality all while reducing costs to the manufacturers and the consumers.
[00208] Some embodiments disclosed herein comprise constructs of use for studying genetic variations of a gene or gene segment wherein the gene or gene segment is capable of generating a protein. A construct can be generated for any number of residues, such as one, two, more than two, or all residue modifications of a target protein that is linked to a trackable agent such as a barcode. A barcode indicative of a genetic variation of a gene of a target protein can be located outside of the open reading frame of the gene. In some embodiments such a barcode can be located many hundreds or thousands of bases away from the gene. It is contemplated herein that these methods can be performed in vivo. In some examples, such a construct comprises a trackable polynucleic acid or plasmid as disclosed herein.
[00209] Constructs described herein can be used to compile a comprehensive library of genetic variations encompassing all residue changes of one target protein, more than one target protein or target proteins that contribute to a trait. In certain embodiments, libraries disclosed herein can be used to select proteins with improved qualities to create an improved single or multiple protein system for example for producing a byproduct, such as a chemical, biofuels, biological agent, pharmaceutical agent, or for biomass, or biologic compared to a non-selective system. Protein Sequence-Activity Relationship (ProSAR) Mapping
[00210] Understanding the relationship between a protein's amino acid structure and its overall function continues to be of great practical, clinical, and scientific significance for biologists and engineers. Directed evolution can be a powerful engineering and discovery tool, but the random and often combinatorial nature of mutations makes their individual impacts difficult to quantify and thus challenges further engineering. More systematic analysis of contributions of individual residues or saturation mutagenesis remains labor- and time-intensive for entire proteins and simply is not possible on reasonable timescales for multiple proteins in parallel, such as metabolic pathways or multi-protein complexes, using standard methods.
[00211] Provided herein are methods which can be used to rapidly and efficiently examine the roles of some or all genes in a viral, microbial, or eukaryotic genome using mixtures of barcoded oligonucleotides. In some embodiments, these compositions and methods can be used to develop a powerful new technology for comprehensively mapping protein structure-activity relationships (ProSAR).
[00212] Using methods and compositions disclosed herein, multiplex cassette synthesis can be combined with recombineering, to create mutant libraries of specifically designed and barcoded mutations along one or more genes of interest in parallel. Screens and/or selections followed by high-throughput sequencing and/or barcode microarray methods can allow for rapid mapping of protein sequence-activity relationships (ProSAR). In some embodiments, systematic ProSAR mapping can elucidate individual amino acid mutations for improved function and/or activity and/or stability etc.
[00213] Methods can be iterated to combinatorially improve the function, activity, or stability. Cassettes can be generated by oligonucleotide synthesis. Given that existing capabilities of multiplex oligonucleotide synthesis can reach over 120,000 oligonucleotides per array, combined with recombineering, the methods disclosed herein can be scaled to construct mutant libraries for dozens to hundreds of proteins in a single experiment. In some examples, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 25, 50, 75, 100, 150, 200, 250, 300, 400, 500, 600, 700, 800, 900, 1000, or more proteins can be partially or completely covered by mutant libraries generated by the methods disclosed herein.
[00214] Disclosed herein are strategies to construct barcoded substitution libraries for several different proteins at the same time. Using existing multiplex DNA synthesis technology, as disclosed, a partial or complete substitution library for one or more protein constructs can be barcoded, or non-barcoded if desired, for one or for several hundred proteins at the same time. In some examples, such libraries comprise trackable plasmids as disclosed herein.
[00215] Some embodiments herein apply to analysis and structure/function/stability library construction of any protein with a corresponding screen or selection for activity. Cassette library size can depend on the number (N) of amino acids in a protein of interest, with a full saturation library, including all 20 amino acids at each position and optionally non-naturally occurring amino acids, scaling as 19 (or more)xN and an alanine-mapping library scaling as l xN. Thus, in some examples, screening of even very large proteins of more than 1,000 amino acids can be tractable given current multiplex oligo synthesis capabilities of at least 120,000 oligos per array.
[00216] In addition or as an alternative to activity screens, more general properties with developed high-throughput screens and selections can be efficiently tested using methods and cassettes disclosed herein. For example, universal protein folding and solubility reporters can be engineered for expression in the cytoplasm, periplasm, and the inner membrane. In some examples, a protein library can be screened under different conditions such as different temperatures, different substrates or co-factors, in order to identify residue changes required for expression of various traits. In other embodiments, because residues can be analyzed one at a time, mutations at residues important for a particular trait, such as thermostability, resistance to environmental pressures, or increases or decreases in functionality or production, can be combined via multiplex recombineering with mutations important for various other traits, such as catalytic activity, to create combinatorial libraries for multi-trait optimization.
[00217] Methods disclosed herein can provide for creating and/or evaluating comprehensive, in vivo, mutational libraries of one or more target protein(s). These approaches can be extended via a recorder cassettes or barcoding technology to generate trackable mutational libraries for any number of residues or every residue in a protein. This approach can be based on protein sequence-activity relationship mapping method extended to work in vivo, capable of working on one or a few to hundreds of proteins simultaneously depending on the technology selected. For example, these methods permit one to map in a single experiment any number of, the majority of, or all possible residue changes over a collection of desired proteins onto a trait of interest, as part of individual proteins of interest or as part of a pathway.
[00218] In some examples, these approaches can be used at least for the following by mapping i) any number of or all residue changes for any number of or all proteins in a specific biochemical pathway, such as lycopene production, or that catalyze similar reactions, such as dehydrogenases or other enzymes of a pathway of use to produce a desired effect or produce a product, or ii) any number of or all residues in the regulatory sites of any number of or all proteins with a specific regulatory mechanism, such as heat shock response, or iii) any number of or all residues of a biological agent used to treat a health condition, such as insulin, a growth factor (HCG), an anti-cancer biologic, or a replacement protein for a deficient population.
[00219] Scores related to various input parameters can be assigned in order to generate one or more composite score(s) for designing genomically-engineered organisms or systems. These scores can reflect quality of genetic variations in genes or genetic loci as they relate to selection of an organism or design of an organism for a predetermined production, trait or traits. Certain organisms or systems can be designed based on a need for improved organisms for biorefining, biomass, such as crops, trees, grasses, crop residues, or forest residues, biofuel production, and using biological conversion, fermentation, chemical conversion and catalysis to generate and use compounds, biopharmaceutical production and biologic production. In certain embodiments, this can be accomplished by modulating growth or production of microorganism through genetic manipulation methods disclosed herein.
[00220] Genetic manipulation by methods disclosed herein of genes encoding a protein can be used to make desired genetic changes that can result in desired phenotypes and can be accomplished through numerous techniques including but not limited to, i) introduction of new genetic material, ii) genetic insertion, disruption or removal of existing genetic material, as well as, iii) mutation of genetic material, such as a point mutation, or any combinations of i, ii, and iii, that results in desired genetic changes with desired phenotypic changes. Mutations can be directed or random, in addition to those including, but not limited to, error prone or directed mutagenesis through PCR, mutator strains, and random mutagenesis. Mutations can be incorporated using trackable plasmids and methods as disclosed herein.
[00221] Disclosed methods can be used for inserting and accumulating higher order modifications into a microorganism's genome or a target protein; for example, multiple different site-specified mutations in the same genome, at high efficiency to generate libraries of genomes with over 1, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, or more targeted modifications are described. In some examples, these mutations are within regulatory modules, regulatory elements, protein-coding regions, or non-coding regions. Protein coding modifications can include, but are not limited to, amino acid changes, codon optimization, and translation tuning.
[00222] In some instances, methods are provided for the co-delivery of reagents to a single biological cell. The methods generally involve the attachment or linkage of two or more cassettes, followed by delivery of the linked cassettes to a single cell. Generally, the methods provided herein involve the delivery of two or more cassettes to a single cell. In many cases, it is desirable that each individual cell receives the two or more cassettes. Traditional methods of reagent delivery may often be inefficient and/or inconsistent, leading to situations in which some cells receive only one of the cassettes. The methods provided herein may improve the efficiency and/or consistency of reagent delivery, such that a majority of cells in a cell population each receive the two or more cassettes. For example, more than 50%, 55%, 60%, 65%, 70%, 75%,
80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% of the cells in a cell population may receive the two or more cassettes.
[00223] The two or more cassettes may be linked by any known method in the art and generally the method chosen will be commensurate with the chemistry of the cassettes. Generally, the two or more cassettes are linked by a covalent bond (i.e., covalently-linked), however, other types of non-covalent chemical bonds are envisioned, such as hydrogen bonds, ionic bonds, and metallic bonds. In this way, the editing cassette and the recorder cassette may be linked and delivered into a single cell. A known edit is then associated with a known recorder or barcode sequence for that cell.
[00224] In one example, the two or more cassettes are nucleic acids, such as two or more nucleic acids. The nucleic acids may be RNA, DNA, or a combination of both, and may contain any number of chemically-modified nucleotides or nucleotide analogues. In some cases, two or more RNA cassettes are linked for delivery to a single cell. In other cases, two or more DNA cassettes are linked for delivery to a single cell. In yet other cases, a DNA cassettes and an RNA cassettes are linked for delivery to a single cell. The nucleic acids may be derived from genomic RNA, complementary DNA (cDNA), or chemically or enzymatically synthesized DNA.
[00225] A cassettes may be of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, about 110, about 120, about 130, about 140, about 150, about 160, about 170, about 180, about 190, about 200, about 210, about 220, about 230, about 240, about 250, about 275, about 300, about 325, about 350, about 375, about 400, about 425, about 450, about 475, about 500, about 525, about 550, about 575, about 600, about 625, about 650, about 675, about 700, about 725, about 750, about 775, about 800, about 825, about 850, about 875, about 900, about 925, about 950, about 975, about 1000, about 1100, about 1200, about 1300, about 1400, about 1500, about 1750, about 2000, about 2500, about 3000, about 4000, about 5000, about 6000, about 7000, about 8000, about 9000, about 10,000 or greater nucleotide residues in length, up to a full length protein encoding or regulatory genetic element. [00226] Two or more cassettes may be linked on a linear nucleic acid molecule or may be linked on a plasmid or circular nucleic acid molecule. The two or more cassettes may be linked directly to one another or may be separated by one or more nucleotide spacers or linkers.
[00227] Two or more cassettes may be covalently linked on a linear cassettes or may be covalently linked on a plasmid or circular nucleic acid molecule. The two or more cassettes may be covalently linked directly to one another or may be separated by one or more nucleotide spacers or linkers.
[00228] Any number and variety of cassettes may be linked for co-delivery. For example, the two or more cassettes may include nucleic acids, lipids, proteins, peptides, small molecules, or any combination thereof. The two or more cassettes may be essentially any cassettes that are amenable to linkage.
[00229] In preferred examples, the two or more cassettes are covalently linked (e.g., by a chemical bond). Covalent linkage may help to ensure that the two or more cassettes are co- delivered to a single cell. Generally, the two or more cassettes are covalently linked prior to delivery to a cell. Any method of covalently linking two or more molecules may be utilized, and it should be understood that the methods used will be at least partly determined by the types of cassettes to be linked.
[00230] In some instances, methods are provided for the co-delivery of reagents to a single biological cell. The methods generally involve the covalent attachment or linkage of two or more cassettes, followed by delivery of the covalently-linked cassettes into a single cell. The methods provided may help to ensure that an individual cell receives the two or more cassettes. Any known method of reagent delivery may be utilized to deliver the linked cassettes to a cell and will at least partly depend on the chemistry of the cassettes to be delivered. Non-limiting examples of reagent delivery methods may include: transformation, lipofection, electroporation, transfection, nanoparticles, and the like.
[00231] In various embodiments, cassettes, or isolated, donor, or editing nucleic acids may be introduced to a cell or microorganism to alter or modulate an aspect of the cell or microorganism, for example survival or growth of the microorganism as disclosed herein. The isolated nucleic acid may be derived from genomic RNA, complementary DNA (cDNA), chemically or enzymatically synthesized DNA. Additionally or alternatively, isolated nucleic acids may be of use for capture probes, primers, labeled detection oligonucleotides, or fragments for DNA assembly.
[00232] A "nucleic acid" can include single- stranded and/or double-stranded molecules, as well as DNA, RNA, chemically modified nucleic acids and nucleic acid analogs. It is contemplated that a nucleic acid may be of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44,
45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, about 110, about 120, about 130, about 140, about 150, about 160, about 170, about 180, about 190, about 200, about 210, about 220, about 230, about 240, about 250, about 275, about 300, about 325, about 350, about 375, about 400, about 425, about 450, about 475, about 500, about 525, about 550, about 575, about 600, about 625, about 650, about 675, about 700, about 725, about 750, about 775, about 800, about 825, about 850, about 875, about 900, about 925, about 950, about 975, about 1000, about 1100, about 1200, about 1300, about 1400, about 1500, about 1750, about 2000, about 2500, about 3000, about 4000, about 5000, about 6000, about 7000, about 8000, about 9000, about 10,000 or greater nucleotide residues in length, up to a full length protein encoding or regulatory genetic element.
[00233] Isolated nucleic acids may be made by any method known in the art, for example using standard recombinant methods, assembly methods, synthetic techniques, or combinations thereof. In some embodiments, the nucleic acids may be cloned, amplified, assembled, or otherwise constructed.
[00234] The nucleic acids may conveniently comprise sequences in addition to a portion of a lysine riboswitch. For example, a multi-cloning site comprising one or more endonuclease restriction sites may be added. A nucleic acid may be attached to a vector, adapter, or linker for cloning of a nucleic acid. Additional sequences may be added to such cloning and sequences to optimize their function, to aid in isolation of the nucleic acid, or to improve the introduction of the nucleic acid into a cell. Use of cloning vectors, expression vectors, adapters, and linkers is well known in the art.
[00235] Isolated nucleic acids may be obtained from cellular, bacterial, or other sources using any number of cloning methodologies known in the art. In some embodiments, oligonucleotide probes which selectively hybridize, under stringent conditions, to other oligonucleotides or to the nucleic acids of an organism or cell. Methods for construction of nucleic acid libraries are known and any such known methods may be used.
[00236] Cellular genomic DNA, RNA, or cDNA may be screened for the presence of an identified genetic element of interest using a probe based upon one or more sequences. Various degrees of stringency of hybridization may be employed in the assay.
[00237] High stringency conditions for nucleic acid hybridization are well known in the art. For example, conditions may comprise low salt and/or high temperature conditions, such as provided by about 0.02 M to about 0.15 M NaCl at temperatures of about 50° C. to about 70° C. It is understood that the temperature and ionic strength of a desired stringency are determined in part by the length of the particular nucleic acid(s), the length and nucleotide content of the target sequence(s), the charge composition of the nucleic acid(s), and by the presence or concentration of formamide, tetram ethyl ammonium chloride or other solvent(s) in a hybridization mixture. Nucleic acids may be completely complementary to a target sequence or may exhibit one or more mismatches.
[00238] Nucleic acids of interest may also be amplified using a variety of known amplification techniques. For instance, polymerase chain reaction (PCR) technology may be used to amplify target sequences directly from DNA, RNA, or cDNA. PCR and other in vitro amplification methods may also be useful, for example, to clone nucleic acid sequences, to make nucleic acids to use as probes for detecting the presence of a target nucleic acid in samples, for nucleic acid sequencing, or for other purposes.
[00239] Isolated nucleic acids may be prepared by direct chemical synthesis by methods such as the phosphotriester method, or using an automated synthesizer. Chemical synthesis generally produces a single stranded oligonucleotide. This may be converted into double stranded DNA by hybridization with a complementary sequence or by polymerization with a DNA polymerase using the single strand as a template.
[00240] Any method known in the art for identifying, isolating, purifying, using and assaying activities of target proteins contemplated herein are contemplated. Target proteins contemplated herein include protein agents used to treat a human condition or to regulate processes (e.g. part of a pathway such as an enzyme) involved in disease of a human or non-human mammal. Any method known for selection and production of antibodies or antibody fragments is also contemplated. Additionally or alternatively, target proteins can be proteins or enzymes involved in a pathway or process in a virus, cell, or organism.
Targetable nucleic acid cleavage systems
[00241] Some methods disclosed herein comprise targeting cleavage of specific nucleic acid sequences using a site-specific, targetable, and/or engineered nuclease or nuclease system. Such nucleases can create double-stranded break (DSBs) at desired locations in a genome or nucleic acid molecule. In other examples, a nuclease can create a single strand break. In some cases, two nucleases are used, each of which generates a single strand break.
[00242] The one or more double or single strand break can be repaired by natural processes of homologous recombination (HR) and non-homologous end-joining (NHEJ) using the cell's endogenous machinery. Additionally or alternatively, endogenous or heterologous recombination machinery can be used to repair the induced break or breaks.
[00243] Engineered nucleases such as zinc finger nucleases (ZFNs), Transcription Activator- Like Effector Nucleases (TALENs), engineered homing endonucleases, and RNA or DNA guided endonucl eases, such as CRISPR/Cas such as Cas9 or CPF1, and/or Argonaute systems, are particularly appropriate to carry out some of the methods of the present invention. Additionally or alternatively, RNA targeting systems can use used, such as CRISPR/Cas systems including c2c2 nucleases.
[00244] Methods disclosed herein can comprise cleaving a target nucleic acid using a CRISPR systems, such as a Type I, Type II, Type III, Type IV, Type V, or Type VI CRISPR system. CRISPR/Cas systems can be multi-protein systems or single effector protein systems. Multi- protein, or Class 1, CRISPR systems include Type I, Type III, and Type IV systems. Alternatively, Class 2 systems include a single effector molecule and include Type II, Type VI, and Type VI.
[00245] CRISPR systems used in methods disclosed herein can comprise a single or multiple effector proteins. An effector protein can comprise one or multiple nuclease domains. An effector protein can target DNA or RNA, and the DNA or RNA may be single stranded or double stranded. Effector proteins can generate double strand or single strand breaks. Effector proteins can comprise mutations in a nuclease domain thereby generating a nickase protein. Effector proteins can comprise mutations in one or more nuclease domains, thereby generating a catalytically dead nuclease that is able to bind but not cleave a target sequence. CRISPR systems can comprise a single or multiple guiding RNAs. The gRNA can comprise a crRNA. The gRNA can comprise a chimeric RNA with crRNA and tracrRNA sequences. The gRNA can comprise a separate crRNA and tracrRNA. Target nucleic acid sequences can comprise a protospacer adjacent motif (PAM) or a protospacer flanking site (PFS). The PAM or PFS may be 3' or 5' of the target or protospacer site. Cleavage of a target sequence may generate blunt ends, 3 ' overhangs, or 5' overhangs.
[00246] A gRNA can comprise a spacer sequence. Spacer sequences can be complementary to target sequences or protospacer sequences. Spacer sequences can be 10, 11, 12, 13, 14, 15, 16,
17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 nucleotides in length. In some examples, the spacer sequence can be less than 10 or more than 36 nucleotides in length.
[00247] A gRNA can comprise a repeat sequence. In some cases, the repeat sequence is part of a double stranded portion of the gRNA. A repeat sequence can be 10, 11, 12, 13, 14, 15, 16, 17,
18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 nucleotides in length. In some examples, the spacer sequence can be less than 10 or more than 50 nucleotides in length.
[00248] A gRNA can comprise one or more synthetic nucleotides, non-naturally occurring nucleotides, nucleotides with a modification, deoxyribonucleotide, or any combination thereof. Additionally or alternatively, a gRNA may comprise a hairpin, linker region, single stranded region, double stranded region, or any combination thereof. Additionally or alternatively, a gRNA may comprise a signaling or reporter molecule.
[00249] A CRISPR nuclease can be endogenously or recombinantly expressed within a cell. A CRISPR nuclease can be encoded on a chromosome, extrachromosomally, or on a plasmid, synthetic chromosome, or artificial chromosome. A CRISPR nuclease can be provided or delivered to the cell as a polypeptide or mRNA encoding the polypeptide. In such examples, polypeptide or mRNA can be delivered through standard mechanisms known in the art, such as through the use of cell permeable peptides, nanoparticles, or viral particles.
[00250] gRNAs can be encoded by genetic or episomal DNA within a cell. In some examples, gRNAs can be provided or delivered to a cell expressing a CRISPR nuclease. gRNAs can be provided or delivered concomitantly with a CRISPR nuclease or sequentially. Guide RNAs can be chemically synthesized, in vitro transcribed, or otherwise generated using standard RNA generation techniques known in the art.
[00251] A CRISPR system can be a Type II CRISPR system, for example a Cas9 system. The Type II nuclease can comprise a single effector protein, which, in some cases, comprises a RuvC and HNH nuclease domains. In some cases a functional Type II nuclease can comprise two or more polypeptides, each of which comprises a nuclease domain or fragment thereof. The target nucleic acid sequences can comprise a 3' protospacer adjacent motif (PAM). In some examples, the PAM may be 5' of the target nucleic acid. Guide RNAs (gRNA) can comprise a single chimeric gRNA, which contains both crRNA and tracrRNA sequences. Alternatively, the gRNA can comprise a set of two RNAs, for example a crRNA and a tracrRNA. The Type II nuclease can generate a double strand break, which is some cases creates two blunt ends. In some cases, the Type II CRISPR nuclease is engineered to be a nickase such that the nuclease only generates a single strand break. In such cases, two distinct nucleic acid sequences can be targeted by gRNAs such that two single strand breaks are generated by the nickase. In some examples, the two single strand breaks effectively create a double strand break. In some cases where a Type II nickase is used to generate two single strand breaks, the resulting nucleic acid free ends can either be blunt, have a 3' overhang, or a 5' overhang. In some examples, a Type II nuclease may be catalytically dead such that it binds to a target sequence, but does not cleave. For example, a Type II nuclease could have mutations in both the RuvC and HNH domains, thereby rendering the both nuclease domains non-functional. A Type II CRISPR system can be one of three subtypes, namely Type II-A, Type II-B, or Type II-C.
[00252] A CRISPR system can be a Type V CRISPR system, for example a Cpfl, C2cl, or C2c3 system. The Type V nuclease can comprise a single effector protein, which in some cases comprises a single RuvC nuclease domain. In other cases, a function Type V nuclease comprises a RuvC domain split between two or more polypeptides. In such cases, the target nucleic acid sequences can comprise a 5' PAM or 3' PAM. Guide RNAs (gRNA) can comprise a single gRNA or single crRNA, such as can be the case with Cpfl . In some cases, a tracrRNA is not needed. In other examples, such as when C2cl is used, a gRNA can comprise a single chimeric gRNA, which contains both crRNA and tracrRNA sequences or the gRNA can comprise a set of two RNAs, for example a crRNA and a tracrRNA. The Type V CRISPR nuclease can generate a double strand break, which in some cases generates a 5' overhang. In some cases, the Type V CRISPR nuclease is engineered to be a nickase such that the nuclease only generates a single strand break. In such cases, two distinct nucleic acid sequences can be targeted by gRNAs such that two single strand breaks are generated by the nickase. In some examples, the two single strand breaks effectively create a double strand break. In some cases where a Type V nickase is used to generate two single strand breaks, the resulting nucleic acid free ends can either be blunt, have a 3' overhang, or a 5' overhang. In some examples, a Type V nuclease may be catalytically dead such that it binds to a target sequence, but does not cleave. For example, a Type V nuclease could have mutations a RuvC domain, thereby rendering the nuclease domain non-functional.
[00253] A CRISPR system can be a Type VI CRISPR system, for example a C2c2 system. A Type VI nuclease can comprise a HEPN domain. In some examples, the Type VI nuclease comprises two or more polypeptides, each of which comprises a HEPN nuclease domain or fragment thereof. In such cases, the target nucleic acid sequences can by RNA, such as single stranded RNA. When using Type VI CRISPR system, a target nucleic acid can comprise a protospacer flanking site (PFS). The PFS may be 3' or 5'or the target or protospacer sequence. Guide RNAs (gRNA) can comprise a single gRNA or single crRNA. In some cases, a tracrRNA is not needed. In other examples, a gRNA can comprise a single chimeric gRNA, which contains both crRNA and tracrRNA sequences or the gRNA can comprise a set of two RNAs, for example a crRNA and a tracrRNA. In some examples, a Type VI nuclease may be catalytically dead such that it binds to a target sequence, but does not cleave. For example, a Type VI nuclease could have mutations in a HEPN domain, thereby rendering the nuclease domains nonfunctional.
[00254] Non-limiting examples of suitable nucleases, including nucleic acid-guided nucleases, for use in the present disclosure include C2cl, C2c2, C2c3, Casl, CaslB, Cas2, Cas3, Cas4, Cas5, Cas6, Cas7, Cas8, Cas9 (also known as Csnl and Csxl2), CaslO, Cpfl, Csyl, Csy2, Csy3, Csel, Cse2, Cscl, Csc2, Csa5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmrl, Cmr3, Cmr4, Cmr5, Cmr6, Csbl, Csb2, Csb3, Csxl7, Csxl4, CsxlOO, Csxl6, CsaX, Csx3, Csxl, Csxl5, Csfl, Csf2, Csf3, Csf4, homologues thereof, orthologues thereof, or modified versions thereof. Suitable nucleic acid-guided nucleases can be from an organism from a genus which includes but is not limited to Thiomicrospira, Succinivibrio, Candidatus, Porphyromonas, Acidomonococcus, Prevotella, Smithella, Moraxella, Synergistes, Francisella, Leptospira, Catenibacterium, Kandleria, Clostridium, Dorea, Coprococcus, Enterococcus, Fructobacillus, Weissella, Pediococcus, Corynebacter, Sutterella, Legionella, Treponema, Roseburia, Filifactor, Eubacterium, Streptococcus, Lactobacillus, Mycoplasma, Bacteroides, Flaviivola, Flavobacterium, Sphaerochaeta, Azospirillum, Gluconacetobacter, Neisseria, Roseburia, Parvibaculum, Staphylococcus, Nitratifractor, Mycoplasma, Alicyclobacillus, Brevibacilus, Bacillus, Bacteroidetes, Brevibacilus, Carnobacterium, Clostridiaridium, Clostridium, Desulfonatronum, Desulfovibrio, Helcococcus, Leptotrichia, Listeria, Methanomethyophilus, Methylobacterium, Opitutaceae, Paludibacter, Rhodobacter, Sphaerochaeta, Tuberibacillus, and Campylobacter. Species of organism of such a genus can be as otherwise herein discussed. Suitable nucleic acid-guided nucleases can be from an organism from a genus or unclassified genus within a kingdom, which includes but is not limited to Firmicute, Actinobacteria, Bacteroidetes, Proteobacteria, Spirochates, and Tenericutes. Suitable nucleic acid-guided nucleases can be from an organism from a genus or unclassified genus within a phylum which includes but is not limited to Erysipelotrichia, Clostridia, Bacilli, Actinobacteria, Bacteroidetes, Flavobacteria, Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Deltaproteobacteria, Epsilonproteobacteria, Spirochaetes, and Mollicutes. Suitable nucleic acid- guided nucleases can be from an organism from a genus or unclassified genus within an order which includes but is not limited to Clostridiales, Lactobacillales, Actinomycetales, Bacteroidales, Flavobacteriales, Rhizobiales, Rhodospirillales, Burkholderiales, Neisseriales, Legionellales, Nautiliales, Campylobacterales, Spirochaetales, Mycoplasmatales, and Thiotrichales. Suitable nucleic acid-guided nucleases can be from an organism from a genus or unclassified genus within a family which includes but is not limited to Lachnospiraceae, Enterococcaceae, Leuconostocaceae, Lactobacillaceae, Streptococcaceae,
Peptostreptococcaceae, Staphylococcaceae, Eubacteriaceae, Corynebacterineae, Bacteroidaceae, Flavobacterium, Cryomoorphaceae, Rhodobiaceae, Rhodospirillaceae, Acetobacteraceae, Sutterellaceae, Neisseriaceae, Legionellaceae, Nautiliaceae, Campylobacteraceae, Spirochaetaceae, Mycoplasmataceae, Pisciririckettsiaceae, and Francisellaceae.
[00255] Other nucleic acid-guided nucleases suitable for use in the methods, systems, and compositions of the present disclosure include those derived from an organism such as, but not limited to, Thiomicrospira sp. XS5, Eubacterium rectale, Succinivibrio dextrinosolvens, Candidatus Methanoplasma termitum, Candidatus Methanomethylophilus alvus, Porphyromonas crevioricanis, Flavobacterium branchiophilum, Acidomonococcus sp., Lachnospiraceae bacterium COEl, Prevotella brevis ATCC 19188, Smithella sp. SCADC, Moraxella bovoculi, Synergistes jonesii, Bacteroidetes oral taxon 274, Francisella tularensis, Leptospira inadai serovar Lyme str. 10, Acidomonococcus sp. crystal structure (5B43) S. mutans, S. agalactiae, S. equisimilis, S. sanguinis, S. pneumonia; C. jejuni, C. coli; N. salsuginis, N. tergarcus; S. auricularis, S. carnosus; N. meningitides, N. gonorrhoeae; L. monocytogenes, L. ivanovii; C. botulinum, C. difficile, C. tetani, C. sordellii; Francisella tularensis 1, Prevotella albensis, Lachnospiraceae bacterium MC2017 1, Butyrivibrio proteoclasticus, Peregrinibacteria bacterium GW2011_GWA2_33_10, Parcubacteria bacterium GW2011_GWC2_44_17, Smithella sp. SCADC, Acidaminococcus sp. BV3L6, Lachnospiraceae bacterium MA2020, Candidatus Methanoplasma termitum, Eubacterium eligens, Moraxella bovoculi 237, Leptospira inadai, Lachnospiraceae bacterium D2006, Porphyromonas crevioricanis 3, Prevotella disiens, Porphyromonas macacae, Catenibacterium sp. CAG:290, Kandleria vitulina, Clostridiales bacterium KA00274, Lachnospiraceae bacterium 3-2, Dorea longicatena, Coprococcus catus GD/7, Enterococcus columbae DSM 7374, Fructobacillus sp. EFB-N1, Weissella halotolerans, Pediococcus acidilactici, Lactobacillus curvatus, Streptococcus pyogenes, Lactobacillus versmoldensis, and Filifactor alocis ATCC 35896.
[00256] Suitable nucleases for use in any of the methods disclosed herein include, but are not limited to, nucleases having the sequences listed in Table 1, or homologues having at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%), or 99% sequence identity to any of the nucleases listed in Table 1.
Table 1.
[00257] In some methods disclosed herein, Argonaute (Ago) systems can be used to cleave target nucleic acid sequences. Ago protein can be derived from a prokaryote, eukaryote, or archaea. The target nucleic acid may be RNA or DNA. A DNA target may be single stranded or double stranded. In some examples, the target nucleic acid does not require a specific target flanking sequence, such as a sequence equivalent to a protospacer adjacent motif or protospacer flanking sequence. The Ago protein may create a double strand break or single strand break. In some examples, when a Ago protein forms a single strand break, two Ago proteins may be used in combination to generate a double strand break. In some examples, an Ago protein comprises one, two, or more nuclease domains. In some examples, an Ago protein comprises one, two, or more catalytic domains. One or more nuclease or catalytic domains may be mutated in the Ago protein, thereby generating a nickase protein capable of generating single strand breaks. In other examples, mutations in one or more nuclease or catalytic domains of an Ago protein generates a catalytically dead Ago protein that can bind but not cleave a target nucleic acid.
[00258] Ago proteins can be targeted to target nucleic acid sequences by a guiding nucleic acid. In many examples, the guiding nucleic acid is a guide DNA (gDNA). The gDNA can have a 5' phosphorylated end. The gDNA can be single stranded or double stranded. Single stranded gDNA can be 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 nucleotides in length. In some examples, the gDNA can be less than 10 nucleotides in length. In some examples, the gDNA can be more than 50 nucleotides in length.
[00259] Argonaute-mediated cleavage can generate blunt end, 5' overhangs, or 3' overhangs. In some examples, one or more nucleotides are removed from the target site during or following cleavage.
[00260] Argonaute protein can be endogenously or recombinantly expressed within a cell. Argonaute can be encoded on a chromosome, extrachromosomally, or on a plasmid, synthetic chromosome, or artificial chromosome. Additionally or alternatively, an Argonaute protein can be provided or delivered to the cell as a polypeptide or mRNA encoding the polypeptide. In such examples, polypeptide or mRNA can be delivered through standard mechanisms known in the art, such as through the use of cell permeable peptides, nanoparticles, or viral particles.
[00261] Guide DNAs can be provided by genetic or episomal DNA within a cell. In some examples, gDNA are reverse transcribed from RNA or mRNA within a cell. In some examples, gDNAs can be provided or delivered to a cell expressing an Ago protein. Guide DNAs can be provided or delivered concomitantly with an Ago protein or sequentially. Guide DNAs can be chemically synthesized, assembled, or otherwise generated using standard DNA generation techniques known in the art. Guide DNAs can be cleaved, released, or otherwise derived from genomic DNA, episomal DNA molecules, isolated nucleic acid molecules, or any other source of nucleic acid molecules.
[00262] In some instances, compositions are provided comprising a nuclease such as an nucleic acid-guided nuclease (e.g., Cas9, Cpfl, MAD2, or MAD7) or a DNA-guided nuclease (e.g., Ago), linked to a chromatin-remodeling enzyme. Without wishing to be bound by theory, a nuclease fusion protein as described herein may provide improved accessibility to regions of highly-structured DNA. Non-limiting examples of chromatin-remodeling enzymes that can be linked to a nucleic-acid guided nuclease may include: histone acetyl transferases (HATs), histone deacetylases (HDACs), histone methyltransferases (HMTs), chromatin remodeling complexes, and transcription activator-like (Tal) effector proteins. Histone deacetylases may include HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9, HDAC10, HDAC11, sirtuin 1, sirtuin 2, sirtuin 3, sirtuin 4, sirtuin 5, sirtuin 6, and sirtuin 7. Histone acetyl transferases may include GCN5, PCAF, Hatl, Elp3, Hpa2, Hpa3, ATF-2, Nutl, Esal, Sas2, Sas3, Tip60, MOF, MOZ, MORF, HBOl, p300, CBP, SRC-1, ACTR, TIF-2, SRC-3, TAFII250, TFIIIC, Rttl09, and CLOCK. Histone methyltransferases may include ASH1L, DOT1L, EHMT1, EHMT2, EZH1, EZH2, MLL, MLL2, MLL3, MLL4, MLL5, NSD1, PRDM2, SET, SETBP1, SETD1A, SETD1B, SETD2, SETD3, SETD4, SETD5, SETD6, SETD7, SETD8, SETD9, SETDB1, SETDB2, SETMAR, SMYD1, SMYD2, SMYD3, SMYD4, SMYD5, SUV39H1, SUV39H2, SUV420H1, and SUV420H2. Chromatin-remodeling complexes may include SWI/SNF, ISWI, NuRD/Mi-2/CHD, F O80 and SWR1.
[00263] In some instances, the nuclease is a wild-type nuclease. In other instances, the nuclease is a chimeric engineered nuclease. Chimeric engineered nucleases as disclosed herein can comprise one or more fragments or domains, and the fragments or domains can be of a nuclease, such as nucleic acid-guided nuclease, orthologs of organisms of genuses, species, or other phylogenetic groups disclosed herein; advantageously the fragments are from nuclease orthologs of different species. A chimeric engineered nuclease can be comprised of fragments or domains from at least two different nucleases. A chimeric engineered nuclease can be comprised of fragments or domains from at least two different species. A chimeric engineered nuclease can be comprised of fragments or domains from at least 2, 3, 4, 5, 6, 7, 8, 9, 10, or more different nucleases or different species. In some cases, more than one fragment or domain from one nuclease or species, wherein the more than one fragment or domain are separated by fragments or domains from a second nuclease or species. In some examples, a chimeric engineered nuclease comprises 2 fragments, each from a different protein or nuclease. In some examples, a chimeric engineered nuclease comprises 3 fragments, each from a different protein or nuclease. In some examples, a chimeric engineered nuclease comprises 4 fragments, each from a different protein or nuclease. In some examples, a chimeric engineered nuclease comprises 5 fragments, each from a different protein or nuclease.
[00264] Nuclease fusion proteins can be recombinantly expressed within a cell. A nuclease fusion protein can be encoded on a chromosome, extrachromosomally, or on a plasmid, synthetic chromosome, or artificial chromosome. A nuclease and a chromatin-remodeling enzyme may be engineered separately, and then covalently linked, prior to delivery to a cell. A nuclease fusion protein can be provided or delivered to the cell as a polypeptide or mRNA encoding the polypeptide. In such examples, polypeptide or mRNA can be delivered through standard mechanisms known in the art, such as through the use of cell permeable peptides, nanoparticles, or viral particles.
Cell-cycle-dependent expression of targeted nucleases.
[00265] In some instances, compositions comprising a cell-cycle-dependent nuclease are provided. A cell-cycle dependent nuclease generally includes a targeted nuclease as described herein linked to an enzyme that leads to degradation of the targeted nuclease during Gl phase of the cell cycle, and expression of the targeted nuclease during G2/M phase of the cell cycle. Such cell-cycle dependent expression may, for example, bias the expression of the nuclease in cells where homology-directed repair (HDR) is most active (e.g., during G2/M phase). In some cases, the nuclease is covalently linked to cell-cycle regulated protein such as one that is actively degraded during Gl phase of the cell cycle and is actively expressed during G2/M phase of the cell cycle. In a non-limiting example, the cell-cycle regulated protein is Geminin. Other non- limiting examples of cell-cycle regulated proteins may include: Cyclin A, Cyclin B, Hsll, Cdc6, Finl, p21 and Skp2.
[00266] In some instances, the nuclease is a wild-type nuclease.
[00267] In other instances, the nuclease is a engineered nuclease. Engineered nucleases can be non-naturally occurring.
[00268] Non-naturally occurring targetable nucleases and non-naturally occurring targetable nuclease systems can address many of these challenges and limitations.
[00269] Disclosed herein are non-naturally targetable nuclease systems. Such targetable nuclease systems are engineered to address one or more of the challenges described above and can be referred to as engineered nuclease systems. Engineered nuclease systems can comprise one or more of an engineered nuclease, such as an engineered nucleic acid-guided nuclease, an engineered guide nucleic acid, an engineered polynucleotides encoding said nuclease, or an engineered polynucleotides encoding said guide nucleic acid. Engineered nucleases, engineered guide nucleic acids, and engineered polynucleotides encoding the engineered nuclease or engineered guide nucleic acid are not naturally occurring and are not found in nature. It follows that engineered nuclease systems including one or more of these elements are non-naturally occurring.
[00270] Non-limiting examples of types of engineering that can be done to obtain a non- naturally occurring nuclease system are as follows. Engineering can include codon optimization to facilitate expression or improve expression in a host cell, such as a heterologous host cell. Engineering can reduce the size or molecular weight of the nuclease in order to facilitate expression or delivery. Engineering can alter PAM selection in order to change PAM specificity or to broaden the range of recognized PAMs. Engineering can alter, increase, or decrease stability, processivity, specificity, or efficiency of a targetable nuclease system. Engineering can alter, increase, or decrease protein stability. Engineering can alter, increase, or decrease processivity of nucleic acid scanning. Engineering can alter, increase, or decrease target sequence specificity. Engineering can alter, increase, or decrease nuclease activity. Engineering can alter, increase, or decrease editing efficiency. Engineering can alter, increase, or decrease transformation efficiency. Engineering can alter, increase, or decrease nuclease or guide nucleic acid expression.
[00271] Examples of non-naturally occurring nucleic acid sequences which are disclosed herein include sequences codon optimized for expression in bacteria, such as E. coli (e.g., SEQ ID NO: 41-60), sequences codon optimized for expression in single cell eukaryotes, such as yeast (e.g., SEQ ID NO: 127-146), sequences codon optimized for expression in multi cell eukaryotes, such as human cells (e.g., SEQ ID NO: 147-166), polynucleotides used for cloning or expression of any sequences disclosed herein (e.g., SEQ ID NO: 61-80), plasmids comprising nucleic acid sequences (e.g., SEQ ID NO: 21-40) operably linked to a heterologous promoter or nuclear localization signal or other heterologous element, proteins generated from engineered or codon optimized nucleic acid sequences (e.g., SEQ ID NO: 1-20), or engineered guide nucleic acids comprising any one of SEQ ID NO: 84-107. Such non-naturally occurring nucleic acid sequences can be amplified, cloned, assembled, synthesized, generated from synthesized oligonucleotides or dNTPs, or otherwise obtained using methods known by those skilled in the art.
[00272] Additional examples of non-naturally occurring nucleic acid sequences which are disclosed herein include sequences codon optimized for expression in bacteria, such as E. coli (e.g., SEQ ID NO: 168), sequences codon optimized for expression in single cell eukaryotes, such as yeast (e.g., SEQ ID NO: 169), sequences codon optimized for expression in multi cell eukaryotes, such as human cells (e.g., SEQ ID NO: 170), polynucleotides used for cloning or expression of any sequences disclosed herein (e.g., SEQ ID NO: 171), plasmids comprising nucleic acid sequences (e.g., SEQ ID NO: 167) operably linked to a heterologous promoter or nuclear localization signal or other heterologous element, proteins generated from engineered or codon optimized nucleic acid sequences (e.g., SEQ ID NO: 108-110), or engineered guide nucleic acids compatible with any targetable nuclease disclosed herein. Such non-naturally occurring nucleic acid sequences can be amplified, cloned, assembled, synthesized, generated from synthesized oligonucleotides or dNTPs, or otherwise obtained using methods known by those skilled in the art..
[00273] A guide nucleic acid can be DNA. A guide nucleic acid can be RNA. A guide nucleic acid can comprise both DNA and RNA. A guide nucleic acid can comprise modified of non- naturally occurring nucleotides. In cases where the guide nucleic acid comprises RNA, the RNA guide nucleic acid can be encoded by a DNA sequence on a polynucleotide molecule such as a plasmid, linear construct, or editing cassette as disclosed herein.
[00274] Nucleic acid-guided nucleases can be compatible with guide nucleic acids that are not found within the nucleases endogenous host. Such orthogonal guide nucleic acids can be determined by empirical testing. Orthogonal guide nucleic acids can come from different bacterial species or be synthetic or otherwise engineered to be non-naturally occurring.
[00275] Orthogonal guide nucleic acids that are compatible with a common nucleic acid- guided nuclease can comprise one or more common features. Common features can include sequence outside a pseudoknot region. Common features can include a pseudoknot region (e.g., 172-181). Common features can include a primary sequence or secondary structure.
[00276] A guide nucleic acid can be engineered to target a desired target sequence by altering the guide sequence such that the guide sequence is complementary to the target sequence, thereby allowing hybridization between the guide sequence and the target sequence. A guide nucleic acid with an engineered guide sequence can be referred to as an engineered guide nucleic acid. Engineered guide nucleic acids are often non-naturally occurring and are not found in nature.
[00277] In other instances, the nuclease is a chimeric nuclease. Chimeric nucleases can be engineered nucleases. Chimeric nucleases as disclosed herein can comprise one or more fragments or domains, and the fragments or domains can be of a nuclease, such as nucleic acid- guided nuclease, orthologs of organisms of genuses, species, or other phylogenetic groups; advantageously the fragments are from nuclease orthologs of different species. A chimeric nuclease can be comprised of fragments or domains from at least two different nucleases. A chimeric nuclease can be comprised of fragments or domains from at least two different species. A chimeric nuclease can be comprised of fragments or domains from at least 2, 3, 4, 5, 6, 7, 8, 9, 10, or more different nucleases or different species. In some cases, more than one fragment or domain from one nuclease or species, wherein the more than one fragment or domain are separated by fragments or domains from a second nuclease or species. In some examples, a chimeric nuclease comprises 2 fragments, each from a different protein or nuclease. In some examples, a chimeric nuclease comprises 3 fragments, each from a different protein or nuclease. In some examples, a chimeric nuclease comprises 4 fragments, each from a different protein or nuclease. In some examples, a chimeric nuclease comprises 5 fragments, each from a different protein or nuclease.
EXAMPLES
Example 1 - CREATE-plasmids and libraries
[00278] Figures 1A-C depict an example of an overview of CRISPR EnAbled Trackable genome Engineering (CREATE) design and workflow. Figure 1A shows an example of the CREATE methodology which allows programmatic genome modifications to be focused on key amino acid residues or promoter targets across the genome. Such libraries thus enable systematic assessment of sequence/activity relationships for a wide variety of genomic targets in parallel. Figure IB depicts an example of CREATE cassettes designed to encode both homology arm (HA) and guide RNA (gRNA) sequences to target a specific locus in the E. coli genome. The 100 bp homology arm was designed to introduce a specific codon mutation (target codon) that can be selectively enriched by a synonymous PAM mutation to rescue the sequence from Cas9 cleavage and allow highly efficient mutagenesis. The PI and P2 sites (black) serve as general priming sites allowing multiplexed amplification, cloning and sequencing of many libraries in parallel. The promoter (J23119, green) is a constitutive promoter that drives expression of the gRNA. Detailed example the HA design for introducing a stop codon at residue 145 in the galK locus is also depicted at the bottom of Figure IB. The top sequence shows the wildtype genome sequence with the PAM (CCG; the reverse complement of which is CGG, which is recognized by S. pyogenes Cas9) and target codon (TAT, encoding Y) highlighted. The HA design introduces a "silent scar" at the PAM site (CgG, the reverse complement of which is CCG, which is not recognized by S. pyogenes Cas9) and a single nucleotide TAT>TAA mutation at codon 145 (resulting in a STOP). This design strategy was implemented programmatically for coding regions across the genome. Figure 1C depicts an overview of an example CREATE workflow. CREATE cassettes are synthesized on a microarray delivered as large oligo pools (10 4 to 10 6 individual library members). Parallel cloning and recombineering allowed processing of these pools into genomic libraries, in some cases in 23 days. Deep sequencing of the CREATE plasmids can be used to track the fitness of thousands of precision mutations genome wide following selection or screening of the mutant libraries. Example 2 - CREATE plasmid validation
[00279] Figure 2A-D depicts an example of the effect of Cas9 activity on transformation and editing efficiencies. The galK 120/17 CREATE cassette (120 bp HA and 17 bp PAM/codon spacing) targeting codon 145 in galK gene or a control non-targeting gRNA vector was transformed in cells carrying pSFM5 along with dCas9 (e.g. left set of bars in Figure 2A) or Cas9 (e.g. right set of bars in Figure 2A) plasmids. The pSFM5 plasmid carries lambda red recombination machinery. The cas9 gene was cloned into the pBTBX-2 backbone under the control of a pBAD promoter to allow control of the cleavage activity by addition of arabinose. Transformation efficiencies of each vector are shown with dark grey bars. The total number of recombinant cells (light grey bars) were calculated based on red/white colony screening on MacConkey agar. In cases where white colonies were undetectable by plate based screening we assumed 10 4 editing efficiencies. A 10 2 fold reduction in transformation efficiency compared to the non-targeting gRNA control was also observed for CREATE cassettes transformed into the Cas9 background.
[00280] Figure 2B depicts an example of the characterization of CREATE cassette HA length and PAM/codon spacing on editing efficiency. All cassettes were designed to introduce a TAA stop at codon 145 in the gene using PAMs at the indicated distance (PAM/codon bottom) from the target codon and variable homology arms lengths (HA, bottom). Dark grey and light grey bars correspond to uninduced or induced expression of Cas9 under the pBAD promoter using 0.2% arabinose. In the majority of cases the editing efficiency appears to be unaffected by induction suggesting that low amounts of Cas9 due to leaky expression are sufficient for high efficiency editing.
[00281] Figure 2C shows example data from sequencing of the genomic loci from CREATE recombineering reactions. The galK cassettes from Figure 2B are labeled according to the HA length and PAM codon spacing. The other loci shown were cassettes isolated from multiplexed library cloning reactions. The bar plot (Figure 2C) indicates the number of times each genotype was observed by genomic colony sequencing following recombineering with each CREATE cassette. The + and labels at the bottom indicate the presence or absence of the designed mutation at the two relevant sites in each clone. The circular inset indicates the relative position of each gene on the E. coli genome.
[00282] Figure 2D depicts an example of library coverage from multiplexed cloning of CREATE plasmids. Deep sequencing counts each variant are shown with respect to their position on the genome. The inset shows a histogram of these plasmid counts for the entire library. The distribution follows expected Poisson distribution for low average counts. Example 3 - CREATE-recording used to engineer trackable episomal DNA libraries
[00283] Figure 3A depicts an example of an overview of the method used to generate a trackable episomal DNA library. Transformation of a CREATE recorder plasmid generates modifications of the target DNA at two sites. One edit occurs to the desired target gene (gray) introducing a codon or promoter mutation designed to test specific engineering objectives. The second edit targets a functionally neutral site and introduces a 15 nucleotide barcode (BC, black). By virtue of coupling these libraries on a single CREATE plasmid the target DNA is edited at both sites and each unique barcode can be used to track edits throughout the rest of the plasmid.
[00284] Figure 2B depicts an example of the CREATE barcode design. A degenerate library is constructed from overlapping oligos and cloned in a separate site of the CREATE vector to make a library of CREATE recorder cassettes that can be coupled to the designer editing libraries.
[00285] Figure 2C depicts an exemplary CREATE record mapping strategy. Deep sequencing of both the target DNA (left) and CREATE plasmids allows a simple sequence mapping strategy by allowing each editing cassette to be uniquely assigned by the barcode sequence. This allows the relative fitness of each barcode (and thus edit) to be tracked during selection or screening processes and can be shuttled between different organisms using standard vectors.
Example 4 - CREATE-mediated editing of episomal DNA
[00286] Methods and compositions disclosed herein were used to mutate a key residue of the cas9 gene used for the CREATE process (e.g. Figure 4A-4B). A cassette was designed to make an R1335K mutation in the Cas9 protein. This cassette was cloned into a CREATE plasmid and transformed into MG1655 E. coli carrying the pSEVI5 and X2-Cas9 vectors. The pSEVI5 vector comprises lambda red recombination machinery. The X2-Cas9 vector comprises an arabinose- inducible Cas9 expression cassette. Following three hours recovery in LB supplemented with 0.4% arabinose to induce Cas9 expression, the cells were plated on agar containing antibiotics that maintain selective pressure for replication of both the X2-Cas9 and CREATE plasmids. Colony PCR of random clones revealed the designed edits from the CREATE plasmid were efficiently transferred into the X2-Cas9 plasmid (e.g. Figure 4B). Of the clones that were sequenced, 100% contained the silent PAM mutation in X2Cas9 and 6/14 (43%) also containing desired coding edit. This is the first demonstration that plasmid based editing using CREATE is robust despite higher copy numbers associated with the plasmid target as compared to previous genome engineering efforts.
Example 5 - CREATE-mediated editing and tracking of E. coli genome - double cassette
[00287] To test the performance of the recording strategy in a genomic context we tested the ability to edit two distal genomic loci in the E. coli genome (e.g. Figure 5 A). To do so we cloned CREATE recording cassette libraries designed to embed the 15 nucleotide barcodes into the galK locus. After cloning, we isolated a few unique barcodes and cloned a second editing cassette designed to incorporate an F153R mutation in the dihydrofolate reductase (DHFR)//e>M gene that was identified by our previous CREATE studies as conferring tolerance to the antibiotic trimethoprim. Genotyping of E. coli strains following transformation of the dual CREATE recording vector according to previously described protocols yielded the data in Figure 5 A. The efficiency of barcoding (100%) was higher than the target genome edit (80-90%), ensuring that edited genomes can be tracked. Of the transformed population we observed > 80% of colonies contained the barcode edit in the galK locus as determined by red white colony screening (e.g. Figure 5B). From the barcoded colonies we found that 85% of the colonies also encoded the DFIFR F153R mutation indicating that we have a strong tracking between the barcode and codon edits. Figure 5B depicts the total number of colonies (CFUs) in duplicate experiments that are edited and/or barcoded. The edited CFUs numbers were calculated by extrapolation of the data in Figure 5A to the total number of CFUs on the plate. The barcoded CFUs numbers were calculated by counting the number of white colonies in a galK screening (site in which barcode is integrated). These data show that the majority of barcoded colonies contained the designed genomic edit.
Example 6- Plasmid curing for combinatorial engineering
[00288] Figure 6 depicts an example of combinatorial genome engineering and tracking. Three recursive CREATE plasmids are used, each with a gRNA targeting one of the other markers in this series (indicated by T-lines). During each transformation, an edit and barcode are incorporated into the genome and the previous CREATE plasmid is cured. In this way rapid iterative transformations can be performed to construct either a defined combination of mutations or a combinatorial library to search for improved phenotypes. The recording site is compatible with short read sequencing technologies that allow the fitness of combinations to be tracked across a population. Such an approach allows rapid investigation of genetic epistasis and optimization of phenotypes relevant to basic research or for commercial biological applications.
[00289] Figure 3D and Figure 3E depict another example of combinatorial genome engineering. With each round of engineering, an editing cassette (blue rectangle in Figure 3D) is incorporated into the target sequence in the genome (blue star) and a recorder cassette (green rectangle in Figure 3D) is incorporated into a different target sequence of the genome (green dash in middle panel of Figure 3D). In this example, each recorder sequence comprises a 15 nucleotide barcode. As shown in the right panel of Figure 3D, the recorder sequences are each inserted adjacent to the last recorder sequence, despite where the editing cassette was inserted. Each recorder cassette can simultaneously delete a PAM site. After completion of each round of engineering, the engineered cells can be selected and then the inserted mutations can be tracked by sequencing the recorder region that comprises all of the inserted recorder cassettes. By sequencing the starting plasmid library, each editing cassette can be linked or associated with one or more unique barcodes within the recorder cassette. Since each recorder cassette corresponds to the associate editing cassette, then the mutations incorporated by the editing cassettes can be tracked or identified by the sequence of the recorder cassette, or the sequence of the barcodes within the recorder cassette. As is demonstrated in Figure 3E, by sequencing all of the recorder cassettes or barcodes within the recorder cassettes, each of the inserted mutations can be identified and tracked. The inserted recorder sequences can be referred to as a recorder site, recorder array, or barcode array. As a result, after recursive rounds of engineering, sequencing the barcode array or recorder site allows tracking of the history of genomic editing events in the strain. When the recorder cassettes are inserted in order as depicted, for example, in Figure 3D, then the barcode array or recorder site can identify the order in which the mutations were inserted as well as what the mutation is.
Example 7 - Recursive Engineering using iterative CREATE-recording engineering events
[00290] The example of recursive engineering depicted in Figure 7A was used for plasmid curing to demonstrate that the design is extremely efficient at eliminating previous vectors (Figure 7B). Each CREATE plasmid can be positively selected for based on the indicated antibiotics (Trimeth: trimethoprim, Carb: carbenicillin, Tet: tetracycline) and contains a gRNA targeting one of the other antibiotic markers. For example, the reCREATEl plasmid can be selected for on carbenicillin and encodes a gRNA that will selectively target the trimethoprim resistance gene for destruction. One pass through the carb/tetracycline/trimethoprim antibiotic marker series allows selective incorporation of up to three targeted edits. The recording function would be implemented as illustrated in Figure 5, but is omitted here for simplicity.
[00291] Figure 7B depicts an example of data from iterative rounds of CREATE engineering. A serial transformation series began with cells transformed with X2cas9 (kan) and the reCREATEl vector. The spot plating results indicate that curing is 99.99% effective at each transformation step, ensuring highly efficient engineering in each round of transformation. Simultaneous genome editing and plasmid curing in each transformation step with high efficiencies was achieved by introducing the requisite recording and editing CREATE cassettes into recursive vectors as disclosed herein (e.g. Figure 7B).
Example 8- CREATE design and workflow
[00292] An example overview of CRISPR EnAbled Trackable genome Engineering (CREATE) design workflow is depicted in Figures 8A-8B. Figure 8A shows example anatomy of a CREATE cassette designed for protein engineering. Cassettes encode a spacer (red) along with part of a guide RNA (gRNA) sequence and a designer homology arm (HA) that can template homologous recombination at the genomic cut site. For protein engineering purposes the HA is designed to systematically couple mutations to a specified codon or target site (TS, blue) to a nearby synonymous PAM mutation (SPM, red) to rescue the sequence from Cas9 cleavage and allow highly efficient mutagenesis. The priming sites (PI and P2, black) are designed to allow multiplexed amplification and cloning of specific subpools from massively parallel array based synthesis. A constitutive promoter (green) drives expression of the gRNA.
Figure 8 A further shows a detailed example of HA design for introducing a stop codon at residue
145 in the galK locus. The top sequence shows is of the wt genome with the PAM and TS codon highlighted. The translation sequences are shown to illustrate that the resulting mutant contains a single nonsynonymous mutation at the target site. Figure 8B shows an example overview of the
CREATE workflow. CREATE oligos are synthesized on a microarray and delivered as large pools (10 4 -10 6 individual library members). These cassettes are amplified and cloned in multiplex with the ability to subpool designs. After introduction of the CREATE plasmids into cells expressing Cas9 mutations are transferred to the genome with high efficiencies.
Measurement of the frequency of each plasmid before (fi, tl) and after selection (fi, t2) by deep sequencing provides enrichment scores (Ei) for each CREATE cassette. These scores allow rapid identification of adaptive variants at up to single nucleotide or amino acid resolution for thousands loci in parallel.
Example 9- CREATE design validation
[00293] Figure 9A depicts an example of the effects of Cas9 activity on transformation and editing efficiencies were measured using no a cassette with a spacer and 120 bp HA targeted to the galK (galK Y " 145* _120 y Ί7) The total transformants (TT white) produced by this CREATE vector are shown in white and the total number of recombinants (TR) in dark blue. TR is calculated as the product of the editing efficiency and Tt. Asterisks indicate experiments in which recombinants could not be observed by plate based screening. Figure 9B shows an example of characterization of CREATE cassette HA length and PAM/codon spacing on editing efficiency. All cassettes were designed to introduce a TAA stop at codon 145 in the gene using PAMs at the indicated distance (PAM/codon bottom) from the target codon and variable homology arms lengths (HA, bottom). White and blue bars correspond to uninduced or induced expression of Cas9 under the pBAD promoter using 0.2% arabinose. In the majority of cases the editing efficiency appears to be unaffected by induction suggesting that low amounts of Cas9 due to leaky expression are sufficient for high efficiency editing. Figure 9C depicts an example of determination of editing efficiency for oligo derived cassettes by sequencing of the genomic loci. The gor/ _Y145*_120/17 cassette from Figures 9A and 9B is shown in white for reference. The bar plot indicates the number of times each genotype was observed by genomic colony sequencing following recombineering with each CREATE cassette. The circular inset indicates the relative position of each gene on the E. coli genome. Figure 9D depicts distance between
SPM and the TS (as exemplified in Figure 8A) is strongly correlated with editing efficiency
(correct edits/total sequences sampled). The galK cassettes with 44 and 59 bp in Figure 9B were omitted from this analysis. The depicted error bars are derived from N=3 independent replicates of the indicated experiment.
Example 10- Scanning saturation mutagenesis of an essential chromosomal gene
[00294] Figure 1 OA- IOC depict an example where CREATE was used to generate a full scanning saturation mutagenesis library of the folA gene for identification of mutations that can confer resistance to TMP. The count weighted average enrichment score from two trials of selection is plotted as a function of residue position (right). Cassettes encoding nonsynonymous mutations are shown in gray, and those encoding synonymous mutations in black. Cassettes with enrichment scores greater than 1.8 are highlighted in red and mutations that affect previously reported sites are labeled for reference. The dashed lines indicate enrichment values that are significantly different (p<0.05) from the synonymous dataset as determined by bootstrapping of the confidence intervals. These values are shown as a histogram for reference (middle). Mutations that appear to significantly impact DHFR resistance are highlighted as red spheres to the far right. Figures 10D-10F depict example growth analysis of wt (left) F153W (middle) and F153R (right) variants in the indicated range of TMP concentrations (shown right).
Example 11- Reconstruction of ALE mutation set and forward engineering of
thermotolerant genotypes
[00295] Figure 11A depicts example genomic plots of enrichment scores for CREATE libraries grown at 42.2°C in minimal media conditions. The innermost plot illustrates the counts of the plasmid library before selection with labels for the top 20 representatives. The outer ring shows the fitness of pooled library variants after growth in minimal media at elevated temperature (42.2°C). The bars are colored according to log2 enrichment. Blue bars represent detrimental mutations, red bars represent significantly enriched mutations and gray bars indicate mutations that appear neutral in this assay. The 20 most enriched variants are labeled for reference and labels corresponding to ALE-derived variants are colored red. Figure 1 IB shows a histogram of enrichment scores of all library variants (gray), ALE-derived mutants (red) and synonymous mutants (black) under 42.2°C growth conditions. The dotted gray line indicates significant enrichment scores compared to the synonymous population. The histograms are normalized as a fraction of the total number of variants passing the counting threshold (number indicated in parentheses). Note that 231 of 251 unique nonsynonmous ALE cassettes sampled by this experiment appear to provide significant growth benefits. Figure 11C depicts enrichment of mutations based on mutational distance from wt. Mutations that require 2 and 3 nucleotide (nt) transitions are exceedingly rare or absent in ALE approaches however we note that the two most enriched clones from the pooled library selection (targeting the Crp regulator) require two nucleotide substitutions and are highlighted at the far right.
Example 12- Genome scale mapping of amino acid substitutions for the study of antibiotic resistance and tolerance
[00296] Figure 12A depicts example genomic plots of enrichment (log2) of library variants in the presence of erythromycin (outer) and rifampicin (middle). The innermost plot illustrates the count distribution of the input plasmids for reference. Coloring and labeling are as in Figure 11A-11C. Figure 12B depicts CREATE mutation mapping at the individual amino acid level. CREATE cassettes that introduce bulky side chains to amino acids 1572, S531 and L533 (red) of the RNA polymerase β subunit (rpoB) are highly enriched in the presence of rifampicin from genome wide targeting libraries. Figure 11C depicts a zoomed in region of the MarA transcription factor bound to its cognate DNA target is shown for reference (PDB ID 1BL0). The wt Q89 residue protrudes away from the DNA binding interface due to unfavorable steric and electrostatic interactions between this side chain and the DNA. The Q89N substitution identified by selection introduces a H-donor and shortens the side chain such that productive H-bonding can occur between this residue and the DNA backbone. Such an interaction likely favors stronger DNA binding and induction of downstream resistance genes. Figure 12D depicts enrichment plot of genome wide targeting libraries with 10 g/L acetate or 2 g/L furfural respectively. Coloring is the same as in Figure 11 A. Figure 12E depicts CREATE mapping at a gene level reveals trends at the gene level. Strong enrichment fis metA and fadR targeting mutations in acetate suggests important roles for these genes in acetate tolerance, as depicted in Figure 12F, same as in the furfural selections depicted in Figure 12E.
Example 13- CREATE-enabled flexible design strategies
[00297] Illustration of example designs compatible with CREATE strategy are depicted in Figures 13A-13D. Figure 13 A shows protein engineering applications a silent codon approach is taken (top, see also Figure 8A-8B). This mutation strategy allows targeted mutagenesis of key protein regions to alter features such as DNA binding, protein-protein interactions, catalysis, or allosteric regulation. Above an illustration of a DNA binding saturation mutagenesis library designed for the global transcription factor Fis designed for this study is illustrated. Figure 13B shows promoter mutations PAM sites in proximity to a specified transcription start site (TSS) can be disrupted through nucleotide replacement or integration cassettes. To simplify this design procedure used in this study consensus CAP or UP elements were designed for integration at a fixed location relative to the TSS without taking into account possible effects of these mutations may have on proximal genes. Figure 13C shows an example cassette design for mutagenizing a ribosome binding site (RBS). Figure 13D depicts an example of a simple deletion design. Points a and b are included to illustrate distance between two sites at the gene deletion locus. In all cases cassette designs disrupt a targeted PAM to allow selective enrichment of the designed mutant.
Example 14- Engineering the lycopene pathway
[00298] Figures 14A-14B depict edits made the DMAPP pathway in E. coli which is the precursor to lycopene. Edits were made to the ORF's for 11 genes. Eight edits were designed to improve activity and 3 edits were designed to reduce activity of competitive enzymes. Approximately 10,000 variants within the lycopene pathway were constructed and screened.
Example 15- Cas9 editing efficiency controls
[00299] Figure 15 depicts Cas9 editing control experiments. The CREATE galK_120/17 off cassette (relevant edits shown in red at bottom) was transformed into different backgrounds to assess the efficiency of homologous recombination between the CREATE plasmid and the target genome. Red colonies represent unedited (wt) genomic variants and white colonies represent edited variants. Transformation into cells containing only pSEVI5 or pSEVI5/X2 and dCas9 plasmids exhibited no detectable recombination as indicated by the lack of white colonies. In the presence of active Cas9 (X2-Cas9 far right) we observe high efficiency editing (>80%), indicating the requirements for dsDNA cleavage to achieve high efficiency editing and library coverage.
Example 16- Toxicity of gRNA dsDNA cleavage in E. coli
[00300] Figures 16A-16C depict experiments testing the toxicity of generating double strand breaks in E. coli. The toxicity of a single gRNA cut in E. coli as observed in control experiments with a gRNA targeting galK (spacer sequence TTAACTTTGCGTAACAACGC) or folA ( spacer sequence GTAATTTTGTATAGAATTTA). In the absence of a repair template we observe strong killing from the gRNA. Rescue efficiencies of 10 3 -10 4 are observed upon co- transformation of a single stranded donor oligo indicating the need for a homologous repair template to alleviate this toxicity, b) Toxicity of multiple CREATE edits. The targeted sites are illustrated graphically on the left and at the bottom of the bar graph. A non-targeting gRNA control was used to estimate transformation efficiency based on no edits (far left, no target sites). A CREATE cassette targeting either folA (green) or galK (red) or a combination of the two. Note the multiplicative toxicity in E. coli of having additional gRNAs expressed from the same plasmid. In this scenario there is homologous repair for each site suggesting that off-target gRNA cleavage would be highly lethal. These data suggest that off target cleavage by a CREATE cassette would be selectively removed from the population early in the library construction phase.
[00301] Figures 16D-16E depicts data from another such cell survival assay. The editing cassette contained a F153R mutation, which leads to temperature sensitivity of the folA gene. The recorder cassette contained a 15 nucleotide barcode designed to disrupt the galK gene, which allows screening of colonies on MacConkey agar plates. In this example, generating two cuts decreased cell survival compared to generating zero or one cut.
[00302] Figure 16F depicts data from a transformation and survival assay comparing a low copy number plasmid (Ec23) expressing Cas9 and a high copy number plasmid (MG) expressing Cas9. Different vectors with distinct editing cassettes were used to target different gene target sites (folA, lacZ, xylA, and rhaA). The recorder cassettes were designed to target different sequences within the galK gene, either site SI, S2, or S3. The recursive vector used had a different vector backbone compared to the others and is part of a 3-vector system designed for iterative engineering that cures the cell of the previous round vector. The data indicates that lower Cas9 expression (Ec23 vector) increases survival and/or transformation efficiency. The decreased Cas9 expression increased transformation efficiency by orders of magnitude in cells undergoing two genomic cuts (editing cassette and recording cassette).
[00303] Figure 16G shows the correlation between editing efficiency and recording efficiency in cells transformed with the low copy number plasmid (Ec23) expressing Cas9 and the high copy number plasmid (MG) expressing Cas9. Editing and recording efficiencies were similar for high (MG) and lower (Ec23) expression of cas9. Ec23 yielded more colonies and had better survival (as shown in Figure 16E), while maintaining a high efficiency of dual editing (editing cassette and recorder cassette incorporation). .
Example 17- CREATE strategy for gene deletion
[00304] Figure 17A-D depict an example CREATE strategy for gene deletion. Figure 17A depicts an example cassette design for deleting 100 bp from the galK ORF. The HA is designed to recombine with regions of homology with the designated spacing, with each 50 bp side of the CREATE HA designed to recombine at the designated site (blue). The PAM/spacer location (red) is proximal to one of the homology arms and is deleted during recombination, allowing selectable enrichment of the deleted segment. Figure 17B depicts electrophoresis of chromosomal PCR amplicons from clones recombineered with this cassette. Figure 17C depicts design for 700 bp deletion as in a). Figure 17D depicts colony PCR of 700 bp deletion cassettes as in Figure 17B). The asterisks in Figure 17B and 17D indicate colonies that appear to have the designed deletion. Note that some clones appear to have bands pertaining to both wt and deletion sizes indicating that chromosome segregation in some of the colonies is incomplete when plated 3 hrs post recombineering.
Example 18- Editing efficiency controls by cotransformation of gRNA and linear dsDNA cassettes
[00305] Figure 18 depicts effect of PAM distance on editing efficiency using linear dsDNA PCR amplicons and co-transformation with a gRNA. On the left is an illustration of the experiments using PCR amplicons containing a dual (TAATAA) stop codon on one side (asterisk) and a PAM mutation just downstream of the galK gene (gray box) on the other end were co-transformed with a gRNA targeting the downstream galK PAM site. The primers were designed such that the mutations were 40 nt from the end of the amplicon to ensure enough homology for recombination. Data was obtained from these experiments by red/white colony screening. A linear fit to the data is shown at the bottom. Cassettes in which only the PAM mutation is present were included as assay controls were observed to have very low rates of GalK inactivation. These experiments were performed in a BW25113 strain of E. coli in which the mutS gene was knocked out to allow high efficiency editing with double stranded DNA templates. This approach in MG1655 did not achieve high efficiency editing due to the active mutS allele.
Example 19- Library cloning analysis and statistics
[00306] Figure 19A depicts reads from an example plasmid library following cloning are shown according to the number of total mismatches between the read and the target design sequence. The majority of plasmids are matches to the correct design. However, there are a large number of 4 base pair indel/mismatch mutants that were observed in this cloned population. Figure 19B depicts a plot of the mutation profile for the plasmid pool as a function of cassette position. An increase in the mutation frequency is observed near the center of the homology arm (HA) indicating a small error bias in the sequencing or synthesis of this region. We suspect that this is due to the presence of sequences complementary to the spacer element in the gRNA. Figure 19C depicts a histogram of the distances between the PAM and codon for the CREATE cassettes designed in this study. Large majority (> 95%) were within the design constraints tested in Figure 9A-9D. The small fraction that are beyond 60 bp were made in cases where there was no synonymous PAM mutation within closer proximity. Figure 19D depicts library coverage from multiplexed cloning of CREATE plasmids. Deep sequencing counts each variant are shown with respect to their position on the genome. The inset shows a histogram of the number of variants having the indicated plasmid counts in the cloned libraries. Example 20- Precision of CREATE cassette tracking of recombineered populations
[00307] Figure 20A depicts a correlation plot of CREATE cassette read frequencies in the plasmid population prior to Cas9 exposure (x-axis) and after 3 hours post transformation into a Cas9 background. Figure 20B depicts a correlation plot between replicate recombineering reactions following overnight recovery. The gray lines indicate the line of perfect correlation for reference. R2 and p values were calculated from a linear fit to the data using the Python SciPy statistics package. A counting threshold of 5 for each replicate experiment was applied to the data to filter out noise from each data set.
Example 21- Growth characteristics of folA mutations in M9 minimal media
[00308] Figure 21 depicts growth characteristics of folA mutations in M9 minimal media.
While F153R appears to maintain normal growth characteristics the growth rate of the F153W mutation is significantly slower under these conditions, suggesting that these two amino acid substitutions at the same site have very different effects on organismal fitness presumably due to different changes invoked in the stability/dynamics of this protein.
Example 22- Enrichment profiles for folA CREATE cassettes in minimal media
[00309] Figure 22 depicts enrichment profiles for folA CREATE cassettes in minimal media.
Cassettes that encode synonymous HA are shown in black and non-synonymous cassettes in gray, the dashed lines indicate enrichment scores with p<0.05 significance compared to the synonymous population mean as estimated from a bootstrap analysis. The enrichment score observed for each mutant cassette at each position in the protein sequence is shown to the left and a histogram of these enrichment scores as a fraction of the total variants to the right. The two populations appear to be largely similar. Conserved residues that are highly deleterious are shown in blue for reference.
Example 23- Validation of newly identified acrB mutations for improved solvent and antibiotic tolerance
[00310] Figure 23A depicts on the left a global overview of AcrB efflux pump. Substrates enter the pump through the openings in the periplasmic space and are extruded via the AcrB/AcrA/TolC complex across the outer membrane and into the extracellular space. Library targeted residues are highlighted by blue spheres for reference and the red dot indicates the region where many of the enriched variants clustered. On the right is a blow up of the loop-helix motif abutting the central funnel where enriched mutations in isobutanol were identified (red and teal spheres), presumably affecting solute transport from the periplasmic space. Mutants targeting the T60 position (teal spheres) was also enriched in the presence of erythromycin. Figure 23B depicts confirmation of N70D and D73L mutations for tolerance to isobutanol. The N70D mutation in particular appears to improve the final OD to a significant degree. Reconstructed strains were measured for final OD in capped 1.5 mL eppendorf tubes following 48 hours incubation. Error bars are derived from N=3 trials and p-values derived from a one- tailed T-test. Figure 23C depicts improved growth of the AcrB T60N mutant was observed in inhibitory concentrations of erythromycin (200 μg/mL) and isobutanol (1.2%) in shaking 96 well plate, indicating that this mutation may enhance the efflux activity of this pump towards many compounds. For these experiments CREATE cassette designs were individually synthesized, cloned and sequence verified before recombineering into E. coli MG1655 to reconstruct the mutations and the genomic modifications were sequence verified by colony PCR to confirm the genotype-phenotype association.
Example 24- Benefits of rational mutagenesis for sampling novel adaptive genotypes
[00311] Figures 24A-24D depict the number of variants detected in CREATE experiments involving 500 μg/mL rifampicin (Figure 24A), 500 μg/mL erythromycin (Figure 24B), 10 g/L acetate (Figure 24C), and 2 g/L furfural (Figure 24D). While naturally evolving systems or error- prone PCR are highly biased towards sampling single nucleotide polymorphisms (e.g. 1 nt mutations, red) these histograms illustrate the potential advantages for rational design approaches that can identify rare or inaccessible mutations (2 and 3 nt, green and blue respectively). For example, the highest fitness solutions appear to be biased toward these rare mutations in rifampicin, erythromycin and furfural selections to varying degrees. These results indicate that procedures such as CREATE should allow more rapid and thorough analysis of fitness improving mutations, in much the same way that computational approaches are being used to improve directed evolution for protein engineering.
Example 25- Reconstruction of mutations identified by erythromycin selection
[00312] Figure 25 depicts reconstructed strains grown in 0.5 mL in capped 1.5 mL eppendorf tubes following 48 hours incubation in the presence of 200 μg/mL erythromycin and final OD measurements assessed. Error bars are derived from N=3 trials. A one tailed T-test was performed on each set of measurements to determine p-values indicated for significance of growth benefit.
Example 26- Validation of Crp S28P mutation for furfural or thermal tolerance
[00313] Figure 26A depicts a crystal structure of the Crp regulatory protein with variants identified by furfural selection highlighted in red (PDB ID 3N4M). A number of the CREATE designs targeting residues near the cyclic- AMP binding site (aa. 28-30, 65) of this regulator were highly enriched in minimal media selections for furfural or thermal tolerance suggesting that these mutations may enhance E. coli growth in minimal media under a variety of stress conditions. Figure 26B depicts validation the Crp S28P mutant identified in 2 g/L furfural selections in M9 media. This mutant was reconstructed as described for AcrB T60S in Example 23.
Example 27- Genome-scale sequence to activity relationship mapping at single nucleotide resolution
[00314] Advances in DNA synthesis and sequencing have motivated increasingly complex efforts to rationally program genomic modifications on laboratory timescales. Realization of such efforts requires strategies that span the design-build-test forward-engineering cycle by not only precisely and efficiently generating large numbers of mutant designs but also by mapping the effects of these mutations at similar throughputs. CRISPR EnAbled Trackable genome Engineering (CREATE) couples highly efficient CRISPR editing with massively parallel oligomer synthesis to enable trackable precision editing on a genome wide scale. This can be accomplished using synthetic cassettes that link a targeting guide RNA with rationally programmable homologous repair cassettes that can be systematically designed to edit loci across a genome and track their phenotypic effects. We demonstrated the flexibility and ease of use of CREATE for genome engineering by parallel mapping of sequence-activity relationships for applications ranging from site saturation mutagenesis, rational protein engineering, complete residue substitution libraries and reconstruction of prior adaptive laboratory evolution experiments.
[00315] Validation of CREATE cassette design
[00316] In order to realize our engineering objectives we took into account a number of key design considerations to both maximize the editing efficiency as well as distill a complex design process into an easily executable workflow. For example, each CREATE cassette is designed to include both a targeting guide RNA (gRNA) and a homology arm (HA) that introduces rational mutations at the chromosomal cleavage site (e.g. Figure 8A). The HA encodes both the genomic edit of interest coupled to a synonymous PAM mutation that is designed to abrogate Cas9 cleavage after repair (e.g. Fig 8B). This arrangement not only ensures that the desired edit can be selectively enriched to high levels by Cas9 but also that the sequences required to guide cleavage and HR are covalently coupled during synthesis and thus delivered simultaneously to the same cell during transformation. The high efficiency editing of CRISPR based selection in E. coli should also ensure a strong correlation between the CREATE plasmid and genomic sequences and allow the plasmid sequence to serve as a transacting barcode or proxy for the genomic edit (e.g. Figure 8C). Assuming that changes in the plasmid frequency under different selective pressures are correlated to their associated genomic edit thereby allows the impact of precise genomic modifications at many loci to be monitored in parallel using a simple downstream sequencing approach to map enriched genotypes on a population scale, analogous to previous genomic tracking methodologies.
[00317] To test this concept we first performed control experiments using a CREATE cassette designed to inactivate the galK gene by introducing a single point mutation to convert codon 145 from TAT to a TAA stop codon (e.g. Figure 8B) using a 120 bp HA. The editing efficiency of this cassette using Cas9 and the nuclease deficient dCas9 control was evaluated using a red/white colony screening assay (e.g. Figure 8A-B, Figure 15A-15C). These experiments also indicated that HR between a circular double stranded plasmid and the chromosome is strongly dependent on the Cas9 cleavage as recombination is not observed in the absence of the active enzyme (e.g. Figure 15A-15D). This is in contrast to single stranded recombineering approaches in which oligonucleotides anneal with high efficiency at the lagging strand of the replication fork. Cas9 also adversely impacts the overall transformation efficiency due to toxicity of dsDNA cleavage in E. coli (e.g. Figure 9A-9D). This toxicity is further exacerbated when performing CREATE at two sites simultaneously in the same cell (e.g. Figure 16A-16E); which when combined with the absence of an effective nonhomologous end joining pathway strongly supports the fact that off target editing events should be rare within a recombineered library. Additionally, toxicity limits the size of library construction and coverage, however we note that the observed 10 4 -10 5 DNA (e.g. Figure 9A) is on a scale compatible with current oligo synthesis capabilities (10 4"5 oligos per order). Thus, we anticipated that using the CREATE synthetic oligo design, we would be able to simultaneously generate ~10 5 or more designer mutations at any location in the genome and precisely map such mutations onto a targeted phenotype.
[00318] To further characterize how changes in the CREATE cassette design influence the editing efficiency we varied the HA length (80-120 bp) and the distance between the PAM- codon/ TS (17-59 bp) (e.g. Figure 9B). Induction of Cas9 revealed that all of these cassette variants can support high efficiency HR. High efficiency conversion is also observed in the absence of Cas9 induction indicating that low level expression of Cas9, due to a leaky inducible promoter, is sufficient to drive cleavage and HR (e.g. Figure 9B). To verify that the edits matched our intended design we sequenced the chromosome of randomly chosen clones and found that 71% (27/38) contained a perfect match to the CREATE design, while 26% (10/38) contained only the PAM edit and the remaining 3% (1/38) appeared to be wt escapers. As an additional test of design flexibility performed similar experiments using deletion cassettes that that introduce different sized deletions (e.g. Figure 17A-17D) and observed similar efficiencies (>70%) indicating that the same design automation and tracking capabilities should readily extend to a variety of design objectives (e.g. Figure 13A-13D). [00319] High-throughput design and multiplexed library construction
[00320] To scale the CREATE process for genome-wide applications we developed a custom software to automate cassette design that takes into account the above mentioned criteria to systematically identify a PAM sequence nearest to a target site (TS) of interest and modify it to create a synonymous PAM mutation. This design software is part of a suite of web-based design tools that can be implemented for E. coli and is under further development for other organisms as well as an expanded set of CRISPR-Cas systems. This software platform enables high-throughput rational design of genomic libraries in a format that is compatible with parallelized array based oligo synthesis and simple homology based cloning methods that can be performed in batch for library construction (e.g. Figure 8B).
[00321] Using this design software we generated a total of 52,356 CREATE cassettes for a range of applications where sequence to activity mapping by traditional methods would be time-consuming and prohibitively expensive. Briefly, the library designs included: 1) a complete saturation of the folA gene to map the entire mutational landscape of an essential gene in its chromosomal context 2) saturation mutagenesis of functional residues in 35 global regulators, efflux pumps and metabolic enzymes implicated in a wide range of tolerance and production phenotypes in E. coli 3) a reconstruction of the complete set of nonsynonymous mutations identified by a recent adaptive laboratory evolution (ALE) study of thermotolerance, and 4) promoter engineering libraries designed to incorporate UP elements or CAP binding elements at transcription start sites annotated in RegulonDB (e.g. Figure 13A-13D).
[00322] The pooled oligo libraries were amplified and cloned in parallel and a subset of single variants were isolated to further characterize editing efficiency at different loci (e.g. Figure 9C). Amplification and sequencing of the genomic loci after transformation with the CREATE plasmids revealed editing efficiencies of 70% on average (106 of 144 clones sampled at seven different loci), with a range of 30% for the metA_V20L cassette to 100% for the rpoH_V179H cassette. Interestingly, the differences in editing efficiency for each cassette were highly correlated with the distance between the PAM and target codon (e.g. Figure 9D), a feature that also appears to affect the ability of linear DNA templates to effectively introduce targeted mutations (e.g. Figure 18A-18B). This relationship suggests that subsequent CREATE designs should readily increase editing efficiency by optimizing PAM selection criteria. We also note that differences in editing efficiency may reflect detrimental effects of some mutations on organismal fitness (metA is considered an essential gene in most media conditions), and that there may be an upper bound on the number of mutations that can be observed for a particular protein. Finally, these data were obtained outside of any specific selective or screening steps that enrich for chromosomal mutants of interest, and as such demonstrate the ability of this approach to construct mutational libraries.
[00323] To further characterize the fidelity of the multiplexed synthesis and cloning procedures we performed deep sequencing on the pooled libraries (e.g. Figure 19A-D). From 594,998 total reads of the cloned CREATE cassette libraries, 550,152 (92%) passed quality filtering and produced hits against the design database. Of these we observed a perfect match for 34,291 (65%) of the possible unique variants and note that many cassettes that were missing in this initial pool were observed in later selections, suggesting that at the cloning stage we can readily cover the majority of the intended design space. In depth analysis of these reads revealed that 46% of the reads passing quality filter were exact matches to their intended design, with the remainder containing 1-4 bp indels or mismatches, primarily in the HA region near the designed mutation site (e.g. Figure 19A). The mutational bias in this region suggests that the repetitive spacer elements in the HA and gRNA portions of the cassette may form secondary structures that adversely affect sequencing or synthesis (e.g. Figure 19B). We note that these variant designs are easily identified via the CREATE plasmid-barcoding strategy, and that in some cases it may be desired to have this added diversity in the generated library. We also observed significant (p<0.05) correlation between variant frequencies from the cloned pools and after overnight recovery following recombineering, as well as between replicate recombineering experiments (e.g. Figure 20A-20B). These results suggest that well represented variants should be readily tracked by our methodology with a precision similar to previous CRISPR based saturation mutagenesis procedures performed at a single loci.
[00324] CREATE based protein engineering
[00325] To test the robustness of the CREATE methodology for protein engineering at a single gene level we performed deep-scanning mutagenesis of the essential folA gene. This gene encodes the dihydrofolate reductase (DHFR) enzyme responsible for the production of tetrahydrofolate and the biosynthesis of pyrimidines, purines and nucleic acids. DHFR is also the primary target of the antibiotic trimethoprim (TMP) and other antifolates that are used as antibiotics or chemotherapeutics. The wealth of structural and biochemical data DHFR function and antibiotic resistance make it an ideal model for validation of the approach.
[00326] A CREATE library designed to saturate every codon from 2-158 of the DHFR enzyme was recombineered into E. coli MG1655 and allowed to recover overnight. Following recovery - 10 9 cells (1 mL saturated culture) was transferred into media containing inhibitory TMP concentrations and allowed to grow for 48 hours. The resulting plasmid populations were then sequenced to assess our ability to capture information at the level of single amino acid substitutions that can confer TMP resistance (e.g. Figure 10A-10B). Bootstrapped confidence intervals for mutational effect were derived using the enrichment data of the 158 synonymous mutations included in this experiment (e.g. Figure 10A-10B). Using this criteria, we observed significant (P<0.05) levels of enrichment for 74 substitutions (2.3% of the design space) covering 49 aa positions in the protein. Although this degree of mutational flexibility of an essential enzyme may seem counterintuitive, it supports previous conclusions that this enzyme has not reached its evolutionary optimum and that many mutations that can improve TMP tolerance through enhancement of the endogenous enzymatic activity or alteration of the dynamic folding landscape of this enzyme.
[00327] These results also support the fact that we probe more deeply into the mutation space of improved fitness variants using rational mutagenesis strategies. For example, we observed 7 significantly enriched substitutions at position F153 (e.g. Figure 10A-10B), none of which have been previously identified by error-prone PCR and adaptive laboratory evolution (ALE). To validate these specific mutations, we reconstructed F153R and F153W variants, which had not been previously reported in the literature and spanned a large range of the measured enrichment scale at this position (e.g. Figure 10D-10F). We confirmed that the highly enriched F153R mutant grows rapidly under a large range of TMP concentrations while the F153W mutant demonstrates growth only at the moderate TMP concentration used in the selection, consistent with their respective enrichment scores (e.g. Figure 10A-10F). Moreover, 6 of the 7 mutations we identified using CREATE require two nucleotide changes to convert the wt TTT codon to one of the observed amino acids (I: 1 nt,W: 2 nt ,D: 2 nt,R: 2 nt,P: 2 nt,M: 2 nt,H: 2 nt). The F153R and F153W mutations also appear to impact the native enzyme activity in distinct ways (e.g. Figure 21), implying that these substitutions may confer tolerance by altering the enzymatic cycle of this enzyme in distinct manners.
[00328] In addition to mapping substitutions that confer TMP resistance, we also attempted to identify substitutions that affect the native activity of DHFR. To do so, we compared the frequencies of each plasmid variant after overnight growth in M9 (e.g. Figure 22A-22C). In this case, we observed similar overall enrichment profiles for both synonymous and nonsynonymous mutation sets, with very few mutations observed to have significant impact on growth. This unexpected result suggests a need for greater sequencing depth and/or alternate selection strategies to assign high confidence to low fitness variants.
[00329] As a separate validation of protein engineering applications, we generated a 4,240 variant library targeting the AcrB multidrug efflux pump in E. coli (e.g. Figure 23 A-23F). This protein acts as a proton exchange pump that exports a wide variety of chemicals including antibiotics, chemical mutagens, and short chain alcohols that are being pursued as next generation biofuels and motivating numerous engineering efforts. The library was designed to target the interior chamber, the exit funnel that channels substrates towards the outer- membrane component of the AcrB/AcrA/TolC complex, and key regions of the transmembrane domain where mutations conferring tolerance to isobutanol and longer chain alcohols have been identified (e.g. Figure 23A-23C). We then constructed the AcrB CREATE library identically as for the FolA library and grew the library in the presence of 1.2% isobutanol. Sequencing identified multiple mutations to the loop-helix motif adjacent to the central efflux funnel that were significantly enriched, suggesting this substructure may provide a novel target for engineering enhanced efflux activity. Reconstruction of the AcrB N70D and D73L mutations also confirmed the ability of these mutations to enhance overall growth in the presence of this solvent stress (e.g. Figure 23D).
[00330] Parallel evaluation of genotype fitness from large scale adaptation studies
[00331] We next sought to expand our efforts from the single protein scale and validate the use of CREATE at the genome-scale. To do so we chose to reconstruct and map mutations resulting from a prior adaptive laboratory evolution study of E. coli thermal tolerance. ALE has been used extensively as a tool to study the bacterial adaptation in response to a broad range of environmental stressors. However, in the majority of cases the genome undergoes multiple mutations making it difficult to assess the contribution of each mutation to the phenotype in question. Here, we designed and constructed a CREATE library to include all 645 nonsynonymous mutants from the Tenaillon et al ALE experiment and then subjected this library to growth selection in minimal media at 42.2°C. To assess any possible effects that could arise from the synonymous PAM mutation we included redundancy in the design of this library such that each target codon was coupled to two different PAM mutations to provide a 4 fold design redundancy for each nonsynonymous mutation. For calibration purposes the ALE library was pooled with the protein targeting libraries to allow for relative enrichment comparisons from the non-ALE derived libraries as a benchmark (e.g. Figure 11A- 11C). Of the more than 50,000 cassettes in this experiment we observed 405 cassettes from the ALE derived library above the minimal counting threshold, pertaining to 252 unique variants (e.g. Figure 11B). Of these 346 cassettes (encoding 231 nonsynonymous changes) were significantly enriched compared with the synonymous controls (e.g. Figure 1 IB), suggesting that 92% (231/252) of the mutations sampled confer significant selective growth advantages as individual chromosomal mutations, consistent with their fixation during adaptive growth. Additionally we found that 141 mutations from the additional CREATE libraries were also significantly enriched, with 86 of these targeting residues in or around the cAMP binding site of Crp, a central regulator of carbon metabolism. The identification of such a large number of Crp mutants is highly suggestive of a role for Crp in thermal-tolerance in agreement with previous findings.
[00332] For each mutant we also calculated the number of mutations required to convert the wt codon to each of the other 19 amino acids (e.g. Figure 11C). As with folA, we found that highly impactful mutations, such as the crp S28P and L30Y mutations, require more than a single nucleotide substitution and would therefore be inaccessible or exceedingly rare in naturally evolving systems under laboratory timescales. In fact, this seemed to be a recurrent theme across many of the selections we performed (e.g. Figure 24A-24D) highlighting again the value of synthetic DNA driven search strategies for genomic engineering applications.
[00333] High-throughput mapping of selectable precision edits on a genome wide scale
[00334] To further validate the method for genome-scale mapping and exploration we challenged genome wide targeting libraries with antibiotics or solvents relevant to bioproduction (e.g. Figure 12A-12F). In the case of selections performed with rifampicin, an antibiotic that inhibits transcription by the RNA polymerase (e.g. Figure 12A, inner circle) we observed a number of enriched variants that highlighted the robustness of the CREATE approach for atomic resolution mapping. For example, 10 of the top 50 hits identified mutations to residues 1572, L533 and S531 of the RNA polymerase β subunit (encoded by rpoB) including variants that form part of the rifampicin binding site (e.g. Figure 12B). In 6 of the 7 enriched variants the data suggest that a bulky substitution is necessary to sterically hinder 7 rifampicin binding. In addition to the β-subunit mutations the rifampicin selections enriched a number mutations to the MarA transcriptional activator, whose over-expression due to marR knockout is a well studied aspect of multiple antibiotic resistance (MAR) phenotypes in E. coli . In the DNA bound crystal structure of MarA, Q89 is positioned near the DNA backbone but pointed into solution due to a steric clash between other possible rotamers and nearest phosphate group on the DNA backbone (e.g. Figure 12C). Modeling of the MarA Q89N and Q89D mutations identified by this selection suggests that shortening the side chain by a single carbon unit may enable new protein-DNA H-bonding interactions and thereby improve the overall MAR induction response.
[00335] To compare these results to an antibiotic that interferes with translation we performed another round of selections in the presence of erythromycin (e.g. outer circle Figure 12A). The enrichment profiles from this selection again highlighted loci previously implicated in resistance to this antibiotic. For example, we observed strong enrichment of 4 different mutations to the AcrB efflux pump which acts as the primary exporter of this drug from the periplasmic space (e.g. Figure 12A). Interestingly, one of the variants (AcrB T60N) appears at the same residue identified from isobutanol selections (e.g. Figure 23A-23F). As with the other mutations, reconstruction validated that at least two of these mutations (e.g. T60N in Figure 23E-23F and D73L in Figure 25) can significantly improve tolerance to both erythromycin as well as isobutanol isobutanol, further supporting the idea that this motif may provide a useful engineering target for broad range of tolerance phenotypes. In addition to AcrB we also observed enrichment of multiple soxR and rpoS mutants, both of which have been previously implicated in stress tolerance and general antibiotic resistance phenotypes. In total, we observed 136 of the
341 significantly enriched mutations (40%) were identified within the RpoB, MarA, MarR,
SoxR, AcrB, or dxs proteins, each of which has extensive prior validation as antibiotic resistance genes.
[00336] Finally, we performed selections using furfural or acetate, common components of cellulosic hydrolysate that inhibit bacterial growth under industrial fermentation conditions and are thus the target of many strain engineering efforts (e.g. Figure 12D-12F). In the presence of high acetate concentrations (10 g/L , e.g. inner plot Figure 12D) the top 100 ranking mutations were predominated by cassettes targeting the fis, fadR, rho and fnr genes respectively (e.g. Figure 12E). The Fis, Fnr and FadR regulators are all involved transcriptional regulation of the primary acetate utilization gene acs, and implicated in the so-called "acetate- switch" which allows the cell to effectively scavenge acetate. Knockout of these regulators leads to constitutive expression of the acetate utilization pathways and improved acetate growth phenotypes suggesting that the mutations identified in this study (e.g. Figure 12E-12F) likely inhibit these regulatory functions by destabilizing their respective protein targets.
[00337] In contrast to the weak acid tolerance of acetate, the enrichment profiles obtained the presence of growth inhibiting concentrations of furfural (2g/L) were significantly different with the most frequently observed mutations targeting the oxidative stress response regulator rpoS (e.g. Figure 12F). Furfural growth inhibition is thought to occur through depletion of cellular NADPH pools, an important cofactor in the prevention of oxidative stress and anabolic pathways for cell growth. In line with our findings, previous studies of RpoS have demonstrated that inactive alleles are favored in such nutrient depleted scenarios. Interestingly, we also observed some of the same mutations in crp that were observed in the 42.2°C selections (e.g. Figure 11A and 11C) and upon reconstruction confirmed that the Crp S28P mutant can substantially improve growth in the presence of furfural (e.g. Figure 26A-26B). We also found that this selection uniquely enriched for variants of the PntA transhydrogenase, a membrane bound transhydrogenase that transfers hydride ions from NADH to NADP+ to maintain sufficient pools for anabolism. A mutation to 1258 A in close proximity to the substrate binding cleft may therefore impart enhanced NADPH production.
[00338] Collectively, these selections validate the CREATE strategy by demonstrating the ability to map known associations as well as highlight power of this method for rapid mapping of novel mutations to traits of interest. It is also important to note that in contrast to the most other functional genomics technologies that mainly identify loss of function mutations, the ability to perform such broad scale scanning mutagenesis opens the door for more general genomic searches that can also identify novel gain of function mutations.
[00339] In this work we have demonstrated that CREATE allows parallel mapping of tens of thousands of amino acid and promoter mutations in a single experiment. The construction, selection, and mapping of >50,000 genome-wide mutations (e.g. Figures 11A-11C and 12A-12F) can in some examples be accomplished in 1-2 weeks by a single researcher, offering orders of magnitude improvement in economics, throughput, and target scale over the current state of the art methods in synthetic biology. Importantly, the ability to track the enrichment of library variants allows multiplex sequence to activity mapping by a simple PCR based workflow using just a single set of primers as opposed to more complicated downstream sequencing approaches that are limited to a few dozen loci. In addition, the ability to map the effects of single nucleotide or amino acid level variation in coding regions or promoters allows CREATE to address a considerably more diverse set of design objectives than previous high-throughput genomic technologies such as trackable multiplexed recombineering (TRMR) or Tn-seq approaches that are limited to gene resolution analysis. Such capabilities enable new paradigms for deciphering gene function and engineering cellular traits including workflows in which iterative rounds of CREATE could be implemented to perform design-driven genome engineering and address a broad range of ambitions.
[00340] Notably, as a further distinction from prior approaches, the high efficiency mutagenesis (e.g. Figure 9A-9D) reported in this work was not only an order of magnitude improved but was also achieved in a wild type MG1655 strain in which all of the native DNA repair pathways are intact. The majority of previously reported recombineering efforts in E. coli have used single-stranded oligo engineering which requires deletion of the mismatch repair genes or chemically modified oligonucleotides to achieve mutagenesis at 1-30% efficiency. The combination of plasmid based homologous recombination substrates and Cas9 dsDNA cleavage appears to circumvent these requirements (e.g. Figure 13A-13D and Figure 9A-9D), eliminating the need for specialized genetic modifications outside of the Cas9 and λ-RED genes to perform efficient editing and tracking on a population scale (e.g. Figure 9A-9D). This fact alongside the broad utility of CRISPR editing suggests that the CREATE approach will readily port to a wide range of microorganisms such as Saccharomyces cerevisiae and other recombinogenic bacteria for which high-efficiency transformation protocols are available. The CREATE strategy should also be compatible with a wide range of CRISPR/Cas systems using similar automation approaches to design and tracking. Extension of this methodology to higher eukaryotes however will require the development of strategies to overcome non-homologous end-joining as well as alternative tracking systems that can stably replicate.
[00341] The CREATE strategy provides a streamlined approach for sequence to activity mapping and directed evolution by integrating multiplexed oligo synthesis, CRISPR- CAS editing, and high-throughput sequencing.
Example 28- Genome-scale sequence to activity relationship mapping at single nucleotide resolution, additional examples
[00342] Possible effects of inconsistent mapping of plasmid barcode to genomic edit
[00343] We note that the initial CREATE library included designs that we would expect to have low confidence mapping between the plasmid barcode and the genomic edit (as explained primarily by distance between the PAM and target mutation in the CREATE cassette, see Fig 2d). We describe below the various scenarios that may arise in the fraction of cases where the plasmid tracking may lead to erroneous conclusions regarding a genomic variant. A few things to note in evaluating these scenarios include i) the plasmid cassette should have minimal or no functional influence relative to the genomic edit, ii) the genomic loci will only be either the WT sequence or the sequence from the editing cassette that we obtain via sequencing, and iii) offsite editing is highly unlikely given the toxicity of CRISPR-Cas editing of multiple sites (e.g. Figure 16A-16E) or when performed in the absence of an added editing-repair template. Finally, we note that the use of replicate experiments and deeper sequencing can also address these issues.
[00344] Tracking of high fitness variants (positive enrichment tracking)
[00345] In cases where there is a strong selective advantage for the genomic modification (and thus the associated plasmid) we will only observe cells with the edit in the chromosome post selection. Thus, this is almost always a true positive particularly when selection times are short, thus limiting the possibility of random mutations due to replication error sweeping the population. While this phenomenon may lead to a quantitative underestimation of the true fitness of a mutation due to an enrichment profile that represents the convolution of modified and wt fitness, it will not produce false positives. Moreover, the use of replicated experiments and/or longer selections can also address this potential issue and eliminate erroneous conclusions regarding a mutations impact on fitness.
[00346] Tracking of low fitness variants (negative enrichment tracking)
[00347] In cases where the encoded mutation has a negative fitness contribution but is linked to a PAM only or unmodified chromosome we would incorrectly overestimate the fitness of the mutant and assume that it is closer to wt, especially for longer selection times (e.g. see Figure 22A-22C). However, any deep sequencing approach must deal with similar limitations due to the lack of information regarding such mutations following selection and the problems associated with counting statistics in these scenarios. Moreover, we would note that this scenario is only relevant to the subset of truly negative fitness mutants (which should be 10-20% based on historic directed evolution and ALE data) within the unedited fraction (-30%) and that remain in the unedited fraction in multiple replicate transformations. In other words, it is a small percentage (4-5%) scenario that can be detected and/or addressed through replicate transformations where one would observe inconsistencies in the particular mutant showing up occasionally with WT fitness.
[00348] Incomplete coverage
[00349] In cases where a variant is not present in the initial population (due to both low transformation efficiency and low editing efficiency) a couple of scenarios could arise. As implied by the points above, if the mutation is beneficial one could falsely conclude that it does not confer a fitness advantage, and if it is truly deleterious it also could be incorrectly assigned a neutral fitness score. This appears to be encountered sometimes in this work and impacts both the error associated with replicate measurements and our ability to distinguish low fitness variants from a synonymous control. However, our ability to identify beneficial mutants is robust despite these issues as evidenced by our ability to readily identify novel and previously validated mutations. Strategies to address this by overcoming Cas9 toxicity and improving recombineering efficiencies hold promise to largely eliminate such problems. Furthermore, increasing the number of replicates, increasing sequencing depth, and/or improving the library coverage by performing larger scale transformation also can help to address these issues.
[00350] Off target gRNA cleavage
[00351] Off target gRNA cleavage should be rare in E. coli due to the relatively small size of its genome (4 Mb), and thus lack of (non-targeted) regions of homology to the CREATE cassette. Moreover, the toxicity of gRNAs in the presence of Cas9 (e.g. Figure 9A) ensures that cells survival is compromised in E. coli due to dsDNA breaks. Each additional cut introduced into E. coli appears to incur multiplicative toxicity effects, even when homologous repair templates are provided for each cut site (e.g. Figure 16A-16E). This toxicity effect would be further exacerbated by the absence of a repair template to guide HR (e.g. Figure 16A-16E), as would be the case for an off-target cleavage event from a single gRNA targeting two sites but containing only a single HA.
[00352] Random off target mutagenesis (evolution)
[00353] The probability that a CREATE variant is strongly enriched due to an off target mutation even is highly improbable due to 2 factors: 1) the toxicity effect for the reasons stated above and 2) the low mutation rates of MG1655 or other mutation repair proficient strains compared with the mutagenesis rates of CREATE, particularly in multiple replicates of selection.
We also have validated that we can transfer the plasmid pool back into a naive parental background and rapidly verify the enrichment of fitness improving CREATE plasmids from the initial population. Like replicate data, this allows us to decouple each CREATE plasmid from the potential of background mutations that would interfere with our analysis. These factors simplify the assumptions made during our analysis, the validity of which is supported both by externally and internally validated genotypes that were identified during this work.
[00354] Possible effects of Synonymous mutations
[00355] Synonymous mutations (e.g. in the PAM region) can confer unexpected effects on phenotype. We have controlled for this in a number of manners. In every experiment we included an internal control that consists of a library of synonymous mutations (1/20 at each codon or 5% of total input), each of which samples different PAM and codon combinations and thus give us an idea of the range of possible effects we may have on a gene by measuring the enrichment profile of many synonymous changes. Using this population as a control we can accurately identify significant fitness changes at the resolution of single amino acids as the work suggests. We can also control for this effect by utilizing redundant sampling approaches where a site is coupled to multiple PAM mutations similar to what was done for the ALE study described herein.
[00356] CREATE library design considerations
[00357] A variety of design principles were implemented in the gene targeting libraries described in some work disclosed herein. For example, the folA library (3140 cassettes) was designed to be an unbiased, exploratory library for full single site saturation mutagenesis and sequence activity. However, for the majority of the genes we sought to maximize the probability of interesting genotypes by choosing to focus the diversity of sites most likely to have a functional impact on the targeted protein (e.g. DNA binding sites, active sites, regions identified as mutational hotspots by previous selections). The sites that were included in these library designs were selected based on information deposited in databases including Ecocyc (biocyc.org/), Uniprot (uniprot.org/), and the PDB (rcsb.org/pdb) as well as relevant literature citations that identified residues or regions of interest using directed evolution approaches. The Uniprot and Ecocyc databases provide manually curated sequence features that indicate mutational effects and important domains of each protein. In cases where there was enough structural information to model ligand or DNA binding sites the relevant crystal structures were loaded into Pymol and manual residue selections were made and exported as numerical lists. For promoter libraries we took into account the spacing of these sites relative to the transcription start site and the canonical recognition sequence of either the CRP binding site (AAATGTGAtctagaTCACATTT located between -72 and -40 relative to the transcription start site) or the UP element (AAAATTTTTTTTCAAAAGTA -60 from the transcription start site) that directly recruit the alpha subunit of the RNA polymerase. These sequences were designed to integrate at these positions relative to the publicly available transcriptional start site annotations in RegulonDB using a variation of the automated CREATE design software designed for protein targeting (e.g. Figure 13A-13D). These cassettes were made with the intent of assessing the effects of gene dosage and regulation on fitness. Finally, we designed a library to reconstruct all of the 645 non-synonymous mutations targeting 197 genes that were identified by a comprehensive ALE experiment in which the complete genomes of 115 isolates were sequenced after a year of adaptation to growth at elevated temperature (e.g. 42.2°C). In all, we designed 52,356 oligomers, with 48,080 intended to saturate 2404 codon positions across 35 genes, 2,550 oligos were made for regenerating the ALE mutations, 379 UP promoter mutants and 772 CAP promoter mutations in a manner that would allow simultaneous sequence to activity relationship mapping.
[00358] Cassette design and automation principles
[00359] Based on the control experiments with galK (e.g. Figure 9A-9D) and current maximal commercial synthesis length constraints (200 bp from Agilent) we developed a general design for each CREATE cassette (e.g. Figure 8A-8B).
[00360] Design of the CREATE cassettes was automated using custom Python scripts. The basic algorithm takes a gene sequence, a list of target residues, and a list of codons as inputs. The gene sequence is searched for all available PAM sites with the corresponding spacer sequence. This list is then sorted according to relative proximity to the targeted codon position. For each PAM site in the initial list the algorithm checks for synonymous mutations that can be made in-frame that also directly disrupt the PAM site, in the event that this condition is met the algorithm proceeds to making the prescribed codon change and designing the full CREATE cassette with the accompanying spacer and iterates for each input codon and position respectively. For each PAM mutation, all possible synonymous codon substitutions are checked before proceeding to the next PAM site. For the codon saturation libraries in this study we chose the most frequent codons (genscript.com/cgi-bin/tools/codon_freq_table) for each designed amino acid substitution according to the E. coli usage statistics. The script can be run rapidly on a laptop computer and was used to generate the full design of these libraries in < 10 minutes. The algorithm used in this study was designed to make the most conservative mutations possible by sometimes using only the PAM as the selectable mutation marker.
[00361] Plasmids [00362] The X2-cas9 broad host range vector was constructed by amplifying the cas9 gene from genomic S. pyogenes DNA into the pBTBX2 backbone (Lucigen). A vector map and sequence of this vector and the galK_Y145*_120/17 CREATE cassette are provided at the following locations: benchling.eom/s/3c941j/edit; benchling.com/s/xRBDwcMy/edit.
[00363] The editing experiments performed in some of this work employed the X2-cas9 vector in combination with the pSIM5 vector (redrecombineering.ncifcrf.gov/strains~ plasmids.html) to achieve the reported efficiencies.
[00364] Recombineering of CREATE libraries
[00365] Genomic libraries were prepared by transforming CREATE plasmid libraries into a wildtype E. coli MG1655 strain carrying the temperature sensitive pSIM5 plasmid (lambda RED) and a broad host range plasmid containing an inducible cas9 gene from cloned from S. pyogenes genomic DNA into the pBTBX-2 backbone (X2cas9, e.g. Figure 15A-15D). pSEVI5 was induced for 15 min at 42°C followed by chilling on ice for 15 min. The cells were washed 3 times with ½ the initial culture volume of ddH20 (e.g. 10 mL washes for 50 mL culture). Following electroporation the cells were recovered in LB + 0.4% arabinose to induce Cas9. The cells were recovered 1-2 hrs before spot plating to determine library coverage and transferred to a 10X volume for overnight recovery in LB+ 0.4% arabinose + 50 μg/mL kanamycin + 100 μg/mL carbenicillin. Saturated overnight cultures were pelleted and resuspended in 5 mL of LB. 1 mL was used to make glycerol stocks and the other 1 mL washed with the appropriate selection media before proceeding with selection.
[00366] For the control experiments with galK we used CREATE cassettes designed to convert Y145 (TAT) into a stop codon (TAA) with a single point mutation at this position and a second point mutation to make a synonymous mutation that abolishes the targeted PAM site (e.g. Figure 8B and Figure 13A-13D). Editing efficiencies (e.g. Figure 13A-13D and Figure 9A-9B) were estimated using red/white plate based screening on 1% galactose supplemented MacConkey agar as previously described.
[00367] Selection procedures
[00368] Following overnight recovery, the cells were harvested by pelleting and resuspension in fresh selection media. All selections were performed in shake flask and inoculated at an initial OD600 of 0.1. Three serial dilutions (48-96 hrs depending on growth rates in the target condition) were carried out for each selection by transferring 1/lOOth the media volume after the cultures reached stationary phase. The 42°C selections were performed in M9 media + 0.2% glucose to mimic low carbon availability from the initial adaptation. Antibiotic selections were carried out in LB + 500 μg/mL rifampicin or erythromycin to ensure stringent selection. The solvent selections were performed in M9 + 0.4% glucose and either 10 g/L acetate (unbuffered) or 2 g/L furfural. Selections were harvested by pelleting 1 mL of the final culture and the cell pellet was boiled in 100 μΙ_, TE buffer to preserve both the plasmid and the genomic DNA for further desired analyses.
[00369] Library preparation and sequencing
[00370] Custom Illumina compatible primers were designed to allow a single amplification step from the CREATE plasmid and assignment of experimental reads using barcodes. The CREATE cassettes were amplified directly from the plasmid sequences of boiled cell lysates using 20 cycles of PCR with the Phusion (NEB) polymerase using 60°C annealing and 1 :30 minute extension times. As in the cloning procedure a minimal number of PCR cycles was maintained to prevent accumulation of mutations and recombined CREATE cassettes that were observed when an excessive number of PCR cycles was implemented (e.g. >25-30). Amplified fragments were verified and quantified by 1% agarose gel electrophoresis and pooled according to the desired read depth for each sample. The pooled library was cleaned using Qiaquick PCR cleanup kit and processed for NGS using standard Illumina preparation kits. The Dlumina sequencing and sample preparation were performed with the primers.
[00371] Preprocessing of high-throughput sequencing and count generation
[00372] Paired-end Illumina sequencing reads were sorted according to the golay barcode index with allowance of up to 3 mismatches then merged using the usearch -fastq merge algorithm. Sorted reads were then matched against the database of designed CREATE cassettes using the usearch global algorithm at an identity threshold of 90% allowing up to 60 possible hits for each read. The resulting hits were further sorted according to percent identity and read assignment was made using the best matching CREATE cassette design at a final cutoff 98% identity to the initial design. It should be noted that this read assignment strategy attempts to identify correlations between the designed genotypes and may therefore miss other important features that arise due to mutations that could occur during the experimental procedure. This approach was taken both to simplify data analysis as well as evaluate the 'forward' design and annotation procedure and it's ability to accurately identify meaningful genetic phenomena.
[00373] Data analysis and fitness calculation
[00374] Enrichment scores (or absolute fitness scores were calculated as the log2 enrichment score using the following equation: , where F X;f is the frequency of cassette X at the final time point and F x i is the initial frequency of cassette X and W is the absolute fitness of each variant. Frequencies were determined by dividing the read counts for each variant by the total experimental counts including those that were lost to filtering. Each selection was performed in duplicate and the count weighted average of the two measurements was used to infer the average fitness score of each mutation as
follows:
[00375] These scores were used to rank and assess the fitness contributions of each mutation under the various selection pressures investigated. For all selections we took average absolute fitness scores for all of the synonymous mutants as a composite measure of the average growth rate. Absolute enrichment scores were considered significant if the mutant enrichment was at least +/- 2*σ (e.g. p=0.05 assuming a normal distribution) of the wild-type value. We performed two replicates of each selection reported in this study to derive these figures and applied a cutoff threshold of 10 across the replicate experiments for inclusion in each analysis.
[00376] For every codon targeted our designs also included a synonymous variant to provide an internal experimental control. Thus 5% of the protein targeting cassettes encoded synonymous mutations that allow us to estimate confidence intervals for mutation effects using custom Python bootstrapping scripts. The enrichment data for each experiment was resampled with replacement 20000 to obtain 95% confidence interval estimations that were used to infer statistical significance of enrichment scores for each analysis presented in the manuscript.
[00377] Mutant reconstructions and growth measurements
[00378] The AcrB T60N and Crp S28P and FolA F153R/W CREATE cassettes were ordered as separate gblocks from IDT, cloned and sequence verified. Each cassette was transformed into MG1655 and colony screened to identify a clone with the designed genomic edit. These strains (e.g. Figure 21 and Figure 22A-22C) were then subjected to the growth conditions from the pooled library selection as indicated. The growth curves were taken in triplicate for each condition in 100 μÎ. in a 96 well plate reader set to measure absorbance at 600 nm. The plate was covered and water added to empty wells to reduce evaporation during the growth.
[00379] Software and figure generation
[00380] Circle plots were generated using Circos v0.67. Plots were generated in Python 2.7 using the matplotlib plotting libraries and figures were made using Adobe Illustrator CS5. Entropy scores for the FolA (Figure 10A) were determined using the ProDy Python package and the Pfam accession PF00186 representative proteome alignment RP35.
[00381] Figures of the protein libraries and high fitness mutations were made using The PyMol Molecular Graphics System, Schrodinger, LLC. The following are the proteins and PDBs used in the figure generation: AcrB (3W9H, 4K7Q, 3AOC), Fis (3JR9), Ihf (1IHF), RNA polymerase (4KMU, 4IGC), Crp (3N4M), MarA (1BLO), and SoxR (2ZHG). Example 29: Testing Edit-Barcode correlation
[00382] A strain expressing a low copy number plasmid (Ec23) which is a Cas9-pSIM5 dual vector,, was tested using different gene editing cassettes (lacZ, xylA, and rhaA) and recorder cassettes with different barcodes and insertion sites (galK site 1, galK site 2, and galK site 3) (Summarized in Figure 27A). The possible outcomes are depicted in Figure 27B. Pre-selection, all combinations of edit/barcodeAVT are possible. After selection, edits cells could be enriched whether they are barcoded or not in this experimental design.
[00383] The transformations were plated on selective media that allowed for enrichment of cells contaiing the gene edits. 30 colonies from each combination transformation were sequenced to determine if they contained the desired barcode.
[00384] Figure 27C shows the results from the sequencing data. Two of the edit/barcode combinations were found in 100% of the tested colonies (30/30 colonies), and the other edit/barcode combination transformation was found in approximately 97% of tested colonies (29/30 colonies). The single colony that was not properly engineered contained the gene edit, but not the barcode.
[00385] Overall, 89 out of 90 tested colonies has the designed gene edit and barcode.
Example 30: Selectable Recording
[00386] When a barcode is not selected for, it allows for enrichment of non-barcoded cells even if the corresponding gene edit is incorporated and selected for. Figure 28 depicts an example strategy for selecting for the recording event (e.g., incorporation of the barcode by the recorder cassette), in addition to selecting for the editing cassette incorporation, thereby increasing the efficiency of recovering cells that have been both edited and barcoded.
[00387] As depicted in Figure 28, sequences SO, SI, S2, etc. are designed to be targeted by the guide RNA associated with the recorder cassette of the next round. In the depicted example, in the first round of engineering, a PAM mutation, a barcode, SI site, and regulatory elementary necessary to turn on a selectable marker are incorporated into the SO site in the target region. This turns on the TetR selectable marker and allows for enrichment of barcoded mutants variants with the SI site that have the first round PAM site deleted. In the second round of engineering, a new recorder cassette comprising a second PAM mutation, a second barcode, a S2 site, and a mutation that turns off the selectable marker is incorporated into the S I site from the previous round. This allows for counter-selection of variants that have incorporated the second barcode and S2 site. The subsequent rounds continue to flip the selectable marker between an on and off state and using selection or counter-selection respectively to enrich the desired variants. The recorder cassette from each round is designed to incorporate into a unique sequence (e.g., SO, SI, etc.) that was incorporated in the previous round. This ensures that the last round of barcoding was successful so that all desired engineering steps are contained in the final product. The incorporation of PAM mutations at each step also helps ensure that the desired barcoded variants are selected for since cells having the unmodified PAM sequences will be killed as they can't escape CRISPR enzyme cleavage.
[00388] This strategy uses multiple methods to increase the efficiency of isolating desired variants that contain all of the engineered edits from each round of engineering. The PAM mutation, selectable marker switch, and unique landing site incorporated in each round separately increase efficiency and together increase efficiency as well. These tools allow for selection of each recording round and allow design of highly active recording guide RNAs. An array of equally spaced (or not equally spaced, depending on the design) barcodes is generated and facilitates downstream analysis such as sequencing the barcode array to determine which corresponding edits are incorporated throughout the genome.
[00389] Figure 29 depicts an experimental design to test the selectable recorder strategy described above. A plasmid (pRECl) containing an editing cassette and a recorder cassette was transformed into cells. The editing cassette either contained a non-targeting editing cassette, or a mutation that incorporated a mutation (not TS) or a temperature sensitive mutation (TS) into a target gene. The recorder cassette was designed to incorporate into the SO site in the target gene that originally had the tetR selectable marker turned off. The recorder cassette also contained a PAM mutation that deleted the SO PAM site, first barcode (BCl), a unique SI site for the subsequent engineering round recording cassette to incorporate into, and a corrective mutation that will turn on the TetR selectable marker. A guide RNA on the recorder cassette that targets a PAM site in the SO site (SO-gRNA) allows a CRISPR enzyme, in this case Cas9, to cleave the SO site. The recorder cassette recombines into the cleaved SO site. The PAM mutation is incorporated, which means the SO-gRNA can no longer target the SO site, thereby killing WT cells and enriching for cells that received the barcode. The TetR selectable marker was also turned on, allowing further selection of the barcoded variant.
[00390] The data in Figures 30A and 30B show the results from the experiment described above and depicted in Figure 29. Of the Tet Resistant colonies that were recovered from the transformation and engineering round, 16 were sequence and determined to all contain the designed barcode (Figure 30A). Figure 30B shows that the control cells that did not contain the recorder target site (non-target) did not survive the presence of Tet, while cells that contained the target site were successfully barcoded as evidences by the turning on of TetR, allowing cells to be selected on Tet containing media. The Tet resistant colonies were confirmed at the genomic site to have TetR gene turned on. These data showed that selectable recording was successful. Example 31: Expression of MAD nucleases
[00391] Wild-type nucleic acid sequences for MAD1-MAD20 include SEQ ID NOs 21-40, respectively. These MAD nucleases were codon optimized for expression in E. coli and the codon optimized sequences are listed as SEQ ID NO: 41-60, respectively (summarized in Table 2).
Codon optimized MAD1-MAD20 were cloned into an expression construct comprising a constitutive or inducible promoter (e.g., T7 promoter SEQ ID NO: 83, or pBAD promoter SEQ ID NO: 81 or SEQ ID NO: 82) and an optional 6X-His tag. The generated MAD1-MAD20 expression constructs are provided as SEQ ID NOs: 61-80, respectively.
Table 2.
Example 32: MAD2 and MAD7 nucleases
[00392] MAD2 and MAD7 nucleases are nucleic acid-guided nuclease that can be used in the methods disclosed herein. Nucleases Mad2 (SEQ ID NO: 2) and Mad 7 (SEQ ID NO: 7) were cloned and transformed into cells. Editing cassettes designed to mutate a target site in a galK gene were designed with mutations, which allowed for white/red screening of successfully editing colonies. The editing cassettes also encoded a guide nucleic acid designed to target galK. The editing cassettes were transformed into E. coli cells expressing MAD2, MAD7, or Cas9. Figure 31A shows the editing efficiency of Mad2 and Mad7 compared to Cas9 (SEQ ID NO: 110). Figure 3 IB shows the transformation efficiency as evidenced by cell survival rates. In this example, the guide nucleic acid used with MAD2 and MAD7 comprised a scaffold-12 sequence and a guide sequence targeting galK. The guide nucleic acid used with Cas9 comprised a sequence compatible with the S. pyogenes Cas9.
[00393] Figure 32 and Table 3 show more examples of gene editing using the MAD2 nuclease. In this experiment, different guide nucleic acid sequences were tested. The guide sequence of the guide nucleic acids targeted the galK gene as described above. The scaffold sequence of the guide nucleic acids were one of various sequences tested as indicated. Guide nucleic acids with scaffold-5, scaffold-10, scaffold-11, and scaffold-12 were able to form functional complexes with MAD2.
[00394] Figure 33 and Table 4 show more examples of gene editing using the MAD7 nuclease. In this experiment, different guide nucleic acid sequences were tested. The guide sequence of the guide nucleic acids targeted the galK gene as described above. The scaffold sequence of the guide nucleic acids were one of various sequences tested as indicated. Guide nucleic acids with scaffold-10, scaffold-11, and scaffold-12 (e.g., Figure 31 A) were able to form functional complexes with MAD7. Amino acid sequences are provided in Table 2 and scaffolding sequences are provided in Table 3 and Table 4. Table 3 and Table 4 also provided the designed mutations in the editing cassettes that were used to mutate the galK target gene.
[00395] Further details and characterization of MAD2, MAD7, and other MAD nucleases are described in US Application No. 15/631,989, filed June 23, 2017, and US Application No. 15/632,001, filed June 23, 2017, each of which are incorporated herein in their entirety. Table 3.
[00396] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby. SEQUENCE LISTING
Table 5.
SE I Sequence
Q
no
N
O:
" SE MGKMYYLGLDIGTNSVGYAVTDPSYHLLKFKGEPMWGAHVFAAGNQSAERRSFRTSRRRL DRRQQ Q RVKLVQEIFAPVISPIDPRFFIRLHESALWRDDVAETDKHIFFNDPTYTDKEYYSDYPTI HHLIVDLME
E) SSEKHDPRLVYLAVAWLVAHRGHFLNEVDKDNIGDVLSFDAFYPEFLAFLSDNGVSPWVC ESKALQ N ATLLSRNSVNDKYKALKSLIFGSQKPEDNFDANISEDGLIQLLAGKKVKVN LFPQESNDASFTLND
O: KEDAIEEILGTLTPDECEWIAHIRRLFDWAIMKHALKDGRTISESKVKLYEQHHHDLTQL KYFVKTY
1 LAKEYDDIFRNVDSETTK YVAYSYHVKEVKGTLPKNKATQEEFCKYVLGKVKNIECSEADKVDFD EMIQRLTDNSFMPKQVSGENRVIPYQLYYYELKTILNKAASYLPFLTQCGKDAISNQDKL LSIMTFRI PYFVGPLRKDNSEHAWLERKAGKIYPWNFNDKVDLDKSEEAFIRRMTNTCTYYPGEDVLP LDSLIYE KFMILNEINNimDGYPISVDVKQQWGLFEKKRRVTVKDIQNLLLSLGALDKHGKLTGIDT TIHSNYN TYHHFKSLMERGVLTRDDVERIVERMTYSDDTKJ VRLWLN YGTLTADDVKHISR^
SKMFLTGLKGVHKETGERASILDFMWNTNDNLMQLLSECYTFSDEITKLQEAYYAKAQLS LNDFLD SMYISNAVKRPIYRTLAVVNDIRKACGTAPKRIFIEMARDGESKKKRSVTRREQIKNLYR SIRKDFQQ EVDFLEKILENKSDGQLQSDALYLYFAQLGRDMYTGDPIKLEHIKDQSFYNIDHIYPQSM VKDDSLD NKVLVQSEINGEKSSRYPLDAAIRNKMKPLWDAYYNHGLISLKKYQRLTRSTPFTDDEKW DFINRQL VETRQSTKALAILLKRKFPDTEIVYSKAGLSSDFRHEFGLVKSRNINDLHHAKDAFLAIV TGNVYHER FNRRWFMVNQPYSVKTKTLFTHSIKNGNFVAWNGEEDLGRIVKMLKQNKNTIHFTRFSFD RKEGLF DIQPLKASTGLVPRKAGLDVVKYGGYDKSTAAYYLLVRFTLEDKKTQHKLMMIPVEGLYK ARIDH DKEFLTDYAQTTISEILQKDKQKVINIMFPMGTRHIKLNSMISIDGFYLSIGGKSSKGKS VLCHAMVPL IWHKIECYIKAMESFARKFKEN KLmVEKFDKITVEDNLNLYELFLQKLQHNPYNKTFSTQFDVLT NGRSTFT LSPEEQVQTLLNILSIFKTCRSSGCDLKSINGSAQAARIMISADLTGLSKKYSDIRLVEQ SA SGLFVSKSQNLLEYL*
SE MSSLTKFTNKYSKQLTIKNELIPVGKTLENIKENGLIDGDEQLNENYQKAKIIVDDFLRD FINKALNNT Q QIGNWRELADALNKEDEDNIEKLQDKIRGIIVSKFETFDLFSSYSIKKDEKIIDDDNDVE EEELDLGKK HO TSSFKYIFKKNLFKLVLPSYLKTTNQDKLKIISSFDNFSTYFRGFFENRKNIFTKKPIST SIAYRIVHDNF N PKFLDNIRCFNVWQTECPQLIVKADNYLKSKNVIAKDKSLANYFTVGAYDYFLSQNGIDF YNNIIGG
O: LPAFAGHEKIQGLNEFINQECQKDSELKSKLKNRHAFKMAVLFKQILSDREKSFVIDEFE SDAQVIDA
2 VKNFYAEQCKDNNVIFNLLNLn NIAFLSDDELDGIFIEGKYLSSVSQKLYSDWSKLRNDIEDSANSK QGN ELAKKIKTNKGDVEKAISKYEFSLSELNSIVHDNTKESDLLSCTLHKVASEKLVKVNEGD WPK HLKNNEEKQKIKEPLDALLEIYNTLLIFNCKSFNKNGNFYVDYDRCINELSSVWLYNKTR NYCTKK PYNTDKFKLNFNSPQLGEGFSKSKENDCLTLLFKKDDNYYVGIIRKGAKINFDDTQAIAD NTDNCIFK MNYFLLKDAKKFIPKCSIQLKEVKAHFKKSEDDYILSDKEKFASPLVIKKSTFLLATAHV KGKKGNIK KFQKEYSKENPTEYRNSLNEWIAFCKEFLKTYKAATIFDITTLKKAEEYADIVEFYKDVD NLCYKLEF CPIKTSFIENLIDNGDLYLFRIN KDFSSKSTGTKNLHTLYLQAIFDERNLN PTIMLNGGAELFYRKE SIEQKNPJTHKAGSILWKVCKDGTSLDDKIRNEIYQYEN FIDTLSDEAKKVLPNVIKKEATHDITKD
KRFTSDKFFFHCPLTINYKEGDTKQFN EVLSFLRGNPDINIIGIDRGER LIYVTVINQKGEILDSVSF
NTWNKSSKIEQTVDYEEKLAVREKERIEAKRSWDSISKIATLKEGYLSAIVHEICLL MIKHNAIVVLE
NLNAGFKRIRGGLSEKSWQKFEKMLINKLNYFVSKKESDWNKPSGLLNGLQLSDQFE SFEKLGIQS
GFIFYVPAAYTSKIDPTTGFANVLNLSKVRNVDAIKSFFSNFNEISYSKKEALFKFS FDLDSLSKKGFSS
FVKFSKSKWNWTFGERIIKPKNKQGYREDKRINLTFEMKKLLNEYKVSFDLENNLIP NLTSANLKD
TFWKELFFIFKTTLQLRNSVTNGKEDVLISPVKNAKGEFFVSGTHNKTLPQDCDANG AYHIALKGLM
ILERN LVREEKDTKKIMAISNVDWFEYVQKRRGVL*
SE MN YDEFT LYPIQKTIRFELKPQGRTMEHLETFNFFEEDRDRAEKYKILKEAIDEYHKKFIDEHLTN
Q MSLDWNSLKQISEKYYKSREEKDKK LSEQKRMRQEIVSEFKKDDRFKDLFSKKLFSELLKEEIYK
no KGNHQEIDALKSFDKFSGYFIGLHENRKNMYSDGDEITAISNRIVNENFPKFLDNLQKYQ EARKKYP
N EWIIKAESALVAHNIKMDE SLEYFNKVLNQEGIQRYNLALGGYVTKSGEKMMGLNDALNLAHQ
O: SEKSSKGRIHMTPLFKQILSEKESFSYIPDVFTEDSQLLPSIGGFFAQIENDKDGNIFDR ALELISSYAEY
3 DTERIYIRQADINRVSNVIFGEWGTLGGLMREYKADSINDINLERTCKKVDKWLDSKEFA LSDVLEAI
KRTGNNDAFNEYISKMRTAREKIDAARKEMKFISEKISGDEESIHIIKTLLDSVQQF LHFFNLFKARQD
IPLDGAFYAEFDEVHSKLFAIWLYNKVR YLTKN LNTKKIKLNFKNPTLANGWDQNKVYDYASLI
FLRDGNYYLGIINPKRKKNIKFEQGSGNGPFYRKMWKQIPGPNKNLPR LTSTKGKKEYKPSKEII
EGYEADKHIRGDKFDLDFCHKLIDFFKESIEKHKDWSKFNFYFSPTESYGDISEFYL DVEKQGYRMHF
ENISAETroEYVEKGDLFLFQIYN DFVKAATGKKDMHTIYWNAAFSPENLQDVVVKLNGEAELFY
RDKSDIKEIVHREGEILVNRTYNGRTP DKIHKKLTDYHNGRTKDLGEAKEYLDKVRYFKAHYDIT
KDRRYLNDKIYFHVPLTLNFKANGKKNLNKMVIEKFLSDEKAHIIGIDRGERNLLYY SIIDRSGKIIDQ
QSLNVIDGFDYREKLNQREIEMKDARQSWNAIGKIKDLKEGYLSKAVHEITKMAIQY NAIVVMEEL
NYGFKRGRFKVEKQIYQKFENMLIDKMNYLVFKDAPDESPGGVLNAYQLTNPLESFA KLGKQTGIL
FYVPAAYTSKIDPTTGFVNLFNTSSKTNAQERKEFLQKFESISYSAKDGGIFAFAFD YRKFGTSKTDH
KNVWTAYTNGERMRYIKEKKR ELFDPSKEIKEALTSSGIKYDGGQNILPDILRSN NGLIYTMYSSF
IAAIQMRVYDGKEDYIISPIKNSKGEFFRTDPKRRELPIDADANGAYNIALRGELTM RAIAEKFDPDSE
KMAKLELKHKD WFEFMQTRGD *
SE MTKTFDSEFFNLYSLQKTVRFELKPVGETASFVEDFKNEGLKRVVSEDERRAVDYQKVKE IIDDYHR
Q DFIEESLNYFPEQVSKDALEQAFHLYQKLKAAKVEEREKALKEWEALQKKLREKVVKCFS DSNKAR
no FSRIDKKELIKEDLINWLVAQNREDDIPTVETFN FTTYFTGFHENRKNIYSKDDHATAISFRLIHENL
N PKFFDNVISFNKLKEGFPELKFDKVKEDLEVDYDLKHAFEIEYFVNFVTQAGIDQYNYLL GGKTLED
O: GTKKQGMNEQINLFKQQQTRDKARQIPKLIPLFKQILSERTESQSFIPKQFESDQELFDS LQKLHNNCQ 4 DKFTVLQQAILGLAEADLKKVFIKTSDLNALSNTIFGNYS SDALNLYKESLKTKKAQEAFEKLPA
HSIHDLIQYLEQFNSSLDAEKQQSTDTVLNYFIKTDELYSRFIKSTSEAFTQVQPLF ELEALSSKRRPPE
SEDEGAKGQEGFEQIKRIKAYLDTLMEAVHFAKPLYLVKGRKMIEGLDKDQSFYEAF EMAYQELES
LIIPIYNKARSYLSRKPFKADKFKINFDNNTLLSGWDANKETANASILFKKDGLYYL GIMPKGKTFLF
DYFVSSEDSEKLKQRRQKTAEEALAQDGESYFEKIRYKLLPGASKMLPKVFFSNKNI GFYNPSDDILR
IRNTASHTKNGTPQKGHSKVEFNLNDCHKMIDFFKSSIQKHPEWGSFGFTFSDTSDF EDMSAFYREV
ENQGYVISFDKIKETYIQSQVEQGNLYLFQIYNKDFSPYSKGKPNLHTLYWKALFEE ANLNNVVAKL
NGEAEIFFRRHSIKASDKVVHPANQAIDNKNPHTEKTQSTFEYDLVKDKRYTQDKFF FHVPISLNFKA
QGVSKFNDKVNGFLKGNPDVNIIGIDRGERHLLYFTVVNQKGEILVQESLNTLMSDK GHVNDYQQK
LDKKEQERDAARKSWTTVENIKELKEGYLSHVVHKLAHLIIKYNAIVCLEDLNFGFK RGRFKVEKQ VYQKFEKALIDKLNYLVFKEKELGEVGHYLTAYQLTAPFESFKKLGKQSGILFYVPADYT SKIDPTT GFVNFLDLRYQSVEKAKQLLSDFNAIRFNSVQNYFEFEIDYKKLTPKRKVGTQSKWVICT YGDVRY QNRRNQKGHWETEEVNVTEKLKALFASDSKTTTVIDYANDDNLIDVILEQDKASFFKELL WLLKLT MTLRHSKIKSEDDFILSPVKNEQGEFYDSRKAGEVWPKDADANGAYHIALKGLWNLQQIN QWEKG KTLNLAIKNQDWFSFIQEKPYQE*
SE MHTGGLLSMDAKEFTGQYPLSKTLRFELRPIGRTWDNLEASGYLAEDRHRAECYPRAKEL LDDNHR
Q AFLNRVLPQIDMDWHPIAEAFCKVHKNPGNKELAQDYNLQLSKRRKEISAYLQDADGYKG LFAKPA
no LDEAMKIAKENGNESDIEVLEAFNGFSVYFTGYHESRENIYSDEDMVSVAYRITEDNFPR FVSNALIF
N DKLNESHPDIISEVSGNLGVDDIGKYFDVSNYN FLSQAGIDDYNHIIGGHTTEDGLIQAFNVVLNLR
O: HQKDPGFEKIQFKQLYKQILSVRTSKSYIPKQFDNSKEMVDCICDYVSKIEKSETVERAL KLVRNISSF 5 DLRGIFWKKNLRILSNK IGDWDAIETALMHSSSSENDKKSWDSAEAFTLDDIFSSVKKFSDASAE
DIGNRAEDICRVISETAPFINDLRAVDLDSLNDDGYEAAVSKIRESLEPYMDLFHEL EIFSVGDEFPKC
AAFYSELEEVSEQLIEIIPLFNKARSFCTRKRYSTDKIKVNLKFPTLADGWDLNKER DNKAAILRKDG
KYYLAILDMKKDLSSIRTSDEDESSFEKMEYKLLPSPVKMLPKIFVKSKAAKEKYGL TDRMLECYDK
GMHKSGSAFDLGFCHELIDYYKRCIAEYPGWDVFDFKFRETSDYGSMKEFNEDVAGA GYYMSLRKI
PCSEWRLLDEKSIYLFQIYN DYSENAHGNKNMHTMYWEGLFSPQNLESPVFKLSGGAELFFRKSS
IPNDAKTVHPKGSVLWRNDVNGRRIPDSIYRELTRYFNRGDCRISDEAKSYLDKVKT KKADHDIVK
DRRFTVDKM FHWIAMNFKAISKPNLN VIDGIIDDQDLKIIGIDRGER^
DSLNILNGYDYRKALDVREYDN EARRNWTKVEGIRKMKEGYLSLAVSKLADMIIENNAIIVMEDL
NHGFKAGRSKIEKQWQKFESMLINKLGYMVLKDKSIDQSGGALHGYQLANHVTTLAS VGKQCGVI
FYIPAAFTSKIDPTTGFADLFALSNVKNVASMREFFSKMKSVIYDKAEGKFAFTFDY LDYNVKSECG
RTLWTVYTVGERFTYSRVNREYVRKVPTDIIYDALQKAGISVEGDLRDRIAESDGDT LKSIFYAFKY
ALDMRVENREEDYIQSPVKNASGEFFCSKNAGKSLPQDSDANGAYNIALKGILQLRM LSEQYDPNA
ESIRLPLITNKAWLTFMQSGMKTWKN*
SE MD SLKDFTNLYP VSKTLRFELKP VGKTLENIEKAGILKEDEHRAES YRRVKKIIDTYHKVFID S SLEN
Q MAKMGIENEIKAMLQSFCELYKKDHRTEGEDKALDKIRAVLRGLIVGAFTGVCGRRENTV QNEKYE
no SLFKEKLKEILPDFVLSTEAESLPFSVEEATRSLKEFDSFTSYFAGFYENRKNIYSTKPQ STAIAYRLIH
N ENLPKFIDNILVFQKIKEPIAKELEHIRADFSAGGYIKKDERLEDIFSLNYYIHVLSQAG IEKYNALIGKI
O: VTEGDGEMKGLNEHINLYNQQRGREDRLPLFRPLYKQILSDREQLSYLPESFEKDEELLR ALKEFYD
6 HIAEDILGRTQQLMTSISEYDLSRIYVR DSQLTDISKKMLGDWNAIYMARERAYDHEQAPKRITAK
YERDRIKALKGEESISLANLNSCIAFLDNVRDCRVDTYLSTLGQKEGPHGLSNLVEN VFASYHEAEQ
LLSFPYPEEN LIQDKDNVVLIKNLLDNISDLQRFLKPLWGMGDEPDKDERFYGEYNYIRGALDQVIP
LYNKVR YLTRKPYSTRKVKLNFGNSQLLSGWDRNKEKDNSCVILRKGQNFYLAIMNNRHKRSFE
NKVLPEYKEGEPWEKMDYKFLPDPNKMLPK LSKKGIEIYKPSPKLLEQYGHGTHKKGDTFSMD
DLHELIDFFKHSIEAHEDWKQFGFKFSDTATYENVSSFYREVEDQGYKLSFRKVSES YVYSLIDQGKL
YLFQIYN DFSPCSKGTPNLHTLYWRMLFDERNLADVIYKLDGKAEIFFREKSLKNDHPTHPAGKPI
KKKSRQKKGEESLFEYDLVKDRHYTMDKEQFHWITMNFKCSAGSKVNDMVNAHI
IDRGERNLLYICVIDSRGTILDQISLNTINDIDYHDLLESRDKDRQQERRNWQTIEG IKELKQGYLSQA
VHmAELNWAYKAVVALEDLNMGFKRGRQKVESSVYQQFEKQLIDKLNYLVDKKKRPE DIGGLLR
AYQFTAPFKSFKEMGKQNGFLFYIPAWNTSNIDPTTGFVNLFHAQYENVDKAKSFFQ KFDSISYNPK
KDWFEFAFDYKNFTKKAEGSRSMWILCTHGSRIKNFRNSQKNGQWDSEEFALTEAFK SLFVRYEID
YTADLKTAIVDEKQKDFFVDLLKLFKLTVQMRNSWKEKDLDYLISPVAGADGRFFDT REGNKSLPK DADANGAYNIALKGLWALRQIRQTSEGGKLKLAISNKEWLQFVQERSYEKD*
SE MNNGTN FQNFIGISSLQKTLRNALIPTETTQQFIVKNGIIKEDELRGENRQILKDIMDDYYRGFIS ETL
Q SSIDDIDWTSLFEK EIQLKNGDN DTLIKEQTEYRKAIHKKFANDDRFKNMFSAKLISDILPEFVIHN
no N YSASEKEEKTQVIKLFSRFATSFKDYFKNRANCFSADDISSSSCHRIVNDNAEIFFSNAL VYRRIVK
N SLSNDDINKISGDMKDSLKEMSLEEIYSYEKYGEFITQEGISFYNDICGKVNSFMNLYCQ KNKENKNL
0: YKLQKLHKQILCIADTSYEVPYKFESDEEVYQSVNGFLDNISSKHIVERLRKIGDNYNGY NLDKIYIV
7 SKFYESVSQKTYRDWETINTALEIHYNNILPGNGKSKADKVKKAVKNDLQKSITEINELV SNYKLCS
DDNIKAETYIHEISHILN FEAQELKYNPEIHLVESELKASELKNVLDVIMNAFHWCSVFMTEELVDK
DN FYAELEEIYDEIYPVISLYNLVR YVTQKPYSTKKIKLNFGIPTLADGWSKSKEYSNNAIILMRD
NLYYLGIFNAKNKPDKKIIEGNTSENKGDYKKMIYNLLPGPNKMIPKVFLSSKTGVE TYKPSAYILEG
YKQNKHIKSSKDFDITFCHDLIDYFKNCIAIHPEWKNFGFDFSDTSTYEDISGFYRE VELQGYKIDWT
YISEKDIDLLQEKGQLYLFQIYNKDFSKKSTGNDNLHTMYLKNLFSEENLKDIVLKL NGEAEIFFRKS
SIKNPIIFn KGSILVNRTYEAEEKDQFGNIQIVRKNIPENIYQELYKYFNDKSDKELSDEAAKLKNVVG
HHEAATNIVKDYRYTYDKYFLHMPITINFKANKTGFINDRILQYIAKEKDLHVIGID RGERNLIYVSVI
DTCGNIVEQKSFNIVNGYDYQIKLKQQEGARQIARKEWKEIGKIKEIKEGYLSLVIH EISKMVIKYNAI
IAMEDLSYGFKKGRFKVERQWQKFETMLINKLNYLVFKDISITENGGLLKGYQLTYI PDKLKNVGH
QCGCIFYVPAAYTSKIDPTTGFWIFKFKDLTVDAKREFIKKFDSIRYDSEKNLFCFT FDYN FITQNT
VMSKSSWSWTYGWIKRRFWGRFSNESDTIDITKDMEKTLEMTDINWRDGHDLRQDII DYEIVQHI
FEIFRLTVQMRNSLSELEDRDYDRLISPVLNENNIFYDSAKAGDALPKDADANGAYC IALKGLYEIKQ
ITENWKEDGKFSRDKLKISNKDWFDFIQNKRYL*
SE MTN FTNQYSLSKTLRFELIPQGKTLEFIQEKGLLSQDKQRAESYQEMKKTIDKFHKYFIDLAL SNAK
Q LTHLETYLELYNKSAET KEQKFKDDLKKVQDNLRKEIVKSFSDGDAKSIFAILDKKELITVELEKWF
no EN EQKDIYFDEKFKTFTTYFTGFHQNRKNMYSVEPNSTAIAYRLIHENLPKFLENAKAFEKI KQVES
N LQVNFRELMGEFGDEGLIFWELEEMFQINYYNDVLSQNGITIYNSIISGFTKNDIKYKGL NEYIN YN
0: QTKDKKDRLPKLKQLYKQILSDRISLSFLPDAFTDGKQVLKAIFDFYKINLLSYTIEGQE ESQNLLLLI 8 RQTIENLSSFDTQKIYLKNDTHLTTISQQ GDFS STALNYWYETKVNPKFETEYSKA EKKREIL
DKAKA TKQDYFSIAFLQEVLSEYILTLDHTSDIVKKHSSNCIADYFKNHFVAKKENETDKTFDFI A
NITAKYQCIQGILENADQYEDELKQDQKLIDNLKFFLDAILELLHFIKPLHLKSESI TEKDTAFYDVFE
NYYEALSLLTPLYNMVRNYVTQKPYSTEKIKLNFENAQLLNGWDAN EGDYLTTILKKDGNYFLAI
MDKKHNKAFQKFPEGKENYEKMWKLLPGVNKMLPK FSNKNIAYFNPSK^
DTFNLEHCHTLIDFFKDSLNKHEDWKYFDFQFSETKSYQDLSGFYREVEHQGYKINFKNI DSEYIDGL
VNEGKLFLFQIYSKDFSPFSKGKPNMHTLYWKALFEEQNLQNVIYKLNGQAEIFFRK ASIKPKNIILH
KKKIKIAKKHFIDKKTKTSEIWVQTIKNLNMYYQGKISEKELTQDDLRYIDNFSIFN EKNKTIDIIKDK
RFTVDKFQFHWITMNFKATGGSYINQTVLEYLQNNPEVKIIGLDRGERHLVYLTLID QQGNILKQES
LNTITDSKISTPYHKLLDNKENERDLARKNWGTVENIKELKEGYISQVVHKIATLML EENAIVVMED
LNFGFKRGRFKVEKQIYQKLEKMLIDKLNYLVLKDKQPQELGGLYNALQLTNKFESF QKMGKQSGF
LFYWAWNTSKIDPTTGFVNYFYTKYENVDKAKAFFEKFEAIRFNAEKKYFEFEVKKY SDFNPKAEG
TQQAWTICTYGERIETKRQKDQN FVSTPINLTEKIEDFLGKNQIVYGDGNCIKSQIASKDDKAFFE
TLLYWFKMTLQMRNSETRTDIDYLISPVMNDNGTFYNSRDYEKLENPTLPKDADANG AYHIAKKGL
MLLNKIDQADLTKKVDLSISNRDWLQFVQKNK*
SE MEQEYYLGLDMGTGSVGWAVTDSEYHVLRKHGKALWGVRLFESASTAEERRMFRTSRRRL DRRN
Q WRIEILQEIFAEEISKKDPGFFLRMKESKYYPEDKRDINGNCPELPYALFVDDDFTDKDY HKKFPTIYH no LRK LMNTEETPDIRLWLAIHHMMKH^
N EEYAVVESILKDNMLNRSTKKTP IKALKAKSICEKAVLNLLAGGTVKLSDIFGLEELNETEPJKISFA
O: DNGYDDYIGEVENELGEQFYIIETAKAVYDWAVLVEILGKYTSISEAKVATYEKHKSDLQ FLKKIVR
9 KYLTKEEYKDIFVSTSDKLKNYSAYIGMTKINGKKVDLQSKRCSKEEFYDFIKKNVLKKL EGQPEYE
YLKEELEP^TFLPKQVNRDNGVIPYQIHLYELKKILGNLRDKIDLIKENEDKLVQLF EFRIPYYVGPLN
KIDDGKEGKFTWAVRKSNEKIYPWNFENVVDIEASAEKFIRRMTNKCTYLMGEDVLP KDSLLYSKY
MVLNELNNVKLDGEKLSVELKQRLYTDVFCKYRKVTVKKIKNYLKCEGIISGNVEIT GIDGDFKASL
TAYHDFKEILTGTELAKKDKENIITNIVLFGDDKKLLKKRLNRLYPQITPNQLKKIC ALSYTGWGRFS
KKFLEEITAPDPETGE NIITALWESN NLMQLLSNEYRFMEEVETYNMGKQTKTLSYETVENMY
VSPSVKRQIWQTLKIVKELEKVMKESPKRVFIEMAREKQESKRTESRKKQLIDLYKA CKNEEKDWV
KELGDQEEQKLRSDKLYLYYTQKGRCMYSGEVIELKDLWDNTKYDIDHIYPQSKTMD DSLNNRVL
VKKKYNATKSDKYPLNENIRHERKGFWKSLLDGGFISKEKYERLIRNTELSPEELAG FIERQIVETRQ
STKAVAEILKQVFPESEIVYVKAGTVSRFRKDFELLKVREVNDLHHAKDAYLNIVVG NSYYVKFTK
NASWFKENPGRTYNLKKMFTSGWNIERNGEVAWEVGKKGTIVTVKQIMNKNNILVTR QVHEAKG
GLFDQQIMKKGKGQIAIKETDERLASIEKYGGYNKAAGAYFMLVESKDKKGKTIRTI EFIPLYLKNKI
ESDESIALNFLEKGRGLKEPKILLKKIKE)TLFDVDGFKMWLSGRTGDRLLFKCANQ LILDEKIIVTMK
KIVKFIQRRQENRELKLSDKDGIDNEVLMEIYNTFVDKLENTVYRIRLSEQAKTLID KQKEFERLSLE
DKSSTLFEILHIFQCQSSAANLKMIGGPGKAGILVMNNNISKCNKISIINQSPTGIF ENEIDLLK
SE MN FENFTGLYPISKTLRFELIPQGKTLEYIEKSEILENDNYRAEKYEEVKDIIDGYHKWFIN ETLHDL
Q HINWSELKVALENNRIEKSDASKKELQRVQKIKREEIYNAFIEHEAFQYLFKENLLSDLL PIQIEQSED
no LDAEKKKQAVETFNRFSTYFTGFHENRKNIYSKEGISTSVTYmVHDNFPKFLENMKVFEI LRNECPE
N VISDTANELAPFIDGVRIEDIFLIDFFNSTFSQNGIDYYNRILGGVTTETGEKYRGINEF TNLYRQQHPE
O: FGKSKKATKMVVLFKQILSDRDTLSFIPEMFGNDKQVQNSIQLFYNREISQFENEGVKTD VCTALATL 10 TSKIAEFDTEKIYIQQPELPNVSQRLFGSWNELNACLFKYAELKFGTAEKVANRKKIDKW LKSDLFSF
TELNKALEFSGKDERIENYFSETGIFAQLVKTGFDEAQSILETEYTSEVHLKDQQTD IEKIKTFLDALQ
NLMHLLKSLCVSEEADRDAAFYNEFDMLYNQLKLVWLYNKVR YITQKLFRSDKIKIYFENKGQF
LGGWVDSQTENSDNGTQAGGYIFRKENVINEYDYYLGICSDPKLFRRTTIVSENDRS SFERLDYYQL
KTASVYGNSYCGKHPYTEDKNELVNSIDRFVHLSGNNILIEKIAKDKVKSNPTTNTP SGYLNFIHREA
PNTYECLLQDENFVSLNQRWSALKATLATLVRVPKALVYAKKDYHLFSEIINDIDEL SYEKAFSYFP
VSQTEFENSSNRTIKPLLLFKISNKDLSFAENFEKGNRQKIGKKNLHTLYFEALMKG NQDTIDIGTGM
VFHRVKSLNYNEKTLKYGHHSTQLNEKFSYPIIKDKRFASDKFLFHLSTEINYKEKR KPLNNSIIEFLT
N PDINIIGLDRGERHLIYLTLINQKGEILRQKTFNIVGNTNYHEKLNQREKERDNARKSWA TIGKIKE
LKEGFLSLVIHEIAKIMVENNAIVVLEDLNFGFKRGRFKVEKQIYQKFEKMLIDKLN YLVFKDKKAN
EAGGVLKGYQLAEKFESFQKMGKQSGFLFYWAAYTSKIDPTTGFVNMLNLNYTNMKD AQTLLSG
MDKISFNADANYFEFELDYEKFKTNQTDHTNKWTICTVGEKRFTYNSATKETTTVNV TEDLKKLLD
KFEVKYSNGDNIKDEICRQTDAKFFEIILWLLKLTMQMRNSNTKTEEDFILSPVKNS NGEFFRSNDDA
NGIWPADADANGAYHIALKGLYLVKECFNKNEKSLKIEHKNWFKFAQTRFNGSLTKN G*
SE NffiNFKNLYPINKTLRFELRPYGKTLENFKKSGLLEKDAFKANSRRSMQAIIDEKFKET ffiERLKYTEF
Q SECDLGNMTSKDKKITDKAATNLKKQVILSFDDEIFNNYLKPDKNIDALFKNDPSNPVIS TFKGFTTY
no FVNFFEIRKHIFKGESSGSMAYRIIDENLTTYLNNIEKIKKLPEELKSQLEGIDQIDKLN YNEFITQSGI
N THYNEIIGGISKSENVKIQGINEGINLYCQKNKVKLPRLTPLYKMILSDRVSNSFVLDTI ENDTELIEMI
O: SDLINKTEISQDVIMSDIQNIFIKYKQLGNLPGISYSSIVNAICSDYDN FGDGKRKKSYENDRKKHLE 11 TNWSINYISELLTDTDVSSNIKMRYKELEQNYQVCKENFNATNWMNIKNIKQSEKTNLIK DLLDILK
SIQPJYDLFDIVDEDKNPSAEFYTWLSKNAEKLDFEFNSWNKSRNYLTPJ QYSDKKIKLNFDSPTLA
KGWDANKEIDNSTIIMPJ FN DRGDYDYFLGIWNKSTPA EKIIPLEDNGLFEKMQYKLYPDPSKM^
PKQFLSKIWKAKHPTTPEFDKKYKEGRHKKGPDFEKEFLHELIDCFKHGLVNHDEKY QD GFNLR
NTEDYNSYTEFLEDVERCNYNLSFNKIADTSNLINDGKLY QIWSKDFSIDSKGTKNLNTIYFESLFS
EENMIEKMFKLSGEAEIFYRPASLNYCEDIIKKGHHHAELKDKFDYPIIKDKRYSQD KFFFHVPMVIN
YKSEKLNSKSLN RTNENLGQFTHIIGIDRGERHLIYLTVVDVSTGEIVEQKHLDEIINTDTKGVEHKT
HYLNKLEEKSKTRDNERKSWEAIETIKELKEGYISHVINEIQKLQEKYNALIVMENL NYGFKNSRIKV
EKQVYQKFETALIKKFNYIIDKKDPETYIHGYQLTNPITTLDKIGNQSGIVLYIPAW NTSKIDPVTGFV
NLLYADDLKYKNQEQAKSFIQKIDNIYFENGEFKFDIDFSKWN RYSISKTKWTLTSYGTRIQTFRNP
QKN KWDSAEYDLTEEFKLILNIDGTLKSQDVETYKKFMSLFKLMLQLRNSVTGTDIDYMISPV TDK
TGTHFDSRENIKNLPADADANGAYNIARKGIMAIENIMNGISDPLKISNEDYLKYIQ NQQE
SE MTQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQGFIEEDKARNDHYKELKPIIDRIYKT YADQCLQL
Q VQLDWENLSAAIDSYRKEKTEETRNALIEEQATYRNAIHDYFIGRTDNLTDAINKRHAEI YKGLFKAE
ID LFNGKVLKQLGTVTTTEHENALLRSFDKFTTYFSGFYENRKNVFSAEDISTAIPHRIVQD NFPKFKEN N CHIFTRLITAVPSLREHFENVKKAIGIFVSTSIEEVFSFPFYNQLLTQTQIDLYNQLLGG ISREAGTEKIK
O: GLNEVLNLAIQKNDETAHIIASLPHRFIPLFKQILSDRNTLSFILEEFKSDEEVIQSFCK YKTLLRNENVL 12 ETAEALFNELNSIDLTHIFISHKKLETISSALCDHWDTLRNALYERRISELTGKITKSAK EKVQRSLKH
EDINLQEIISAAGKELSEAFKQKTSEILSHAHAALDQPLPTTLKKQEEKEILKSQLD SLLGLYHLLDWF
AVDESNEVDPEFSARLTGIKLEMEPSLSFYNKARNYATKXPYSVEKFKLNFQMPTLA SGWDV^
NNGAILFVKNGLYYLGIMPKQKGRYKALSFEPTEKTSEGFDKMYYDYFPDAAKMIPK CSTQLKAVT
AHFQTHTTPILLSNNFIEPLEITKEIYDLN PEKEPKKFQTAYAKKTGDQKGYREALCKWIDFTRDFLS
KYTKTTSIDLSSLRPSSQYKDLGEYYAELNPLLYHISFQRIAEKEIMDAVETGKLYL FQIYN DFAKG
HHGKPNLHTLYWTGLFSPENLAKTSIKLNGQAELFYRPKSRMKRMAHRLGEKMLNKX LKDQKTP
DTLYQELYDYVNHRLSHDLSDEARALLPNVITKEVSHEIIKDRRFTSDKFFFHVPIT LNYQAANSPSKF
NQRVNAYLKEHPETPIIGIDRGERNLIYITVIDSTGKILEQRSLNTIQQFDYQKKLD NREKERVAARQA
WSVVGTIKDLKQGYLSQVIHEIVDLMIHYQAVVVLENLNFGFKSKRTGIAEKAVYQQ FEKMLIDKL
NCLVLKDYPAEKVGGVLNPYQLTDQFTSFAKMGTQSGFLFYVPAPYTSKIDPLTGFV DPFVWKTIKN
HESRKHFLEGFDFLHYDVKTGDFILHFKMNRNLSFQRGLPGFMPAWDIVFEKNETQF DAKGTPFIAG
KRIWVIENHRFTGRYRDLYPANELIALLEEKGI RDGSNILPKLLENDDSHAIDTMVALIRSVLQMR
NSNAATGEDYINSPVRDLNGVCFDSRFQNPEWPMDADANGAYHIALKGQLLLNHLKE SKDLKLQN
GISNQDWLAYIQELRN*
SE MAVKSIKVKLRLDDMPEIRAGLWKLHKEVNAGVRYYTEWLSLLRQENLYRRSPNGDGEQE CDKTA
Q EECKAELLERLRARQVENGHRGPAGSDDELLQLARQLYELLVPQAIGAKGDAQQIARKFL SPLADK
ID DAVGGLGIAKAGN PRWVRMREAGEPGWEEEKEKAETRKSADRTADVLRALADFGLKPLMRVYT N DSEMSSVEWKPLRKGQAWTWDRDMFQQAIERMMSWESWNQRVGQEYAKLVEQKNRFEQKN FV
O: GQEHLVHLVNQLQQDMKEASPGLESKEQTAHYVTGRALRGSDKVFEKWGKLAPDAPFDLY DAEIK 13 NVQRRNTRRFGSHDLFAKLAEPEYQALWREDASFLTRYAVYNSILRKLNHAKMFATFTLP DATAHP
IWTRFDKLGGNLHQYTFLFNEFGERRHAIRFHKLLKVENGVAREVDDVTVPISMSEQ LDNLLPRDPN
EPIALYFRDYGAEQHFTGEFGGAKIQCRRDQLAHMHRRRGARDVYLNVSVRVQSQSE ARGERRPPY
AAVFRLVGDNHRAFVHFDKLSDYLAEHPDDGKLGSEGLLSGLRVMSVDLGLRTSASI SVFRVARKD
ELKPNSKGRVPFFFPIKGNDNLVAVHERSQLLKLPGETESKDLRAIREERQRTLRQL RTQLAYLRLLV RCGSEDVGPJ ERSWAKLIEQPVDAA HMTPDWP^AFENELQKLKSLHGICSDKEWMDAVYESVRR
VWRHMGKQVRDWRKDVRSGERPKIRGYAKDVVGGNSIEQIEYLERQYKFLKSWSFFG KVSGQVIR
AEKGSRFAITLREHIDHAKEDRLKKLADRIIMEALGYVYALDERGKGKWVAKYPPCQ LILLEELSEY
QFN DRPPSENNQLMQWSHRGVFQELINQAQVHDLLVGTMYAAFSSRFDARTGAPGIRCRRVPA RC
TQEHNPEPFPWWLNKFWEHTLDACPLRADDLIPTGEGEIFVSPFSAEEGDFHQIHAD LNAAQNLQQ
RLWSDFDISQIRLRCDWGEVDGELVLIPRLTGKRTADSYSNKVFYTNTGVTYYERER GKKRRKVFA
QEKL SEEEAELL VE ADE AREKS VVLMRDP SGIINRGNWTRQKEF WSMVNQRIEGYL VKQIRSRVPLQ
DSACENTGDI*
SE MATRSFILKIEPNEEVKKGLWKTHEVLNHGIAYYMNILKLIRQEAIYEHHEQDPKNPKKV SKAEIQAE
Q LWDFVLKMQKCNSFTHEVDKDV NILRELYEELWSSVEKKGEANQLSNKFLYPLVDPNSQSGKG
no TASSGRKPRWYNLKIAGDPSWEEEKKKWEEDKKKDPLAKILGKLAEYGLIPLFIPFTDSN EPIVKEIK
N WMEKSRNQSVRRLDKDMFIQALERFLSWESWNLKVKEEYEKVEKEHKTLEERIKEDIQAF KSLEQY
O: EKERQEQLLRDTLNTNEYRLSKRGLRGWREIIQKmKMDENEPSEKYLEVFKDYQRKHPRE AGDYS 14 WEFLSKKENHFIWR HPEYPYLYATFCEIDKKKKDAKQQATFTLADPINHPLWVRFEERSGSNLNK
YRILTEQLHTEKLKKKLTVQLDRLIYPTESGGWEEKGKVDIVLLPSRQFYNQIFLDI EEKGKHAFTYK
DESIKFPLKGTLGGARVQFDRDHLRRYPHKVESGNVGRIYFNMTVNIEPTESPVSKS LKIHRDDFPKF
VNFKPKELTEWIKDSKGKKLKSGIESLEIGLRVMSIDLGQRQAAAASIFEVVDQKPD IEGKLFFPIKGT
ELYAVHRASFNIKLPGETLVKSREVLRKAREDNLKLMNQKLNFLRNVLHFQQFEDIT EREKRVTKWI
SRQENSDVPLVYQDELIQIRELMYKPYKDWVAFLKQLHKRLEVEIGKEVKHWRKSLS DGRKGLYGI
SLKNIDEIDRTRKFLLRWSLRPTEPGEVRRLEPGQRFAIDQLNHLNALKEDRLKKMA NTIIMHALGYC
YDVRKKKWQAKNPACQIILFEDLSNYNPYEERSRFENSKLMKWSRREIPRQVALQGE IYGLQVGEV
GAQFSSRFHAKTGSPGIRCSVVTKEKLQDNRFFKNLQREGRLTLDKIAVLKEGDLYP DKGGEKFISLS
KDRKLVTTHADINAAQNLQKRFWTRTHGFYKVYCKAYQVDGQTVYIPESKDQKQKII EEFGEGYFI
LKDGVYE WGNAGKLKIKKGS SKQ S S SEL VD SDILKD SFDL ASELKGEKLMLYRDP SGNVFPSDKWM
AAGVFFGKLERILISKLTNQYSISTIEDDSSKQSM*
SE MPTRTINLKLVLGKNPENATLRRALFSTHRLVNQATKRIEEFLLLCRGEAYRTVDNEGKE AEIPRHA
Q VQEEALAFAKAAQRHNGCISTYEDQEILDVLRQLYERLVPSVNEN EAGDAQAANAWVSPLMSAES
no EGGLSWDKVLDPPPVWMKLKEEKAPGWEAASQIWIQSDEGQSLLNKPGSPPRWIRKLRSG QPWQD
N DFVSDQKKKQDELTKGNAPLIKQLKEMGLLPLVNPFFRHLLDPEGKGVSPWDRLAVRAAV AHFISW
O: ESWNHRTRAEYNSLKLRRDEFEAASDEFKDDFTLLRQYEAKRHSTLKSIALADDSNPYRI GVRSLRA 15 WNRVREEWIDKGATEEQRVTILSKLQTQLRGKFGDPDLFNWLAQDRHVHLWSPRDSVTPL VRINAV
DKVLRRRKPYALMTFAHPRFHPRWILYEAPGGSNLRQYALDCTENALHITLPLLVDD AHGTWIEKKI
R LAPSGQIQDLTLEKLEKKKNRLYYRSGFQQFAGLAGGAEVLFHRPYMEHDERSEESLLER PGAV
WFKLTLDVATQAPPNWLDGKGRWTPPEVHHFKTALSNKSKHTRTLQPGLRVLSVDLG MRTFASCS ELIEGKPETGRAFPVADERSMDSPN LWAKHERSFKLTLPGETPSRKEEEERSIARAEIYALKRDIQ
RLKSLLRLGEEDNDNRRDALLEQFFKGWGEEDVVPGQAFPRSLFQGLGAAPFRSTPE LWRQHCQTY
YDKAEACLAKHISDWRKRTRPRPTSREMWYKTRSYHGGKSIWMLEYLDAVRKLLLSW SLRGRTYG
AINRQDTARFGSLASRLLHHINSLKEDRIKTGADSIVQAARGYIPLPHGKGWEQRYE PCQLILFEDLA
RYRFRVDRPRRENSQLMQWNHRAIVAETTMQAELYGQIVENTAAGFSSRFHAATGAP GVRCRFLLE
RDFDNDLPKPYLLRELSWMLGNTKVESEEEKLRLLSEKIRPGSLVPWDGGEQFATLH PKRQTLCVIH
ADMNAAQNLQRRFFGRCGEAFRLVCQPHGDDVLRLASTPGARLLGALQQLENGQGAF ELVRDMGS
TSQMNRFVMKSLGKKKIKPLQDNNGDDELEDVLSVLPEEDDTGRITVFRDSSGIFFP CNVWIPAKQF WPAVRAMIWKVMASHSLG*
SE MTKLPJmQKKLTHDWAGSKKREVLGSNGKLQNPLLMPVKKGQVTEFRKAFSAYARATKGE MTDG
Q R NMFTHSFEPFKTKPSLHQCELADKAYQSLHSYLPGSLAHFLLSAHALGFRIFSKSGEATA FQASSK
no IEAYESKLASELACVDLSIQNLTISTLFNALTTSVRGKGEETSADPLIARFYTLLTGKPL SRDTQGPERD
N LAEVISRKIASSFGTWKEMTANPLQSLQFFEEELHALDANVSLSPAFDVLIKMNDLQGDL KNRTIVFD
O: PDAP EYNAEDPADIIIKLTARYAKEAVIKNQNVGNYVKNAITTTNANGLGWLLNKGLSLLPVST D 16 DELLEFIGVERSHP SCH ALIELI AQLE APELFEKNVF SDTRSEVQGMID S AVSNHI ARLS S SRNSLSMD S
EELERLIKSFQIHTPHCSLFIGAQSLSQQLESLPEALQSGVNSADILLGSTQYMLTN SLVEESIATYQRT
LNRINYLSGVAGQINGAIKRKAIDGEKIHLPAAWSELISLPFIGQPVIDVESDLAHL KNQYQTLSNEFD
TLISALQKNFDLNFNKALLNRTQHFEAMCRSTKKNALSKPEIVSYRDLLARLTSCLY RGSLVLRRAGI
EVLKKHKIFESNSELREHVHERKHF VSPLDRKAKKLLRLTDSRPDLLHVIDEILQHDNLENKDRES
LWLVRSGYLLAGLPDQLSSSFINLPIITQKGDRRLIDLIQYDQINRDAFVMLVTSAF KSNLSGLQYRAN
KQSFVVTRTLSPYLGSKLVYVPKDKDWLVPSQMFEGRFADILQSDYMVWKDAGRLCV IDTAKHLS
NIKKSVFSSEEVLAFLRELPHRTFIQTEVRGLGVNVDGIAFNNGDIPSLKTFSNCVQ VKVSRTNTSLVQ
TLNRWFEGGKVSPPSIQFERAYYKKDDQIHEDAAKRKIRFQMPATELVHASDDAGWT PSYLLGIDPG
EYGMGLSLVSINNGEVLDSGFIHINSLINFASKKSNHQTKVVPRQQYKSPYANYLEQ SKDSAAGDIA
HILDRLIYKLNALPVFEALSGNSQSAADQVWTKVLSFYTWGDNDAQNSIRKQHWFGA SHWDIKGM
LRQPPTEKKPKPYIAFPGSQVSSYGNSQRCSCCGR PIEQLREMAKDTSIKELKIRNSEIQLFDGTIKLF
NPDPSTVIERRRHNLGPSRIPVADRTFKNISPSSLEFKELITIVSRSIRHSPEFIAK KRGIGSEYFCAYSDC
NS SLNSE AN AAANV AQKFQKQLFFEL *
SE MKRILNSLKVAALRLLFRGKGSELVKTVKYPLVSPVQGAVEELAEAIRHDNLHLFGQKEI VDLMEK
Q DEGTQVYSVVDFWLDTLRLGMFFSPSANALKITLGKFNSDQVSPFRKVLEQSPFFLAGRL KVEPAERI
no LSVEIRKIGKRENRVENYAADVETCFIGQLSSDEKQSIQKLANDIWDSKDHEEQRMLKAD FFAIPLIK
N DPKAVTEEDPENETAGKQKPLELCVCLVPELYTRGFGSIADFLVQRLTLLRDKMSTDTAE DCLEYVG
O: IEEEKGNGMNSLLGTFLKNLQGDGFEQIFQFMLGSYVGWQGKEDVLRERLDLLAEKVKRL PKPKFA 17 GEWSGHRMFLHGQLKSWSSNFFRLFNETRELLESIKSDIQHATMLISYVEEKGGYHPQLL SQYRKLM
EQLPALRTKVLDPEIEMTHMSEAVRSYIMIHKSVAGFLPDLLESLDRDKDREFLLSI FPRIPKIDKKTK
EIVAWELPGEPEEGYLFTANNLFRNFLENPKHWRFMAERIPEDWTRLRSAPVWFDGM VKQWQKV
VNQLVESPGALYQFNESFLRQRLQAMLTVYKRDLQTEKFLKLLADVCRPLVDFFGLG GNDIIFKSCQ
DPRKQWQTVIPLSWADVYTACEGLAIRLRETLGFEWKNLKGHEREDFLRLHQLLGNL LFWIRDAK
LVVKLEDWMNNPCVQEYVEARKAIDLPLEIFGFEWIFLNGYLFSELRQLELLLRRKS VMTSYSVKTT
GSPNRLFQLVYLPLNPSDPEKKNSNNFQERLDTPTGLSRRFLDLTLDAFAGKLLTDP VTQELKTMAG
FYDHLFGFKLPCKL AAMSNHPGS S SKMV VL AKPKKG VASNIGFEPIPDP AHP VFRVRS S WPELKYLE
GLLYLPEDTPLTIELAETSVSCQSVSSVAFDLKNLTTILGRVGEFRVTADQPFKLTP IIPEKEESFIGKTY
LGLDAGERSGVGFAIVTVDGDGYEVQRLGVHEDTQLMALQQVASKSLKEPVFQPLRK GTFRQQERI
RKSLRGCYWNFYHALMIKYRAKVVHEESVGSSGLVGQWLRAFQKDLKKADVLPKKGG KNGVDK
KKRESSAQDTLWGGAFSKKEEQQIAFEVQAAGSSQFCLKCGWWFQLGMREVNRVQES GVVLDWN
RSIVTFLIESSGEKWGFSPQQLEKGFRPDIETFKKMVRDFMRPPMFDRKGRPAAAYE RFVLGRRHRR
YRFDK EERFGRSALFICPRVGCGNFDHSSEQSAVVLALIGYIADKEGMSGKKLVYVRLAELMAE
WKLKKLERSR VEEQ S S AQ *
SE MAESKQMQCRKCGASMKYEVIGLGKKSCRYMCPDCGNHTSARKIQNKKKRDKKYGSASKA QSQR
Q I AV AG AL YPDKKVQTIKTYKYP ADLNGEVHD S GVAEKI AQ AIQEDEIGLLGP S SEY ACWI ASQKQSE no PYSVVDFWFDAVCAGGVFAYSGARLLSTVLQLSGEESVLRAALASSPFVDDINLAQAEKF LAVSRRT
N GQDKLGKRIGECFAEGRLEALGIKDPJVIP^FVQAIDVAQTAGQPJAAKLKIFGISQMPE AKQWN DS O: GLTVCILPDYYVPEENRADQLVVLLRRLREIAYCMGIEDEAGFEHLGIDPGALSNFSNGN PKRGFLGR 18 LLN DIIALANNMSAMTPYWEGRKGELIERLAWLKHRAEGLYLKEPHFGNSWADHRSRIFSRIA GW
LSGCAGKLKIAKDQISGVRTDLFLLKRLLDAVPQSAPSPDFIASISALDRFLEAAES SQDPAEQVRALY
AFHLNAPAWSIANKAVQRSDSQEWLIKELDAVDHLEFNKAFPFFSDTGKKKKKGANS NGAPSEEE
YTETESIQQPEDAEQEVNGQEGNGASKNQKKFQRIPRFFGEGSRSEYRILTEAPQYF DMFCN MRAIF
MQLESQPRKAPRDFKCFLQNRLQKLYKQTFLNARSNKCRALLESVLISWGEFYTYGA NEKKFRLRH
EASERSSDPDYVVQQALEIARRLFLFGFEWRDCSAGERVDLVEIHKKAISFLLAITQ AEVSVGSYNWL
GNSTVSRYLSVAGTDTLYGTQLEEFLNATVLSQMRGLAIRLSSQELKDGFDVQLESS CQDNLQHLLV
YRASRDLAACKRATCPAELDPKILVLPVGAFIASVMKMIERGDEPLAGAYLRHRPHS FGWQIRVRGV
AEVGMDQGTALAFQKPTESEPFKIKPFSAQYGPVLWLNSSSYSQSQYLDGFLSQPKN WSMRVLPQA
GSWVEQRVALIWNLQAGKMRLERSGARAFFMPVPFSFRPSGSGDEAVLAPNRYLGLF PHSGGIEYA
VVDVLDSAGFKILERGTIAWGFSQKRGERQEEAHREKQRRGISDIGRKKPVQAEVDA ANELHRKYT
DVATRLGCRIVVQWAPQPKPGTAPTAQTVYARAVRTEAPRSGNQEDHARMKSSWGYT WGTYWEK
RKPEDILGISTQVYWTGGIGESCPAVAVALLGHIRATSTQTEWEKEEVVFGRLKKFF PS*
SE MEKRINKIRKKLSADNATKPVSRSGPMKTLLWVMTDDLKKRLEKRRKKPEVMPQVISNNA AN^
Q MLLDDYTKMKEAILQWWQEFKDDHVGLMCKFAQPASKKIDQNKLKPEMDEKGNLTTAGFA CSQ
no CGQPLFVYKLEQVSEKGKAYTNYFGRCNVAEHEKLILLAQLKPEKDSDEAVTYSLGKFGQ RALDFY
N SIHVTKESTHPVKPLAQIAGNRYASGPVGKALSDACMGTIASFLSKYQDIIIEHQKVVKG NQKRLESL
O: REL AGKENLEYP S VTLPPQPHTKEGVD AYNE VI ARVRMWVNLNL WQKLKL SRDD AKPLLRLKGFP S 19 FPVVERRENEVDWWNTINEVKKLIDAKRDMGR WSGVTAEKRNTILEGYNYLPNENDHKKREG
LENPKKPAKRQFGDLLLYLEKKYAGDWGKVFDEAWERIDKKIAGLTSHIEREEARNA EDAQSKAVL
TDWLRAKASFVLERLKEMDEKEFYACEIQLQKWYGDLRGNPFAVEAENRVVDISGFS IGSDGHSIQY
RNLLAWKYLENGKREFYLLMNYGKKGRIRFTDGTDIKKSGKWQGLLYGGGKAKVIDL TFDPDDEQ
LIILPLAFGTRQGREFIWNDLLSLETGLIKLANGRVIEKTIYNKKIGRDEPALFVAL TFERREVVDPSNI
KPVNLIGVDRGENIPAVIALTDPEGCPLPEFKDSSGGPTDILRIGEGYKEKQRAIQA AKEVEQRRAGG
YSRKFASKSRNLADDMWNSARDLFYHAVTHDAVL ENLSRGFGRQGKRTFMTERQYTKMEDW
LTAKLAYEGLTSKTYLSKTLAQYTSKTCSNCGFTITTADYDGMLVRLKKTSDGWATT LN KELKAE
GQITYYNRYKRQTVEKELSAELDRLSEESGN DISKWTKGRRDEALFLLKKRFSHRPVQEQFVCLDC
GHEVHADEQAALNIARSWLFLNSNSTEFKSYKSGKQPFVGAWQAFYKRRLKEVWKPN A
SE MKRINKIRRRLVKDSNTKKAGKTGPMKTLLVR
Q LTDYTEMKKAILHVYWEEFQKDPVGLMSRVAQPAPKNIDQRKLIPVKDGNERLTSSGFAC SQCCQP
ID LYVYKLEQVNDKGKPHTNYFGRCNVSEHERLILLSPHKPEANDELVTYSLGKFGQRALDF YSIHVTR
N ESNHP VKPLEQIGGNS CAS GP VGKAL SD ACMGAVASFLTKYQDIILEHQKVIKKNEKRL ANLKDI AS
O: ANGLAFPKITLPPQPHTKEGIEAYNNVVAQIVIWVNLNLWQKLKIGRDEAKPLQRLKGFP SFPLVERQ 20 ANEVDWWDMVCNVKKLINEKKEDGK WQNLAGYKRQEALLPYLSSEEDRKKGKKFARYQFGD
LLLHLEKKHGEDWGKVYDEAWERIDKKVEGLSKHIKLEEERRSEDAQSKAALTDWLR AKASFVIEG
LKEADKDEFCRCELKLQKWYGDLRGKPFAIEAENSILDISGFSKQYNCAFIWQKDGV KKLNLYLIIN
YFKGGKLRFKKIKPEAFEANRFYTVINKXSGEIWMEVNFNFDDPNLIILPLAFGKRQ GREFIW^
LETGSLKL ANGRVIEKTLYNRRTRQDEP ALF V ALTFERRE VLD S SNIKPMNLIGIDRGENIP AVI ALTD
PEGCPLSRFKDSLGNPTHILRIGESYKEKQRTIQAAKEVEQRRAGGYSRKYASKAKN LADDMVRNT ARDLLYYAVTQDAMLIFENLSRGFGRQGKRTFMAERQYTRMEDWLTAKLAYEGLPSKTYL SKTLA QYTSKTCSNCGFTITSADYDRVLEKLKKTATGWMTTINGKELKVEGQITYYNRYKRQNVV KDLSVE LDRLSEESVNNDISSWTKGRSGEALSLLKKRFSHRPVQEKFVCLNCGFETHADEQAALNI ARSWLFL RSQEYKKYQTNKTTGNTDKRAFVETWQSFYRKKLKEVWKP
SE atgGGAAAAATGTATTATCTTGGTCTGGATATAGGAACAAATTCTGTTGGATATGCCGTA ACCGA
Q CCCATCGTACCATTTGCTCAAATTTAAAGGCGAACCGATGTGGGGTGCCCACGTGTTTGC TGCG
no GGGAATCAATCAGCTGAACGGAGAAGCTTTCGTACGAGCCGCAGACGCCTTGACCGCAGG CAA
N CAGCGTGTCAAACTGGTTCAAGAAATCTTTGCTCCCGTGATTAGTCCCATTGATCCACGT TTTTT
O: TATCAGACTTCATGAGAGCGCTTTATGGCGGGATGATGTGGCTGAAACGGATAAACATAT TTTC 21 TTTAATGACCCGACCTATACGGATAAGGAATATTATTCTGACTATCCAACCATCCATCAT CTCAT
TGTGGACCTTATGGAAAGCAGTGAAAAGCATGACCCGCGGCTTGTTTATTTGGCTGT TGCCTGG
CTGGTTGCTCATCGTGGTCATTTCCTCAATGAAGTGGATAAGGATAATATTGGGGAT GTCCTGAG
TTTTGACGCCTTTTATCCTGAGTTTCTGGCATTTCTTTCCGATAATGGGGTGTCACC TTGGGTATG
TGAGTCAAAAGCACTCCAAGCGACCCTGCTTTCACGAAACTCCGTCAACGATAAGTA TAAAGCC
TTGAAGTCTCTGATCTTTGGCAGCCAAAAGCCGGAGGATAATTTTGATGCCAATATC AGTGAAG
ATGGACTTATCCAACTTTTAGCAGGAAAAAAGGTCAAGGTCAATAAACTTTTTCCTC AAGAAAG
TAATGATGCTTCCTTTACACTCAATGATAAGGAAGATGCAATTGAGGAAATCTTAGG AACGCTT
ACACCGGATGAGTGTGAATGGATTGCGCATATTAGGAGGCTGTTTGATTGGGCCATC ATGAAAC
ATGCTCTCAAAGATGGCAGAACAATCTCCGAATCGAAAGTAAAGCTCTATGAACAGC ATCACCA
TGACTTGACACAGCTCAAGTATTTTGTGAAGACCTATCTAGCAAAGGAATATGATGA CATTTTTC
GAAACGTAGATAGTGAAACAACCAAAAACTATGTCGCATATTCCTATCATGTAAAAG AAGTCAA
GGGTACATTGCCCAAAAATAAGGCAACCCAAGAAGAATTTTGCAAGTATGTCCTTGG AAAGGTA
AAGAACATCGAATGCAGTGAAGCTGATAAGGTTGATTTTGATGAAATGATTCAGCGT CTTACAG
ACAATTCCTTTATGCCGAAACAAGTATCAGGTGAAAACAGGGTTATCCCTTACCAGC TTTACTAT
TATGAACTAAAGACTATTTTGAATAAAGCCGCTTCTTATCTGCCTTTTTTGACCCAA TGCGGAAA
AGATGCCATCTCCAATCAAGATAAGCTCCTTTCCATCATGACCTTTCGGATTCCGTA TTTCGTTG
GGCCCTTGCGCAAGGACAATTCAGAGCATGCCTGGCTGGAACGAAAAGCAGGGAAAA TCTATC
CGTGGAATTTTAACGACAAAGTTGACCTTGATAAAAGTGAAGAAGCGTTCATTCGGA GAATGAC
GAATACCTGCACTTATTATCCCGGTGAAGATGTTTTGCCACTTGACTCCCTTATTTA TGAAAAAT
TCATGATCCTCAATGAAATCAATAATATCCGAATTGATGGTTATCCTATTTCTGTAG ATGTAAAA
TGCTTTCCTTGGGTGCCTTGGATAAGCATGGTAAATTGACGGGAATCGATACTACCA TCCATAGC
AATTACAATACATACCATCATTTTAAATCGCTCATGGAGCGTGGCGTTCTTACTCGT GATGATGT
GGAACGCATTGTGGAGCGTATGACCTATAGTGATGATACAAAACGCGTCCGTCTTTG GCTGAAC
AATAATTATGGAACGCTCACTGCTGACGACGTAAAGCATATTTCAAGGCTCCGAAAG CATGATT
TTGGCCGGCTTTCCAAAATGTTCCTCACAGGCCTAAAGGGAGTTCATAAGGAAACGG GGGAACG
AGCTTCCATTTTGGATTTTATGTGGAATACCAATGATAACTTGATGCAGCTTTTATC TGAATGTT
ATACTTTTTCGGATGAAATTACCAAGCTGCAGGAAGCATACTATGCCAAGGCGCAGC TTTCCCT
GAATGATTTTCTGGACTCCATGTATATTTCAAATGCTGTCAAACGTCCTATCTATCG AACTCTTG
CCGTTGTAAATGACATACGCAAAGCCTGTGGGACGGCGCCAAAACGCATTTTTATCG AAATGGC
AAGAGATGGGGAAAGCAAAAAGAAAAGGAGCGTAACAAGAAGAGAACAAATCAAGAA TCTTT
ATAGGTCCATCCGCAAGGATTTTCAGCAGGAGGTAGATTTCCTTGAAAAAATCCTTG AAAACAA AAGCGATGGACAGCTGCAAAGCGATGCGCTCTATCTATACTTTGCGCAGCTTGGAAGGGA TATG
TATACCGGGGACCCTATCAAGTTGGAGCATATCAAGGACCAGTCCTTCTATAATATT GATCATAT
CTATCCCCAAAGCATGGTCAAGGACGATAGTCTTGATAACAAGGTGTTGGTTCAATC GGAAATT
AATGGAGAGAAGAGCAGTCGATATCCTCTTGATGCTGCTATCCGTAATAAAATGAAG CCTCTTT
GGGATGCTTATTATAACCATGGCCTGATTTCCCTCAAGAAGTATCAGCGTTTGACGC GGAGCAC
TCCCTTTACAGATGATGAAAAGTGGGATTTCATCAATCGGCAGCTTGTTGAGACAAG ACAATCC
ACGAAGGCCTTGGCAATCTTACTAAAAAGGAAGTTCCCTGATACGGAGATTGTCTAC TCCAAGG
CAGGGCTTTCTTCTGATTTTCGGCATGAGTTTGGTCTCGTAAAATCGAGGAATATCA ATGACCTG
CACCATGCAAAGGACGCATTTCTTGCGATTGTAACAGGAAATGTCTATCATGAACGC TTTAATC
GCCGGTGGTTTATGGTGAACCAGCCCTATTCCGTCAAGACCAAGACGTTGTTTACGC ATTCTATT
AAAAATGGTAATTTTGTAGCTTGGAATGGAGAAGAGGATCTTGGCCGCATTGTTAAA ATGTTAA
AGCAAAATAAGAACACTATTCATTTCACGCGGTTCTCTTTTGATCGAAAGGAAGGCC TGTTTGAT
ATTCAGCCACTAAAAGCGTCAACCGGTCTTGTACCAAGAAAAGCCGGACTAGACGTG GTAAAAT
ATGGTGGCTATGACAAATCGACAGCAGCTTATTATCTCCTTGTTCGATTTACACTAG AAGATAAA
AAGACTCAACATAAATTGATGATGATTCCTGTAGAAGGCTTGTATAAAGCTCGAATT GACCATG
ATAAGGAATTCTTAACGGACTATGCACAAACTACAATCAGTGAAATCCTACAAAAAG ATAAAC
AAAAGGTGATAAATATAATGTTTCCAATGGGAACAAGGCACATTAAACTGAATTCCA TGATTTC
AATCGATGGTTTTTATCTTTCCATTGGAGGAAAGTCTAGTAAGGGAAAATCGGTGTT GTGTCATG
CTATGGTACCTCTTATTGTACCTCATAAGATAGAATGTTATATTAAGGCGATGGAGT CTTTTGCA
CGTAAATTTAAAGAAAATAATAAATTAAGGATTGTGGAAAAGTTTGATAAGATTACG GTGGAA
GATAACTTGAACCTATACGAACTATTTTTACAAAAACTTCAACATAACCCATATAAT AAGTTCTT
CTCCACACAATTTGATGTGCTGACTAATGGAAGAAGTACATTTACTAAATTATCTCC AGAGGAA
CAAGTTCAAACGTTATTGAATATCTTATCAATTTTTAAAACTTGTCGGAGCTCTGGC TGCGATTT
AAAATCCATTAACGGTTCTGCTCAAGCTGCCAGAATTATGATCAGCGCAGATTTAAC TGGACTC
TCAAAAAAATATTCCGATATTCGGCTTGTTGAGCAATCAGCATCTGGACTTTTTGTT AGTAAATC
ACAAAATCTTTTGGAGTATTTAtga
SE atgtcttcattaacaaaatttacaaataaatacagtaagcagctaaccataaaaaatgaa ctcatcccagtaggaaagactctcgagaacattaaggaaaacggtc
Q tcatagatggagatgaacagctaaacgagaattatcaaaaagcaaagataatcgttgatg attttctacgagatttcataaataaagctttaaataatacccaaatag no gaaattggagagaattagcagatgctttaaataaagaagatgaagataacatagaaaagc tccaagacaaaatcagaggaataattgtaagtaaattcgagaca
N tttgatttgttttcttcttactcgataaagaaagacgaaaagataatagatgatgataat g^
O: aatatatttttaagaaaaacctttttaaattagtacttccttcttatttaaagacaacaa atcaggataaactgaaaataatctcttcttttga
22 aggattctttgagaacagaaaaaatattttcactaagaagcctatatctacgtcaattgc ctacagaattgtccatgataactttccaaagtttctagataacat^ gttttaatgtgtggcaaacagaatgcccacagttaattgtaaaggctgataattatt^
gtaggagcatatgattacttcttatcccagaatggcattgatttctacaacaacattatc ggcggtctaccagcatttgctggtcatgagaaaatccaaggacttaat gaatttataaatcaagaatgccaaaaggacagcgaactaaaatctaaactgaaaaacaga catgctttcaaaatggctgttctatttaagcaaattctttcagatag agaaaaaagttttgttatagacgagttcgaatctgatgctcaggtcatagatgcggttaa gaacttctatgcagaacaatgtaaggataataatgttatttttaac taaatcttatcaagaatatagcgttcttatctgatgatgaattagatggaattttMagaa ggcaagtatttaagctctgtttcccaaaagctatatt^ agcttcgaaatgatattgaagatagtgcaaacagtaaacaaggaaataaagagttagcaa agaaaattaaaacaaataaaggcgatgttgaaaaggccataagt aaatatgagttttcttMcagaacttaactcaattgtacatgataatacaaaattcagtga ccttctttcttgtacgttacataaagtggctagcgaaaaacte gttaatgaaggggactggccaaaacacctgaaaaataatgaagaaaaacaaaagataaaa gagcctttagatgcattgttagaaatttataatacattgctgatat tcaactgcaagtcatttaataagaacggtaatttcMgttgattatgacagatgcataaa ¾^
aaagaaaccttataacacagacaaattcaaattaaactttaacagtcctcaattaggaga gggctttagtaagtcgaaagaaaatgactgtctgacattattatte aaaagacgacaattactatgttggaattatcagaaaaggggcaaaaattaactttgatga tacacaagccattgcagacaatacagataactgtatatttaagatga attatttcctattaaaagatgctaaaaagtttattcctaaatgttcaatt^
aaagaaaaatttgcctctccccttgttattaagaaatcaacatttttattagcaacagca catgtaaaaggaaagaaaggaaacataaaaaaattccaaaaggaat attctaaggaaaatccaacagaatatagaaattctctgaatgaatggattgcattttgta aagaatttctaaaaacatataaggcggcaacaatctttgacattacaa cgttaaaaaaagctgaagaatatgctgatattgttgagttttataaggatgtag
attgataatggggacttatatttattcagaatcaataataaagatttcagttcaaaatct actggtacaaagaatcttcatacgctcMcttcaggcaatctttga agaaacctcaataatcctactattatgttaaatggcggagcagagttattttatcgaaaa gaaagcattgaacagaaaaataggataactcataaggcaggatcaa ttcttgtaaacaaggtttgtaaggatggaacaagtctagatgacaaaatcagaaacgaaa taMcaaM^
aaaaagttttacctaatgtaataaaaaaagaagcaactcacgacataacaaaagataagc gatttacat^^
taaggaaggagatacaaaacaatttaacaatgaggttttatctttccttagaggtaatcc agacattaatatcatcggaattgacagaggagaaagaaaccttatat acgtaactgttattaatcagaaaggcgaaatacttgacagcgtttcgtttaacacagtaa caaacaagtcgagcaaaattgaacaaactgttgattatgaggaaaa gcttgctgttagggaaaaagaaagaatagaagcaaaaagatcctgggattcaatatcaaa gatagcaaccttaaaagaaggttatctatcagctattgttcatgag atatgcctactgatgatcaaacacaacgcaatcgttgtacttgagaatctaaatgcagga tttaagagaattagaggaggattatcagaaaagtctgtttatcagaa attcgagaagatgctMtaacaaactaaattactttgtatctaaaaaagaatcagactgga ataaacctagtggacttttaaatggtttacaactttcagaccagttc gagtcatttgagaaattaggaattcaatctgggttcatcttcMgttcctgcagcata^
aaggtaagaaatgttgatgcaataaagagttttttcagtaatttcaatgaaat^^
gaagggcttcagctcatttgtaaaattcagtaaatctaaatggaatgtatatacatttgg agagagaataataaaaccaaagaataagcaagggtatcgtgaagat aagagaattaatttaacatttgaaatgaaaaaacttctgaatgaatataaagtaagtttt g
taccttctggaaagaactattctttatttttaaaacaactctgcagctta^
aggagagttctttgtatcaggaactcataacaagacattacctcaagactgtgatgcaaa tggagcatatcatatcgccctaaaaggtctgatgattcttgaacgta acaatcttgttagagaagaaaaagacacaaagaagataatggcaatttctaatgttgact ggtttgagtatgttcaaaaaaggagaggtgtcctgtaa
SE ATGAACAACTATGATGAGTTTACCAAACTGTACCCAATACAGAAAACGATAAGGTTCGAA TTGA
Q AGCCGCAGGGAAGAACGATGGAACACCTCGAAACATTCAACTTTTTCGAAGAGGACAGGG ATA
no GAGCGGAGAAATATAAGATTTTAAAGGAAGCAATCGACGAGTATCATAAGAAGTTTATAG ACG
N AACATCTAACAAATATGTCTCTTGACTGGAATTCTTTAAAACAGATTTCAGAGAAATACT ATAA
O: GAGTAGAGAGGAAAAAGACAAGAAAGTTTTTCTGTCAGAACAGAAACGCATGAGGCAAGA GAT
23 AGTTTCTGAGTTCAAAAAAGACGATCGGTTTAAAGATCTTTTTTCAAAAAAATTGTTTTC TGAAC
TTCTCAAGGAAGAGATTTACAAAAAAGGAAACCATCAGGAAATTGACGCATTGAAAA GTTTTG
ATAAATTCTCAGGCTATTTTATTGGGTTGCATGAGAACCGAAAAAATATGTATTCTG ACGGAGA
CGAGATCACGGCTATCTCTAACCGTATTGTAAATGAGAATTTCCCGAAGTTCCTCGA CAACCTTC
AGAAATATCAGGAAGCTCGTAAAAAATATCCAGAGTGGATCATTAAGGCAGAATCTG CTTTAGT
TGCACATAATATCAAGATGGATGAAGTCTTTTCCTTAGAGTATTTCAACAAAGTCCT GAATCAA
GAAGGAATACAGAGATACAATCTCGCCCTAGGTGGCTATGTGACCAAAAGTGGTGAG AAAATG
ATGGGGCTTAATGATGCACTTAATCTTGCCCATCAAAGTGAAAAAAGCAGCAAGGGA AGGATA
CACATGACTCCACTCTTCAAACAGATTCTGAGTGAAAAAGAGTCCTTTTCTTATATA CCAGATGT
TTTTACAGAAGACTCTCAACTTTTACCATCCATTGGTGGGTTCTTTGCACAAATAGA AAATGATA
AGGACGGGAATATTTTTGACAGAGCATTAGAATTGATATCTTCTTATGCAGAATACG ATACAGA
AAGGATATATATCAGGCAAGCGGACATAAACAGAGTTTCTAATGTTATTTTCGGGGA GTGGGGA
ACACTGGGGGGGTTAATGAGGGAATACAAAGCAGACTCTATCAACGACATCAATTTG GAGAGA
ACATGCAAGAAGGTAGACAAGTGGCTCGACTCAAAGGAGTTTGCGTTATCAGATGTA TTAGAGG
CAATAAAAAGAACCGGCAATAATGATGCTTTTAATGAATATATCTCAAAGATGCGCA CTGCCAG
GGAAAAGATTGACGCTGCAAGAAAGGAAATGAAATTCATTTCGGAAAAAATATCTGG AGACGA AGAATCGATCCATATTATCAAAACCTTATTGGACTCGGTGCAACAGTTTTTACATTTTTT CAATT
TATTCAAAGCGCGTCAGGACATTCCTCTTGATGGAGCATTCTATGCGGAGTTCGATG AAGTCCAT
AGCAAACTGTTTGCTATTGTTCCGTTGTATAATAAGGTTAGGAACTATCTTACGAAA AATAACCT
TAACACGAAAAAGATAAAGCTAAACTTCAAGAATCCAACTCTGGCAAACGGATGGGA TCAAAA
CAAGGTATATGACTACGCCTCCTTAATCTTTCTCCGCGATGGTAATTATTATCTCGG AATAATAA
ATCCAAAAAGGAAAAAGAATATTAAATTCGAACAAGGGTCTGGAAATGGCCCATTCT ACCGGA
AGATGGTGTACAAACAAATTCCAGGGCCGAACAAGAACTTACCAAGAGTCTTCCTCA CATCTAC
GAAAGGCAAAAAAGAGTACAAGCCGTCAAAGGAGATAATAGAAGGATATGAAGCGGA CAAAC
ACATAAGAGGAGATAAATTCGATCTGGATTTCTGTCATAAGCTGATAGACTTCTTCA AGGAATC
CATCGAGAAGCACAAGGACTGGAGTAAGTTCAACTTCTATTTCTCTCCAACTGAATC ATATGGA
GACATCAGCGAATTCTATCTGGATGTAGAAAAACAGGGATACCGGATGCATTTTGAG AATATTT
CTGCCGAGACGATTGATGAGTATGTCGAAAAGGGGGACTTATTCCTCTTCCAGATAT ACAACAA
AGACTTTGTGAAAGCGGCAACCGGAAAAAAAGATATGCACACCATTTATTGGAACGC GGCATTC
TCGCCCGAGAACCTTCAGGATGTGGTAGTGAAACTGAACGGTGAAGCAGAACTTTTC TACAGAG
ACAAGAGCGACATCAAGGAGATAGTTCACAGGGAGGGAGAGATACTGGTCAATCGTA CCTACA
ACGGCAGGACACCTGTGCCTGACAAGATCCACAAAAAATTAACAGATTATCATAATG GCCGTAC
CAAAGATCTCGGAGAAGCAAAAGAATACCTCGATAAGGTCAGATATTTCAAAGCGCA CTACGA
CATCACAAAGGATCGCAGATACCTGAATGATAAAATATACTTCCATGTGCCTCTGAC ATTGAAT
TTCAAAGCAAACGGGAAGAAGAATCTCAATAAGATGGTAATTGAAAAGTTCCTCTCG GACGAA
AAAGCGCATATTATTGGGATTGATCGCGGGGAAAGGAATCTTCTTTACTATTCTATC ATTGACAG
GTCAGGTAAAATAATCGATCAACAGAGCCTCAACGTCATCGATGGATTCGATTACCG AGAGAAA
CTGAATCAGAGGGAGATCGAGATGAAGGATGCCAGACAAAGCTGGAATGCTATCGGG AAGATA
AAGGACCTCAAGGAAGGGTATCTTTCAAAAGCGGTCCACGAAATTACCAAGATGGCG ATACAA
TACAATGCCATTGTTGTCATGGAGGAACTCAATTATGGGTTCAAACGCGGACGTTTC AAAGTTG
AGAAGCAGATATATCAGAAATTCGAGAATATGCTGATTGACAAGATGAATTATCTGG TATTCAA
GGATGCTCCGGATGAAAGTCCGGGAGGAGTCCTCAATGCATATCAGCTTACTAATCC GCTTGAA
AGTTTCGCTAAACTTGGGAAACAGACAGGAATTCTTTTCTATGTTCCGGCAGCCTAT ACTTCGAA
GATAGATCCGACGACCGGGTTTGTCAATCTTTTCAATACTTCAAGTAAAACGAACGC ACAGGAA
AGAAAAGAATTCTTGCAAAAATTCGAGTCGATCTCCTATTCCGCTAAAGACGGAGGA ATATTCG
CATTCGCGTTCGATTATCGGAAGTTCGGAACGTCAAAAACAGACCACAAAAATGTAT GGACCGC
ATACACGAACGGGGAAAGGATGAGGTACATAAAAGAGAAAAAACGCAACGAACTGTT CGACCC
CTCGAAGGAGATCAAAGAGGCTCTCACTTCATCAGGAATCAAATATGACGGCGGACA GAACAT
ATTGCCAGATATCCTGAGGAGCAACAATAACGGTCTGATCTACACAATGTATTCCTC TTTCATAG
CGGCCATTCAAATGAGGGTCTATGACGGGAAAGAAGACTATATCATCTCGCCGATAA AGAACA
GCAAGGGAGAGTTCTTCAGGACCGATCCGAAAAGAAGGGAACTTCCGATAGACGCGG ATGCGA
ACGGCGCGTATAACATTGCTCTCAGGGGCGAATTGACGATGCGTGCGATAGCGGAGA AGTTCGA
TCCGGACTCGGAAAAGATGGCGAAGCTAGAACTGAAACATAAGGACTGGTTCGAATT CATGCA
GACAAGGGGGGATTGA
SE ATGACAAAAACATTTGATTCAGAATTTTTTAATTTATATTCTCTTCAAAAAACAGTTCGT TTTGA
Q ACTCAAGCCGGTTGGTGAAACAGCCTCGTTTGTTGAAGATTTTAAAAACGAAGGTTTGAA ACGA
no GTTGTTTCAGAGGATGAACGGCGTGCGGTTGATTACCAAAAAGTGAAAGAAATTATTGAT GACT
N ACCACCGAGATTTTATTGAAGAATCGCTGAACTATTTTCCTGAGCAGGTCTCAAAAGACG CTTTG GAACAAGCTTTTCACCTTTATCAAAAACTAAAAGCCGCTAAGGTTGAAGAGCGTGAAAAA GCAT
TGAAAGAATGGGAAGCCCTTCAGAAAAAACTGCGCGAAAAAGTTGTTAAATGTTTTT CAGATTC
AAACAAAGCACGCTTTTCCCGCATTGATAAAAAAGAACTGATTAAAGAAGATTTAAT TAACTGG
TTGGTTGCACAAAATCGCGAAGATGACATTCCAACCGTTGAAACCTTTAACAACTTT ACGACTT
ATTTTACGGGGTTTCATGAAAACCGAAAAAACATTTATTCAAAAGACGATCATGCCA CAGCCAT
TTCATTTCGACTCATTCATGAAAACCTGCCTAAGTTTTTTGATAATGTGATCAGCTT TAATAAATT
GAAGGAAGGATTTCCAGAGCTGAAATTTGATAAGGTTAAGGAAGATTTAGAAGTTGA TTATGAC
TTGAAACATGCCTTTGAAATCGAATACTTTGTCAATTTTGTTACCCAAGCCGGAATT GACCAATA
TAACTATCTTTTGGGGGGTAAAACCTTAGAAGACGGCACCAAAAAGCAAGGCATGAA TGAACA
AATCAATCTGTTCAAGCAACAGCAAACCCGAGACAAAGCCCGACAAATTCCCAAACT CATACCA
TTGTTTAAACAAATTCTAAGCGAACGAACGGAAAGCCAATCGTTTATTCCAAAACAA TTTGAAT
CAGACCAAGAGCTATTTGACTCACTGCAAAAACTGCATAACAACTGCCAAGATAAAT TTACCGT
ACTGCAACAAGCCATTTTAGGCTTAGCCGAAGCAGATCTGAAAAAAGTATTCATTAA AACATCT
GATCTTAATGCGCTATCAAATACCATTTTTGGAAATTACAGTGTGTTTTCGGATGCG TTGAATTT
ATACAAAGAATCGCTCAAAACAAAAAAGGCGCAAGAAGCGTTTGAAAAACTACCCGC TCACAG
CATTCATGACTTGATTCAATATTTGGAGCAATTTAATAGCTCTTTGGATGCAGAAAA ACAGCAAT
CAACTGACACCGTACTGAATTACTTTATTAAAACAGACGAGCTGTATTCTCGGTTCA TAAAATCA
ACGAGCGAAGCCTTCACACAAGTACAACCACTCTTTGAATTGGAAGCATTAAGCTCA AAACGTC
GTCCACCGGAAAGTGAAGACGAAGGCGCAAAAGGTCAGGAAGGGTTTGAGCAAATTA AACGCA
TAAAAGCCTATTTGGATACCTTGATGGAGGCGGTGCATTTTGCAAAACCACTTTATC TGGTGAA
GGGGCGCAAAATGATTGAAGGTCTGGACAAAGACCAAAGTTTCTATGAAGCCTTTGA AATGGCT
TACCAAGAACTAGAAAGTCTGATTATTCCAATCTACAACAAAGCTCGTAGTTATTTA AGTCGTA
AACCGTTTAAAGCGGACAAATTCAAAATTAATTTTGATAATAATACATTGCTTTCCG GTTGGGAT
GCTAATAAAGAAACGGCTAACGCTTCAATTTTGTTTAAGAAGGATGGTTTGTATTAT TTAGGAAT
CATGCCTAAAGGAAAAACGTTTTTGTTCGATTACTTCGTTTCATCGGAAGATTCTGA AAAGTTAA
AACAAAGAAGACAAAAAACCGCCGAAGAAGCGCTTGCGCAAGATGGCGAAAGCTACT TTGAAA
AAATTCGTTACAAGCTGTTACCTGGCGCCAGCAAAATGTTGCCGAAAGTATTTTTTT CCAACAAA
AACATAGGGTTTTACAACCCAAGTGATGACATACTTCGTATCAGGAATACAGCCTCT CACACTA
AAAACGGAACACCGCAAAAAGGGCACTCTAAAGTAGAGTTTAATTTGAATGATTGTC ATAAGAT
GATTGATTTCTTTAAATCAAGCATTCAAAAGCATCCAGAGTGGGGAAGTTTTGGATT CACCTTTT
CAGATACATCAGATTTTGAAGATATGAGCGCCTTTTATCGAGAAGTCGAAAACCAAG GTTATGT
CATTAGTTTCGATAAAATAAAAGAAACTTACATTCAGAGTCAAGTTGAACAGGGGAA CCTATAT
TTATTCCAAATCTACAATAAAGACTTCTCGCCCTACAGCAAAGGCAAACCAAATTTA CACACGC
TTTACTGGAAAGCGTTGTTTGAGGAAGCCAACCTAAATAATGTGGTGGCAAAACTCA ATGGTGA
AGCTGAAATTTTCTTTAGGCGACACTCAATCAAAGCATCTGATAAAGTGGTGCACCC AGCGAAT
CAAGCCATTGACAATAAAAACCCGCATACCGAAAAAACGCAAAGCACCTTTGAATAT GATCTTG
TAAAAGACAAGCGCTATACCCAAGACAAATTCTTCTTCCATGTACCGATTTCATTGA ACTTTAAG
GCACAAGGTGTTTCAAAATTTAACGATAAAGTGAATGGATTTTTAAAGGGTAACCCA GATGTCA
ATATTATTGGCATTGACCGAGGCGAACGACACCTTCTGTATTTCACTGTGGTGAATC AGAAAGG
TGAAATTTTGGTTCAAGAGTCGCTTAATACCCTAATGAGTGATAAAGGGCATGTGAA TGACTAC
CAGCAAAAACTCGACAAAAAAGAACAAGAACGCGATGCCGCTCGCAAAAGCTGGACG ACGGTT
GAAAATATCAAAGAATTAAAAGAAGGCTATTTATCTCATGTTGTTCATAAGTTGGCA CACCTGA TTATTAAATACAATGCCATTGTTTGCTTGGAAGACCTGAATTTTGGTTTCAAACGCGGGC GTTTT
AAAGTGGAAAAACAAGTTTATCAGAAATTTGAAAAAGCGCTTATTGATAAGCTTAAC TACTTGG
TATTTAAAGAAAAAGAGTTAGGCGAGGTGGGCCATTATCTAACCGCCTATCAGTTGA CCGCACC
GTTTGAAAGTTTCAAGAAGTTAGGCAAGCAAAGTGGCATATTGTTTTATGTTCCGGC GGATTAC
ACCTCCAAAATTGACCCAACCACCGGGTTTGTCAACTTTCTTGATCTGCGTTATCAG AGTGTCGA
AAAAGCCAAACAGCTCTTAAGCGACTTTAATGCCATTCGTTTTAATTCAGTACAAAA CTATTTTG
AGTTCGAAATAGATTACAAAAAACTCACACCCAAACGTAAAGTTGGTACTCAGAGTA AATGGGT
GATTTGTACCTATGGAGATGTCCGCTATCAAAATCGGCGTAATCAAAAAGGTCACTG GGAAACG
GAAGAAGTCAATGTGACTGAAAAACTAAAAGCCCTTTTCGCCAGTGATTCCAAAACT ACAACCG
TAATCGATTACGCCAATGACGACAACCTAATTGACGTCATTCTGGAACAGGACAAAG CCAGCTT
CTTCAAAGAACTGTTATGGTTATTAAAACTCACCATGACGCTCCGCCACAGCAAAAT CAAAAGT
GAAGACGACTTTATTCTTTCACCCGTTAAAAACGAACAAGGCGAGTTTTACGATAGT CGAAAAG
CGGGCGAGGTGTGGCCTAAAGATGCAGACGCCAATGGCGCTTATCACATAGCGTTGA AAGGCTT
GTGGAATCTGCAACAGATCAATCAGTGGGAAAAGGGTAAAACACTTAATCTGGCGAT TAAAAA
CCAGGATTGGTTCAGTTTTATTCAAGAAAAGCCCTATCAAGAATAA
SE ATGCACACAGGCGGATTACTTAGCATGGATGCCAAGGAGTTTACCGGACAGTACCCCCTT TCGA
Q AGACTCTGCGTTTTGAACTGAGACCGATAGGCAGAACGTGGGACAATCTCGAAGCATCGG GGTA
no TCTTGCGGAGGACAGACACCGTGCAGAATGCTATCCCAGGGCAAAAGAGCTCTTGGACGA CAA
N CCATCGTGCATTCCTCAACCGTGTCCTGCCTCAGATCGATATGGATTGGCACCCGATCGC AGAG
O: GCATTCTGCAAAGTCCACAAGAATCCGGGAAACAAGGAATTGGCTCAGGATTACAATCTT CAGC 25 TGTCCAAACGCAGAAAGGAGATTTCGGCCTATCTGCAGGATGCGGACGGCTATAAAGGTC TGTT
TGCCAAACCTGCATTGGATGAAGCAATGAAGATCGCGAAAGAAAACGGAAATGAATC GGACAT
AGAGGTTCTTGAGGCATTCAACGGTTTCTCCGTATACTTCACCGGATATCATGAGAG CAGGGAG
AACATCTATTCGGACGAGGATATGGTGTCGGTAGCTTATCGCATCACCGAAGACAAT TTCCCGA
GATTCGTTTCCAATGCGCTTATATTCGATAAGCTGAATGAGTCGCACCCCGATATAA TCTCGGAA
GTATCCGGAAATCTGGGCGTAGACGACATCGGAAAATATTTTGATGTGTCTAACTAC AATAATT
TCCTGTCGCAGGCCGGTATAGATGACTACAATCACATCATCGGCGGCCATACGACGG AGGACGG
TCTGATCCAGGCATTCAATGTTGTTCTGAATCTCAGGCATCAGAAAGACCCCGGATT CGAAAAA
ATCCAATTCAAACAGCTGTACAAACAGATACTCAGCGTCCGTACATCCAAATCCTAT ATCCCGA
AACAGTTCGATAATTCGAAGGAGATGGTGGACTGCATCTGCGACTATGTGTCCAAGA TCGAAAA
ATCCGAAACGGTCGAGAGAGCATTGAAGCTGGTAAGGAACATATCTTCTTTTGATTT GCGCGGA
ATATTCGTAAACAAGAAGAATCTCCGCATTCTTTCCAACAAACTGATTGGTGATTGG GACGCGA
TCGAAACCGCGCTGATGCACTCCTCCTCTTCGGAAAATGATAAGAAATCCGTCTACG ACAGCGC
CGAGGCATTTACGCTGGATGATATCTTTTCGTCCGTTAAAAAATTCTCAGATGCATC TGCAGAGG
ATATCGGAAACCGGGCGGAGGACATATGCAGAGTCATATCTGAGACCGCTCCGTTCA TAAACGA
TCTGAGGGCTGTCGATTTGGACAGTTTGAATGACGACGGTTACGAGGCGGCGGTTTC CAAGATA
AGGGAATCTCTGGAACCATATATGGATCTGTTTCATGAACTGGAGATATTCTCCGTA GGCGATG
AATTCCCGAAATGTGCAGCTTTCTACAGTGAACTTGAAGAAGTCTCCGAACAGCTAA TCGAGAT
TATACCGTTATTCAACAAGGCCCGTTCGTTCTGTACGCGCAAGAGATACAGTACGGA CAAGATA
AAGGTCAATTTGAAATTCCCGACACTCGCCGACGGATGGGATCTCAACAAAGAACGC GACAAC
AAAGCCGCAATACTCAGGAAAGACGGAAAGTACTACCTGGCCATACTGGATATGAAG AAAGAT
CTTTCTTCGATCAGAACTTCGGATGAAGACGAATCCAGTTTTGAGAAAATGGAGTAC AAGCTTC TTCCGAGTCCGGTAAAGATGCTGCCAAAGATCTTCGTAAAATCGAAGGCGGCCAAGGAGA AGT
ACGGTCTGACCGACCGTATGCTGGAGTGCTACGATAAAGGGATGCACAAGAGCGGCA GTGCAT
TCGATCTCGGATTTTGTCACGAATTGATCGATTACTACAAGAGGTGCATCGCAGAAT ATCCCGG
CTGGGACGTCTTCGATTTCAAGTTCAGGGAAACATCGGATTATGGCAGCATGAAGGA GTTCAAT
GAGGATGTTGCAGGGGCCGGATACTATATGTCCCTCAGAAAGATCCCTTGTTCGGAG GTCTACA
GGCTTCTTGATGAGAAATCGATATATCTTTTCCAGATCTACAACAAAGATTATTCGG AAAACGCT
CATGGGAATAAGAACATGCATACCATGTATTGGGAAGGGCTCTTTTCCCCCCAGAAT CTGGAAT
CCCCTGTGTTTAAACTCAGCGGCGGTGCGGAGCTTTTCTTCCGTAAATCCTCCATAC CCAATGAC
GCCAAAACGGTCCATCCGAAGGGAAGCGTCCTGGTTCCGCGCAATGATGTAAACGGC CGCAGG
ATACCTGACAGCATATATCGGGAGCTCACCAGATATTTCAACCGCGGAGATTGCCGC ATAAGCG
ACGAGGCAAAGAGTTATCTGGACAAGGTGAAAACCAAGAAAGCTGACCACGATATCG TGAAAG
ACAGGAGGTTCACGGTGGACAAGATGATGTTCCACGTCCCTATCGCCATGAATTTCA AAGCGAT
TTCGAAGCCGAATCTCAATAAAAAGGTGATTGACGGCATAATCGACGACCAAGATCT GAAGATC
ATCGGCATAGACCGCGGAGAGCGCAACCTCATCTACGTAACCATGGTGGATCGCAAA GGGAAC
ATCCTCTATCAGGATAGCCTCAATATTCTGAACGGATACGATTACCGTAAGGCCCTC GACGTCC
GCGAATATGACAATAAAGAGGCTCGGAGGAACTGGACGAAGGTCGAAGGCATCCGTA AGATGA
AAGAGGGGTATCTGTCGCTTGCAGTCAGCAAATTGGCAGATATGATCATAGAGAACA ATGCGAT
TATCGTCATGGAGGATCTCAATCACGGATTCAAGGCAGGGCGTTCGAAGATAGAGAA ACAGGT
CTATCAGAAGTTCGAATCCATGCTCATAAACAAACTCGGTTACATGGTCCTCAAGGA TAAGTCT
ATCGATCAGAGCGGCGGAGCTCTCCACGGATACCAGCTTGCCAACCATGTGACAACA TTGGCAT
CTGTAGGTAAACAATGTGGAGTGATATTCTACATCCCTGCTGCATTTACATCCAAGA TAGATCCG
ACAACAGGATTTGCAGATCTGTTCGCCCTCAGCAATGTTAAAAACGTGGCATCTATG AGAGAAT
TTTTCTCCAAGATGAAGTCTGTAATCTATGATAAGGCGGAGGGAAAATTCGCATTTA CCTTCGAC
TATCTTGATTATAATGTGAAATCCGAGTGCGGAAGGACCCTTTGGACCGTGTATACG GTCGGAG
AGAGATTCACATACAGCAGGGTCAATAGAGAATATGTCAGAAAAGTTCCGACAGACA TAATCT
ACGACGCATTGCAAAAGGCAGGAATATCTGTTGAAGGGGATCTCAGGGACAGGATTG CTGAAT
CGGATGGCGACACTCTGAAGAGCATATTCTATGCATTCAAGTATGCATTGGATATGA GAGTAGA
GAACCGCGAAGAGGATTACATACAGTCTCCTGTCAAAAATGCCTCCGGAGAATTCTT CTGTTCC
AAGAACGCAGGCAAATCGCTCCCTCAGGATTCCGATGCGAACGGTGCATACAATATC GCACTCA
AGGGGATCCTGCAGCTACGTATGCTTTCCGAGCAGTATGATCCGAATGCAGAGAGCA TACGGTT
GCCACTGATAACCAACAAGGCCTGGCTGACCTTTATGCAGTCCGGTATGAAGACATG GAAGAAC
TGA
SE atgGATAGTTTGAAAGATTTCACCAATCTGTACCCTGTCAGTAAGACATTGAGATTTGAA TTAAAG
Q CCCGTTGGAAAGACTTTAGAAAATATCGAGAAAGCAGGTATTTTGAAAGAGGATGAGCAT CGT
no GCAGAAAGTTATCGGAGGGTGAAGAAAATAATTGATACTTATCATAAGGTATTTATCGAT TCTT
N CTCTTGAAAATATGGCTAAAATGGGTATTGAGAATGAAATAAAAGCAATGCTCCAAAGTT TCTG
O: CGAATTGTATAAAAAAGATCATCGCACTGAGGGTGAAGACAAGGCATTAGATAAAATTCG AGC 26 AGTACTTCGTGGCCTGATTGTTGGGGCTTTCACTGGTGTTTGCGGAAGACGGGAAAATAC AGTC
CAAAACGAGAAGTACGAGAGTTTGTTCAAAGAAAAGTTGATAAAAGAAATTTTACCT GATTTTG
TGCTCTCTACTGAGGCTGAAAGCTTGCCTTTCTCTGTTGAAGAAGCTACGAGGTCAC TGAAGGA
GTTTGATAGCTTTACATCCTACTTTGCTGGTTTTTACGAGAATAGAAAGAATATATA CTCGACGA
AACCTCAATCCACTGCCATTGCTTATCGTCTTATTCATGAGAACTTGCCGAAGTTCA TTGATAAT ATTCTTGTTTTTCAGAAGATCAAAGAGCCTATAGCCAAAGAGCTGGAACATATTCGTGCG GACT
TTTCTGCCGGGGGGTACATAAAAAAGGATGAGAGATTGGAGGATATTTTTTCGTTGA ACTATTA
TATCCACGTGTTATCTCAGGCTGGGATCGAAAAATATAACGCATTGATTGGGAAGAT TGTGACA
GAAGGAGATGGAGAGATGAAAGGGCTCAATGAACACATCAACCTTTACAACCAACAA AGAGGC
AGAGAGGATCGGCTCCCTCTTTTTAGGCCTCTTTATAAACAGATATTGAGTGACAGA GAGCAAT
TATCATACTTGCCTGAGAGTTTTGAAAAAGATGAGGAGCTCCTCAGGGCTCTAAAAG AGTTCTA
TGATCATATCGCAGAAGACATTCTCGGACGTACTCAACAGTTGATGACTTCTATTTC AGAATATG
ATTTATCTCGGATATACGTAAGGAACGATAGCCAATTGACTGATATATCAAAAAAAA TGTTGGG
AGATTGGAATGCTATCTACATGGCTAGAGAACGAGCATATGACCACGAGCAGGCTCC CAAAAG
AATCACGGCGAAATACGAGAGGGACAGGATTAAAGCTCTTAAAGGAGAAGAGAGTAT AAGTCT
GGCAAATCTTAATAGTTGTATTGCCTTTCTGGACAATGTTAGAGATTGCCGTGTAGA TACTTATC
TTTCCACACTGGGCCAGAAGGAAGGACCACATGGTCTATCTAATCTCGTTGAGAACG TTTTTGCC
TCATACCATGAAGCAGAGCAATTGTTGAGCTTTCCATACCCCGAAGAGAATAATCTG ATTCAGG
ACAAGGACAATGTGGTGTTAATTAAGAATCTTCTCGACAATATCAGTGATCTGCAGA GGTTCTT
GAAACCTCTTTGGGGTATGGGAGACGAACCCGATAAAGATGAAAGATTTTATGGAGA GTATAAT
TATATCCGAGGAGCTCTAGATCAGGTGATCCCTCTGTACAATAAGGTAAGGAACTAC CTCACTC
GGAAGCCTTATTCGACCAGAAAAGTAAAACTCAATTTTGGGAATTCTCAATTGCTTA GTGGTTG
GGATAGAAATAAGGAAAAGGATAATAGCTGTGTGATTTTGCGTAAGGGGCAGAACTT CTATTTG
GCTATTATGAACAATAGGCACAAAAGAAGTTTCGAAAACAAGGTGTTGCCCGAGTAT AAGGAG
GGAGAACCTTACTTCGAAAAGATGGATTATAAATTTTTGCCTGATCCTAATAAAATG CTTCCTAA
GGACATGGAACTCACAAAAAGGGAGATACCTTTAGTATGGATGATTTGCACGAACTG ATCGATT
TCTTCAAACACTCAATCGAGGCTCATGAAGATTGGAAGCAATTCGGATTCAAATTTT CTGATAC
GGCTACTTATGAGAATGTATCTAGTTTCTATAGAGAAGTTGAGGATCAGGGGTATAA GCTCTCTT
TCCGAAAAGTTTCGGAATCTTATGTCTATTCATTAATAGATCAAGGCAAGTTGTATT TATTTCAG
ATATACAACAAGGACTTTTCTCCCTGCAGCAAAGGGACACCTAATCTGCATACCTTG TATTGGA
GAATGCTTTTTGACGAGCGCAATTTGGCAGATGTCATATACAAACTGGATGGGAAGG CTGAAAT
CTTTTTCCGAGAGAAGAGTTTGAAAAATGATCATCCCACGCATCCGGCTGGTAAGCC TATCAAA
AAGAAAAGTCGACAAAAAAAAGGAGAGGAGAGTCTGTTTGAGTATGATTTAGTCAAG GATAGG
CACTATACGATGGATAAGTTCCAGTTTCATGTGCCTATTACTATGAATTTTAAATGT TCTGCAGG
AAGCAAAGTCAATGATATGGTTAATGCTCATATTCGAGAGGCAAAGGATATGCATGT CATTGGA
ATTGATCGTGGAGAACGCAATCTGCTGTATATATGCGTGATAGATAGTCGAGGGACG ATTTTGG
ATCAAATTTCTCTGAATACGATTAACGATATAGACTATCATGATTTATTGGAGAGTC GAGACAA
AGACCGTCAGCAGGAGCGCCGAAACTGGCAAACTATCGAAGGGATCAAGGAGCTAAA ACAAGG
CTACCTTAGTCAGGCGGTTCATCGGATAGCCGAACTGATGGTGGCTTATAAGGCTGT AGTTGCTT
TGGAGGATTTGAATATGGGGTTCAAACGTGGGCGGCAGAAAGTAGAAAGTTCTGTTT ATCAGCA
GTTTGAGAAACAGCTGATAGATAAGCTCAACTATCTTGTGGACAAGAAGAAAAGGCC TGAAGA
TATTGGAGGATTGTTGAGAGCCTATCAATTTACGGCCCCATTTAAGAGTTTTAAGGA AATGGGA
AAGCAAAACGGCTTCTTGTTTTATATCCCGGCTTGGAACACGAGCAACATAGATCCG ACTACTG
GATTTGTTAATTTATTTCATGCCCAGTATGAAAATGTAGATAAAGCGAAGAGCTTCT TTCAAAAG
TTTGATTCAATTAGTTACAACCCGAAGAAAGACTGGTTTGAGTTTGCATTCGATTAT AAAAACTT
TACT AAAAAGGCTGAAGGAAGTCGTTCTATGTGGAT ATT ATGCACACATGGTTCCCGAATAAAG AATTTTAGAAATTCCCAGAAGAATGGTCAATGGGATTCCGAAGAATTCGCCTTGACGGAG GCTT TTAAGTCTCTTTTTGTGCGATATGAGATAGATTATACCGCTGATTTGAAAACAGCTATTG TGGAC GAAAAGCAAAAAGACTTCTTCGTGGATCTTCTGAAGCTATTCAAATTGACAGTACAGATG CGCA ACAGCTGGAAAGAGAAGGATTTGGATTATCTAATCTCTCCTGTAGCAGGGGCTGATGGCC GTTT CTTCGATACAAGAGAGGGAAATAAAAGTCTGCCTAAGGATGCAGATGCCAATGGAGCTTA TAA TATTGCCCTAAAAGGACTTTGGGCTCTACGCCAGATTCGGCAAACTTCAGAAGGCGGTAA ACTC AAATTGGCGATTTCCAATAAGGAATGGCTACAGTTTGTGCAAGAGAGATCTTACGAGAAA GACt ga
SE atgaataatggaacaaataactttcagaattttatcggaatttcttctttgcagaagact cttaggaatgctctcattccaaccgaaacaacacagcaatttattgttaa
Q aaacggaataattaaagaagatgagctaagaggagaaaatcgtcagatacttaaagatat catggatgattattacagaggtttcatttcagaaactttatcgtcaa no ttgatgaMtgactggacttctttatttgagaaaatggaaattcagttaaaaaatggagat aacaaagacactcttataaaagaacagactgaataccgtaaggca
N attcataaaaaatttgcaaatgatgatagatttaaaaatatgttcagtgcaaaate
O: aaaggaagaaaaaacacaggtaattaaattattttccagatttgcaacgtcattcaagga ctattttaaaaacagggctaattgtttttcggctgatgataMctte
27 cttcttgtcatagaatagttaatgataatgcagagatattttttagtaa¾^
gagatatgaaggattcattaaaggaaatgtctctggaagaaatttattcttatgaaaaat a¾^
gtaaagtaaattcatttatgaatttatattgccagaaaaataaagaaaacaaaaatctct ataagctgcaaaagcttcataaacagatactgtgcatagcagatactt ctMgaggtgccgtataaatttgaatcagatgaagaggttMcaatcagtgaatggattttt ggacaatattagttcgaaacaMcgttgaaagattgcgtaagatt ggagacaactataacggctacaatcttgataagatttaMtgttagtaaattctatgaatc agtttcacaaaagacatatagagattgggaaacaataaatactgcat tagaaattcattacaacaatatattacccggaaatggtaaatctaaagctgacaaggtaa aaaaagcggtaaagaatgatctgcaaaaaagcattactgaaatca atgagcttgttagcaattataaatMgttcggatgataatattaaagctgagacataMaca tgaaaMcacatattttgaataattttgaagcacaggagcttaagt ataatcctgaaattcatctggtggaaagtgaattgaaagcatctgaattaaaaaatgttc tcgatgtaataatgaatgcttttcattggtgttcggtttte gagctggtagataaagataataattttMgccgagttagaagagaMatgacgaaatatatc cggtaatttcattgtataatcttgtgcgtaattatgtaacgcaga agccatatagtacaaaaaaaattaaattgaattttggtattcctacactagcggatggat ggag^
ataatttgtactatttaggaatatttaatgcaaaaaataagcctgacaaaaagataattg aaggtaatacatcagaaaataaaggggattataagaagatgatttate atcttctgccaggaccaaataaaatgatccccaaggtattcctctcttcaaaaaccggag tggaaacatataagccgtctgcctatatattggagggctataaaca aaacaagcatattaaatcctctaaggattttgatataacattttgtcacgatttgattga ttattttaagaactgtatagcaatacatcctgaatggaaga^ gatttttctgacacctccacatatgaagatatcagcggattttacagagaagtcgaatta caaggttataaaatcgactggacatatatcagcgaaaaggatattga tttgttgcaggaaaaaggacagttatatttattccaaatatataacaaagatttttccaa gaaaagtaccggaaatgataatcttcatactatgtattt^ agtgaagagaatttaaaggatattgtactgaaattaaacggtgaggcggaaatcttcttt agaaaate
tcttgttaatagaacatatgaagcagaggaaaaagatcaatttggaaatatccagatagt cagaaaaaacataccggaaaatatatatcaggagctttataaatatt tcaatgataaaagtgataaagaactttcggatgaagcagctaagcttaagaatgtagtag gtcatcatgaggctgctacaaacatagtaaaagattatagatatac atatgataaatattttcttcatatgccMtacaatcaattttaaagccaataagacaggct t
gtaataggcattgatcgtggtgaaagaaacctgataMgtttcagtaattgatacttgtgg aaatattgttgaacaaaaatcgtttaacattgttaa^ cagattaagctcaagcagcaggagggggcgcgacaaatcgcacgaaaagaatggaaagaa atcggcaaaataaaagaaattaaagaaggctatttatctctt gtaattcatgaaatttcaaagatggttattaaatataatgccataattgcaatggaggat ttaagctacggatttaaaaaaggtcgtttcaaggttgagcgaca accagaagtttgagacaatgcttatcaacaaactcaactatctggtatttaaagatatat ccataacggaaaacggtggtcttctaaagggataccagcttacatat attccagataaactgaaaaatgtgggtcatcaatgtggctgtatattttatgtacctgct gcctatacatcaaaaatagatcctacaaccggatttgtaaatatattcaa atttaaagatttaacagttgatgcgaagagagaatttataaaaaaatttgacagtatcag aMgattcagaaaaaaatctgttttgttttacattcgattata^ attacgcaaaatactgttatgtcaaagtcaagctggagtgtatatacgtacggagttagg ataaaaagaagatttgtcaatggcaggttctcaaatgaatcggatac aattgatataacaaaagatatggaaaaaacactcgaaatgacagatataaattggagaga tggtcatgatctgaggcaggatattattgattatgaaatcgtacaa cacatatttgagatttttagattgactgtacaaatgagaaacagtttaagtgaattagaa gacagggatMgaccgtttgatttctccggtgctcaatgaaaataaM attttatgattcagctaaagcaggagatgcgttacctaaagacgcagatgctaatggtgc atattgtatagctctaaaaggcttgtatgaaatcaaacaaattacag agaattggaaagaagacggtaagttttcaagagataaacttaaaatttccaataaggact ggtttgactttattcaaaataaaaggtatttataa
SE atgacaaacaaatttacaaaccagtactcgctttccaaaacacttcgatttgagttgatt ccacaaggaaaaacattggaatttattcaagaaaaaggattgctctct
Q caagataaacaacgagcggagagttatcaagaaatgaaaaaaactattgataaatttcat aaatacttt^
no aaacttacttggaattatacaataaaagtgctgaaacaaaaaaagaacaaaaatttaaag acgatt^
N atctttttcagatggtgatgcaaaatcaatttttgcaattttggataaaaaagaactgat taccgtagaacttgaaaaatggtttgaaaacaacgaacaaaaagacat^ O: Mtttgacgaaaaattcaaaacgtttactacttattttactggtttte^
28 ttcatgaaaatttacctaaatttttagaaaatgctaaagcatttgaaaaaataaaacaag tagaaa
tgaagggctaattttcgtaaatgaattagaagaaatgtttcaaatcaattattataatga tgtgctttcacaaaatggaattacaatttataatagt^ accaaaaatgatataaaatataaaggtctaaatgaatacataaataattacaatcaaacc aaagacaaaaaagaccgtttgccaaaattaaaacaattgtataaac agattttgagtgataggatttcactttcgtttttgcccgatgcttttacggatgggaaac aagttttgaaagccatatttgacttttataaaatcaactte^ attgaaggacaggaagaaagccaaaatcttttactattaattcgtcagacaattgaaaac rt^
aaccactatttcacaacaagtatttggcgatttttcggtgttto
ccaacgaaaaaaaacgagaaattttagataaagccaaagcggtatttacaaaacaagatt atttttcaattgcttttttacaagaagtactttcggaatacattct^ cttagatcacacttctgaMtgtaaaaaagcattcctccaactgtattgcggattatttta aaaatcattttgtagccaaaaaagaaaatgaaaccgacaaaacctt^ gattttattgctaatattactgcaaaataccaatgtattcaaggtattttagaaaatgca gaccaatacgaagacgaactcaaacaagaccaaaaattaattgataa tgaaattctttttagatgctattttagaattgttgcattttattaaacctttgcatttaa aatcagaaagcattaccgaaaaagacactgctttttatg^
attacgaagcattgagtttgttgaccccattatataatatggtgcgaaactatgtaacgc aaaagccgtacagcaccgaaaaaataaaattaaattttgaaaatgca caattattgaatggttgggatgccaataaagaaggtgattacctaactaccattttgaaa aaagacggtaattattttttagccataatggataaaaagcataa^ gcgtttcaaaagtttccagaaggaaaagaaaattatgaaaaaatggtgtataaactattg cctggagtaaataagatgttgccaaaagtatttttttccaa attgcttacttcaacccatcaaaagagttattagaaaactataaaaaagagacgcacaaa aaaggagacacattcaatttagaacattgtcatacgttgatcgatttt ttcaaggactctttaaacaaacatgaagactggaaatactttgattttcaattttctgaa acaaaatcgtatcaagatttgagtggtttttate^
aggctacaaaatcaattttaaaaaMcgattcagaatatattgatggtttggtgaacgaag g^
aaagggaaaccgaacatgcacactttgtattggaaagccttatttgaagaacaaaatttg caaaatgtaatctataaattgaatggacaagccgaaatatttttt^ aaagcctctataaaacctaaaaatataaMtgcacaaaaagaaaattaaaattgccaaaaa gcatt^
aaacaataaaaaacctcaaMgtactaccaaggaaaaataagtgaaaaagaattaacacaa gatgatttaaggtatattgataattttagcattttcaa ataaaacaattgatattataaaagacaaacgatttacggttgataaatttcagtttcatg tgccgattaccatgaactttaaagcaacgggcggaagttatatcaatca aaccgtattagaatatttgcaaaacaatcccgaagttaagattattggattggatagagg cgaacgccatttggtatatctgacactgatagaccagcaaggaaac atcttgaaacaagaaagtttgaatacaatcaccgattctaaaatctcgacaccttatcat aagttgttggataacaaggaaaacgagcgtgacttggctcgaaaaa attggggaacggtggaaaacatcaaagaactcaaagaaggctacatcagtcaagtggtgc ataaaattgctacgttgatgctggaagaaaatgccattgtggta atggaagatttgaattttggatttaaacgtggacgttttaaagtggaaaaa^
agacaaacaacctcaggaattaggcggattgtacaacgcattacaactcaccaataaatt tgaaagtttccaaaaaatgggtaaacaatcgggctttttgttttatgt acccgcttggaacacctccaaaatagacccaaccacagggtttgtcaattatttttatac caaaMgaaaatgttgacaaagccaaagccttttttgaaaaatttga ggcgattcgtttcaatgcagaaaagaagtattttgaatttgaagtaaaaaaatatagcga ttttaacccaaaagccgaaggcactcaacaagcctggaccatttgc acgtatggcgaacgaatagaaaccaaacgacaaaaagaccaaaacaacaaatttgtaagc actccaattaatctaaccgaaaagatagaagactttttgggtaa aaaccaaattgttMggtgatggtaattgcatcaaatctcaaattgctagcaaagac^^
gcgaaacagcgaaacaagaacagatatagattatctaatttcgcccgtgatgaatgacaa cggaacattttacaacagccgagattatgaaaaattagaaaatcc aactttgcccaaagatgccgatgccaacggagcgtatcatattgccaaaaaaggattgat gcttttgaataaaatagaccaagccgacttgacaaaaaaagtgg atttatctattagtaacagagattggttgcaatttgtacaaaaaaataaataa
SE atggaacaggagtactatttaggactggatatgggaaccggatctgtaggatgggctgtt acagattcggaatatcatgtcttgcgtaaacatggaaaagcactat
Q ggggagtccgattatttgaaagtgcatcgacagcagaagaacgaagaatgttccgaacat caagaagaagactagatcgaagaaactggagaattgaaatttt no acaggaaatttttgcagaggaaataagtaagaaagatccaggatttttcttgcgaatgaa agaaagcaaatattatccagaagataagcgagatatcaatggaaa
N ttgtccggaactgccatatgcattatttgttgatgacgattttacagataaagattatca taaaaaatttccgacaatttatcatctcaggaaaatgttgatgaata^ O: aggagacaccggatatccggttggtgtatctggcaattcatcatatgatgaagcataggg gccatttcttgttatctggtgacattaatgagattaaggagttcgga
29 acgacattttcaaaattgttggagaatatcaaaaatgaggaattggattggaatcttgaa ctgggaaaagaagaaMgctgttgtagaaagtattttaaaagataa catgttaaaccgatccacaaagaaaaccagattaataaaagcattaaaagcaaaatcaat atgtgaaaaggctgtactgaatttattggctggtggaacggtgaa attgagtgatatatttggtcttgaagaattaaatgagacagaaagaccgaagatttcctt tgctgataatggatacgatgattatatcggagaagttgaaaatgagct gggagaacaattctatattatagagacggcaaaagcagtgtatgactgggcggtattagt tgaaatattgggaaaatatacgtcaatttcagaagcgaaagtagc aacgtatgaaaaacataaatcggatttacaatttttgaaaaagatagttcggaaaMctga caaaggaggaatataaagaMttttgtaagtacgagtgacaaatt gaaaaattactctgcttatataggaatgacgaaaataaatggaaaaaaggttgatttgca gagc^
acgtacttaaaaagctagaaggacaacctgaatatgaatatttgaaagaagagctagaaa gagaaacatttctaccaaaacaggtgaacagggataatggtgta ataccgtatcagattcatttgtacgagttgaaaaagatattaggaaatttacgggataaa atagacctcattaaagagaacgaagataaactggttcaattatt¾^ ttcagaattccgtattatgttggtccgctgaataagatagatgacggaaaagagggaaaa tttacatgggctgtacggaaaagtaatgaaaagatatatccatgga attttgaaaatgtagttgatatagaagcaagtgcagaaaaatttatccggagaatgacaa ataagtgtacatatctgatgggcgaagatgtattgccgaaggattc attgctttacagtaaataMggttttaaatgaattaaataatgtaaagttggat^^
gtatcggaaagtaactgtaaagaagataaaaaattacttgaaatgtgaaggtatcatatc cggcaatgtcgaaataactggaattgatggtgattttaaggcatcgt taacggcatatcatgattttaaagaaatcttgacaggaacagaattggctaaaaaggaca aagaaaatattattaccaatatagtattgtttggagatgataaaaag ctgctgaaaaagagactgaatcgattatatcctcagattacgccgaatcagttgaagaaa atatgtgcgctatcctatacaggctggggaagattttctaaaaagtt cttagaagaaataacagctccagatccggaaacgggagaggtatggaatatcattacggc attgtgggaatcgaataataatctgatgcaattattaagtaatga atatcggtttatggaagaagtcgaaacatacaatatgggaaaacagactaaaacattgtc gtacgaaacagtagagaatatgtatgtttctccatctgtgaaaaga cagatatggcagacgctgaaaatcgtgaaagaattagaaaaagtaatgaaagaatctccg aaacgtgtatttattgagatggcgagagaaaagcaagaaagta agagaaccgaatcgcgtaaaaaacaactaatagatttgtataaggcttgtaaaaatgaag aaaaagattgggtaaaagaactgggagatcaggaagaacaga aattacgaagcgataagttgtacctaMtatacgcaaaagggtcgttgtatgtattctggc gaggtaatagaactgaaagacttatgggataatacaaaat^^ attgatcatatatatccacaatctaaaacgatggatgacagtcttaataatcgcgtattg gtaaaaaagaaatataatgcaacaaaatcagataagtatccattaaat gaaaatatacgacatgagagaaaaggcttttggaagtcactgttagatggagggtttata agtaaagaaaaatatgaacgcttaataagaaatacagaattgagt ccggaagaattagcaggatttattgaaaggcagattgttgaaacgaggcagagtacaaaa gctgtagcggaaatattaaagcaagtgtttccggaaagtgaaat tgtatatgtcaaagcaggtacggtttcaagattcagaaaagattttgaattactgaaagt tcgagaagtgaatgatttgcatcacgcaaaggatgcgtatttaaatatt gtagttggtaatagtMMgtgaaatttactaagaatgcatcatggtttataaaagaaaatc cgggacgtacttacaacttaaaaaagatgtttacatcaggtt atattgaacgaaatggagaagttgcatgggaagtcgggaaaaaaggaacaattgtaacgg taaaacaaataatgaataaaaataatatattggtgacaagacag gttcatgaagcgaaaggtgggctgtttgatcagcagattatgaaaaaaggaaaaggtcag attgctataaaggaaactgatgaacgtcttgcatcaatagaaaa gtatggaggctataataaagctgccggggcatattttatgctggtagaatctaaagataa aaaaggaaaaacaattcgaacgatagaatttataccattatatttaa agaataaaatcgagtcggatgaatcaatagcattgaactttttagaaaaaggcagaggtt tgaaagaaccaaagatactattgaaaaaaattaagattgatacatt atttgatgtggacggattcaaaatgtggttgtctggaagaacaggggacagactactatt ^
gaaaaaaattgtaaagtttattcaaaggagacaagaaaatagagaattaaaatMctgata aagat
gtggataagttagaaaacacagtgtatagaatacgattatccgaacaggcaaaaacgctt atagataaacaaaaagaatttgaaaggttatcactagaggataaa agtagtactttgtttgaaattttacatatttttcagtgtcaaagtagtgcggccaattta aaaatgataggcggacctggaaaagcaggaatattagtta atataagtaagtgtaacaaaatttctattataaatcagtctccaacaggaattttcgaaa atgagattgatttgttaaagat
SE ATGAAATCTTTCGATTCATTCACAAATCTTTATTCTCTTTCAAAAACCTTGAAATTTGAG ATGAG
Q ACCTGTCGGAAATACCCAAAAAATGCTCGACAATGCAGGAGTATTTGAAAAAGACAAACT AAT
no TCAAAAAAAGTACGGAAAAACAAAGCCGTATTTCGACAGACTCCACAGAGAATTTATAGA AGA
N AGCGCTCACGGGGGTAGAGCTAATAGGACTAGATGAGAACTTTAGGACACTTGTTGACTG GCAA
O: AAAGATAAGAAAAATAATGTCGCAATGAAAGCGTATGAAAATAGTTTGCAGCGGCTGAGA ACG
30 GAAATAGGTAAAATATTTAACCTAAAGGCTGAGGATTGGGTAAAGAACAAATATCCAATA TTA
GGGCTGAAAAATAAAAATACCGATATTTTATTCGAAGAGGCTGTATTCGGGATATTG AAAGCCC
GATATGGAGAAGAAAAAGATACTTTTATAGAAGTAGAGGAAATAGATAAAACCGGCA AATCAA AGATCAATCAAATATCAATTTTCGATAGTTGGAAAGGATTTACAGGATATTTCAAAAAAT TTTTT
GAAACCAGAAAGAATTTTTACAAAAACGACGGAACTTCTACAGCAATTGCTACAAGG ATCATTG
ATCAAAATCTGAAAAGATTCATAGATAATCTGTCAATAGTTGAAAGTGTGAGACAAA AGGTTGA
TCTCGCCGAGACAGAAAAATCTTTCAGCATATCTCTATCGCAATTCTTCTCAATAGA CTTTTATA
ACAAGTGTCTCCTTCAAGATGGTATTGATTACTACAACAAGATAATCGGTGGAGAAA CTCTCAA
AAATGGCGAAAAACTAATAGGTCTCAATGAACTAATAAATCAATATAGGCAGAATAA TAAGGA
ATGAAATAAAAAATGACACAGAACTGATCGAGGCGCTGAGTCAGTTCGCAAAAACAG CCGAAG
AAAAAACAAAAATTGTCAAAAAGCTTTTTGCCGATTTTGTAGAAAATAATTCCAAAT ACGATCT
TGCACAGATTTATATTTCCCAAGAAGCATTCAATACTATATCAAACAAGTGGACAAG CGAAACT
GAGACGTTCGCTAAATATCTATTCGAAGCAATGAAGAGTGGAAAACTTGCAAAGTAT GAGAAA
AAAGATAATAGCTATAAATTTCCTGATTTTATTGCCCTTTCACAGATGAAGAGTGCT TTATTAAG
TATCAGCCTTGAGGGACATTTTTGGAAAGAGAAATACTACAAAATTTCAAAATTCCA AGAGAAG
ACCAATTGGGAGCAGTTTCTTGCAATTTTTCTATACGAGTTTAACTCTCTTTTCAGC GACAAAAT
AAATACAAAAGATGGAGAAACAAAGCAAGTTGGATACTATCTATTTGCCAAAGACCT GCATAA
TCTTATCTTAAGTGAGCAGATTGATATTCCAAAAGATTCAAAAGTCACAATAAAAGA TTTTGCC
GATTCTGTACTCACAATCTACCAAATGGCAAAATATTTTGCGGTAGAAAAAAAACGA GCGTGGC
TTGCCGAGTATGAACTAGATTCATTTTATACCCAGCCAGACACAGGCTATTTACAGT TTTATGAT
AACGCCTACGAGGATATTGTGCAGGTATACAACAAGCTTCGAAACTATCTGACCAAA AAGCCAT
ATAGCGAGGAGAAATGGAAGTTGAATTTTGAAAATTCTACGCTGGCAAATGGATGGG ATAAGA
ACAAAGAATCTGATAATTCAGCAGTTATTCTACAAAAAGGTGGAAAATATTATTTGG GACTGAT
TACTAAAGGACACAACAAAATTTTTGATGACCGTTTTCAAGAAAAATTTATTGTGGG AATTGAA
GGTGGAAAATATGAAAAAATAGTCTATAAATTTTTCCCCGACCAGGCAAAAATGTTT CCCAAAG
TGTGCTTTTCTGCAAAAGGACTCGAATTTTTTAGACCGTCTGAAGAAATTTTAAGAA TTTATAAC
AATGCAGAGTTTAAAAAAGGAGAAACTTATTCAATAGATAGTATGCAGAAGTTGATT GATTTTT
ATAAAGATTGCTTGACTAAATATGAAGGCTGGGCATGTTATACCTTTCGGCATCTAA AACCCAC
AGAAGAATACCAAAACAATATTGGAGAGTTTTTTCGAGATGTTGCAGAGGACGGATA CAGGATT
GATTTTCAAGGCATTTCAGATCAATATATTCATGAAAAAAACGAGAAAGGCGAACTT CACCTTT
TTGAAATCCACAATAAAGATTGGAATTTGGATAAGGCACGAGACGGAAAGTCAAAAA CAACAC
AAAAAAACCTTCATACACTCTATTTCGAATCGCTCTTTTCAAACGATAATGTTGTTC AAAACTTT
CCAATAAAACTCAATGGTCAAGCTGAAATTTTTTATAGACCGAAAACGGAAAAAGAC AAATTA
GAATCAAAAAAAGATAAGAAAGGGAATAAAGTGATTGACCATAAACGCTATAGTGAG AATAAG
ATTTTTTTTCATGTTCCTCTCACACTAAACCGCACTAAAAATGACTCATATCGCTTT AATGCTCAA
ATCAACAACTTTCTCGCAAATAATAAAGATATCAACATCATCGGTGTAGATAGGGGA GAAAAGC
ATTTAGTCTATTATTCGGTGATTACACAAGCTAGTGACATCTTAGAAAGTGGCTCAC TAAATGAG
CTAAATGGCGTGAATTATGCTGAAAAACTGGGAAAAAAGGCAGAAAATCGAGAACAA GCACGC
AGAGACTGGCAAGACGTACAAGGGATCAAAGACCTCAAGAAAGGATATATTTCACAG GTGGTG
CGAAAGCTTGCTGATTTAGCAATTAAACACAATGCCATTATCATTCTTGAAGATTTG AATATGAG
ATTTAAACAAGTTCGGGGCGGTATCGAAAAATCCATTTATCAACAGTTAGAAAAAGC ACTGATA
GATAAATTAAGCTTTCTTGTAGACAAAGGTGAAAAAAATCCCGAGCAAGCAGGACAT CTTCTGA
AAGCATATCAGCTTTCGGCCCCATTTGAGACATTTCAAAAAATGGGCAAACAGACGG GTATAAT
CTTTTATACACAAGCTTCGTATACCTCAAAAAGTGACCCTGTAACAGGTTGGCGACC ACACCTGT ATCTCAAATATTTCAGTGCCAAAAAAGCAAAAGACGATATTGCAAAGTTTACAAAAATAG AATT TGTAAACGATAGGTTTGAGCTTACCTATGATATAAAGGACTTTCAGCAAGCAAAAGAATA TCCA AATAAAACTGTTTGGAAAGTTTGCTCAAATGTAGAGAGATTCAGGTGGGACAAAAACCTC AATC AAAACAAAGGCGGATATACTCACTACACAAATATAACTGAGAATATCCAAGAGCTTTTTA CAAA ATATGGAATTGATATCACAAAAGATTTGCTCACACAGATTTCTACAATTGATGAAAAACA AAAT
TCTGAGATTGCTAAAAAGAATGGGAAAGATGATTTTATACTGTCACCTGTTGAGCCG TTTTTCGA
TAGCCGAAAAGACAATGGAAATAAACTTCCTGAGAATGGAGATGATAACGGCGCGTA TAACAT
AGCAAGAAAAGGGATTGTCATACTCAACAAAATCTCACAATATTCAGAGAAAAACGA AAATTG
CGAGAAAATGAAATGGGGGGATTTGTATGTATCAAACATTGACTGGGACAATTTTGT AACCCAA
GCTAATGCACGGCATTAA
SE ATGATTATCTTATATATTAGTACCTCGAATATGAACATGGAAGGAGTATTTATGGAAAAT TTTAA
Q AAACTTGTATCCAATAAACAAAACACTTCGATTTGAATTAAGACCCTATGGAAAAACATT GGAA
no AATTTTAAAAAATCCGGACTTTTAGAAAAAGATGCCTTTAAGGCAAATAGTAGACGAAGT ATGC
N AAGCTATAATCGATGAAAAATTCAAAGAGACTATCGAAGAACGCTTAAAGTACACTGAAT TCA
O: GTGAATGTGATCTTGGAAACATGACATCAAAAGATAAAAAAATAACTGATAAAGCAGCTA CAA 31 ATTTAAAAAAGCAAGTTATCTTATCTTTTGACGATGAAATATTTAATAATTACCTAAAAC CTGAT
AAAAATATTGACGCATTATTTAAAAATGATCCTTCAAATCCTGTAATCTCTACATTT AAAGGTTT
CAATGGCATACCGAATTATAGATGAAAACCTGACAACATACTTGAATAATATTGAAA AAATAAA
AAAACTGCCAGAAGAATTAAAATCACAGCTAGAAGGCATTGATCAGATTGATAAACT TAATAAT
TATAATGAGTTCATTACACAGTCAGGTATAACACACTATAATGAAATCATCGGCGGT ATATCAA
AATCAGAGAATGTCAAAATACAGGGAATTAATGAAGGAATTAATCTATACTGTCAGA AGAACA
AAGTTAAACTTCCTCGACTGACTCCGCTATACAAAATGATATTATCAGACAGAGTTT CCAACTCT
TTTGTATTAGACACTATTGAAAATGACACAGAATTAATTGAAATGATAAGTGATTTG ATTAATA
AGACTGAGATTTCGCAAGATGTTATAATGTCAGATATTCAAAATATTTTCATAAAAT ACAAACA
ACTTGGTAATTTGCCGGGTATCTCATATTCTTCAATAGTTAATGCTATTTGCTCGGA TTATGACA
ACAATTTCGGAGATGGGAAGCGAAAAAAATCTTACGAAAATGATCGCAAAAAGCATT TGGAGA
CTAATGTATACTCCATAAATTATATTTCTGAATTGCTTACAGATACCGATGTTTCAT CAAATATC
AAGATGAGATATAAAGAGCTTGAGCAAAATTATCAGGTTTGCAAAGAAAATTTTAAT GCCACAA
ACTGGATGAATATTAAAAATATAAAACAATCTGAAAAAACAAACCTTATTAAAGATT TGTTAGA
TATACTTAAATCGATTCAACGTTTCTATGATTTGTTTGATATTGTTGACGAAGATAA AAATCCAA
GTGCTGAATTTTATACCTGGTTATCAAAAAATGCTGAAAAGCTTGACTTTGAATTCA ATTCTGTA
TATAACAAGTCACGAAACTATCTCACCAGGAAACAATACTCTGATAAAAAAATCAAG CTGAATT
TTGATTCTCCAACATTGGCCAAAGGGTGGGATGCTAACAAAGAAATAGATAACTCCA CGATTAT
AATGCGTAAATTTAATAATGACAGAGGCGATTATGATTACTTCCTTGGCATATGGAA TAAATCC
ACACCTGCAAATGAAAAAATAATCCCACTGGAGGATAATGGATTATTCGAAAAAATG CAATAT
AAGCTGTATCCAGATCCTAGTAAGATGTTACCGAAACAATTTCTATCAAAAATATGG AAGGCAA
AGCATCCTACGACACCTGAATTTGATAAAAAATATAAAGAGGGAAGACATAAAAAAG GTCCTG
ATTTCGAAAAAGAATTCCTGCATGAATTGATTGATTGCTTCAAACATGGTCTTGTTA ATCACGAT
GAAAAATATCAGGATGTTTTTGGCTTCAATCTCCGTAACACTGAAGATTATAATTCA TATACAGA
GTTTCTCGAAGATGTGGAAAGATGCAATTACAATCTTTCATTTAACAAAATTGCTGA TACTTCAA ACCTTATTAATGATGGGAAATTGTATGTATTTCAGATATGGTCAAAAGACTTTTCTATTG ATTCA
AAAGGTACTAAAAACTTGAATACAATCTATTTTGAATCACTATTTTCAGAAGAAAAC ATGATAG
AAAAAATGTTCAAGCTTTCTGGAGAGGCTGAGATATTCTATCGACCAGCATCGTTGA ATTATTGT
GAAGATATCATAAAAAAAGGTCATCACCATGCAGAATTAAAAGATAAGTTTGACTAT CCTATAA
TAAAAGATAAGCGATATTCACAAGATAAGTTTTTCTTTCATGTGCCAATGGTTATAA ATTATAAA
TCTGAGAAACTGAATTCCAAAAGCCTTAACAACCGAACAAATGAAAACCTGGGACAG TTTACAC
ATATTATAGGTATAGACAGGGGCGAGCGGCACTTGATTTATTTAACTGTTGTTGATG TTTCCACT
GGTGAAATCGTTGAACAGAAACATCTGGACGAAATTATCAATACTGATACCAAGGGA GTTGAA
CACAAAACCCATTATTTGAATAAATTGGAAGAAAAATCTAAAACAAGAGATAACGAG CGTAAA
TCATGGGAAGCTATTGAAACTATCAAAGAATTAAAAGAAGGCTATATTTCTCATGTA ATTAATG
AAATACAAAAGCTGCAAGAAAAATATAATGCCTTAATCGTAATGGAAAATCTTAACT ATGGGTT
CAAAAACTCACGAATCAAAGTTGAAAAACAGGTTTATCAAAAATTCGAGACAGCATT GATTAA
AAAGTTCAATTATATTATTGATAAAAAAGATCCAGAAACCTATATACATGGTTACCA GCTTACA
AATCCTATTACCACTCTGGATAAGATTGGAAATCAATCTGGAATAGTGCTGTATATT CCTGCGTG
GAATACTTCTAAGATAGATCCCGTCACAGGATTTGTAAACCTTCTGTACGCAGATGA TTTGAAGT
ATAAAAATCAGGAGCAGGCCAAATCATTCATTCAGAAAATAGACAACATATATTTTG AAAATGG
AGAGTTTAAATTTGATATTGATTTTTCCAAATGGAATAATCGCTACTCAATAAGTAA AACTAAAT
GGACGTTAACAAGTTATGGGACTCGCATCCAGACATTTAGAAATCCCCAGAAAAACA ATAAGTG
GGATTCTGCTGAATATGATTTGACAGAAGAGTTTAAATTAATTTTAAATATAGACGG AACGTTA
AAGTCACAGGACGTAGAAACATACAAAAAATTCATGTCTTTATTTAAACTAATGCTA CAGCTTC
GAAACTCTGTTACAGGAACCGACATTGATTATATGATCTCTCCTGTCACTGATAAAA CAGGAAC
ACATTTCGATTCAAGAGAAAATATTAAAAATCTTCCTGCCGATGCAGATGCCAATGG TGCCTAC
AACATTGCGCGCAAAGGAATAATGGCTATTGAAAATATAATGAACGGTATAAGCGAT CCACTA
AAAATAAGCAACGAAGACTATTTAAAGTATATTCAGAATCAACAGGAATAA
SE ATGACCCAATTTGAAGGTTTTACCAATTTATACCAAGTTTCGAAGACCCTTCGTTTTGAA CTGAT
Q TCCCCAAGGAAAAACACTCAAACATATCCAGGAGCAAGGGTTCATTGAGGAGGATAAAGC TCG
no CAATGACCATTACAAAGAGTTAAAACCAATCATTGACCGCATCTATAAGACTTATGCTGA TCAA
N TGTCTCCAACTGGTACAGCTTGACTGGGAGAATCTATCTGCAGCCATAGACTCCTATCGT AAGG
O: AAAAAACCGAAGAAACACGAAATGCGCTGATTGAGGAGCAAGCAACATATAGAAATGCGA TTC
32 ATGACTACTTTATAGGTCGGACGGATAATCTGACAGATGCCATAAATAAGCGCCATGCTG AAAT
CTATAAAGGACTTTTTAAAGCTGAACTTTTCAATGGAAAAGTTTTAAAGCAATTAGG GACCGTA
ACCACGACAGAACATGAAAATGCTCTACTCCGTTCGTTTGACAAATTTACGACCTAT TTTTCCGG
CTTTTATGAAAACCGAAAAAATGTCTTTAGCGCTGAAGATATCAGCACGGCAATTCC CCATCGA
ATCGTCCAGGACAATTTCCCTAAATTTAAGGAAAACTGCCATATTTTTACAAGATTG ATAACCGC
AGTTCCTTCTTTGCGGGAGCATTTTGAAAATGTCAAAAAGGCCATTGGAATCTTTGT TAGTACGT
CTATTGAAGAAGTCTTTTCCTTTCCCTTTTATAATCAACTTCTAACCCAAACGCAAA TTGATCTTT
ATAATCAACTTCTCGGCGGCATATCTAGGGAAGCAGGCACAGAAAAAATCAAGGGAC TTAATG
AAGTTCTCAATCTGGCTATCCAAAAAAATGATGAAACAGCCCATATAATCGCGTCCC TGCCGCA
TCGTTTTATTCCTCTTTTTAAACAAATTCTTTCCGATCGAAATACGTTATCCTTTAT TTTGGAAGA
ATTCAAAAGCGATGAGGAAGTCATCCAATCCTTCTGCAAATATAAAACCCTCTTGAG AAACGAA
AATGTACTGGAGACTGCAGAAGCCCTTTTCAATGAATTAAATTCCATTGATTTGACT CATATCTT
TATTTCCCATAAAAAGTTAGAAACCATCTCTTCAGCGCTTTGTGACCATTGGGATAC CTTGCGCA ATGCACTTTACGAAAGACGGATTTCTGAACTCACTGGCAAAATAACAAAAAGTGCCAAAG AAA
AAGTTCAAAGGTCATTAAAACATGAGGATATAAATCTCCAAGAAATTATTTCTGCTG CAGGAAA
AGAACTATCAGAAGCATTCAAACAAAAAACAAGTGAAATTCTTTCCCATGCCCATGC TGCACTT
GACCAGCCTCTTCCCACAACATTAAAAAAACAGGAAGAAAAAGAAATCCTCAAATCA CAGCTC
GATTCGCTTTTAGGCCTTTATCATCTTCTTGATTGGTTTGCTGTCGATGAAAGCAAT GAAGTCGA
CCCAGAATTCTCAGCACGGCTGACAGGCATTAAACTAGAAATGGAACCAAGCCTTTC GTTTTAT
AATAAAGCAAGAAATTATGCGACAAAAAAGCCCTATTCGGTGGAAAAATTTAAATTG AATTTTC
AAATGCCAACCCTTGCCTCTGGTTGGGATGTCAATAAAGAAAAAAATAATGGAGCTA TTTTATT
CGTAAAAAATGGTCTCTATTACCTTGGTATCATGCCTAAACAGAAGGGGCGCTATAA AGCCCTG
TCTTTTGAGCCGACAGAAAAAACATCAGAAGGATTCGATAAGATGTACTATGACTAC TTCCCAG
ATGCCGCAAAAATGATTCCTAAGTGTTCCACTCAGCTAAAGGCTGTAACCGCTCATT TTCAAACT
CATACCACCCCCATTCTTCTCTCAAATAATTTCATTGAACCTCTTGAAATCACAAAA GAAATTTA
TGACCTGAACAATCCTGAAAAGGAGCCTAAAAAGTTTCAAACGGCTTATGCAAAGAA GACAGG
CGATCAAAAAGGCTATAGAGAAGCGCTTTGCAAATGGATTGACTTTACGCGGGATTT TCTCTCT
AAATATACGAAAACAACTTCAATCGATTTATCTTCACTCCGCCCTTCTTCGCAATAT AAAGATTT
AGGGGAATATTACGCCGAACTGAATCCGCTTCTCTATCATATCTCCTTCCAACGAAT TGCTGAAA
AGGAAATCATGGATGCTGTAGAAACGGGAAAATTGTATCTGTTCCAAATCTACAATA AGGATTT
TGCGAAGGGCCATCACGGGAAACCAAATCTCCACACCCTGTATTGGACAGGTCTCTT CAGTCCT
GAAAACCTTGCGAAAACCAGCATCAAACTTAATGGTCAAGCAGAATTGTTCTATCGA CCTAAAA
GCCGCATGAAGCGGATGGCCCATCGTCTTGGGGAAAAAATGCTGAACAAAAAACTAA AGGACC
AGAAGACACCGATTCCAGATACCCTCTACCAAGAACTGTACGATTATGTCAACCACC GGCTAAG
CCATGATCTTTCCGATGAAGCAAGGGCCCTGCTTCCAAATGTTATCACCAAAGAAGT CTCCCAT
GAAATTATAAAGGATCGGCGGTTTACTTCCGATAAATTTTTCTTCCATGTTCCCATT ACACTGAA
TTATCAAGCAGCCAATAGTCCCAGTAAATTCAACCAGCGTGTCAATGCCTACCTTAA GGAGCAT
CCGGAAACGCCCATCATTGGTATCGATCGTGGAGAACGCAATCTAATCTATATTACC GTCATTG
ACAGTACTGGGAAAATTTTGGAGCAGCGTTCCCTGAATACCATCCAGCAATTTGACT ACCAAAA
AAAATTGGACAACAGGGAAAAAGAGCGTGTTGCCGCCCGTCAAGCCTGGTCCGTCGT CGGAAC
GATCAAAGACCTTAAACAAGGCTACTTGTCACAGGTCATCCATGAAATTGTAGACCT GATGATT
CATTACCAAGCTGTTGTCGTCCTTGAAAACCTCAACTTCGGATTTAAATCAAAACGG ACAGGCA
TTGCCGAAAAAGCAGTCTACCAACAATTTGAAAAGATGCTAATAGATAAACTCAACT GTTTGGT
TCTCAAAGATTATCCTGCTGAGAAAGTGGGAGGCGTCTTAAACCCGTATCAACTTAC AGATCAG
TTCACGAGCTTTGCAAAAATGGGCACGCAAAGCGGCTTCCTTTTCTATGTACCGGCC CCTTATAC
CTCAAAGATTGATCCCCTGACTGGTTTTGTCGATCCCTTTGTATGGAAGACCATTAA AAATCATG
AAAGTCGGAAGCATTTCCTAGAAGGATTTGATTTCCTGCATTATGATGTCAAAACAG GTGATTTT
ATCCTCCATTTTAAAATGAATCGGAATCTCTCTTTCCAGAGAGGGCTTCCTGGCTTC ATGCCAGC
TTGGGATATTGTTTTCGAAAAGAATGAAACCCAATTTGATGCAAAAGGGACGCCCTT CATTGCA
GGAAAACGAATTGTTCCTGTAATCGAAAATCATCGTTTTACGGGTCGTTACAGAGAC CTCTATCC
CGCTAATGAACTCATTGCCCTTCTGGAAGAAAAAGGCATTGTCTTTAGAGACGGAAG TAATATA
TTACCCAAACTTTTAGAAAATGATGATTCTCATGCAATTGATACGATGGTCGCCTTG ATTCGCAG
TGTACTCCAAATGAGAAACAGCAATGCCGCAACGGGGGAAGACTACATCAACTCTCC CGTTAGG
GATCTGAACGGGGTGTGTTTCGACAGTCGATTCCAAAATCCAGAATGGCCAATGGAT GCGGATG
CCAACGGAGCTTATCATATTGCCTTAAAAGGGCAGCTTCTTCTGAACCACCTCAAAG AAAGCAA AGATCTGAAATTACAAAACGGCATCAGCAACCAAGATTGGCTGGCCTACATTCAGGAACT GAG AAACTGA
SE ATGGCCGTCAAATCCATCAAAGTGAAACTTCGTCTCGACGATATGCCGGAGATTCGGGCC GGTC
Q TATGGAAACTTCATAAGGAAGTCAATGCGGGGGTTCGATATTACACGGAATGGCTCAGTC TTCT
no CCGTCAAGAGAACTTGTATCGAAGAAGTCCGAATGGGGACGGAGAGCAAGAATGTGATAA GAC
N TGCAGAAGAATGCAAAGCCGAATTGTTGGAGCGGCTGCGCGCGCGTCAAGTGGAGAATGG ACA
O: CCGTGGTCCGGCGGGATCGGACGATGAATTGCTGCAGTTGGCGCGTCAACTCTATGAGTT GTTG
33 GTTCCGCAGGCGATAGGTGCGAAAGGCGACGCGCAGCAAATTGCCCGCAAATTTTTGAGC CCCT
TGGCCGACAAGGACGCAGTTGGTGGGCTTGGAATCGCGAAGGCGGGGAACAAACCGC GGTGGG
TTCGCATGCGCGAAGCGGGGGAACCAGGCTGGGAAGAGGAGAAGGAGAAGGCTGAGA CGAGG
AAATCTGCGGATCGGACTGCGGATGTTTTGCGCGCGCTCGCGGATTTTGGGTTAAAG CCACTGA
TGCGCGTATACACCGATTCTGAGATGTCATCGGTGGAGTGGAAACCGCTTCGGAAGG GACAAGC
CGTTCGGACGTGGGATAGGGACATGTTCCAACAAGCTATCGAACGGATGATGTCGTG GGAGTCG
TGGAATCAGCGCGTTGGGCAAGAGTACGCGAAACTCGTAGAACAAAAAAATCGATTT GAGCAG
AAGAATTTCGTCGGCCAGGAACATCTGGTCCATCTCGTCAATCAGTTGCAACAAGAT ATGAAAG
AAGCATCGCCCGGACTCGAATCGAAAGAGCAAACCGCGCACTATGTGACGGGACGGG CATTGC
GCGGATCGGACAAGGTATTTGAGAAGTGGGGGAAACTCGCCCCCGATGCACCTTTCG ATTTGTA
CGACGCCGAAATCAAGAATGTGCAGAGACGTAACACGAGACGATTCGGATCACATGA CTTGTTC
GCAAAATTGGCAGAGCCAGAGTATCAGGCCCTGTGGCGCGAAGATGCTTCGTTTCTC ACGCGTT
ACGCGGTGTACAACAGCATCCTTCGCAAACTGAATCACGCCAAAATGTTCGCGACGT TTACTTT
GCCGGATGCAACGGCGCACCCGATTTGGACTCGCTTCGATAAATTGGGTGGGAATTT GCACCAG
TACACCTTTTTGTTCAACGAATTTGGAGAACGCAGGCACGCGATTCGTTTTCACAAG CTATTGAA
AGTCGAGAATGGTGTCGCAAGAGAAGTTGATGATGTCACCGTGCCCATTTCAATGTC AGAGCAA
TTGGATAATCTGCTTCCCAGAGATCCCAATGAACCGATTGCGCTATATTTTCGAGAT TACGGAGC
CGAACAGCATTTCACAGGTGAATTTGGTGGCGCGAAGATCCAGTGCCGCCGGGATCA GCTGGCT
CATATGCACCGACGCAGAGGGGCGAGGGATGTTTATCTCAATGTCAGCGTACGTGTG CAGAGTC
AGTCTGAGGCGCGGGGAGAACGTCGCCCGCCGTATGCGGCAGTATTTCGTCTGGTCG GGGACAA
CCATCGCGCGTTTGTCCATTTCGATAAACTATCGGATTATCTTGCGGAACATCCGGA TGATGGGA
AGCTCGGGTCGGAGGGGTTGCTTTCCGGGCTGCGGGTGATGAGTGTCGATCTCGGCC TTCGCAC
ATCTGCATCGATTTCCGTTTTTCGCGTTGCCCGGAAGGACGAGTTGAAGCCGAACTC AAAAGGT
CGTGTACCGTTTTTCTTTCCGATAAAAGGGAATGACAATCTCGTCGCGGTTCATGAG CGATCACA
ACTCTTGAAGCTGCCTGGCGAAACGGAGTCGAAGGACCTGCGTGCTATCCGAGAAGA ACGCCA
ACGGACATTGCGGCAGTTGCGGACGCAACTGGCGTATTTGCGGCTGCTCGTGCGGTG TGGGTCG
GAAGATGTGGGGCGGCGTGAACGGAGTTGGGCAAAGCTTATCGAGCAGCCGGTGGAT GCGGCC
AATCACATGACACCGGATTGGCGCGAGGCTTTTGAAAACGAACTTCAGAAGCTTAAG TCACTCC
ATGGTATCTGTAGCGACAAGGAATGGATGGATGCTGTCTACGAGAGCGTTCGCCGCG TGTGGCG
TCACATGGGCAAACAGGTTCGCGATTGGCGAAAGGACGTACGAAGCGGAGAGCGGCC CAAGAT
TCGCGGCTATGCGAAAGACGTGGTCGGTGGAAACTCGATTGAGCAAATCGAGTATCT GGAACGT
CAGTACAAGTTCCTCAAGAGTTGGAGCTTCTTTGGTAAGGTGTCGGGACAAGTGATT CGTGCGG
AGAAGGGATCTCGTTTTGCGATCACGCTGCGCGAACACATTGATCACGCGAAGGAAG ATCGGCT
GAAGAAATTGGCGGATCGCATCATTATGGAGGCTCTCGGCTATGTGTACGCGTTGGA TGAGCGC
GGCAAAGGAAAGTGGGTTGCGAAGTATCCGCCGTGCCAGCTCATCCTGCTGGAGGAA TTGAGC GAGTACCAGTTCAATAACGACAGGCCTCCGAGCGAAAACAACCAGTTGATGCAATGGAGT CAT
CGCGGCGTGTTCCAGGAGTTGATAAATCAGGCCCAAGTCCATGATTTACTCGTTGGG ACGATGT
ATGCAGCGTTCTCGTCGCGATTCGACGCGCGAACTGGGGCACCGGGTATCCGCTGTC GCCGGGT
TCCGGCGCGTTGCACCCAGGAGCACAATCCAGAACCATTTCCTTGGTGGCTGAACAA GTTTGTG
GTGGAACATACGTTGGATGCTTGTCCCCTACGCGCAGACGACCTCATCCCAACGGGT GAAGGAG
AGATTTTTGTCTCGCCGTTCAGCGCGGAGGAGGGGGACTTTCATCAGATTCACGCCG ACCTGAA
TGCGGCGCAAAATCTGCAGCAGCGACTCTGGTCTGATTTTGATATCAGTCAAATTCG GTTGCGGT
GTGATTGGGGTGAAGTGGACGGTGAACTCGTTCTGATCCCAAGGCTTACAGGAAAAC GAACGG
CGGATTCATATAGCAACAAGGTGTTTTATACCAATACAGGTGTCACCTATTATGAGC GAGAGCG
GGGGAAGAAGCGGAGAAAGGTTTTCGCGCAAGAGAAATTGTCGGAGGAAGAGGCGGA GTTGCT
CGTGGAAGCAGACGAGGCGAGGGAGAAATCGGTCGTTTTGATGCGTGATCCGTCTGG CATCATC
AATCGGGGAAATTGGACCAGGCAAAAGGAATTTTGGTCGATGGTGAACCAGCGGATC GAAGGA
TACTTGGTCAAGCAGATTCGCTCGCGCGTTCCATTACAAGATAGTGCGTGTGAAAAC ACGGGGG
ATATTTAA
SE ATGGCGACACGCAGTTTTATTTTAAAAATTGAACCAAATGAAGAAGTTAAAAAGGGATTA TGGA
Q AGACGCATGAGGTATTGAATCATGGAATTGCCTACTACATGAATATTCTGAAACTAATTA GACA
no GGAAGCTATTTATGAACATCATGAACAAGATCCTAAAAATCCGAAAAAAGTTTCAAAAGC AGA
N AATACAAGCCGAGTTATGGGATTTTGTTTTAAAAATGCAAAAATGTAATAGTTTTACACA TGAA
O: GTTGACAAAGATGTTGTTTTTAACATCCTGCGTGAACTATATGAAGAGTTGGTCCCTAGT TCAGT 34 CGAGAAAAAGGGTGAAGCCAATCAATTATCGAATAAGTTTCTGTACCCGCTAGTTGATCC GAAC
AGTCAAAGTGGGAAAGGGACGGCATCATCCGGACGTAAACCTCGGTGGTATAATTTA AAAATA
GCAGGCGACCCATCGTGGGAGGAAGAAAAGAAAAAATGGGAAGAGGATAAAAAGAAA GATCC
CCTTGCTAAAATCTTAGGTAAGTTAGCAGAATATGGGCTTATTCCGCTATTTATTCC ATTTACTG
ACAGCAACGAACCAATTGTAAAAGAAATTAAATGGATGGAAAAAAGTCGTAATCAAA GTGTCC
GGCGACTTGATAAGGATATGTTTATCCAAGCATTAGAGCGTTTTCTTTCATGGGAAA GCTGGAA
CCTTAAAGTAAAGGAAGAGTATGAAAAAGTTGAAAAGGAACACAAAACACTAGAGGA AAGGA
TAAAAGAGGACATTCAAGCATTTAAATCCCTTGAACAATATGAAAAAGAACGGCAGG AGCAAC
TTCTTAGAGATACATTGAATACAAATGAATACCGATTAAGCAAAAGAGGATTACGTG GTTGGCG
TGAAATTATCCAAAAATGGCTAAAGATGGATGAAAATGAACCATCAGAAAAATATTT AGAAGT
ATTTAAAGATTATCAACGGAAACATCCACGAGAAGCCGGGGACTATTCTGTCTATGA ATTTTTA
AGCAAGAAAGAAAATCATTTTATTTGGCGAAATCATCCTGAATATCCTTATTTGTAT GCTACATT
TTGTGAAATTGACAAAAAAAAGAAAGACGCTAAGCAACAGGCAACTTTTACTTTGGC TGACCCG
ATTAACCATCCGTTATGGGTACGATTTGAAGAAAGAAGCGGTTCGAACTTAAACAAA TATCGAA
TTTTAACAGAGCAATTACACACTGAAAAGTTAAAAAAGAAATTAACAGTTCAACTTG ATCGTTT
AATTTATCCAACTGAATCCGGCGGTTGGGAGGAAAAAGGTAAAGTAGATATCGTTTT GTTGCCG
TCAAGACAATTTTATAATCAAATCTTCCTTGATATAGAAGAAAAGGGGAAACATGCT TTTACTT
ATAAGGATGAAAGTATTAAATTCCCCCTTAAAGGTACACTTGGTGGTGCAAGAGTGC AGTTTGA
CCGTGACCATTTGCGGAGATATCCGCATAAAGTAGAATCAGGAAATGTTGGACGGAT TTATTTT
AACATGACAGTAAATATTGAACCAACTGAGAGCCCTGTTAGTAAGTCTTTGAAAATA CATAGGG
ACGATTTCCCCAAGTTCGTTAATTTTAAACCGAAAGAGCTCACCGAATGGATAAAAG ATAGTAA
AGGGAAAAAATTAAAAAGTGGTATAGAATCCCTTGAAATTGGTCTACGGGTGATGAG TATCGAC
TTAGGTCAACGTCAAGCGGCTGCTGCATCGATTTTTGAAGTAGTTGATCAGAAACCG GATATTG AAGGGAAGTTATTTTTTCCAATCAAAGGAACTGAGCTTTATGCTGTTCACCGGGCAAGTT TTAAC
ATTAAATTACCGGGTGAAACATTAGTAAAATCACGGGAAGTATTGCGGAAAGCTCGG GAGGAC
AACTTAAAATTAATGAATCAAAAGTTAAACTTTCTAAGAAATGTTCTACATTTCCAA CAGTTTGA
AGATATCACAGAAAGAGAGAAGCGTGTAACTAAATGGATTTCTAGACAAGAAAATAG TGATGT
TCCTCTTGTATATCAAGATGAGCTAATTCAAATTCGTGAATTAATGTATAAACCCTA TAAAGATT
GGGTTGCCTTTTTAAAACAACTCCATAAACGGCTAGAAGTCGAGATTGGCAAAGAGG TTAAGCA
TTGGCGAAAATCATTAAGTGACGGGAGAAAAGGTCTTTACGGAATCTCCCTAAAAAA TATTGAT
GAAATTGATCGAACAAGGAAATTCCTTTTAAGATGGAGCTTACGTCCAACAGAACCT GGGGAAG
TAAGACGCTTGGAACCAGGACAGCGTTTTGCGATTGATCAATTAAACCACCTAAATG CATTAAA
AGAAGATCGATTAAAAAAGATGGCAAATACGATTATCATGCATGCCTTAGGTTACTG TTATGAT
GTAAGAAAGAAAAAGTGGCAGGCAAAAAATCCAGCATGTCAAATTATTTTATTTGAA GATTTAT
CTAACTACAATCCTTACGAGGAAAGGTCCCGTTTTGAAAACTCAAAACTGATGAAGT GGTCACG
GAGAGAAATTCCACGACAAGTCGCCTTACAAGGTGAAATTTACGGATTACAAGTTGG GGAAGT
AGGTGCCCAATTCAGTTCAAGATTCCATGCGAAAACCGGGTCGCCGGGAATTCGTTG CAGTGTT
GTAACGAAAGAAAAATTGCAGGATAATCGCTTTTTTAAAAATTTACAAAGAGAAGGA CGACTTA
CTCTTGATAAAATCGCAGTTTTAAAAGAAGGAGACTTATATCCAGATAAAGGTGGAG AAAAGTT
TATTTCTTTATCAAAGGATCGAAAGTTGGTAACTACGCATGCTGATATTAACGCGGC CCAAAATT
TACAGAAGCGTTTTTGGACAAGAACACATGGATTTTATAAAGTTTACTGCAAAGCCT ATCAGGT
TGATGGACAAACTGTTTATATTCCGGAGAGCAAGGACCAAAAACAAAAAATAATTGA AGAATT
TGGGGAAGGCTATTTTATTTTAAAAGATGGTGTATATGAATGGGGTAATGCGGGGAA ACTAAAA
ATTAAAAAAGGTTCCTCTAAACAATCATCGAGTGAATTAGTAGATTCGGACATACTG AAAGATT
CATTTGATTTAGCAAGTGAACTTAAGGGAGAGAAACTCATGTTATATCGAGATCCGA GTGGAAA
CGTATTTCCTTCCGACAAGTGGATGGCAGCAGGAGTATTTTTTGGCAAATTAGAAAG AATATTG
ATTTCTAAGTTAACAAATCAATACTCAATATCAACAATAGAAGATGATTCTTCAAAA CAATCAA
TGTAA
SE ATGCCCACCCGCACCATCAATCTGAAACTTGTTCTTGGGAAAAATCCTGAAAACGCAACA TTGC
Q GACGCGCCCTATTTTCGACACACCGTTTGGTTAACCAAGCGACGAAACGTATTGAGGAAT TCTT
no GTTGCTGTGTCGTGGAGAAGCCTACAGAACAGTGGATAATGAGGGGAAGGAAGCCGAGAT TCC
N ACGTCATGCAGTCCAAGAAGAAGCTCTTGCCTTTGCCAAAGCTGCTCAACGCCACAACGG CTGT
O: ATATCCACCTATGAAGACCAAGAGATTCTTGATGTACTGCGGCAACTGTACGAACGTCTT GTTCC
35 TTCGGTCAACGAAAACAACGAGGCAGGCGATGCTCAAGCTGCTAACGCCTGGGTCAGTCC GCTC
ATGTCGGCAGAAAGCGAAGGAGGCTTGTCGGTCTACGACAAGGTGCTTGATCCACCG CCGGTTT
GGATGAAGCTTAAAGAAGAAAAGGCTCCAGGATGGGAAGCCGCTTCTCAAATTTGGA TTCAGA
GTGATGAGGGACAGTCGTTACTTAATAAGCCAGGTAGCCCTCCCCGCTGGATTCGAA AACTGCG
ATCTGGGCAACCGTGGCAAGATGATTTCGTCAGTGACCAAAAGAAAAAGCAAGATGA GCTGAC
CAAAGGGAACGCACCACTTATAAAACAACTCAAAGAAATGGGGTTGTTGCCTCTTGT TAACCCA
TTTTTTAGACATCTTCTTGACCCTGAAGGTAAAGGCGTGAGTCCATGGGACCGTCTT GCTGTACG
CGCTGCAGTGGCTCACTTTATCTCCTGGGAAAGTTGGAATCATAGAACACGTGCAGA ATACAAT
TCCTTGAAACTACGGCGAGACGAGTTTGAGGCAGCATCCGACGAATTCAAAGACGAT TTTACTT
TGCTCCGACAATATGAAGCCAAACGCCATAGTACATTGAAAAGCATCGCGCTGGCCG ACGATTC
GAACCCTTACCGGATTGGAGTACGTTCTCTGCGTGCCTGGAACCGCGTTCGTGAAGA ATGGATA
GACAAGGGTGCAACAGAAGAACAACGCGTGACCATATTGTCAAAGCTTCAAACACAA CTTCGG GGAAAATTCGGCGATCCCGATCTGTTCAACTGGCTAGCTCAGGATAGGCATGTCCATTTG TGGT
CTCCTCGGGACAGCGTGACACCATTGGTTCGCATCAATGCGGTAGATAAAGTTCTGC GTCGACG
AAAACCGTATGCATTGATGACCTTTGCCCATCCCCGCTTCCACCCTCGATGGATACT GTACGAGG
CTCCAGGAGGAAGCAATCTCCGTCAATATGCATTGGATTGTACAGAAAACGCTCTAC ACATCAC
GTTGCCTTTGCTTGTCGACGATGCGCACGGAACCTGGATTGAAAAAAAGATCAGGGT GCCGCTG
GCACCATCCGGACAAATTCAAGATTTAACTCTGGAAAAACTTGAGAAGAAAAAAAAT CGTTTAT
ACTACCGTTCCGGTTTTCAGCAGTTTGCCGGCTTGGCTGGCGGAGCTGAGGTTCTTT TCCACAGA
CCCTATATGGAACACGACGAACGCAGCGAGGAGTCTCTTTTGGAACGTCCGGGAGCC GTTTGGT
TCAAATTGACCCTGGATGTGGCAACACAGGCTCCCCCGAACTGGCTTGATGGTAAGG GCCGTGT
CCGTACACCGCCGGAGGTACATCATTTTAAAACCGCATTGTCGAATAAAAGCAAACA TACACGT
ACGCTGCAGCCGGGTCTCCGTGTCTTGTCAGTAGACTTGGGCATGCGAACATTCGCC TCCTGCTC
AGTATTTGAACTCATCGAGGGAAAGCCTGAGACAGGCCGTGCCTTCCCTGTTGCCGA TGAGAGA
TCAATGGACAGCCCGAATAAACTGTGGGCCAAGCATGAACGTAGTTTTAAACTGACG CTCCCCG
GCGAAACCCCTTCTCGAAAGGAAGAGGAAGAGCGTAGCATAGCAAGAGCGGAAATTT ATGCAC
TGAAACGCGACATACAACGCCTCAAAAGCCTACTCCGCTTAGGTGAAGAAGATAACG ATAACC
GTCGTGATGCATTGCTTGAACAGTTCTTTAAAGGATGGGGAGAAGAAGACGTTGTGC CTGGACA
AGCGTTTCCACGCTCTCTTTTCCAAGGGTTGGGAGCTGCCCCGTTTCGCTCAACTCC AGAGTTAT
GGCGTCAGCATTGCCAAACATATTATGACAAAGCGGAAGCCTGTCTGGCTAAACATA TCAGTGA
TTGGCGCAAGCGAACTCGTCCCCGTCCGACATCGCGGGAGATGTGGTACAAAACACG TTCCTAT
CATGGCGGCAAGTCCATTTGGATGTTGGAATATCTTGATGCCGTTCGAAAACTGCTT CTCAGTTG
GAGCTTACGTGGTCGTACTTACGGTGCCATTAATCGCCAGGATACAGCCCGGTTTGG TTCTTTGG
CATCACGGCTGCTCCACCATATCAATTCCCTAAAGGAAGACCGCATCAAAACAGGAG CCGACTC
TATCGTTCAGGCTGCTCGCGGGTATATTCCTCTCCCTCATGGCAAGGGTTGGGAACA AAGATAT
GAGCCTTGTCAGCTCATATTATTTGAAGACCTCGCACGATATCGCTTTCGCGTGGAT CGACCTCG
TCGAGAGAACAGCCAACTCATGCAGTGGAACCATCGAGCCATCGTGGCAGAAACAAC GATGCA
AGCCGAACTCTACGGACAAATTGTCGAAAATACTGCAGCGGGGTTCAGCAGTCGTTT TCACGCG
GCGACAGGTGCCCCCGGTGTACGTTGTCGTTTTCTTCTAGAAAGAGACTTTGATAAC GATTTGCC
CAAACCGTACCTTCTCAGGGAACTTTCTTGGATGCTCGGCAATACAAAAGTCGAGTC TGAAGAA
GAAAAGCTTCGATTGCTGTCTGAAAAAATCAGGCCAGGCAGTCTTGTTCCTTGGGAT GGAGGCG
AACAGTTCGCTACCCTGCATCCCAAAAGACAAACACTTTGCGTCATTCATGCCGATA TGAATGC
TGCCCAAAATTTACAACGCCGGTTTTTCGGTCGATGCGGCGAGGCCTTTCGGCTTGT TTGTCAAC
CCCACGGTGACGACGTGTTACGACTCGCATCCACCCCAGGAGCTCGTCTTCTTGGAG CCCTGCA
GCAGCTTGAAAATGGACAAGGAGCTTTCGAGTTGGTTCGAGACATGGGGTCAACAAG TCAAAT
GAACCGGTTCGTCATGAAGTCTTTGGGAAAAAAGAAAATAAAACCCCTTCAGGACAA CAATGG
AGACGACGAGCTTGAAGACGTGTTGTCCGTACTCCCGGAGGAAGACGACACAGGACG TATCAC
AGTCTTCCGCGATTCATCAGGAATCTTTTTTCCTTGCAACGTCTGGATACCGGCCAA ACAGTTTT
GGCCAGCAGTACGCGCCATGATTTGGAAGGTCATGGCTTCCCATTCTTTGGGGTGA
SE ATGACAAAGTTAAGACACCGACAGAAAAAATTAACACACGACTGGGCTGGCTCCAAAAAG AGG
Q GAAGTATTAGGCTCAAATGGCAAGCTTCAGAATCCGTTGTTAATGCCGGTTAAAAAAGGT CAGG
no TTACTGAGTTCCGGAAAGCGTTTTCTGCGTATGCTCGCGCAACGAAAGGAGAAATGACTG ACGG
N CCGAAAGAATATGTTTACGCATAGTTTCGAGCCATTTAAGACAAAGCCCTCGCTTCATCA GTGT
O: GAATTGGCAGATAAAGCATATCAATCTTTACATTCGTATCTGCCTGGTTCTCTTGCTCAT TTTCTA TTATCTGCTCACGCATTAGGTTTTCGTATTTTTTCAAAATCTGGTGAAGCAACTGCATTC CAGGC
ATCCTCTAAAATTGAAGCTTACGAATCAAAATTGGCAAGCGAATTAGCTTGTGTAGA TTTATCTA
TTCAAAACTTGACTATTTCAACGCTTTTTAATGCGCTTACAACGTCTGTAAGAGGGA AGGGCGA
AGAAACTAGCGCTGACCCCTTAATTGCACGATTTTACACCTTACTTACTGGCAAGCC TCTGTCTC
GAGACACTCAAGGGCCTGAACGTGATTTAGCAGAAGTTATCTCGCGTAAGATAGCTA GTTCTTT
TGGCACATGGAAAGAAATGACGGCAAACCCTCTTCAGTCATTACAATTTTTTGAAGA GGAACTC
CATGCGCTGGATGCCAATGTCTCGCTCTCACCCGCCTTCGACGTTTTAATTAAAATG AATGATTT
GCAGGGCGATTTAAAAAATCGAACCATTGTTTTTGATCCTGACGCCCCTGTTTTTGA ATATAACG
CAGAAGACCCTGCCGACATAATTATTAAACTTACAGCTCGTTACGCTAAAGAAGCTG TCATCAA
AAATCAAAACGTAGGAAATTACGTTAAAAACGCTATTACTACCACAAATGCCAATGG TCTTGGT
TGGCTTTTGAACAAAGGTTTGTCGTTACTCCCTGTCTCGACCGATGACGAATTGCTA GAGTTTAT
TGGCGTTGAACGATCTCATCCCTCATGCCATGCCTTAATTGAATTGATTGCACAATT AGAAGCCC
CCGAGCTCTTTGAGAAGAACGTATTTTCAGATACTCGTTCTGAAGTTCAAGGTATGA TTGATTCA
GCTGTTTCTAATCATATTGCTCGTCTTTCCAGCTCTAGAAATAGCTTGTCAATGGAT AGTGAAGA
ATTAGAACGTTTAATCAAAAGCTTTCAGATACACACACCTCATTGCTCACTTTTTAT TGGCGCCC
AATCACTTTCACAGCAGTTAGAATCTTTGCCTGAAGCCCTTCAATCGGGCGTTAATT CAGCCGAT
ATTTTACTAGGCTCTACTCAATATATGCTCACCAATTCTTTGGTTGAAGAGTCAATT GCAACTTA
TCAAAGAACACTTAATCGCATCAATTACTTGTCAGGTGTTGCAGGTCAGATTAACGG CGCAATA
AAGCGAAAAGCGATAGATGGAGAAAAAATTCACTTGCCTGCAGCTTGGTCAGAGTTG ATATCTT
TACCATTTATAGGCCAGCCTGTTATAGATGTTGAAAGCGATTTAGCTCATCTAAAAA ATCAATAC
CAAACACTTTCAAATGAGTTTGATACTCTTATATCTGCTTTGCAAAAGAATTTTGAT TTGAACTT
TAATAAAGCGCTCCTTAATCGTACTCAGCATTTTGAAGCCATGTGTAGAAGCACTAA GAAAAAC
GCTTTATCCAAACCAGAGATCGTTTCCTATCGCGACCTGCTTGCTCGATTAACTTCT TGTTTGTAT
CGAGGCTCTTTAGTTTTGCGTCGTGCCGGCATTGAAGTGTTAAAAAAACATAAAATA TTTGAGTC
AAACAGCGAACTTCGTGAACATGTTCATGAAAGAAAGCATTTCGTGTTTGTTAGTCC TCTAGATC
GCAAAGCCAAGAAACTCCTTCGATTAACTGATTCGCGTCCAGACTTGTTACATGTTA TTGATGAA
ATATTGCAGCACGATAATCTTGAAAACAAAGACCGCGAGTCACTTTGGCTAGTTCGC TCTGGTT
ATTTGCTTGCAGGACTTCCAGATCAACTTTCTTCATCTTTTATTAACTTGCCTATCA TTACTCAAA
AAGGAGATAGACGCCTTATAGACCTGATTCAGTATGATCAAATTAATCGTGATGCTT TTGTTATG
TTAGTGACCTCTGCATTCAAGTCTAATTTGTCTGGTCTGCAGTATCGTGCCAATAAG CAATCGTT
CGTTGTTACTCGCACGCTAAGCCCTTATCTCGGCTCAAAACTTGTCTACGTACCCAA GGATAAAG
ATTGGTTAGTTCCTTCTCAAATGTTTGAAGGACGATTTGCTGACATTCTTCAATCAG ATTATATG
GTCTGGAAAGATGCCGGTCGTCTTTGTGTTATTGATACTGCAAAACACCTTTCTAAT ATAAAGAA
AGACCGAAGTTCGCGGCCTTGGCGTTAATGTCGATGGAATTGCATTTAATAATGGTG ATATTCC
GTCATTAAAAACCTTTTCAAATTGCGTTCAGGTAAAAGTTTCTCGGACTAATACATC CCTAGTTC
AAACACTTAATCGTTGGTTTGAAGGAGGAAAAGTTTCTCCTCCGAGCATTCAATTTG AACGGGC
GTATTATAAAAAAGACGATCAAATTCATGAAGACGCAGCGAAAAGAAAGATACGATT CCAGAT
GCCCGCAACTGAGTTGGTTCATGCTTCTGACGATGCGGGGTGGACACCAAGTTATTT GCTCGGC
ATTGATCCTGGCGAGTATGGAATGGGTCTTTCATTGGTTTCGATTAATAACGGAGAA GTCTTAGA
TTCAGGCTTTATTCATATTAATTCTCTGATCAATTTTGCCTCTAAAAAGAGCAACCA TCAAACTA
AGGTTGTTCCGCGTCAGCAGTACAAATCTCCTTATGCAAATTATTTAGAACAATCTA AAGATTCT GCTGCTGGTGATATTGCGCATATACTCGATCGACTTATATACAAATTAAATGCGTTGCCT GTTTT
TGAGGCTCTTTCAGGTAATTCTCAGAGTGCTGCTGATCAAGTTTGGACGAAAGTCTT ATCGTTTT
ACACTTGGGGTGATAATGACGCTCAGAATTCTATTAGAAAGCAGCATTGGTTTGGAG CCAGTCA
TTGGGATATCAAAGGTATGTTAAGGCAACCCCCTACGGAGAAGAAGCCTAAACCGTA TATTGCT
TTTCCTGGCTCTCAGGTTTCTTCGTATGGTAATTCCCAACGTTGCTCTTGCTGCGGT CGCAATCCT
ATTGAACAACTTCGAGAAATGGCAAAGGATACCTCTATTAAAGAGCTAAAAATTCGC AATTCTG
AGATACAGCTTTTTGACGGAACCATTAAATTATTTAATCCAGACCCATCCACTGTGA TAGAGAG
AAGGCGACATAATCTTGGTCCATCAAGAATTCCTGTTGCTGACCGTACTTTCAAAAA CATCAGTC
CATC AAGTCTAGAATTTAAAGAATTGATT ACT ATCGTGTCTCGATCTATCCGTCATTCACCTGAG
TTTATCGCTAAAAAACGCGGCATAGGGTCTGAGTATTTTTGCGCTTATTCCGATTGC AACTCATC
CTTAAATTCTGAAGCTAACGCAGCTGCTAACGTAGCGCAAAAATTTCAAAAACAGTT ATTTTTTG
AGTTATAA
SE ATGAAGAGAATTCTGAACAGTCTGAAAGTTGCTGCCTTGAGACTTCTGTTTCGAGGCAAA GGTT
Q CTGAATTAGTGAAGACAGTCAAATATCCATTGGTTTCCCCGGTTCAAGGCGCGGTTGAAG AACT
no TGCTGAAGCAATTCGGCACGACAACCTGCACCTTTTTGGGCAGAAGGAAATAGTGGATCT TATG
N GAGAAAGACGAAGGAACCCAGGTGTATTCGGTTGTGGATTTTTGGTTGGATACCCTGCGT TTAG
O: GGATGTTTTTCTCACCATCAGCGAATGCGTTGAAAATCACGCTGGGAAAATTCAATTCTG ATCA
37 GGTTTCACCTTTTCGTAAGGTTTTGGAGCAGTCACCTTTTTTTCTTGCGGGTCGCTTGAA GGTTGA
ACCTGCGGAAAGGATACTTTCTGTTGAAATCAGAAAGATTGGTAAAAGAGAAAACAG AGTTGA
GAACTATGCCGCCGATGTGGAGACATGCTTCATTGGTCAGCTTTCTTCAGATGAGAA ACAGAGT
ATCCAGAAGCTGGCAAATGATATCTGGGATAGCAAGGATCATGAGGAACAGAGAATG TTGAAG
GCGGATTTTTTTGCTATACCTCTTATAAAAGACCCCAAAGCTGTCACAGAAGAAGAT CCTGAAA
ATGAAACGGCGGGAAAACAGAAACCGCTTGAATTATGTGTTTGTCTTGTTCCTGAGT TGTATAC
CCGAGGTTTCGGCTCCATTGCTGATTTTCTGGTTCAGCGACTTACCTTGCTGCGTGA CAAAATGA
GTACCGACACGGCGGAAGATTGCCTCGAGTATGTTGGCATTGAGGAAGAAAAAGGCA ATGGAA
TGAATTCCTTGCTCGGCACTTTTTTGAAGAACCTGCAGGGTGATGGTTTTGAACAGA TTTTTCAG
TTTATGCTTGGGTCTTATGTTGGCTGGCAGGGGAAGGAAGATGTACTGCGCGAACGA TTGGATT
TGCTGGCCGAAAAAGTCAAAAGATTACCAAAGCCAAAATTTGCCGGAGAATGGAGTG GTCATC
GTATGTTTCTCCATGGTCAGCTGAAAAGCTGGTCGTCGAATTTCTTCCGTCTTTTTA ATGAGACG
CGGGAACTTCTGGAAAGTATCAAGAGTGATATTCAACATGCCACCATGCTCATTAGC TATGTGG
AAGAGAAAGGAGGCTATCATCCACAGCTGTTGAGTCAGTATCGGAAGTTAATGGAAC AATTACC
GGCGTTGCGGACTAAGGTTTTGGATCCTGAGATTGAGATGACGCATATGTCCGAGGC TGTTCGA
AGTTACATTATGATACACAAGTCTGTAGCGGGATTTCTGCCGGATTTACTCGAGTCT TTGGATCG
AGATAAGGATAGGGAATTTTTGCTTTCCATCTTTCCTCGTATTCCAAAGATAGATAA GAAGACG
AAAGAGATCGTTGCATGGGAGCTACCGGGCGAGCCAGAGGAAGGCTATTTGTTCACA GCAAAC
AACCTTTTCCGGAATTTTCTTGAGAATCCGAAACATGTGCCACGATTTATGGCAGAG AGGATTCC
CGAGGATTGGACGCGTTTGCGCTCGGCCCCTGTGTGGTTTGATGGGATGGTGAAGCA ATGGCAG
AAGGTGGTGAATCAGTTGGTTGAATCTCCAGGCGCCCTTTATCAGTTCAATGAAAGT TTTTTGCG
TCAAAGACTGCAAGCAATGCTTACGGTCTATAAGCGGGATCTCCAGACTGAGAAGTT TCTGAAG
CTGCTGGCTGATGTCTGTCGTCCACTCGTTGATTTTTTCGGACTTGGAGGAAATGAT ATTATCTTC
AAGTCATGTCAGGATCCAAGAAAGCAATGGCAGACTGTTATTCCACTCAGTGTCCCA GCGGATG
TTTATACAGCATGTGAAGGCTTGGCTATTCGTCTCCGCGAAACTCTTGGATTCGAAT GGAAAAAT CTGAAAGGACACGAGCGGGAAGATTTTTTACGGCTGCATCAGTTGCTGGGAAATCTGCTG TTCT
GGATCAGGGATGCGAAACTTGTCGTGAAGCTGGAAGACTGGATGAACAATCCTTGTG TTCAGGA
GTATGTGGAAGCACGAAAAGCCATTGATCTTCCCTTGGAGATTTTCGGATTTGAGGT GCCGATTT
TTCTCAATGGCTATCTCTTTTCGGAACTGCGCCAGCTGGAATTGTTGCTGAGGCGTA AGTCGGTG
ATGACGTCTTACAGCGTCAAAACGACAGGCTCGCCAAATAGGCTCTTCCAGTTGGTT TACCTAC
CTCTAAACCCTTCAGATCCGGAAAAGAAAAATTCCAACAACTTTCAGGAGCGCCTCG ATACACC
TACCGGTTTGTCGCGTCGTTTTCTGGATCTTACGCTGGATGCATTTGCTGGCAAACT CTTGACGG
ATCCGGTAACTCAGGAACTGAAGACGATGGCCGGTTTTTACGATCATCTCTTTGGCT TCAAGTTG
CCGTGTAAACTGGCGGCGATGAGTAACCATCCAGGATCCTCTTCCAAAATGGTGGTT CTGGCAA
AACCAAAGAAGGGTGTTGCTAGTAACATCGGCTTTGAACCTATTCCCGATCCTGCTC ATCCTGTG
TTCCGGGTGAGAAGTTCCTGGCCGGAGTTGAAGTACCTGGAGGGGTTGTTGTATCTT CCCGAAG
ATACACCACTGACCATTGAACTGGCGGAAACGTCGGTCAGTTGTCAGTCTGTGAGTT CAGTCGC
TTTCGATTTGAAGAATCTGACGACTATCTTGGGTCGTGTTGGTGAATTCAGGGTGAC GGCAGATC
AACCTTTCAAGCTGACGCCCATTATTCCTGAGAAAGAGGAATCCTTCATCGGGAAGA CCTACCT
CGGTCTTGATGCTGGAGAGCGATCTGGCGTTGGTTTCGCGATTGTGACGGTTGACGG CGATGGG
TATGAGGTGCAGAGGTTGGGTGTGCATGAAGATACTCAGCTTATGGCGCTTCAGCAA GTCGCCA
GCAAGTCTCTTAAGGAGCCGGTTTTCCAGCCACTCCGTAAGGGCACATTTCGTCAGC AGGAGCG
CATTCGCAAAAGCCTCCGCGGTTGCTACTGGAATTTCTATCATGCATTGATGATCAA GTACCGAG
CTAAAGTTGTGCATGAGGAATCGGTGGGTTCATCCGGTCTGGTGGGGCAGTGGCTGC GTGCATT
TCAGAAGGATCTCAAAAAGGCTGATGTTCTGCCCAAGAAGGGTGGAAAAAATGGTGT AGACAA
AAAAAAGAGAGAAAGCAGCGCTCAGGATACCTTATGGGGAGGAGCTTTCTCGAAGAA GGAAGA
GCAGCAGATAGCCTTTGAGGTTCAGGCAGCTGGATCAAGCCAGTTTTGTCTGAAGTG TGGTTGG
TGGTTTCAGTTGGGGATGCGGGAAGTAAATCGTGTGCAGGAGAGTGGCGTGGTGCTG GACTGGA
ACCGGTCCATTGTAACCTTCCTCATCGAATCCTCAGGAGAAAAGGTATATGGTTTCA GTCCTCAG
CAACTGGAAAAAGGCTTTCGTCCTGACATCGAAACGTTCAAAAAAATGGTAAGGGAT TTTATGA
GACCCCCCATGTTTGATCGCAAAGGTCGGCCGGCCGCGGCGTATGAAAGATTCGTAC TGGGACG
TCGTCACCGTCGTTATCGCTTTGATAAAGTTTTTGAAGAGAGATTTGGTCGCAGTGC TCTTTTCA
TCTGCCCGCGGGTCGGGTGTGGGAATTTCGATCACTCCAGTGAGCAGTCAGCCGTTG TCCTTGCC
CTTATTGGTTACATTGCTGATAAGGAAGGGATGAGTGGTAAGAAGCTTGTTTATGTG AGGCTGG
CTGAACTTATGGCTGAGTGGAAGCTGAAGAAACTGGAGAGATCAAGGGTGGAAGAAC AGAGCT
CGGCACAATAA
SE ATGGCAGAAAGCAAGCAGATGCAATGCCGCAAGTGCGGCGCAAGCATGAAGTATGAAGTA ATT
Q GGATTGGGCAAGAAGTCATGCAGATATATGTGCCCAGATTGCGGCAATCACACCAGCGCG CGC
no AAGATTCAGAACAAGAAAAAGCGCGACAAAAAGTATGGATCCGCAAGCAAAGCGCAGAGC CA
N GAGGATAGCTGTGGCTGGCGCGCTTTATCCAGACAAAAAAGTGCAGACCATAAAGACCTA CAA
O: ATACCCAGCGGATCTTAATGGCGAAGTTCATGACAGCGGCGTCGCAGAGAAGATTGCGCA GGC
38 GATTCAGGAAGATGAGATCGGCCTGCTTGGCCCGTCCAGCGAATACGCTTGCTGGATTGC TTCA
CAAAAACAGAGCGAGCCGTATTCAGTTGTAGATTTTTGGTTTGACGCGGTGTGCGCA GGCGGAG
TATTCGCGTATTCTGGCGCGCGCCTGCTTTCCACAGTCCTCCAGTTGAGTGGCGAGG AAAGCGTT
TTGCGCGCTGCTTTAGCATCTAGCCCGTTTGTAGATGACATTAATTTGGCGCAAGCG GAAAAGTT
CCTAGCCGTTAGCCGGCGCACAGGCCAAGATAAGCTAGGCAAGCGCATTGGAGAATG TTTTGCG
GAAGGCCGGCTTGAAGCGCTTGGCATCAAAGATCGCATGCGCGAATTCGTGCAAGCG ATTGATG TGGCCCAAACCGCGGGCCAGCGGTTCGCGGCCAAGCTAAAGATATTCGGCATCAGTCAGA TGCC
TGAAGCCAAGCAATGGAACAATGATTCCGGGCTCACTGTATGTATTTTGCCGGATTA TTATGTCC
CGGAAGAAAACCGCGCGGACCAGCTGGTTGTTTTGCTTCGGCGCTTACGCGAGATCG CGTATTG
CATGGGAATTGAGGATGAAGCAGGATTTGAGCATCTAGGCATTGACCCTGGTGCTCT TTCCAAT
TTTTCCAATGGCAATCCAAAGCGAGGATTTCTCGGCCGCCTGCTCAATAATGACATT ATAGCGCT
GGCAAACAACATGTCAGCCATGACGCCGTATTGGGAAGGCAGAAAAGGCGAGTTGAT TGAGCG
CCTTGCATGGCTTAAACATCGCGCTGAAGGATTGTATTTGAAAGAGCCACATTTCGG CAACTCCT
GGGCAGACCACCGCAGCAGGATTTTCAGTCGCATTGCGGGCTGGCTTTCCGGATGCG CGGGCAA
GCTCAAGATTGCCAAGGATCAGATTTCAGGCGTGCGTACGGATTTGTTTCTGCTCAA GCGCCTTC
TGGATGCGGTACCGCAAAGCGCGCCGTCGCCGGACTTTATTGCTTCCATCAGCGCGC TGGATCG
GTTTTTGGAAGCGGCAGAAAGCAGCCAGGATCCGGCAGAACAGGTACGCGCTTTGTA CGCGTTT
CATCTGAACGCGCCTGCGGTCCGATCCATCGCCAACAAGGCGGTACAGAGGTCTGAT TCCCAGG
AGTGGCTTATCAAGGAACTGGATGCTGTAGATCACCTTGAATTCAACAAAGCATTTC CGTTTTTT
TCGGATACAGGAAAGAAAAAGAAGAAAGGAGCGAATAGCAACGGAGCGCCTTCTGAA GAAGA
ATACACGGAAACAGAATCCATTCAACAACCAGAAGATGCAGAGCAGGAAGTGAATGG TCAAGA
AGGAAATGGCGCTTCAAAGAACCAGAAAAAGTTTCAGCGCATTCCTCGATTTTTCGG GGAAGGG
TCAAGGAGTGAGTATCGAATTTTAACAGAAGCGCCGCAATATTTTGACATGTTCTGC AATAATA
TGCGCGCGATCTTTATGCAGCTAGAGAGTCAGCCGCGCAAGGCGCCTCGTGATTTCA AATGCTT
TCTGCAGAATCGTTTGCAGAAGCTTTACAAGCAAACCTTTCTCAATGCTCGCAGTAA TAAATGCC
GCGCGCTTCTGGAATCCGTCCTTATTTCATGGGGAGAATTTTATACTTATGGCGCGA ATGAAAAG
AAGTTTCGTCTGCGCCATGAAGCGAGCGAGCGCAGCTCGGATCCGGACTATGTGGTT CAGCAGG
CATTGGAAATCGCGCGCCGGCTTTTCTTGTTCGGATTTGAGTGGCGCGATTGCTCTG CTGGAGAG
CGCGTGGATTTGGTTGAAATCCACAAAAAAGCAATCTCATTTTTGCTTGCAATCACT CAGGCCG
AGGTTTCAGTTGGTTCCTATAACTGGCTTGGGAATAGCACCGTGAGCCGGTATCTTT CGGTTGCT
GGCACAGACACATTGTACGGCACTCAACTGGAGGAGTTTTTGAACGCCACAGTGCTT TCACAGA
TGCGTGGGCTGGCGATTCGGCTTTCATCTCAGGAGTTAAAAGACGGATTTGATGTTC AGTTGGA
GAGTTCGTGCCAGGACAATCTCCAGCATCTGCTGGTGTATCGCGCTTCGCGCGACTT GGCTGCGT
GCAAACGCGCTACATGCCCGGCTGAATTGGATCCGAAAATTCTTGTTCTGCCGGTTG GTGCGTTT
ATCGCGAGCGTAATGAAAATGATTGAGCGTGGCGATGAACCATTAGCAGGCGCGTAT TTGCGTC
ATCGGCCGCATTCATTCGGCTGGCAGATACGGGTTCGTGGAGTGGCGGAAGTAGGCA TGGATCA
GGGCACAGCGCTAGCATTCCAGAAGCCGACTGAATCAGAGCCGTTTAAAATAAAGCC GTTTTCC
GCTCAATACGGCCCAGTACTTTGGCTTAATTCTTCATCCTATAGCCAGAGCCAGTAT CTGGATGG
ATTTTTAAGCCAGCCAAAGAATTGGTCTATGCGGGTGCTACCTCAAGCCGGATCAGT GCGCGTG
GAACAGCGCGTTGCTCTGATATGGAATTTGCAGGCAGGCAAGATGCGGCTGGAGCGC TCTGGAG
CGCGCGCGTTTTTCATGCCAGTGCCATTCAGCTTCAGGCCGTCTGGTTCAGGAGATG AAGCAGT
ATTGGCGCCGAATCGGTACTTGGGACTTTTTCCGCATTCCGGAGGAATAGAATACGC GGTGGTG
GATGTATTAGATTCCGCGGGTTTCAAAATTCTTGAGCGCGGTACGATTGCGGTAAAT GGCTTTTC
CCAGAAGCGCGGCGAACGCCAAGAGGAGGCACACAGAGAAAAACAGAGACGCGGAAT TTCTG
ATATAGGCCGCAAGAAGCCGGTGCAAGCTGAAGTTGACGCAGCCAATGAATTGCACC GCAAAT
ACACCGATGTTGCCACTCGTTTAGGGTGCAGAATTGTGGTTCAGTGGGCGCCCCAGC CAAAGCC
GGGCACAGCGCCGACCGCGCAAACAGTATACGCGCGCGCAGTGCGGACCGAAGCGCC GCGATC
TGGAAATCAAGAGGATCATGCTCGTATGAAATCCTCTTGGGGATATACCTGGGGCAC CTATTGG GAGAAGCGCAAACCAGAGGATATTTTGGGCATCTCAACCCAAGTATACTGGACCGGCGGT ATA GGCGAGTCATGTCCCGCAGTCGCGGTTGCGCTTTTGGGGCACATTAGGGCAACATCCACT CAAA CTGAATGGGAAAAAGAGGAGGTTGTATTCGGTCGACTGAAGAAGTTCTTTCCAAGCTAG
SE ATGGAAAAGAGAATAAACAAGATACGAAAGAAACTATCGGCCGATAATGCCACAAAGCCT GTG
Q AGCAGGAGCGGCCCCATGAAAACACTCCTTGTCCGGGTCATGACGGACGACTTGAAAAAA AGA
no CTGGAGAAGCGTCGGAAAAAGCCGGAAGTTATGCCGCAGGTTATTTCAAATAACGCAGCA AAC
N AATCTTAGAATGCTCCTTGATGACTATACAAAGATGAAGGAGGCGATACTACAAGTTTAC TGGC
O: AGGAATTTAAGGACGACCATGTGGGCTTGATGTGCAAATTTGCCCAGCCTGCTTCCAAAA AAAT
39 TGACCAGAACAAACTAAAACCGGAAATGGATGAAAAAGGAAATCTAACAACTGCCGGTTT TGC
ATGTTCTCAATGCGGTCAGCCGCTATTTGTTTATAAGCTTGAACAGGTGAGTGAAAA AGGCAAG
GCTTATACAAATTACTTCGGCCGGTGTAATGTGGCCGAGCATGAGAAATTGATTCTT CTTGCTCA
ATTAAAACCTGAAAAAGACAGTGACGAAGCAGTGACATACTCCCTTGGCAAATTCGG CCAGAG
GGCATTGGACTTTTATTCAATCCACGTAACAAAAGAATCCACCCATCCAGTAAAGCC CCTGGCA
CAGATTGCGGGCAACCGCTATGCAAGCGGACCTGTTGGCAAGGCCCTTTCCGATGCC TGTATGG
GCACTATAGCCAGTTTTCTTTCGAAATATCAAGACATCATCATAGAACATCAAAAGG TTGTGAA
GGGTAATCAAAAGAGGTTAGAGAGTCTCAGGGAATTGGCAGGGAAAGAAAATCTTGA GTACCC
ATCGGTTACACTGCCGCCGCAGCCGCATACGAAAGAAGGGGTTGACGCTTATAACGA AGTTATT
GCAAGGGTACGTATGTGGGTTAATCTTAATCTGTGGCAAAAGCTGAAGCTCAGCCGT GATGACG
CAAAACCGCTACTGCGGCTAAAAGGATTCCCATCTTTCCCTGTTGTGGAGCGGCGTG AAAACGA
AGTTGACTGGTGGAATACGATTAATGAAGTAAAAAAACTGATTGACGCTAAACGAGA TATGGG
ACGGGTATTCTGGAGCGGCGTTACCGCAGAAAAGAGAAATACCATCCTTGAAGGATA CAACTAT
CTGCCAAATGAGAATGACCATAAAAAGAGAGAGGGCAGTTTGGAAAACCCTAAGAAG CCTGCC
AAACGCCAGTTTGGAGACCTCTTGCTGTATCTTGAAAAGAAATATGCCGGAGACTGG GGAAAGG
TCTTCGATGAGGCATGGGAGAGGATAGATAAGAAAATAGCCGGACTCACAAGCCATA TAGAGC
GCGAAGAAGCAAGAAACGCGGAAGACGCTCAATCCAAAGCCGTACTTACAGACTGGC TAAGGG
CAAAGGCATCATTTGTTCTTGAAAGACTGAAGGAAATGGATGAAAAGGAATTCTATG CGTGTGA
AATCCAACTTCAAAAATGGTATGGCGATCTTCGAGGCAACCCGTTTGCCGTTGAAGC TGAGAAT
AGAGTTGTTGATATAAGCGGGTTTTCTATCGGAAGCGATGGCCATTCAATCCAATAC AGAAATC
TCCTTGCCTGGAAATATCTGGAGAACGGCAAGCGTGAATTCTATCTGTTAATGAATT ATGGCAA
GAAAGGGCGCATCAGATTTACAGATGGAACAGATATTAAAAAGAGCGGCAAATGGCA GGGACT
ATTATATGGCGGTGGCAAGGCAAAGGTTATTGATCTGACTTTCGACCCCGATGATGA ACAGTTG
ATAATCCTGCCGCTGGCCTTTGGCACAAGGCAAGGCCGCGAGTTTATCTGGAACGAT TTGCTGA
GTCTTGAAACAGGCCTGATAAAGCTCGCAAACGGAAGAGTTATCGAAAAAACAATCT ATAACA
AAAAAATAGGGCGGGATGAACCGGCTCTATTCGTTGCCTTAACATTTGAGCGCCGGG AAGTTGT
TGATCCATCAAATATAAAGCCTGTAAACCTTATAGGCGTTGACCGCGGCGAAAACAT CCCGGCG
GTTATTGCATTGACAGACCCTGAAGGTTGTCCTTTACCGGAATTCAAGGATTCATCA GGGGGCC
CAACAGACATCCTGCGAATAGGAGAAGGATATAAGGAAAAGCAGAGGGCTATTCAGG CAGCAA
AGGAGGTAGAGCAAAGGCGGGCTGGCGGTTATTCACGGAAGTTTGCATCCAAGTCGA GGAACC
TGGCGGACGACATGGTGAGAAATTCAGCGCGAGACCTTTTTTACCATGCCGTTACCC ACGATGC
CGTCCTTGTCTTTGAAAACCTGAGCAGGGGTTTTGGAAGGCAGGGCAAAAGGACCTT CATGACG
GAAAGACAATATACAAAGATGGAAGACTGGCTGACAGCGAAGCTCGCATACGAAGGT CTTACG
TCAAAAACCTACCTTTCAAAGACGCTGGCGCAATATACGTCAAAAACATGCTCCAAC TGCGGGT TTACTATAACGACTGCCGATTATGACGGGATGTTGGTAAGGCTTAAAAAGACTTCTGATG GATG
GGCAACTACCCTCAACAACAAAGAATTAAAAGCCGAAGGCCAGATAACGTATTATAA CCGGTA
TAAAAGGCAAACCGTGGAAAAAGAACTCTCCGCAGAGCTTGACAGGCTTTCAGAAGA GTCGGG
CAATAATGATATTTCTAAGTGGACCAAGGGTCGCCGGGACGAGGCATTATTTTTGTT AAAGAAA
AGATTCAGCCATCGGCCTGTTCAGGAACAGTTTGTTTGCCTCGATTGCGGCCATGAA GTCCACGC
CGATGAACAGGCAGCCTTGAATATTGCAAGGTCATGGCTTTTTCTAAACTCAAATTC AACAGAA
TTCAAAAGTTATAAATCGGGTAAACAGCCCTTCGTTGGTGCTTGGCAGGCCTTTTAC AAAAGGA
GGCTTAAAGAGGTATGGAAGCCCAACGCC
SE ATGAAAAGGATAAATAAAATACGAAGGAGATTGGTAAAGGATAGCAACACGAAAAAAGCC GG
Q CAAAACCGGCCCTATGAAAACCTTGCTCGTTCGGGTTATGACACCTGACCTGAGAGAAAG GTTA
no GAGAATCTTCGCAAAAAGCCGGAAAACATTCCTCAGCCCATTTCAAATACTTCACGTGCA AATT
N TAAATAAACTCCTCACTGACTATACGGAAATGAAGAAAGCAATCCTGCATGTTTATTGGG AAGA
O: GTTCCAAAAAGACCCTGTCGGATTGATGAGCAGGGTTGCACAACCAGCGCCCAAGAATAT TGAT 40 CAGAGAAAATTGATTCCGGTGAAGGACGGAAATGAGAGACTAACAAGTTCTGGATTTGCC TGTT
CTCAGTGCTGTCAACCCCTCTATGTTTATAAGCTTGAACAAGTGAATGACAAGGGTA AGCCCCA
TACAAATTACTTTGGCCGTTGTAATGTCTCCGAGCATGAACGTTTGATATTGCTCTC GCCGCATA
AACCGGAGGCAAATGACGAGCTAGTAACGTATTCGTTGGGGAAGTTCGGTCAAAGGG CATTGG
ACTTTTATTCAATCCACGTAACAAGAGAATCGAACCATCCTGTAAAGCCGCTAGAAC AGATCGG
TGGCAATAGCTGCGCAAGTGGTCCCGTTGGTAAGGCTTTATCTGATGCCTGTATGGG AGCAGTA
GCCAGTTTCCTTACAAAGTACCAGGACATCATCCTCGAACACCAAAAGGTTATAAAA AAAAACG
AAAAGAGATTGGCAAATCTAAAGGATATAGCAAGTGCAAACGGGCTTGCATTTCCTA AAATCAC
TCTTCCACCGCAACCGCATACAAAAGAAGGGATTGAAGCTTATAACAATGTTGTTGC TCAGATA
GTGATCTGGGTAAACCTGAATCTTTGGCAGAAACTCAAAATTGGCAGGGATGAGGCA AAGCCCT
TACAGCGGCTTAAGGGTTTTCCGTCCTTCCCTCTTGTTGAACGCCAGGCGAATGAGG TTGATTGG
TGGGATATGGTCTGTAATGTCAAAAAGTTGATTAACGAAAAGAAAGAGGACGGGAAG GTCTTC
TGGCAAAATCTTGCTGGATATAAAAGGCAGGAAGCCTTGCTTCCATATCTTTCGTCT GAAGAAG
ACCGTAAAAAAGGAAAAAAGTTTGCGCGTTATCAGTTTGGTGACCTTTTGCTTCACC TTGAAAA
GAAACACGGTGAAGATTGGGGCAAAGTTTATGATGAGGCATGGGAAAGAATAGATAA AAAAGT
TGAAGGTCTGAGTAAGCACATAAAGTTGGAGGAAGAAAGAAGGTCTGAAGATGCTCA ATCAAA
GGCTGCCCTCACTGATTGGCTCAGGGCAAAGGCCTCTTTTGTTATTGAAGGGCTCAA AGAAGCT
GATAAGGATGAGTTTTGCAGGTGTGAGTTAAAGCTTCAAAAGTGGTATGGAGATTTG AGAGGAA
AACCATTTGCTATAGAAGCAGAGAACAGCATTTTAGATATAAGCGGATTTTCTAAAC AGTATAA
TTGTGCATTTATATGGCAGAAAGACGGCGTAAAGAAGTTAAATCTTTATTTAATAAT AAATTACT
TCAAAGGTGGTAAGCTACGCTTCAAAAAAATCAAGCCAGAAGCTTTTGAAGCAAATA GGTTTTA
TACAGTAATTAATAAAAAAAGCGGTGAGATTGTGCCTATGGAGGTCAACTTCAATTT TGATGAC
CCGAATTTGATAATTCTGCCTTTGGCCTTTGGAAAAAGGCAGGGGAGGGAGTTTATC TGGAACG
ACCTATTGAGCCTTGAGACGGGTTCATTGAAACTCGCCAATGGCAGGGTTATTGAAA AAACGCT
CTATAACAGAAGGACGAGACAGGATGAACCAGCACTTTTTGTTGCCCTGACATTTGA AAGAAGA
GAGGTGCTTGACTCATCGAATATAAAACCGATGAATCTGATAGGAATAGACCGGGGA GAAAAT
ATCCCGGCAGTCATAGCATTAACAGACCCGGAAGGATGCCCCTTGTCAAGATTCAAA GATTCAT
TGGGCAATCCAACGCATATTTTGCGAATAGGAGAAAGTTATAAGGAAAAACAACGGA CTATTC
AGGCTGCTAAAGAAGTTGAACAAAGGCGGGCAGGCGGATATTCGAGAAAATATGCAT CAAAGG CGAAGAATCTGGCGGACGATATGGTAAGAAATACAGCTCGTGACCTCTTATATTATGCTG TTAC
TCAAGATGCAATGCTCATTTTTGAAAATCTTTCCCGCGGTTTTGGTAGACAAGGCAA GAGGACTT
TTATGGCGGAAAGGCAGTACACGAGGATGGAAGACTGGCTGACTGCAAAGCTTGCCT ATGAAG
GTCTGCCATCAAAAACCTATCTTTCAAAGACTCTGGCACAGTATACCTCAAAGACAT GTTCTAAT
TGTGGTTTTACAATCACAAGTGCAGATTATGACAGGGTGCTCGAAAAGCTCAAGAAG ACGGCTA
CTGGATGGATGACTACAATCAATGGAAAAGAGTTAAAAGTTGAAGGACAGATAACAT ACTATA
ACCGGTATAAAAGGCAGAATGTGGTAAAAGACCTCTCTGTAGAGCTGGATAGACTTT CGGAAG
AGTCGGTAAATAATGATATTTCTAGTTGGACAAAAGGCCGCAGTGGTGAAGCTTTAT CTCTGCT
AAAAAAGAGATTTAGTCACAGGCCGGTGCAGGAAAAGTTTGTTTGCCTGAACTGTGG TTTTGAA
ACCCATGCAGACGAACAAGCAGCACTGAATATTGCAAGGTCGTGGCTCTTTCTCCGT TCTCAAG
AATATAAGAAGTATCAAACCAATAAAACGACCGGAAATACTGACAAAAGGGCATTTG TTGAAA
CATGGCAATCCTTTTACAGAAAGAAGCTCAAAGAAGTATGGAAACCA
SE ATGGGTAAAATGTATTACCTTGGTTTAGACATTGGCACGAATTCCGTGGGCTACGCGGTG ACCG
Q ACCCCTCATACCACCTGCTGAAGTTTAAGGGGGAACCAATGTGGGGTGCGCACGTATTTG CCGC
no CGGTAATCAGAGCGCGGAACGACGCTCGTTCCGCACATCGCGTCGTCGTTTGGACCGACG CCAA
N CAGCGCGTTAAACTGGTACAGGAGATTTTTGCCCCGGTGATTAGTCCGATCGACCCACGC TTCTT
O: CATTCGTCTGCATGAATCCGCCCTGTGGCGCGATGACGTCGCGGAGACGGATAAACATAT CTTT 41 TTCAATGATCCTACCTATACCGATAAGGAATATTATAGCGATTACCCGACTATCCATCAC CTGAT
CGTTGATCTGATGGAAAGCTCTGAGAAACACGATCCGCGGCTGGTGTACCTTGCAGT GGCGTGG
TTAGTGGCACACCGTGGTCATTTTCTGAACGAGGTGGACAAGGATAATATTGGAGAT GTGTTGT
CGTTCGACGCATTTTATCCGGAGTTTCTCGCGTTCCTGTCGGACAACGGTGTATCAC CGTGGGTG
TGCGAAAGCAAAGCGCTGCAGGCGACCTTGCTGAGCCGTAACTCAGTGAACGACAAA TATAAA
GCCCTTAAGTCTCTGATCTTCGGATCCCAGAAACCTGAAGATAACTTCGATGCCAAT ATTTCGGA
AGATGGACTCATTCAACTGCTGGCCGGCAAAAAGGTAAAAGTTAACAAACTGTTCCC TCAGGAA
TCGAACGATGCATCCTTCACATTGAATGATAAAGAAGACGCGATAGAAGAAATCCTG GGTACGC
TTACACCAGATGAATGTGAATGGATTGCGCATATACGCCGCCTTTTTGACTGGGCTA TCATGAA
ACATGCTCTGAAAGATGGCAGGACTATTAGCGAGTCAAAAGTCAAACTGTATGAGCA GCACCAT
CACGATCTGACCCAACTTAAATACTTCGTGAAAACCTACCTTGCAAAAGAATACGAC GATATTT
TCCGCAACGTGGATAGCGAAACAACGAAAAACTATGTAGCGTATTCCTATCATGTGA AAGAGGT
GAAAGGCACTCTGCCTAAAAATAAGGCAACGCAAGAAGAGTTTTGTAAGTATGTCCT GGGCAA
GGTTAAAAACATTGAATGCTCTGAAGCAGACAAGGTTGACTTTGATGAGATGATTCA GCGTCTT
ACCGACAACTCTTTTATGCCTAAGCAGGTTTCGGGCGAAAACCGCGTTATTCCTTAT CAGTTATA
TTATTATGAACTGAAGACAATTCTGAATAAAGCAGCCTCGTACCTGCCTTTCCTGAC GCAGTGTG
GAAAAGATGCAATTTCGAACCAGGACAAACTACTGTCGATCATGACGTTCCGTATTC CTTACTTC
GTCGGACCCTTGCGAAAAGATAATTCGGAACATGCATGGCTCGAACGAAAGGCCGGT AAGATTT
ATCCGTGGAACTTTAACGACAAAGTGGACTTGGATAAATCAGAAGAAGCGTTCATTC GCCGAAT
GACCAATACCTGTACCTATTATCCCGGCGAAGATGTTTTACCGTTGGATTCGCTGAT CTATGAGA
AATTTATGATTTTAAATGAAATCAATAATATTCGTATTGACGGCTACCCGATTAGTG TTGACGTT
AAACAGCAGGTTTTTGGCTTGTTCGAAAAAAAACGACGCGTAACCGTGAAAGATATT CAGAACC
TGCTGCTGTCTCTCGGAGCTCTGGACAAACACGGGAAGCTGACAGGCATCGATACCA CTATCCA
CTCAAACTATAATACGTATCACCATTTTAAATCTCTCATGGAACGCGGCGTCCTGAC CCGGGATG
ACGTGGAACGCATCGTTGAAAGGATGACCTACAGCGACGATACTAAGCGTGTGCGTC TGTGGCT GAATAACAACTATGGTACTTTAACCGCCGACGATGTGAAACACATTTCGCGTCTGCGCAA ACAC
GATTTTGGCCGTTTATCCAAAATGTTCTTAACAGGTCTGAAGGGTGTCCATAAGGAG ACCGGTG
AACGTGCCTCCATACTGGATTTCATGTGGAACACGAACGATAACCTGATGCAGCTCC TTTCCGA
ATGCTACACGTTCAGTGATGAAATCACAAAGCTGCAAGAGGCGTATTATGCAAAAGC CCAGTTG
TCTTTAAACGATTTTTTAGACTCGATGTACATCTCTAACGCGGTGAAACGTCCGATT TACAGAAC
TCTGGCAGTGGTGAACGATATTCGAAAAGCATGTGGGACGGCCCCTAAACGCATTTT CATCGAA
ATGGCTCGTGATGGTGAATCAAAAAAAAAGAGAAGTGTTACACGTCGCGAGCAGATC AAAAAC
CTGTACCGCTCGATTCGTAAAGATTTCCAGCAGGAAGTTGATTTTCTGGAAAAGATC CTGGAAA
ATAAATCTGATGGTCAACTTCAGTCAGATGCTTTGTATCTTTACTTTGCACAATTAG GGCGCGAT
ATGTACACGGGCGATCCAATAAAGCTGGAGCACATCAAAGATCAGAGTTTCTATAAC ATAGACC
ATATTTACCCGCAGTCTATGGTGAAAGACGATTCCCTAGATAACAAAGTGCTGGTGC AAAGCGA
AATTAACGGCGAGAAAAGCTCGCGATACCCTTTGGACGCCGCGATCCGCAATAAAAT GAAGCC
CCTTTGGGACGCTTACTATAATCATGGCCTGATCTCCTTAAAGAAATACCAGCGTCT AACGCGCT
CGACCCCGTTTACCGATGATGAAAAATGGGACTTTATTAATCGCCAGTTAGTGGAAA CCCGTCA
ATCTACCAAAGCGCTGGCCATTTTGTTGAAGCGTAAGTTTCCAGACACCGAAATTGT GTATTCGA
AGGCGGGGTTATCGTCCGACTTCAGACATGAATTCGGCCTTGTAAAAAGTCGCAATA TTAATGA
TTTGCACCACGCTAAAGACGCATTCTTGGCTATCGTTACCGGCAATGTGTACCATGA AAGATTCA
ATCGCAGATGGTTTATGGTGAACCAGCCGTACTCAGTTAAAACTAAAACTCTTTTTA CCCACAGC
ATAAAGAATGGCAACTTCGTTGCCTGGAACGGCGAAGAAGATCTCGGTCGTATTGTA AAAATGC
TGAAGCAAAACAAAAATACCATTCACTTCACGCGCTTCTCCTTCGATCGCAAAGAAG GATTATT
TGATATCCAACCTCTGAAAGCCAGCACCGGCTTAGTCCCACGAAAAGCCGGTCTGGA TGTCGTT
AAATACGGCGGATATGACAAATCTACCGCGGCCTATTACCTGCTGGTGAGGTTCACG CTCGAGG
ACAAGAAAACCCAGCACAAGCTGATGATGATTCCTGTAGAAGGCCTGTACAAGGCTC GCATTGA
TCATGACAAGGAATTTCTTACCGATTATGCGCAAACGACTATAAGCGAAATCCTACA GAAAGAT
AAACAGAAAGTGATCAATATTATGTTTCCAATGGGTACGAGGCATATAAAACTCAAT TCAATGA
TTAGTATCGATGGCTTCTATCTTAGTATCGGCGGAAAGTCCTCTAAAGGTAAGTCAG TTCTATGT
CACGCAATGGTTCCACTGATCGTCCCTCACAAAATCGAATGTTACATTAAAGCAATG GAAAGCT
TCGCCCGGAAGTTTAAAGAAAACAACAAGCTGCGCATCGTAGAAAAATTCGATAAAA TCACCG
TTGAAGACAACCTGAATCTCTACGAGCTCTTTCTCCAAAAACTGCAGCATAATCCCT ATAATAA
GTTTTTTTCGACACAGTTTGACGTACTGACGAACGGCCGTTCTACTTTCACAAAACT GTCGCCGG
AGGAACAGGTACAGACGCTCTTGAACATTTTAAGTATCTTTAAAACATGCCGCAGTT CGGGTTG
CGACCTGAAATCCATCAACGGCAGTGCCCAGGCAGCGCGCATCATGATTAGCGCTGA CTTAACT
GGACTGTCGAAAAAATATTCAGATATTAGGTTGGTTGAACAGTCAGCTTCTGGTTTG TTCGTATC
CAAAAGTCAGAACTTACTGGAGTATCTCTAA
SE ATGTCATCGCTCACGAAATTCACTAACAAATACTCTAAACAGCTCACCATTAAGAATGAA CTCA
Q TCCCAGTTGGCAAAACACTGGAGAACATCAAAGAGAATGGTCTGATAGATGGCGACGAAC AGC
no TGAATGAGAATTATCAGAAGGCGAAAATTATTGTGGATGATTTTCTGCGGGACTTCATTA ATAA
N AGCACTGAATAATACGCAGATCGGGAACTGGCGCGAACTGGCGGATGCCCTTAATAAAGA GGA
O: TGAAGATAACATCGAGAAATTGCAGGATAAAATTCGGGGAATCATTGTATCCAAATTTGA AACG 42 TTTGATCTGTTTAGCAGCTATTCTATTAAGAAAGATGAAAAGATTATTGACGACGACAAT GATG
TTGAAGAAGAGGAACTGGATCTGGGCAAGAAGACCAGCTCATTTAAATACATATTTA AAAAAA
ACCTGTTTAAGTTAGTGTTGCCATCCTACCTGAAAACCACAAACCAGGACAAGCTGA AGATTAT TAGCTCGTTTGATAATTTTTCAACGTACTTCCGCGGGTTCTTTGAAAACCGGAAAAACAT TTTTA
CCAAGAAACCGATCTCCACAAGTATTGCGTATCGCATTGTTCATGATAACTTCCCGA AATTCCTT
GATAACATTCGTTGTTTTAATGTGTGGCAGACGGAATGCCCGCAACTAATCGTGAAA GCAGATA
ACTATCTGAAAAGCAAAAATGTTATAGCGAAAGATAAAAGTTTGGCAAACTATTTTA CCGTGGG
CGCGTATGACTATTTCCTGTCTCAGAATGGTATAGATTTTTACAACAATATTATAGG TGGACTGC
CAGCGTTCGCCGGCCATGAGAAAATCCAAGGTCTCAATGAATTCATCAATCAAGAGT GCCAAAA
AGACAGCGAGCTGAAAAGTAAGCTGAAAAACCGTCACGCGTTCAAAATGGCGGTACT GTTCAA
ACAGATACTCAGCGATCGTGAAAAAAGTTTTGTAATTGATGAGTTCGAGTCGGATGC TCAAGTT
ATTGACGCCGTTAAAAACTTTTACGCCGAACAGTGCAAAGATAACAATGTTATTTTT AACTTATT
AAATCTTATCAAGAATATCGCTTTCTTAAGTGATGACGAACTGGACGGCATATTCAT TGAAGGG
AAATACCTGTCGAGCGTTAGTCAAAAACTCTATAGCGATTGGTCAAAATTACGTAAC GACATTG
AGGATTCGGCTAACTCTAAACAAGGCAATAAAGAGCTGGCCAAGAAGATCAAAACCA ACAAAG
GGGATGTAGAAAAAGCGATCTCGAAATATGAGTTCTCGCTGTCGGAACTGAACTCGA TTGTACA
TGATAACACCAAGTTTTCTGACCTCCTTAGTTGTACACTGCATAAGGTGGCTTCTGA GAAACTGG
TGAAGGTCAATGAAGGCGACTGGCCGAAACATCTCAAGAATAATGAAGAGAAACAAA AAATCA
AAGAGCCGCTTGATGCTCTGCTGGAGATCTATAATACACTTCTGATTTTTAACTGCA AAAGCTTC
AATAAAAACGGCAACTTCTATGTCGACTATGATCGTTGCATCAATGAACTGAGTTCG GTCGTGT
ATCTGTATAATAAAACACGTAACTATTGCACTAAAAAACCCTATAACACGGACAAGT TCAAACT
CAATTTTAACAGTCCGCAGCTCGGTGAAGGCTTTTCCAAGTCGAAAGAAAATGACTG TCTGACT
CTTTTGTTTAAAAAAGACGACAACTATTATGTAGGCATTATCCGCAAAGGTGCAAAA ATCAATT
TTGATGATACACAAGCAATCGCCGATAACACCGACAATTGCATCTTTAAAATGAATT ATTTCCTA
CTTAAAGACGCAAAAAAATTTATCCCGAAATGTAGCATTCAGCTGAAAGAAGTCAAG GCCCATT
TTAAGAAATCTGAAGATGATTACATTTTGTCTGATAAAGAGAAATTTGCTAGCCCGC TGGTCATT
AAAAAGAGCACATTTTTGCTGGCAACTGCACATGTGAAAGGGAAAAAAGGCAATATC AAGAAA
TTTCAGAAAGAATATTCGAAAGAAAACCCCACTGAGTATCGCAATTCTTTAAACGAA TGGATTG
CTTTTTGTAAAGAGTTCTTAAAAACTTATAAAGCGGCTACCATTTTTGATATAACCA CATTGAAA
AAGGCAGAGGAATATGCTGATATTGTAGAATTCTACAAGGATGTCGATAATCTGTGC TACAAAC
TGGAGTTCTGCCCGATTAAAACCTCGTTTATAGAAAACCTGATAGATAACGGCGACC TGTATCT
GTTTCGCATCAATAACAAAGACTTCAGCAGTAAATCGACCGGCACCAAGAACCTTCA TACGTTA
TATTTACAAGCTATATTCGATGAACGTAATCTGAACAATCCGACAATTATGCTGAAT GGGGGAG
CAGAACTGTTCTATCGTAAAGAAAGTATTGAGCAGAAAAACCGTATCACACACAAAG CCGGTTC
AATTCTCGTGAATAAGGTGTGTAAAGACGGTACAAGCCTGGATGATAAGATACGTAA TGAAATT
TATCAATATGAGAATAAATTTATTGATACCCTGTCTGATGAAGCTAAAAAGGTGTTA CCGAATG
TCATTAAAAAGGAAGCTACCCATGACATTACAAAAGATAAACGTTTCACTAGTGACA AATTCTT
CTTTCACTGCCCCCTGACAATTAATTATAAGGAAGGCGATACCAAGCAGTTCAATAA CGAAGTG
CTGAGTTTTCTGCGTGGAAATCCTGACATCAACATTATCGGCATTGACCGCGGAGAG CGTAATTT
AATCTATGTAACGGTTATAAACCAGAAAGGCGAGATTCTGGATTCGGTTTCATTCAA TACCGTG
ACCAACAAGAGTTCAAAAATCGAGCAGACAGTCGATTATGAAGAGAAATTGGCAGTC CGCGAG
AAAGAGAGGATTGAAGCAAAACGTTCCTGGGACTCTATCTCAAAAATTGCGACACTA AAGGAA
GGTTATCTGAGCGCAATAGTTCACGAGATCTGTCTGTTAATGATTAAACACAACGCG ATCGTTGT
CTTAGAGAATCTTAATGCAGGCTTTAAGCGTATTCGTGGCGGTTTATCAGAAAAAAG TGTTTATC
AAAAATTCGAAAAAATGTTGATTAACAAACTGAACTATTTTGTCAGCAAGAAGGAAT CCGACTG GAATAAACCGTCTGGTCTGCTGAATGGACTGCAGCTTTCGGATCAGTTTGAAAGCTTCGA AAAA
CTGGGTATTCAGTCTGGTTTTATTTTTTACGTGCCGGCTGCATATACCTCAAAGATT GATCCGAC
CACGGGCTTCGCCAATGTTCTGAATCTGTCGAAGGTACGCAATGTTGATGCGATCAA AAGCTTTT
TTTCTAACTTCAACGAAATTAGTTATAGCAAGAAAGAAGCCCTTTTCAAATTCTCAT TCGATCTG
GATTCACTGAGTAAGAAAGGCTTTAGTAGCTTTGTGAAATTTAGTAAGAGTAAATGG AACGTCT
ACACCTTTGGAGAACGTATCATAAAGCCAAAGAATAAGCAAGGTTATCGGGAGGACA AAAGAA
TCAACTTGACCTTCGAGATGAAGAAGTTACTTAACGAGTATAAGGTTTCTTTTGATC TTGAAAAT
AACTTGATTCCGAATCTCACGAGTGCCAACCTGAAGGATACTTTTTGGAAAGAGCTA TTCTTTAT
CTTCAAGACTACGCTGCAGCTCCGTAACAGCGTTACTAACGGTAAAGAAGATGTGCT CATCTCT
CCGGTCAAAAATGCGAAGGGTGAATTCTTCGTTTCGGGAACGCATAACAAGACTCTT CCGCAAG
ATTGCGATGCGAACGGTGCATACCATATTGCGTTGAAAGGTCTGATGATACTCGAAC GTAACAA
CCTTGTACGTGAGGAGAAAGATACGAAAAAGATTATGGCGATTTCAAACGTGGATTG GTTCGAG
TACGTGCAGAAACGTAGAGGCGTTCTGTAA
SE ATGAACAACTACGACGAATTCACCAAACTGTACCCGATCCAGAAAACCATCCGTTTCGAA CTGA
Q AACCGCAGGGTCGTACCATGGAACACCTGGAAACCTTCAACTTCTTCGAAGAAGACCGTG ACCG
no TGCGGAAAAATACAAAATCCTGAAAGAAGCGATCGACGAATACCACAAAAAATTCATCGA CGA
N ACACCTGACCAACATGTCTCTGGACTGGAACTCTCTGAAACAGATCTCTGAAAAATACTA CAAA
O: TCTCGTGAAGAAAAAGACAAAAAAGTTTTCCTGTCTGAACAGAAACGTATGCGTCAGGAA ATCG 43 TTTCTGAATTCAAAAAAGACGACCGTTTCAAAGACCTGTTCTCTAAAAAACTGTTCTCTG AACTG
CTGAAAGAAGAAATCTACAAAAAAGGTAACCACCAGGAAATCGACGCGCTGAAATCT TTCGAC
AAATTCTCTGGTTACTTCATCGGTCTGCACGAAAACCGTAAAAACATGTACTCTGAC GGTGACG
AAATCACCGCGATCTCTAACCGTATCGTTAACGAAAACTTCCCGAAATTCCTGGACA ACCTGCA
GAAATACCAGGAAGCGCGTAAAAAATACCCGGAATGGATCATCAAAGCGGAATCTGC GCTGGT
TGCGCACAACATCAAAATGGACGAAGTTTTCTCTCTGGAATACTTCAACAAAGTTCT GAACCAG
GAAGGTATCCAGCGTTACAACCTGGCGCTGGGTGGTTACGTTACCAAATCTGGTGAA AAAATGA
TGGGTCTGAACGACGCGCTGAACCTGGCGCACCAGTCTGAAAAATCTTCTAAAGGTC GTATCCA
CATGACCCCGCTGTTCAAACAGATCCTGTCTGAAAAAGAATCTTTCTCTTACATCCC GGACGTTT
TCACCGAAGACTCTCAGCTGCTGCCGTCTATCGGTGGTTTCTTCGCGCAGATCGAAA ACGACAA
AGACGGTAACATCTTCGACCGTGCGCTGGAACTGATCTCTTCTTACGCGGAATACGA CACCGAA
CGTATCTACATCCGTCAGGCGGACATCAACCGTGTTTCTAACGTTATCTTCGGTGAA TGGGGTAC
CCTGGGTGGTCTGATGCGTGAATACAAAGCGGACTCTATCAACGACATCAACCTGGA ACGTACC
TGCAAAAAAGTTGACAAATGGCTGGACTCTAAAGAATTCGCGCTGTCTGACGTTCTG GAAGCGA
TCAAACGTACCGGTAACAACGACGCGTTCAACGAATACATCTCTAAAATGCGTACCG CGCGTGA
AAAAATCGACGCGGCGCGTAAAGAAATGAAATTCATCTCTGAAAAAATCTCTGGTGA CGAAGA
ATCTATCCACATCATCAAAACCCTGCTGGACTCTGTTCAGCAGTTCCTGCACTTCTT CAACCTGT
TCAAAGCGCGTCAGGACATCCCGCTGGACGGTGCGTTCTACGCGGAATTCGACGAAG TTCACTC
TAAACTGTTCGCGATCGTTCCGCTGTACAACAAAGTTCGTAACTACCTGACCAAAAA CAACCTG
AACACCAAAAAAATCAAACTGAACTTCAAAAACCCGACCCTGGCGAACGGTTGGGAC CAGAAC
AAAGTTTACGACTACGCGTCTCTGATCTTCCTGCGTGACGGTAACTACTACCTGGGT ATCATCAA
CCCGAAACGTAAAAAAAACATCAAATTCGAACAGGGTTCTGGTAACGGTCCGTTCTA CCGTAAA
ATGGTTTACAAACAGATCCCGGGTCCGAACAAAAACCTGCCGCGTGTTTTCCTGACC TCTACCA
AAGGTAAAAAAGAATACAAACCGTCTAAAGAAATCATCGAAGGTTACGAAGCGGACA AACACA TCCGTGGTGACAAATTCGACCTGGACTTCTGCCACAAACTGATCGACTTCTTCAAAGAAT CTATC
GAAAAACACAAAGACTGGTCTAAATTCAACTTCTACTTCTCTCCGACCGAATCTTAC GGTGACA
TCTCTGAATTCTACCTGGACGTTGAAAAACAGGGTTACCGTATGCACTTCGAAAACA TCTCTGCG
GAAACCATCGACGAATACGTTGAAAAAGGTGACCTGTTCCTGTTCCAGATCTACAAC AAAGACT
TCGTTAAAGCGGCGACCGGTAAAAAAGACATGCACACCATCTACTGGAACGCGGCGT TCTCTCC
GGAAAACCTGCAGGACGTTGTTGTTAAACTGAACGGTGAAGCGGAACTGTTCTACCG TGACAAA
TCTGACATCAAAGAAATCGTTCACCGTGAAGGTGAAATCCTGGTTAACCGTACCTAC AACGGTC
GTACCCCGGTTCCGGACAAAATCCACAAAAAACTGACCGACTACCACAACGGTCGTA CCAAAG
ACCTGGGTGAAGCGAAAGAATACCTGGACAAAGTTCGTTACTTCAAAGCGCACTACG ACATCAC
CAAAGACCGTCGTTACCTGAACGACAAAATCTACTTCCACGTTCCGCTGACCCTGAA CTTCAAA
GCGAACGGTAAAAAAAACCTGAACAAAATGGTTATCGAAAAATTCCTGTCTGACGAA AAAGCG
CACATCATCGGTATCGACCGTGGTGAACGTAACCTGCTGTACTACTCTATCATCGAC CGTTCTGG
TAAAATCATCGACCAGCAGTCTCTGAACGTTATCGACGGTTTCGACTACCGTGAAAA ACTGAAC
CAGCGTGAAATCGAAATGAAAGACGCGCGTCAGTCTTGGAACGCGATCGGTAAAATC AAAGAC
CTGAAAGAAGGTTACCTGTCTAAAGCGGTTCACGAAATCACCAAAATGGCGATCCAG TACAACG
CGATCGTTGTTATGGAAGAACTGAACTACGGTTTCAAACGTGGTCGTTTCAAAGTTG AAAAACA
GATCTACCAGAAATTCGAAAACATGCTGATCGACAAAATGAACTACCTGGTTTTCAA AGACGCG
CCGGACGAATCTCCGGGTGGTGTTCTGAACGCGTACCAGCTGACCAACCCGCTGGAA TCTTTCG
CGAAACTGGGTAAACAGACCGGTATCCTGTTCTACGTTCCGGCGGCGTACACCTCTA AAATCGA
CCCGACCACCGGTTTCGTTAACCTGTTCAACACCTCTTCTAAAACCAACGCGCAGGA ACGTAAA
GAATTCCTGCAGAAATTCGAATCTATCTCTTACTCTGCGAAAGACGGTGGTATCTTC GCGTTCGC
GTTCGACTACCGTAAATTCGGTACCTCTAAAACCGACCACAAAAACGTTTGGACCGC GTACACC
AACGGTGAACGTATGCGTTACATCAAAGAAAAAAAACGTAACGAACTGTTCGACCCG TCTAAA
GAAATCAAAGAAGCGCTGACCTCTTCTGGTATCAAATACGACGGTGGTCAGAACATC CTGCCGG
ACATCCTGCGTTCTAACAACAACGGTCTGATCTACACCATGTACTCTTCTTTCATCG CGGCGATC
CAGATGCGTGTTTACGACGGTAAAGAAGACTACATCATCTCTCCGATCAAAAACTCT AAAGGTG
AATTCTTCCGTACCGACCCGAAACGTCGTGAACTGCCGATCGACGCGGACGCGAACG GTGCGTA
CAACATCGCGCTGCGTGGTGAACTGACCATGCGTGCGATCGCGGAAAAATTCGACCC GGACTCT
GAAAAAATGGCGAAACTGGAACTGAAACACAAAGACTGGTTCGAATTCATGCAGACC CGTGGT
GACTAA
SE ATGACTAAAACATTTGATTCAGAGTTTTTTAATTTGTACTCGCTGCAAAAAACGGTACGC TTTGA
Q GTTAAAACCCGTGGGAGAAACCGCGTCATTTGTGGAAGACTTTAAAAACGAGGGCTTGAA ACGT
no GTTGTGAGCGAAGATGAAAGGCGAGCCGTCGATTACCAGAAAGTTAAGGAAATAATTGAC GAT
N TACCATCGGGATTTCATTGAAGAAAGTTTAAATTATTTTCCGGAACAGGTGAGTAAAGAT GCTC
O: TTGAGCAGGCGTTTCATCTTTATCAGAAACTGAAGGCAGCAAAAGTTGAGGAAAGGGAAA AAG 44 CGCTGAAAGAATGGGAAGCGCTGCAGAAAAAGCTACGTGAAAAAGTGGTGAAATGCTTCT CGG
ACTCGAATAAAGCCCGCTTCTCAAGGATTGATAAAAAGGAACTGATTAAGGAAGACC TGATAA
ATTGGTTGGTCGCCCAGAATCGCGAGGATGATATCCCTACGGTCGAAACGTTTAACA ACTTCAC
CACATATTTTACCGGCTTCCATGAGAATCGTAAAAATATTTACTCCAAAGATGATCA CGCCACC
GCTATTAGCTTTCGCCTTATTCATGAAAATCTTCCAAAGTTTTTTGACAACGTGATT AGCTTCAAT
AAGTTGAAAGAGGGTTTCCCTGAATTAAAATTTGATAAAGTGAAAGAGGATTTAGAA GTAGATT
ATGATCTGAAGCATGCGTTTGAAATAGAATATTTCGTTAACTTCGTGACCCAAGCGG GCATAGA TCAGTATAATTATCTGTTAGGAGGGAAAACCCTGGAGGACGGGACGAAAAAACAAGGGAT GAA
TGAGCAAATTAATCTGTTCAAACAACAGCAAACGCGAGATAAAGCGCGTCAGATTCC CAAACTG
ATCCCCCTGTTCAAACAGATTCTTAGCGAAAGGACTGAAAGCCAGTCCTTTATTCCT AAACAATT
TGAAAGTGATCAGGAGTTGTTCGATTCACTGCAGAAGTTACATAATAACTGCCAGGA TAAATTC
ACCGTGCTGCAACAAGCCATTCTCGGTCTGGCAGAGGCGGATCTTAAGAAGGTCTTC ATCAAAA
CCTCTGATTTAAATGCCTTATCTAACACCATTTTCGGGAATTACAGCGTCTTTTCCG ATGCACTG
AACCTGTATAAAGAAAGCCTGAAAACGAAAAAAGCGCAGGAGGCTTTTGAGAAACTA CCGGCC
CATTCTATTCACGACCTCATTCAATACTTGGAACAGTTCAATTCCAGCCTGGACGCG GAAAAAC
AACAGAGCACCGACACCGTCCTGAACTACTTCATCAAGACCGATGAATTATATTCTC GCTTCATT
AAATCCACTAGCGAGGCTTTCACTCAGGTGCAGCCTTTGTTCGAACTGGAAGCCCTG TCATCTAA
GCGCCGCCCACCGGAATCGGAAGATGAAGGGGCAAAAGGGCAGGAAGGCTTCGAGCA GATCA
AGCGTATTAAAGCTTACCTGGATACGCTTATGGAAGCGGTACACTTTGCAAAGCCGT TGTATCTT
GTTAAGGGTCGTAAAATGATCGAAGGGCTCGATAAAGACCAGTCCTTTTATGAAGCG TTTGAAA
TGGCGTACCAAGAACTTGAATCGTTAATCATTCCTATCTATAACAAAGCGCGGAGCT ATCTGTC
GCGGAAACCTTTCAAGGCCGATAAATTCAAGATTAATTTTGACAACAACACGCTACT GAGCGGA
TGGGATGCGAACAAGGAAACTGCTAACGCGTCCATTCTGTTTAAGAAAGACGGGTTA TATTACC
TTGGAATTATGCCGAAAGGTAAGACCTTTCTCTTTGACTACTTTGTATCGAGCGAGG ATTCAGAG
AAACTGAAACAGCGTCGCCAGAAGACCGCCGAAGAAGCTCTGGCGCAGGATGGTGAA AGTTAC
TTCGAAAAAATTCGTTATAAACTGTTACCAGGGGCTTCAAAGATGTTACCGAAAGTC TTTTTTAG
CAACAAAAATATTGGCTTTTACAACCCGTCGGATGACATTTTACGCATTCGCAACAC AGCCTCTC
ACACCAAAAACGGGACCCCTCAGAAAGGCCACTCAAAAGTTGAGTTTAACCTGAATG ATTGTCA
TAAGATGATTGATTTCTTCAAATCATCAATTCAGAAACACCCGGAATGGGGGTCTTT TGGCTTTA
CGTTTTCTGATACCAGTGATTTTGAAGACATGAGTGCCTTCTACCGGGAAGTAGAAA ACCAGGG
TTACGTAATTAGCTTTGACAAAATCAAAGAGACCTATATACAGAGCCAGGTGGAACA GGGTAAT
CTCTACTTATTCCAGATTTATAACAAGGATTTCTCGCCCTACAGCAAAGGCAAACCA AACCTGC
ATACTCTGTACTGGAAAGCCCTGTTTGAAGAAGCGAACCTGAATAACGTAGTGGCGA AGTTGAA
CGGTGAAGCGGAAATCTTCTTCCGTCGTCACTCCATTAAGGCCTCTGATAAAGTTGT CCATCCGG
CAAATCAGGCCATTGATAATAAGAATCCACACACGGAAAAAACGCAGTCAACCTTTG AATATG
ACCTCGTTAAAGACAAACGCTACACGCAAGATAAGTTCTTTTTCCACGTCCCAATCA GCCTCAA
CTTTAAAGCACAAGGGGTTTCAAAGTTTAATGATAAAGTCAATGGGTTCCTCAAGGG CAACCCG
GATGTCAACATTATAGGTATAGACAGGGGCGAACGCCATCTGCTTTACTTTACCGTA GTGAATC
AGAAAGGTGAAATACTGGTTCAGGAATCATTAAATACCTTGATGTCGGACAAAGGGC ACGTTAA
TGATTACCAGCAGAAACTGGATAAAAAAGAACAGGAACGTGATGCTGCGCGTAAATC GTGGAC
CACGGTTGAGAACATTAAAGAGCTGAAAGAGGGGTATCTAAGCCATGTGGTACACAA ACTGGC
GCACCTCATCATTAAATATAACGCAATAGTCTGCCTAGAAGACTTGAATTTTGGCTT TAAACGCG
GCCGCTTCAAAGTGGAAAAACAAGTTTATCAAAAATTTGAAAAGGCGCTTATAGATA AACTGAA
ACGGCCCCGTTCGAATCATTCAAAAAACTGGGCAAACAGTCTGGCATTCTGTTTTAC GTGCCGG
CAGATTATACTTCAAAAATCGATCCAACAACTGGCTTTGTGAACTTCCTGGACCTGA GATATCA
GTCTGTAGAAAAAGCTAAACAACTTCTTAGCGATTTTAATGCCATTCGTTTTAACAG CGTTCAGA
ATTACTTTGAATTCGAAATTGACTATAAAAAACTTACTCCGAAACGTAAAGTCGGAA CCCAAAG
TAAATGGGTAATTTGTACGTATGGCGATGTCAGGTATCAGAACCGTCGGAATCAAAA AGGTCAT TGGGAGACCGAAGAAGTGAACGTGACCGAAAAGCTGAAGGCTCTGTTCGCCAGCGATTCA AAA ACTACAACTGTGATCGATTACGCAAATGATGATAACCTGATAGATGTGATTTTAGAGCAG GATA
ATCAAATCGGAAGATGATTTTATTCTGTCACCGGTCAAGAATGAGCAGGGTGAATTC TATGATA GTAGGAAAGCCGGCGAAGTGTGGCCGAAAGACGCCGACGCCAATGGCGCCTATCATATCG CGC TCAAAGGGCTTTGGAATTTGCAGCAGATTAACCAGTGGGAAAAAGGTAAAACCCTGAATC TGGC TATCAAAAACCAGGATTGGTTTAGCTTTATCCAAGAGAAACCGTATCAGGAATGA
SE ATGCATACAGGCGGTCTTCTTAGTATGGACGCGAAAGAGTTCACAGGTCAGTATCCGTTG TCGA
Q AAACATTACGATTCGAACTTCGGCCCATCGGCCGCACGTGGGATAACCTGGAGGCCTCAG GCTA
no CTTAGCGGAAGACCGCCATCGTGCCGAATGTTATCCTCGTGCGAAAGAGTTATTGGATGA CAAC
N CATCGTGCCTTCCTGAATCGTGTGTTGCCACAAATCGATATGGATTGGCACCCGATTGCG GAGG
O: CCTTTTGTAAGGTACATAAAAACCCTGGTAATAAAGAACTTGCCCAGGATTACAACCTTC AGTT 45 GTCAAAGCGCCGTAAGGAGATCAGCGCATATCTTCAGGATGCAGATGGCTATAAAGGCCT GTTC
GCGAAGCCCGCCTTAGACGAAGCTATGAAAATTGCGAAAGAAAACGGGAACGAAAGT GATATT
GAGGTTCTCGAAGCGTTTAACGGTTTTAGCGTATACTTCACCGGTTATCATGAGTCA CGCGAGA
ACATTTATAGCGATGAGGATATGGTGAGCGTAGCCTACCGAATTACTGAGGATAATT TCCCGCG
CTTTGTCTCAAACGCTTTGATCTTTGATAAATTAAACGAAAGCCATCCGGATATTAT CTCTGAAG
TATCGGGCAATCTTGGAGTTGATGACATTGGTAAGTACTTTGACGTGTCGAACTATA ACAATTTT
CTTTCCCAGGCCGGTATAGATGACTACAATCACATTATTGGCGGCCATACAACCGAA GACGGAC
TGATACAAGCGTTTAATGTCGTATTGAACTTACGTCACCAAAAAGACCCTGGCTTTG AAAAAAT
TCAGTTCAAACAGCTCTACAAACAAATCCTGAGCGTGCGTACCAGCAAAAGCTACAT CCCGAAA
CAGTTTGACAACTCTAAGGAGATGGTTGACTGCATTTGCGATTATGTCAGCAAAATA GAGAAAT
CCGAAACAGTAGAACGGGCCCTGAAACTAGTCCGTAATATCAGTTCTTTCGACTTGC GCGGGAT
CTTTGTCAATAAAAAGAACTTGCGCATACTGAGCAACAAACTGATAGGAGATTGGGA CGCGATC
GAAACCGCATTGATGCATAGTTCTTCATCAGAAAACGATAAGAAAAGCGTATATGAT AGCGCGG
AGGCTTTTACGTTGGATGACATCTTTTCAAGCGTGAAAAAATTTTCTGATGCCTCTG CCGAAGAT
ATTGGCAACAGGGCGGAAGACATCTGTAGAGTGATAAGTGAGACGGCCCCTTTTATC AACGATC
TGCGAGCGGTGGACCTGGATAGCCTGAACGACGATGGTTATGAAGCGGCCGTCTCAA AAATTCG
GGAGTCGCTGGAGCCTTATATGGATCTTTTCCATGAACTGGAAATTTTCTCGGTTGG CGATGAGT
TCCCAAAATGCGCAGCATTTTACAGCGAACTGGAGGAAGTCAGCGAACAGCTGATCG AAATTAT
TCCGTTATTCAACAAGGCGCGTTCGTTCTGCACCCGGAAACGCTATAGCACCGATAA GATTAAA
GTGAACTTAAAATTCCCGACCTTGGCGGACGGGTGGGACCTGAACAAAGAGAGAGAC AACAAA
GCCGCGATTCTGCGGAAAGACGGTAAGTATTATCTGGCAATTCTGGATATGAAGAAA GATCTGT
CAAGCATTAGGACCAGCGACGAAGATGAATCCAGCTTCGAAAAGATGGAGTATAAAC TGTTAC
CGAGTCCAGTAAAAATGCTGCCAAAGATATTCGTAAAATCGAAAGCCGCTAAGGAAA AATATG
GCCTGACAGATCGTATGCTTGAATGCTACGATAAAGGTATGCATAAGTCGGGTAGTG CGTTTGA
TCTTGGCTTTTGCCATGAACTCATTGATTATTACAAGCGTTGTATCGCGGAGTACCC AGGCTGGG
ATGTGTTCGATTTCAAGTTTCGCGAAACTTCCGATTATGGGTCCATGAAAGAGTTCA ATGAAGAT
GTGGCCGGAGCCGGTTACTATATGAGTCTGAGAAAAATTCCGTGCAGCGAAGTGTAC CGTCTGT
TAGACGAGAAATCGATTTATCTATTTCAAATTTATAACAAAGATTACTCTGAAAATG CACATGG
TAATAAGAACATGCATACCATGTACTGGGAGGGTCTCTTTTCCCCGCAAAACCTGGA GTCGCCC
GTTTTCAAGTTGTCGGGTGGGGCAGAACTTTTCTTTCGAAAATCCTCAATCCCTAAC GATGCCAA AACAGTACACCCGAAAGGCTCAGTGCTGGTTCCACGTAATGATGTTAACGGTCGGCGTAT TCCA
GATTCAATCTACCGCGAACTGACACGCTATTTTAACCGTGGCGATTGCCGAATCAGT GACGAAG
CCAAAAGTTATCTTGACAAGGTTAAGACTAAAAAAGCGGACCATGACATTGTGAAAG ATCGCC
GCTTTACCGTGGATAAAATGATGTTCCACGTCCCGATTGCGATGAACTTTAAGGCGA TCAGTAA
ACCGAACTTAAACAAAAAAGTCATTGATGGCATCATTGATGATCAGGATCTGAAAAT CATTGGT
ATTGATCGTGGCGAGCGGAACTTAATTTACGTCACGATGGTTGACAGAAAAGGGAAT ATCTTAT
ATCAGGATTCTCTTAACATCCTCAATGGCTACGACTATCGTAAAGCTCTGGATGTGC GCGAATAT
GACAACAAGGAAGCGCGTCGTAACTGGACTAAAGTGGAGGGCATTCGCAAAATGAAG GAAGGC
TATCTGTCATTAGCGGTCTCGAAATTAGCGGATATGATTATCGAAAATAACGCCATC ATCGTTAT
GGAGGACCTGAACCACGGATTCAAAGCGGGCCGCTCAAAGATTGAAAAACAAGTTTA TCAGAA
ATTTGAGAGTATGCTGATTAACAAACTGGGCTATATGGTGTTAAAAGACAAGTCAAT TGACCAA
TCAGGTGGCGCGCTGCATGGATACCAGCTGGCGAACCATGTTACCACCTTAGCATCA GTTGGAA
AGCAGTGTGGGGTTATCTTTTATATACCGGCAGCGTTCACTAGTAAAATAGATCCGA CCACTGG
TTTCGCCGATCTCTTTGCCCTGAGTAACGTTAAAAACGTAGCGAGCATGCGTGAATT CTTTTCCA
AAATGAAATCTGTCATTTATGATAAAGCTGAAGGCAAATTCGCATTCACCTTTGATT ACTTGGAT
TACAACGTGAAGAGCGAATGTGGTCGTACGCTGTGGACCGTTTACACCGTTGGTGAG CGCTTCA
CCTATTCCCGTGTGAACCGCGAATATGTACGTAAAGTCCCCACCGATATTATCTATG ATGCCCTC
CAGAAAGCAGGCATTAGCGTCGAAGGAGACTTAAGGGACAGAATTGCCGAAAGCGAT GGCGAT
ACGCTGAAGTCTATTTTTTACGCATTCAAATACGCGCTAGATATGCGCGTTGAGAAT CGCGAGG
AAGACTACATTCAATCACCTGTGAAAAATGCCTCTGGGGAATTTTTTTGTTCAAAAA ATGCTGGT
AAAAGCCTCCCACAAGATAGCGATGCAAACGGTGCATATAACATTGCCCTGAAAGGT ATTCTTC
AATTACGCATGCTGTCTGAGCAGTACGACCCCAACGCGGAATCTATTAGACTTCCGC TGATAAC
CAATAAAGCCTGGCTGACATTCATGCAGTCTGGCATGAAGACCTGGAAAAATTAG
SE ATGGATAGTTTAAAAGATTTTACGAATCTATATCCCGTAAGCAAAACTCTTCGTTTTGAA CTGAA
Q ACCTGTTGGAAAAACGTTGGAGAATATCGAGAAAGCGGGCATCCTGAAAGAAGACGAGCA CCG
no TGCCGAAAGCTACAGGCGTGTCAAAAAGATTATCGATACTTATCACAAAGTGTTCATTGA TAGC
N AGTCTGGAGAACATGGCAAAAATGGGCATAGAAAATGAAATCAAAGCAATGCTGCAGAGC TTT
O: TGCGAGCTCTACAAGAAAGATCACCGAACGGAAGGTGAAGATAAAGCACTGGACAAAATT CGC 46 GCCGTTCTTCGCGGTCTGATTGTTGGCGCGTTCACCGGCGTGTGCGGCCGCCGTGAAAAC ACCGT
GCAGAACGAAAAGTACGAGTCGCTGTTCAAAGAAAAACTGATAAAAGAAATTTTGCC TGACTTT
GTGCTTTCGACCGAAGCGGAATCCCTGCCATTTTCTGTCGAAGAAGCGACCCGCAGC CTGAAAG
AATTTGACTCATTCACAAGTTACTTTGCAGGCTTCTACGAAAACCGTAAAAACATCT ACAGCAC
GAAGCCACAGAGCACGGCTATTGCTTATCGCCTGATTCATGAGAACCTGCCGAAGTT CATCGAT
ACTTTTCTGCGGGTGGGTACATTAAAAAAGATGAGCGGCTGGAAGACATCTTCAGTC TAAACTA
TTATATCCACGTTCTGTCGCAGGCAGGCATTGAGAAATATAATGCGCTGATTGGTAA GATTGTC
ACAGAAGGCGATGGTGAGATGAAAGGTCTTAATGAACATATCAATCTGTATAACCAG CAGCGT
GGTCGCGAAGACCGTCTTCCACTGTTCCGCCCACTGTATAAACAGATCCTGTCTGAC CGGGAAC
AGCTGTCCTACCTGCCGGAAAGCTTTGAAAAGGATGAAGAGCTACTTCGCGCATTAA AGGAGTT
TTACGACCATATTGCGGAAGACATTTTGGGTAGAACGCAGCAACTGATGACGTCAAT TTCTGAA
TACGATCTGAGTAGAATCTACGTTAGGAATGATAGCCAGCTGACCGATATTAGCAAA AAAATGC
TGGGCGACTGGAACGCTATCTATATGGCACGTGAACGTGCATATGATCATGAACAAG CACCGAA ACGTATAACCGCGAAATATGAGCGTGATCGCATTAAGGCGCTAAAGGGAGAAGAAAGCAT CTC
ACTCGCAAACCTGAACTCCTGTATCGCTTTCTTAGATAACGTGCGCGATTGTCGCGT CGACACGT
ATCTGTCAACCCTTGGGCAGAAAGAGGGTCCACATGGTCTGTCTAACCTGGTGGAAA ATGTCTT
TGCGAGTTACCATGAAGCGGAACAACTGCTGTCTTTTCCATACCCCGAAGAAAACAA TCTAATA
CAGGATAAAGATAACGTGGTGTTAATCAAAAACCTGCTGGACAACATCAGCGATCTG CAACGTT
TCCTGAAACCTTTGTGGGGTATGGGTGACGAGCCAGACAAAGACGAACGTTTTTATG GTGAGTA
TAATTATATACGTGGCGCCCTTGACCAAGTTATTCCGCTGTATAACAAAGTACGGAA CTATCTGA
CCCGTAAGCCATATTCTACCCGTAAAGTGAAACTGAACTTTGGCAACTCGCAACTGC TGTCGGG
TTGGGATCGTAACAAAGAAAAAGATAATAGTTGTGTTATCCTGCGTAAGGGACAAAA TTTTTAC
CTCGCGATTATGAACAACAGACACAAGCGTTCATTTGAAAATAAGGTTCTGCCGGAG TATAAAG
AGGGCGAACCGTACTTCGAGAAAATGGATTATAAGTTCTTACCAGACCCTAATAAGA TGTTACC
GAAAGTCTTTCTTTCGAAAAAAGGCATAGAAATCTATAAGCCGTCCCCGAAATTACT CGAACAG
TATGGGCACGGGACCCACAAGAAAGGGGATACTTTTAGCATGGACGATCTGCACGAA CTGATC
TACAGCCACATACGAGAATGTGTCTAGTTTTTATCGGGAAGTGGAGGATCAGGGCTA CAAACTT AGTTTTCGTAAAGTTTCAGAGAGTTATGTTTATAGTTTAATTGATCAGGGAAAACTTTAC CTGTT CCAGATCTACAACAAAGATTTCTCGCCATGTAGTAAGGGTACCCCGAATCTGCATACACT CTATT GGAGAATGTTATTCGATGAGCGTAACTTAGCGGATGTCATTTATAAATTGGACGGGAAAG CAGA
AAAAAAAAATCCCGCCAGAAAAAAGGAGAAGAGTCTCTGTTTGAATATGATCTGGTG AAAGAC
CGTCATTACACTATGGATAAATTTCAATTTCATGTTCCAATTACAATGAACTTCAAA TGTTCGGC
GGGTTCCAAAGTAAATGATATGGTAAACGCCCATATTCGCGAAGCGAAAGATATGCA TGTTATT
GGCATCGATAGAGGCGAAAGAAACCTGCTTTATATTTGCGTAATTGACAGCCGTGGT ACCATTC
TGGACCAGATCTCTTTAAACACCATCAATGACATCGATTATCACGACCTGTTGGAGT CTCGGGA
CAAGGACCGCCAGCAGGAGCGCCGTAATTGGCAGACAATTGAAGGCATAAAAGAATT AAAACA
GGGTTACCTTTCCCAGGCCGTACACCGCATAGCGGAACTGATGGTGGCCTACAAAGC CGTAGTT
GCCCTGGAAGACTTGAATATGGGGTTTAAACGTGGCCGTCAAAAAGTCGAGAGCAGC GTGTATC
AGCAATTTGAAAAACAGTTGATTGACAAGTTGAATTATTTGGTTGATAAAAAGAAAC GTCCAGA
AGATATTGGTGGCTTACTGCGTGCATACCAGTTTACGGCACCTTTTAAGTCCTTCAA AGAAATGG
GTAAACAGAACGGGTTTCTGTTTTACATCCCGGCCTGGAATACATCCAACATCGATC CTACCACC
GGGTTTGTCAACCTGTTTCATGCACAATATGAAAACGTGGATAAAGCGAAGAGTTTT TTCCAAA
AATTCGATAGTATTTCGTATAACCCAAAAAAAGATTGGTTTGAGTTTGCGTTCGATT ATAAAAAT
TTTACTAAAAAGGCTGAGGGATCCCGCAGTATGTGGATCCTCTGCACCCATGGCAGT CGTATTA
AAAATTTTCGTAATTCGCAAAAGAATGGCCAGTGGGACTCGGAAGAGTTTGCCCTGA CCGAAGC
GTTCAAATCGCTGTTTGTACGCTACGAAATTGACTACACAGCAGATCTGAAAACAGC CATCGTC
GATGAAAAACAGAAAGATTTTTTTGTAGATCTCCTAAAACTGTTCAAACTGACTGTT CAGATGC
GCAATTCCTGGAAAGAGAAAGACCTGGATTATCTGATTAGCCCGGTAGCCGGTGCTG ATGGACG
ATTTTTCGATACTCGTGAAGGTAACAAAAGTCTCCCGAAAGATGCTGATGCCAATGG TGCATAC
AATATTGCATTAAAGGGGCTATGGGCCTTGCGACAGATCCGCCAGACCAGCGAAGGC GGCAAG
CTGAAATTGGCCATATCGAATAAGGAATGGTTACAATTTGTTCAGGAACGTAGCTAT GAAAAAG
ATTGA
ATGAACAACGGCACAAATAATTTTCAGAACTTCATCGGGATCTCAAGTTTGCAGAAA ACGCTGC Q GCAATGCTCTGATCCCCACGGAAACCACGCAACAGTTCATCGTCAAGAACGGAATAATTA AAGA no AGATGAGTTACGTGGCGAGAACCGCCAGATTCTGAAAGATATCATGGATGACTACTACCG CGGA
N TTCATCTCTGAGACTCTGAGTTCTATTGATGACATAGATTGGACTAGCCTGTTCGAAAAA ATGGA
O: AATTCAGCTGAAAAATGGTGATAATAAAGATACCTTAATTAAGGAACAGACAGAGTATCG GAA
47 AGCAATCCATAAAAAATTTGCGAACGACGATCGGTTTAAGAACATGTTTAGCGCCAAACT GATT
AGTGACATATTACCTGAATTTGTCATCCACAACAATAATTATTCGGCATCAGAGAAA GAGGAAA
AAACCCAGGTGATAAAATTGTTTTCGCGCTTTGCGACTAGCTTTAAAGATTACTTCA AGAACCGT
GCAAATTGCTTTTCAGCGGACGATATTTCATCAAGCAGCTGCCATCGCATCGTCAAC GACAATG
CAGAGATATTCTTTTCAAATGCGCTGGTCTACCGCCGGATCGTAAAATCGCTGAGCA ATGACGA
TATCAACAAAATTTCGGGCGATATGAAAGATTCATTAAAAGAAATGAGTCTGGAAGA AATATAT
TCTTACGAGAAGTATGGGGAATTTATTACCCAGGAAGGCATTAGCTTCTATAATGAT ATCTGTG
GGAAAGTGAATTCTTTTATGAACCTGTATTGTCAGAAAAATAAAGAAAACAAAAATT TATACAA
ACTTCAGAAACTTCACAAACAGATTCTATGCATTGCGGACACTAGCTATGAGGTCCC GTATAAA
TTTGAAAGTGACGAGGAAGTGTACCAATCAGTTAACGGCTTCCTTGATAACATTAGC AGCAAAC
ATATAGTCGAAAGATTACGCAAAATCGGCGATAACTATAACGGCTACAACCTGGATA AAATTTA
TATCGTGTCCAAATTTTACGAGAGCGTTAGCCAAAAAACCTACCGCGACTGGGAAAC AATTAAT
ACCGCCCTCGAAATTCATTACAATAATATCTTGCCGGGTAACGGTAAAAGTAAAGCC GACAAAG
TAAAAAAAGCGGTTAAGAATGATTTACAGAAATCCATCACCGAAATAAATGAACTAG TGTCAA
ACTATAAGCTGTGCAGTGACGACAACATCAAAGCGGAGACTTATATACATGAGATTA GCCATAT
CTTGAATAACTTTGAAGCACAGGAATTGAAATACAATCCGGAAATTCACCTAGTTGA ATCCGAG
CTCAAAGCGAGTGAGCTTAAAAACGTGCTGGACGTGATCATGAATGCGTTTCATTGG TGTTCGG
TTTTTATGACTGAGGAACTTGTTGATAAAGACAACAATTTTTATGCGGAACTGGAGG AGATTTA
CGATGAAATTTATCCAGTAATTAGTCTGTACAACCTGGTTCGTAACTACGTTACCCA GAAACCGT
ACAGCACGAAAAAGATTAAATTGAACTTTGGAATACCGACGTTAGCAGACGGTTGGT CAAAGTC
CAAAGAGTATTCTAATAACGCTATCATACTGATGCGCGACAATCTGTATTATCTGGG CATCTTTA
ATGCGAAGAATAAACCGGACAAGAAGATTATCGAGGGTAATACGTCAGAAAATAAGG GTGACT
ACAAAAAGATGATTTATAATTTGCTCCCGGGTCCCAACAAAATGATCCCGAAAGTTT TCTTGAG
CAGCAAGACGGGGGTGGAAACGTATAAACCGAGCGCCTATATCCTAGAGGGGTATAA ACAGAA
TAAACATATCAAGTCTTCAAAAGACTTTGATATCACTTTCTGTCATGATCTGATCGA CTACTTCA
AAAACTGTATTGCAATTCATCCCGAGTGGAAAAACTTCGGTTTTGATTTTAGCGACA CCAGTACT
TATGAAGACATTTCCGGGTTTTATCGTGAGGTAGAGTTACAAGGTTACAAGATTGAT TGGACAT
ACATTAGCGAAAAAGACATTGATCTGCTGCAGGAAAAAGGTCAACTGTATCTGTTCC AGATATA
CTTTTCTCAGAAGAAAATCTTAAGGATATCGTCCTGAAACTTAACGGCGAAGCGGAA ATCTTCT
TCAGGAAGAGCAGCATAAAGAACCCAATCATTCATAAAAAAGGCTCGATTTTAGTCA ACCGTAC
CTACGAAGCAGAAGAAAAAGACCAGTTTGGCAACATTCAAATTGTGCGTAAAAATAT TCCGGA
AAACATTTATCAGGAGCTGTACAAATACTTCAACGATAAAAGCGACAAAGAGCTGTC TGATGAA
GCAGCCAAACTGAAGAATGTAGTGGGACACCACGAGGCAGCGACGAATATAGTCAAG GACTAT
CGCTACACGTATGATAAATACTTCCTTCATATGCCTATTACGATCAATTTCAAAGCC AATAAAAC
GGGTTTTATTAATGATAGGATCTTACAGTATATCGCTAAAGAAAAAGACTTACATGT GATCGGC
ATTGATCGGGGCGAGCGTAACCTGATCTACGTGTCCGTGATTGATACTTGTGGTAAT ATAGTTGA
ACAGAAAAGCTTTAACATTGTAAACGGCTACGACTATCAGATAAAACTGAAACAACA GGAGGG CGCTAGACAGATTGCGCGGAAAGAATGGAAAGAAATTGGTAAAATTAAAGAGATCAAAGA GGG
CTACCTGAGCTTAGTAATCCACGAGATCTCTAAAATGGTAATCAAATACAATGCAAT TATAGCG
ATGGAGGATTTGTCTTATGGTTTTAAAAAAGGGCGCTTTAAGGTCGAACGGCAAGTT TACCAGA
AATTTGAAACCATGCTCATCAATAAACTCAACTATCTGGTATTTAAAGATATTTCGA TTACCGAG
AATGGCGGTCTCCTGAAAGGTTATCAGCTGACATACATTCCTGATAAACTTAAAAAC GTGGGTC
ATCAGTGCGGCTGCATTTTTTATGTGCCTGCTGCATACACGAGCAAAATTGATCCGA CCACCGGC
TTTGTGAATATCTTTAAATTTAAAGACCTGACAGTGGACGCAAAACGTGAATTCATT AAAAAAT
TTGACTCAATTCGTTATGACAGTGAAAAAAATCTGTTCTGCTTTACATTTGACTACA ATAACTTT
ATTACGCAAAACACGGTCATGAGCAAATCATCGTGGAGTGTGTATACATACGGCGTG CGCATCA
AACGTCGCTTTGTGAACGGCCGCTTCTCAAACGAAAGTGATACCATTGACATAACCA AAGATAT
GGAGAAAACGTTGGAAATGACGGACATTAACTGGCGCGATGGCCACGATCTTCGTCA AGACATT
ATAGATTATGAAATTGTTCAGCACATATTCGAAATTTTCCGTTTAACAGTGCAAATG CGTAACTC
CTTGTCTGAACTGGAGGACCGTGATTACGATCGTCTCATTTCACCTGTACTGAACGA AAATAAC
ATTTTTTATGACAGCGCGAAAGCGGGGGATGCACTTCCTAAGGATGCCGATGCAAAT GGTGCGT
ATTGTATTGCATTAAAAGGGTTATATGAAATTAAACAAATTACCGAAAATTGGAAAG AAGATGG
TAAATTTTCGCGCGATAAACTCAAAATCAGCAATAAAGATTGGTTCGACTTTATCCA GAATAAG
CGCTATCTCTAA
SE ATGACCAATAAATTCACTAACCAGTATTCTCTCTCTAAGACCCTGCGCTTTGAACTGATT CCGCA
Q GGGGAAAACCTTGGAGTTCATTCAAGAAAAAGGCCTCTTGTCTCAGGATAAACAGAGGGC TGA
no ATCTTACCAAGAAATGAAGAAAACTATTGATAAGTTTCATAAATATTTCATTGATTTAGC CTTGT
N CTAACGCCAAATTAACTCACTTGGAAACGTATCTGGAGTTATACAACAAATCTGCCGAAA CTAA
O: GAAAGAACAGAAATTTAAAGACGATTTGAAAAAAGTACAGGACAATCTGCGTAAAGAAAT TGT 48 CAAATCCTTCAGTGACGGCGATGCTAAAAGCATTTTTGCCATTCTGGACAAAAAAGAGTT GATT
ACTGTGGAATTAGAAAAGTGGTTTGAAAACAATGAGCAGAAAGACATCTACTTCGAT GAGAAA
TTCAAAACTTTCACCACCTATTTTACAGGATTTCATCAAAACCGGAAGAACATGTAC TCAGTAG
AACCGAACTCCACGGCCATTGCGTATCGTTTGATCCATGAGAATCTGCCTAAATTTC TGGAGAAT
GCGAAAGCCTTTGAAAAGATTAAGCAGGTCGAATCGCTGCAAGTGAATTTTCGTGAA CTCATGG
GCGAATTTGGTGACGAAGGTCTAATCTTCGTTAACGAACTGGAAGAAATGTTTCAGA TTAATTA
CTACAATGACGTGCTATCGCAGAACGGTATCACAATCTACAATAGTATTATCTCAGG GTTCACA
AAAAACGATATAAAATACAAAGGCCTGAACGAGTATATCAATAACTACAACCAAACA AAGGAC
AAAAAGGATAGGCTTCCGAAACTGAAGCAGTTATACAAACAGATTTTATCTGACAGA ATCTCCC
TGAGCTTTCTGCCGGATGCTTTCACTGATGGGAAGCAGGTTCTGAAAGCGATTTTCG ATTTTTAT
AAGATTAACTTACTGAGCTACACGATTGAAGGTCAAGAAGAATCTCAAAACTTACTG CTCTTGA
TCCGTCAAACCATTGAAAATCTATCATCGTTCGATACGCAGAAAATCTACCTCAAAA ACGATAC
TCACCTGACTACGATCTCTCAGCAGGTTTTCGGGGATTTTAGTGTATTTTCAACAGC TCTGAACT
ACTGGTATGAAACCAAAGTCAATCCGAAATTCGAGACGGAATATTCTAAGGCCAACG AAAAAA
AACGTGAGATTCTTGATAAAGCTAAAGCCGTATTTACTAAACAGGATTACTTTTCTA TTGCTTTC
CTGCAGGAAGTTTTATCGGAGTATATCCTGACCCTGGATCATACATCTGATATCGTT AAAAAAC
ACAGCAGCAATTGCATCGCTGACTATTTCAAAAACCACTTTGTCGCCAAAAAAGAAA ACGAAAC
AGACAAGACTTTCGATTTCATTGCTAACATCACCGCAAAATACCAGTGTATTCAGGG TATCTTGG
AAAACGCCGACCAATACGAAGACGAACTGAAACAAGATCAGAAGCTGATCGATAATT TAAAAT
TCTTCTTAGATGCAATCCTGGAGCTGCTGCACTTCATCAAACCGCTTCATTTAAAGA GCGAGTCC ATTACCGAAAAGGACACCGCCTTCTATGACGTTTTTGAAAATTATTATGAAGCCCTCTCC TTGCT
GACTCCGCTGTATAATATGGTACGCAATTACGTAACCCAGAAACCATATTCTACCGA AAAAATT
AAACTGAACTTTGAAAACGCACAGCTGCTCAACGGTTGGGACGCGAATAAAGAAGGT GACTAC
CTCACCACCATCCTGAAAAAAGATGGTAACTATTTTCTGGCAATTATGGATAAGAAA CATAATA
AAGCATTCCAGAAATTTCCTGAAGGGAAAGAAAATTACGAAAAGATGGTGTACAAAC TCTTACC
TGGAGTTAACAAAATGTTGCCGAAAGTATTTTTTAGTAATAAGAACATCGCGTACTT TAACCCGT
CCAAAGAACTGCTGGAAAATTATAAAAAGGAGACGCATAAGAAAGGGGATACCTTTA ACCTGG
AACATTGCCATACCTTAATAGACTTCTTCAAGGATTCCCTGAATAAACACGAGGATT GGAAATA
TTTCGATTTTCAGTTTAGTGAGACCAAGTCATACCAGGATCTTAGCGGCTTTTATCG CGAAGTAG
AACACCAAGGCTATAAAATTAACTTCAAAAACATCGACAGCGAATACATCGACGGTT TAGTTAA
CGAGGGCAAACTGTTTCTGTTCCAGATCTATTCAAAGGATTTTAGCCCGTTCTCTAA AGGCAAAC
CAAATATGCATACGTTGTACTGGAAAGCACTGTTTGAAGAGCAAAACCTGCAGAATG TGATTTA
TAAACTGAACGGCCAAGCTGAGATTTTTTTCCGTAAAGCCTCGATTAAACCGAAAAA TATCATC
CTTCATAAGAAGAAAATAAAGATCGCTAAAAAACACTTCATAGATAAAAAAACCAAA ACCTCC
GAAATAGTGCCTGTTCAAACAATTAAGAACTTGAATATGTACTACCAGGGCAAGATA TCGGAAA
AGGAGTTGACTCAAGACGATCTTCGCTATATCGATAACTTTTCGATTTTTAACGAAA AAAACAA
GACGATCGACATCATCAAAGATAAACGCTTCACTGTAGATAAGTTCCAGTTTCATGT GCCGATT
ACTATGAACTTCAAAGCTACCGGGGGTAGCTATATCAACCAAACGGTGTTGGAATAC CTGCAGA
ATAACCCGGAAGTCAAAATCATTGGGCTGGACCGCGGAGAACGTCACCTTGTGTACT TGACCTT
AATCGATCAGCAAGGCAACATCTTAAAACAAGAATCGCTGAATACCATTACGGATTC AAAGATT
AGCACCCCGTATCATAAGCTGCTCGATAACAAGGAGAATGAGCGCGACCTGGCCCGT AAAAAC
TGGGGCACGGTGGAAAACATTAAGGAGTTAAAGGAGGGTTATATTTCCCAGGTAGTG CATAAG
ATCGCCACTCTCATGCTCGAGGAAAATGCGATCGTTGTCATGGAAGACTTAAACTTC GGATTTA
AACGTGGGCGATTTAAAGTAGAGAAACAAATCTACCAGAAGTTAGAAAAAATGCTGA TTGACA
AATTAAATTACTTGGTCCTAAAAGACAAACAGCCGCAAGAATTGGGTGGATTATACA ACGCCCT
CCAACTTACCAATAAATTCGAAAGTTTTCAGAAAATGGGTAAACAGTCAGGCTTTCT TTTTTATG
TTCCTGCGTGGAACACATCCAAAATCGACCCTACAACCGGCTTCGTCAATTACTTCT ATACTAAA
TATGAAAACGTCGACAAAGCAAAAGCATTCTTTGAAAAGTTCGAAGCAATACGTTTT AACGCTG
AGAAAAAATATTTCGAGTTCGAAGTCAAGAAATACTCAGACTTTAACCCCAAAGCTG AGGGCAC
ACAGCAAGCGTGGACAATCTGCACCTACGGCGAGCGCATCGAAACGAAGCGTCAAAA AGATCA
GAATAACAAATTTGTTTCAACACCTATCAACCTGACCGAGAAGATTGAAGACTTCTT AGGTAAA
AATCAGATTGTTTATGGCGACGGTAACTGTATAAAATCTCAAATAGCCTCAAAGGAT GATAAAG
CATTTTTCGAAACATTATTATATTGGTTCAAAATGACACTGCAGATGCGCAATAGTG AGACGCG
TACAGATATTGATTATCTTATCAGCCCGGTCATGAACGACAACGGTACTTTTTACAA CTCCAGAG
ACTATGAAAAACTTGAGAATCCAACTCTCCCCAAAGATGCTGATGCGAACGGTGCTT ATCACAT
CGCGAAAAAAGGTCTGATGCTGCTGAACAAAATCGACCAAGCCGATCTGACTAAGAA AGTTGA
CCTAAGCATTTCAAATCGGGACTGGTTACAGTTTGTTCAAAAGAACAAATGA
SE ATGGAACAGGAATATTATCTGGGCTTGGACATGGGCACCGGTTCCGTCGGCTGGGCTGTT ACTG
Q ACAGTGAATATCACGTTCTAAGAAAGCATGGTAAGGCATTGTGGGGTGTAAGACTTTTCG AATC
no TGCTTCCACTGCTGAAGAGCGTAGAATGTTTAGAACGAGTCGACGTAGGCTAGACAGGCG CAAT
N TGGAGAATCGAAATTTTACAAGAAATTTTTGCGGAAGAGATATCTAAGAAAGACCCAGGC TTTT
O: TCCTGAGAATGAAGGAATCTAAGTATTACCCTGAGGATAAAAGAGATATAAATGGTAACT GTCC CGAATTGCCTTACGCATTATTTGTGGACGATGATTTTACCGATAAGGATTACCATAAAAA GTTCC
CAACTATCTACCATTTACGCAAAATGTTAATGAATACAGAGGAAACCCCAGACATAA GACTAGT
TTATCTGGCAATACACCATATGATGAAACATAGAGGCCATTTCTTACTTTCCGGGGA TATCAACG
AAATCAAAGAGTTTGGTACCACATTTAGTAAGTTACTGGAAAACATAAAGAATGAAG AATTGG
ATTGGAACTTAGAACTCGGAAAAGAAGAATACGCGGTTGTCGAATCTATCCTGAAGG ATAATAT
GCTGAATAGGTCGACCAAAAAAACTAGGCTGATCAAAGCACTGAAAGCCAAATCTAT CTGCGA
AAAAGCTGTTTTAAATTTACTTGCTGGTGGCACTGTTAAGTTATCAGACATTTTTGG TTTGGAAG
AATTGAACGAAACCGAGCGTCCAAAAATTAGTTTCGCTGATAATGGCTACGATGATT ACATTGG
TGAGGTGGAAAACGAGTTGGGCGAACAATTTTATATTATAGAGACAGCTAAGGCAGT CTATGAC
TGGGCTGTTTTAGTAGAAATCCTTGGTAAATACACATCTATCTCCGAAGCGAAAGTT GCTACTTA
CGAAAAGCACAAGTCCGATCTCCAGTTTTTGAAGAAAATTGTCAGGAAATATCTGAC TAAGGAA
GAATATAAAGATATTTTCGTTAGTACCTCTGACAAACTGAAAAATTACTCCGCTTAC ATCGGGAT
GACCAAGATTAATGGCAAAAAAGTTGATCTGCAAAGCAAAAGGTGTTCGAAGGAAGA ATTTTA
TGATTTCATTAAAAAGAATGTCTTAAAAAAATTAGAAGGTCAGCCAGAATACGAATA TTTGAAA
GAAGAACTGGAAAGAGAGACATTCTTACCAAAACAAGTCAACAGAGATAATGGGGTA ATTCCA
TATCAAATTCACCTCTACGAATTAAAAAAAATTTTAGGCAATTTACGCGATAAAATT GACCTTAT
CAAAGAAAATGAGGATAAGCTGGTTCAACTCTTTGAATTCAGAATACCCTATTATGT GGGCCCA
CTGAACAAGATTGATGACGGCAAAGAAGGTAAATTCACATGGGCCGTCCGCAAATCC AATGAA
AAAATTTACCCATGGAACTTTGAAAATGTAGTAGATATTGAAGCGTCTGCGGAGAAA TTTATTC
GAAGAATGACTAATAAATGCACTTACTTGATGGGAGAGGATGTTCTGCCTAAAGACA GCTTATT
ATACAGCAAGTACATGGTTCTAAACGAACTTAACAACGTTAAGTTGGACGGTGAGAA ATTAAGT
GTAGAATTGAAACAAAGATTGTATACTGACGTCTTCTGCAAGTACAGAAAAGTGACA GTTAAAA
AAATTAAGAATTACTTGAAGTGCGAAGGTATAATTTCTGGAAACGTAGAGATTACTG GTATTGA
TGGTGATTTCAAAGCATCCCTAACAGCTTACCACGATTTCAAGGAAATCCTGACAGG AACTGAA
CTCGCAAAAAAAGATAAAGAAAACATTATTACTAATATTGTTCTTTTCGGTGATGAC AAGAAAT
TGTTGAAGAAAAGACTGAATAGACTTTACCCCCAGATTACTCCCAATCAACTTAAGA AAATTTG
TGCTTTGTCTTACACAGGATGGGGTCGTTTTTCAAAAAAGTTCTTAGAAGAGATTAC CGCACCTG
ATCCAGAAACAGGCGAAGTATGGAATATAATTACCGCCTTATGGGAATCGAACAATA ATCTTAT
GCAACTTCTGAGCAATGAATATCGTTTCATGGAAGAAGTTGAGACTTACAACATGGG CAAACAG
ACGAAGACTTTATCCTATGAAACTGTGGAAAATATGTATGTATCACCTTCTGTCAAG AGACAAA
TTTGGCAAACCTTAAAAATTGTCAAAGAATTAGAAAAGGTAATGAAGGAGTCTCCTA AACGTGT
GTTTATTGAAATGGCTAGAGAAAAACAAGAGTCAAAAAGAACCGAGTCAAGAAAGAA GCAGTT
AATCGATTTATATAAGGCTTGTAAAAACGAAGAGAAAGATTGGGTTAAAGAATTGGG GGACCA
AGAGGAACAAAAACTACGGTCGGATAAGTTGTATTTATACTATACGCAAAAGGGACG ATGTAT
GTATTCCGGCGAGGTAATAGAATTGAAGGATTTATGGGACAATACAAAATATGACAT AGACCAT
ATATATCCCCAATCAAAAACGATGGACGATAGCTTGAACAATAGAGTACTCGTGAAA AAAAAA
TATAATGCGACCAAATCTGATAAGTATCCTCTGAATGAAAATATCAGACATGAAAGA AAGGGGT
TCTGGAAGTCCTTGTTAGATGGTGGGTTTATAAGCAAAGAAAAGTACGAGCGTCTAA TAAGAAA
CACGGAGTTATCGCCAGAAGAACTCGCTGGTTTTATTGAGAGGCAAATCGTGGAAAC GAGACA
ATCTACCAAAGCCGTTGCTGAGATCCTAAAGCAAGTTTTCCCAGAGTCGGAGATTGT CTATGTC
AAAGCTGGCACAGTGAGCAGGTTTAGGAAAGACTTCGAACTATTAAAGGTAAGAGAA GTGAAC
GATTTACATCACGCAAAGGACGCTTACCTAAATATCGTTGTAGGTAACTCATATTAT GTTAAATT TACCAAGAACGCCTCTTGGTTTATAAAGGAGAACCCAGGTAGAACATATAACCTGAAAAA GAT
GTTCACCTCTGGTTGGAATATTGAGAGAAACGGAGAAGTCGCATGGGAAGTTGGTAA GAAAGG
GACTATAGTGACAGTAAAGCAAATTATGAACAAAAATAATATCCTCGTTACAAGGCA GGTTCAT
GAAGCAAAGGGCGGCCTTTTTGACCAACAAATTATGAAGAAAGGGAAAGGTCAAATT GCAATA
AAAGAAACCGATGAGAGACTAGCGTCAATAGAAAAGTATGGTGGCTATAATAAAGCT GCGGGT
GCATACTTTATGCTTGTTGAATCAAAAGACAAGAAAGGTAAGACTATTAGAACTATA GAATTTA
TACCCCTGTACCTTAAAAACAAAATTGAATCGGATGAGTCAATCGCGTTAAATTTTC TAGAGAA
AGGAAGGGGTTTAAAAGAACCAAAGATCCTGTTAAAAAAGATTAAGATTGACACCTT GTTCGAT
GTAGATGGATTTAAAATGTGGTTATCTGGCAGAACAGGCGATAGACTTTTGTTTAAG TGCGCTA
ATCAATTAATTTTGGATGAGAAAATCATTGTCACAATGAAAAAAATAGTTAAGTTTA TTCAGAG
AAGACAAGAAAACAGGGAGTTGAAATTATCTGATAAAGATGGTATCGACAATGAAGT TTTAAT
GGAAATCTACAATACATTCGTTGATAAACTTGAAAATACCGTATATCGAATCAGGTT AAGTGAA
CAAGCCAAAACATTAATTGATAAACAAAAAGAATTTGAAAGGCTATCACTGGAAGAC AAATCC
TCCACCCTATTTGAAATTTTGCATATATTCCAGTGCCAATCTTCAGCAGCTAATTTA AAAATGAT
TGGCGGACCTGGGAAAGCCGGCATCCTAGTGATGAACAATAATATCTCCAAGTGTAA CAAAATA
TCAATTATTAACCAATCTCCGACAGGTATTTTTGAAAATGAAATAGACTTGCTTAAG ATATAA
SE ATGTCTTTCGACTCTTTCACCAACCTGTACTCTCTGTCTAAAACCCTGAAATTCGAAATG CGTCC
Q GGTTGGTAACACCCAGAAAATGCTGGACAACGCGGGTGTTTTCGAAAAAGACAAACTGAT CCA
no GAAAAAATACGGTAAAACCAAACCGTACTTCGACCGTCTGCACCGTGAATTCATCGAAGA AGC
N GCTGACCGGTGTTGAACTGATCGGTCTGGACGAAAACTTCCGTACCCTGGTTGACTGGCA GAAA
O: GACAAAAAAAACAACGTTGCGATGAAAGCGTACGAAAACTCTCTGCAGCGTCTGCGTACC GAA 50 ATCGGTAAAATCTTCAACCTGAAAGCGGAAGACTGGGTTAAAAACAAATACCCGATCCTG GGTC
TGAAAAACAAAAACACCGACATCCTGTTCGAAGAAGCGGTTTTCGGTATCCTGAAAG CGCGTTA
CGGTGAAGAAAAAGACACCTTCATCGAAGTTGAAGAAATCGACAAAACCGGTAAATC TAAAAT
CAACCAGATCTCTATCTTCGACTCTTGGAAAGGTTTCACCGGTTACTTCAAAAAATT CTTCGAAA
CCCGTAAAAACTTCTACAAAAACGACGGTACCTCTACCGCGATCGCGACCCGTATCA TCGACCA
GAACCTGAAACGTTTCATCGACAACCTGTCTATCGTTGAATCTGTTCGTCAGAAAGT TGACCTGG
CGGAAACCGAAAAATCTTTCTCTATCTCTCTGTCTCAGTTCTTCTCTATCGACTTCT ACAACAAAT
GCCTGCTGCAGGACGGTATCGACTACTACAACAAAATCATCGGTGGTGAAACCCTGA AAAACG
GTGAAAAACTGATCGGTCTGAACGAACTGATCAACCAGTACCGTCAGAACAACAAAG ACCAGA
AAATCCCGTTCTTCAAACTGCTGGACAAACAGATCCTGTCTGAAAAAATCCTGTTCC TGGACGA
AATCAAAAACGACACCGAACTGATCGAAGCGCTGTCTCAGTTCGCGAAAACCGCGGA AGAAAA
AACCAAAATCGTTAAAAAACTGTTCGCGGACTTCGTTGAAAACAACTCTAAATACGA CCTGGCG
CAGATCTACATCTCTCAGGAAGCGTTCAACACCATCTCTAACAAATGGACCTCTGAA ACCGAAA
CCTTCGCGAAATACCTGTTCGAAGCGATGAAATCTGGTAAACTGGCGAAATACGAAA AAAAAG
ACAACTCTTACAAATTCCCGGACTTCATCGCGCTGTCTCAGATGAAATCTGCGCTGC TGTCTATC
TCTCTGGAAGGTCACTTCTGGAAAGAAAAATACTACAAAATCTCTAAATTCCAGGAA AAAACCA
ACTGGGAACAGTTCCTGGCGATCTTCCTGTACGAATTCAACTCTCTGTTCTCTGACA AAATCAAC
ACCAAAGACGGTGAAACCAAACAGGTTGGTTACTACCTGTTCGCGAAAGACCTGCAC AACCTGA
TCCTGTCTGAACAGATCGACATCCCGAAAGACTCTAAAGTTACCATCAAAGACTTCG CGGACTC
TGTTCTGACCATCTACCAGATGGCGAAATACTTCGCGGTTGAAAAAAAACGTGCGTG GCTGGCG
GAATACGAACTGGACTCTTTCTACACCCAGCCGGACACCGGTTACCTGCAGTTCTAC GACAACG CGTACGAAGACATCGTTCAGGTTTACAACAAACTGCGTAACTACCTGACCAAAAAACCGT ACTC
TGAAGAAAAATGGAAACTGAACTTCGAAAACTCTACCCTGGCGAACGGTTGGGACAA AAACAA
AGAATCTGACAACTCTGCGGTTATCCTGCAGAAAGGTGGTAAATACTACCTGGGTCT GATCACC
AAAGGTCACAACAAAATCTTCGACGACCGTTTCCAGGAAAAATTCATCGTTGGTATC GAAGGTG
GTAAATACGAAAAAATCGTTTACAAATTCTTCCCGGACCAGGCGAAAATGTTCCCGA AAGTTTG
CTTCTCTGCGAAAGGTCTGGAATTCTTCCGTCCGTCTGAAGAAATCCTGCGTATCTA CAACAACG
CGGAATTCAAAAAAGGTGAAACCTACTCTATCGACTCTATGCAGAAACTGATCGACT TCTACAA
AGACTGCCTGACCAAATACGAAGGTTGGGCGTGCTACACCTTCCGTCACCTGAAACC GACCGAA
GAATACCAGAACAACATCGGTGAATTCTTCCGTGACGTTGCGGAAGACGGTTACCGT ATCGACT
TCCAGGGTATCTCTGACCAGTACATCCACGAAAAAAACGAAAAAGGTGAACTGCACC TGTTCGA
AATCCACAACAAAGACTGGAACCTGGACAAAGCGCGTGACGGTAAATCTAAAACCAC CCAGAA
AAACCTGCACACCCTGTACTTCGAATCTCTGTTCTCTAACGACAACGTTGTTCAGAA CTTCCCGA
TCAAACTGAACGGTCAGGCGGAAATCTTCTACCGTCCGAAAACCGAAAAAGACAAAC TGGAAT
CTAAAAAAGACAAAAAAGGTAACAAAGTTATCGACCACAAACGTTACTCTGAAAACA AAATCT
TCTTCCACGTTCCGCTGACCCTGAACCGTACCAAAAACGACTCTTACCGTTTCAACG CGCAGATC
AACAACTTCCTGGCGAACAACAAAGACATCAACATCATCGGTGTTGACCGTGGTGAA AAACACC
TGGTTTACTACTCTGTTATCACCCAGGCGTCTGACATCCTGGAATCTGGTTCTCTGA ACGAACTG
AACGGTGTTAACTACGCGGAAAAACTGGGTAAAAAAGCGGAAAACCGTGAACAGGCG CGTCGT
GACTGGCAGGACGTTCAGGGTATCAAAGACCTGAAAAAAGGTTACATCTCTCAGGTT GTTCGTA
AACTGGCGGACCTGGCGATCAAACACAACGCGATCATCATCCTGGAAGACCTGAACA TGCGTTT
CAAACAGGTTCGTGGTGGTATCGAAAAATCTATCTACCAGCAGCTGGAAAAAGCGCT GATCGAC
AAACTGTCTTTCCTGGTTGACAAAGGTGAAAAAAACCCGGAACAGGCGGGTCACCTG CTGAAA
GCGTACCAGCTGTCTGCGCCGTTCGAAACCTTCCAGAAAATGGGTAAACAGACCGGT ATCATCT
TCTACACCCAGGCGTCTTACACCTCTAAATCTGACCCGGTTACCGGTTGGCGTCCGC ACCTGTAC
CTGAAATACTTCTCTGCGAAAAAAGCGAAAGACGACATCGCGAAATTCACCAAAATC GAATTCG
TTAACGACCGTTTCGAACTGACCTACGACATCAAAGACTTCCAGCAGGCGAAAGAAT ACCCGAA
CAAAACCGTTTGGAAAGTTTGCTCTAACGTTGAACGTTTCCGTTGGGACAAAAACCT GAACCAG
AACAAAGGTGGTTACACCCACTACACCAACATCACCGAAAACATCCAGGAACTGTTC ACCAAAT
ACGGTATCGACATCACCAAAGACCTGCTGACCCAGATCTCTACCATCGACGAAAAAC AGAACAC
CTCTTTCTTCCGTGACTTCATCTTCTACTTCAACCTGATCTGCCAGATCCGTAACAC CGACGACTC
TGAAATCGCGAAAAAAAACGGTAAAGACGACTTCATCCTGTCTCCGGTTGAACCGTT CTTCGAC
TCTCGTAAAGACAACGGTAACAAACTGCCGGAAAACGGTGACGACAACGGTGCGTAC AACATC
GCGCGTAAAGGTATCGTTATCCTGAACAAAATCTCTCAGTACTCTGAAAAAAACGAA AACTGCG
AAAAAATGAAATGGGGTGACCTGTACGTTTCTAACATCGACTGGGACAACTTCGTT
SE ATGGAAAACTTTAAAAACTTATACCCAATAAACAAAACGTTACGTTTTGAACTGCGTCCA TATG
Q GTAAAACACTGGAAAACTTTAAAAAAAGCGGTTTGTTGGAGAAGGATGCATTTAAAGCGA ACT
no CTCGCAGATCCATGCAGGCCATCATTGATGAAAAATTTAAAGAGACGATCGAAGAACGTC TGAA
N ATACACGGAATTTAGTGAGTGTGACTTAGGTAATATGACTTCTAAAGATAAGAAAATCAC CGAT
O: AAGGCGGCGACCAACCTGAAGAAGCAAGTCATTTTATCTTTTGATGATGAAATCTTTAAC AACT 51 ATTTGAAACCGGACAAAAACATCGATGCCTTATTTAAAAATGACCCTTCGAACCCGGTGA TTAG
CACATTTAAGGGCTTCACAACGTATTTTGTCAATTTTTTTGAAATTCGTAAACATAT CTTCAAAG
GAGAATCAAGCGGCTCTATGGCTTATCGCATTATTGATGAAAACCTGACGACCTATT TGAATAA CATTGAAAAAATCAAAAAACTGCCAGAGGAATTAAAGTCTCAGTTAGAAGGCATCGACCA GAT
CGACAAACTCAACAACTATAACGAATTTATTACGCAGTCTGGTATCACCCACTATAA TGAAATT
ATTGGAGGTATCAGTAAATCAGAAAATGTGAAAATCCAAGGGATTAATGAAGGCATT AACCTCT
ATTGCCAGAAAAATAAAGTGAAACTGCCGAGGCTGACTCCACTCTACAAAATGATCC TGTCTGA
CCGCGTCTCGAATAGCTTTGTCCTGGACACAATTGAAAACGATACGGAATTGATTGA GATGATA
AGCGATCTGATTAACAAAACCGAAATTTCACAGGATGTAATCATGAGTGATATACAA AACATCT
TTATTAAATATAAACAGCTTGGTAATCTGCCTGGAATTAGCTATTCGTCAATAGTGA ACGCAATC
TGTTCTGATTATGATAACAATTTTGGCGACGGTAAGCGTAAAAAGAGTTATGAAAAC GATAGGA
AAAAACACCTGGAAACTAACGTGTATTCTATCAACTATATCAGCGAACTGCTTACGG ACACCGA
TGTGAGTTCAAACATTAAGATGCGGTATAAGGAGCTTGAACAGAACTACCAGGTCTG TAAGGAA
AACTTCAACGCAACCAACTGGATGAACATTAAAAATATCAAACAATCCGAGAAGACC AACTTA
ATCAAAGATCTGCTGGATATTTTGAAGAGCATTCAACGTTTTTATGATCTGTTCGAT ATCGTTGA
TGAAGACAAGAATCCTAGTGCGGAATTTTATACATGGCTGTCTAAAAATGCGGAGAA ATTGGAT
TTCGAATTCAATTCTGTTTATAATAAATCACGCAACTATTTGACCCGCAAACAATAC AGCGACA
AAAAGATAAAACTAAACTTCGACAGTCCGACATTGGCAAAGGGCTGGGACGCAAATA AGGAAA
TCGATAACTCTACGATAATTATGCGTAAGTTCAATAATGATCGAGGTGATTATGATT ATTTCTTA
GGCATTTGGAACAAAAGCACCCCGGCCAACGAAAAGATAATTCCACTGGAGGATAAC GGTCTG
TTCGAAAAAATGCAGTACAAATTATATCCGGATCCAAGCAAGATGCTTCCAAAGCAG TTTCTGT
CTAAAATTTGGAAAGCTAAGCATCCGACCACCCCAGAATTTGACAAGAAATATAAGG AAGGCC
GCCATAAGAAAGGTCCCGATTTTGAAAAAGAATTCTTGCACGAACTGATTGATTGCT TTAAACA
TGGCTTAGTCAATCACGATGAAAAGTATCAAGATGTTTTTGGATTCAATTTGAGAAA CACAGAA
GACTACAATTCCTACACTGAGTTTCTCGAAGATGTGGAACGATGTAATTATAATCTG AGCTTTAA
CAAAATCGCGGACACCTCGAATCTGATTAACGATGGTAAACTTTATGTTTTCCAGAT CTGGAGC
AAGGATTTCTCTATTGACAGCAAAGGCACCAAAAACCTGAACACCATTTACTTTGAA AGTCTCT
TCAGCGAAGAAAATATGATTGAGAAAATGTTTAAACTTAGCGGTGAAGCTGAAATAT TCTATCG
CCCGGCAAGCCTGAACTATTGCGAAGACATTATCAAAAAGGGTCATCACCACGCTGA ACTGAAA
GATAAATTTGATTATCCTATCATAAAAGATAAACGCTATAGCCAGGATAAATTTTTT TTTCATGT
TCCTATGGTCATTAACTACAAATCAGAAAAACTGAACTCTAAAAGCCTCAATAATCG AACCAAT
GAAAACCTTGGGCAGTTTACCCATATAATTGGAATTGATCGCGGAGAGCGTCATTTA ATCTACC
TGACCGTAGTCGATGTATCGACCGGCGAGATCGTCGAGCAGAAGCACTTAGACGAGA TTATCAA
CACTGATACCAAAGGTGTTGAGCATAAGACGCACTATCTAAACAAGCTGGAGGAAAA ATCGAA
AACCCGTGATAATGAACGTAAGAGTTGGGAGGCAATTGAAACGATTAAAGAACTGAA GGAGGG
TTATATCAGCCACGTAATCAATGAAATTCAAAAACTGCAGGAAAAATACAACGCCCT GATCGTT
ATGGAAAATCTGAATTACGGTTTCAAAAATTCTCGCATCAAAGTGGAAAAACAGGTA TATCAGA
AGTTCGAGACGGCATTAATTAAAAAGTTTAATTACATCATTGACAAAAAAGATCCGG AAACTTA
TATTCATGGCTATCAGCTGACGAACCCGATCACCACACTGGATAAAATTGGTAACCA GTCTGGT
ATCGTGCTTTACATCCCTGCCTGGAATACCAGTAAAATCGATCCGGTAACGGGATTC GTCAACCT
TCTATATGCAGATGACCTCAAATATAAGAATCAGGAACAGGCCAAGTCTTTTATTCA GAAAATC
GATAACATTTACTTTGAGAATGGGGAATTCAAATTTGATATTGATTTTTCTAAATGG AACAATCG
TTATAGTATATCTAAGACGAAATGGACGCTCACCTCGTACGGAACCCGAATCCAGAC ATTCCGC
AATCCGCAGAAGAACAATAAATGGGACAGCGCCGAGTATGATCTCACTGAAGAATTC AAATTG
ATTCTGAACATTGACGGTACCCTGAAAAGCCAGGATGTCGAAACCTATAAAAAATTT ATGTCTC TGTTCAAGCTGATGCTGCAACTTAGGAACTCTGTTACCGGCACTGATATCGATTATATGA TCTCC
CCTGTCACTGATAAAACAGGTACGCATTTCGATTCGCGCGAAAATATCAAAAATCTG CCCGCAG
ATGCCGACGCCAATGGGGCGTACAATATTGCACGCAAGGGTATCATGGCGATCGAAA ACATTAT
GAATGGTATCAGCGACCCGCTGAAAATCTCAAACGAAGATTATTTGAAATATATCCA AAACCAG
CAGGAATAA
SE ATGACCCAGTTCGAAGGTTTCACCAACCTGTACCAGGTTTCTAAAACCCTGCGTTTCGAA CTGAT
Q CCCGCAGGGTAAAACCCTGAAACACATCCAGGAACAGGGTTTCATCGAAGAAGACAAAGC GCG
no TAACGACCACTACAAAGAACTGAAACCGATCATCGACCGTATCTACAAAACCTACGCGGA CCA
N GTGCCTGCAGCTGGTTCAGCTGGACTGGGAAAACCTGTCTGCGGCGATCGACTCTTACCG TAAA
O: GAAAAAACCGAAGAAACCCGTAACGCGCTGATCGAAGAACAGGCGACCTACCGTAACGCG ATC 52 CACGACTACTTCATCGGTCGTACCGACAACCTGACCGACGCGATCAACAAACGTCACGCG GAAA
TCTACAAAGGTCTGTTCAAAGCGGAACTGTTCAACGGTAAAGTTCTGAAACAGCTGG GTACCGT
TACCACCACCGAACACGAAAACGCGCTGCTGCGTTCTTTCGACAAATTCACCACCTA CTTCTCTG
GTTTCTACGAAAACCGTAAAAACGTTTTCTCTGCGGAAGACATCTCTACCGCGATCC CGCACCGT
ATCGTTCAGGACAACTTCCCGAAATTCAAAGAAAACTGCCACATCTTCACCCGTCTG ATCACCG
CGGTTCCGTCTCTGCGTGAACACTTCGAAAACGTTAAAAAAGCGATCGGTATCTTCG TTTCTACC
TCTATCGAAGAAGTTTTCTCTTTCCCGTTCTACAACCAGCTGCTGACCCAGACCCAG ATCGACCT
GTACAACCAGCTGCTGGGTGGTATCTCTCGTGAAGCGGGTACCGAAAAAATCAAAGG TCTGAAC
GAAGTTCTGAACCTGGCGATCCAGAAAAACGACGAAACCGCGCACATCATCGCGTCT CTGCCGC
ACCGTTTCATCCCGCTGTTCAAACAGATCCTGTCTGACCGTAACACCCTGTCTTTCA TCCTGGAA
GAATTCAAATCTGACGAAGAAGTTATCCAGTCTTTCTGCAAATACAAAACCCTGCTG CGTAACG
AAAACGTTCTGGAAACCGCGGAAGCGCTGTTCAACGAACTGAACTCTATCGACCTGA CCCACAT
CTTCATCTCTCACAAAAAACTGGAAACCATCTCTTCTGCGCTGTGCGACCACTGGGA CACCCTGC
GTAACGCGCTGTACGAACGTCGTATCTCTGAACTGACCGGTAAAATCACCAAATCTG CGAAAGA
AAAAGTTCAGCGTTCTCTGAAACACGAAGACATCAACCTGCAGGAAATCATCTCTGC GGCGGGT
AAAGAACTGTCTGAAGCGTTCAAACAGAAAACCTCTGAAATCCTGTCTCACGCGCAC GCGGCGC
TGGACCAGCCGCTGCCGACCACCCTGAAAAAACAGGAAGAAAAAGAAATCCTGAAAT CTCAGC
TGGACTCTCTGCTGGGTCTGTACCACCTGCTGGACTGGTTCGCGGTTGACGAATCTA ACGAAGTT
GACCCGGAATTCTCTGCGCGTCTGACCGGTATCAAACTGGAAATGGAACCGTCTCTG TCTTTCTA
CAACAAAGCGCGTAACTACGCGACCAAAAAACCGTACTCTGTTGAAAAATTCAAACT GAACTTC
CAGATGCCGACCCTGGCGTCTGGTTGGGACGTTAACAAAGAAAAAAACAACGGTGCG ATCCTGT
TCGTTAAAAACGGTCTGTACTACCTGGGTATCATGCCGAAACAGAAAGGTCGTTACA AAGCGCT
GTCTTTCGAACCGACCGAAAAAACCTCTGAAGGTTTCGACAAAATGTACTACGACTA CTTCCCG
GACGCGGCGAAAATGATCCCGAAATGCTCTACCCAGCTGAAAGCGGTTACCGCGCAC TTCCAGA
CCCACACCACCCCGATCCTGCTGTCTAACAACTTCATCGAACCGCTGGAAATCACCA AAGAAAT
CTACGACCTGAACAACCCGGAAAAAGAACCGAAAAAATTCCAGACCGCGTACGCGAA AAAAAC
CGGTGACCAGAAAGGTTACCGTGAAGCGCTGTGCAAATGGATCGACTTCACCCGTGA CTTCCTG
TCTAAATACACCAAAACCACCTCTATCGACCTGTCTTCTCTGCGTCCGTCTTCTCAG TACAAAGA
CCTGGGTGAATACTACGCGGAACTGAACCCGCTGCTGTACCACATCTCTTTCCAGCG TATCGCG
GAAAAAGAAATCATGGACGCGGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTAC AACAAA
GACTTCGCGAAAGGTCACCACGGTAAACCGAACCTGCACACCCTGTACTGGACCGGT CTGTTCT
CTCCGGAAAACCTGGCGAAAACCTCTATCAAACTGAACGGTCAGGCGGAACTGTTCT ACCGTCC GAAATCTCGTATGAAACGTATGGCGCACCGTCTGGGTGAAAAAATGCTGAACAAAAAACT GAA
AGACCAGAAAACCCCGATCCCGGACACCCTGTACCAGGAACTGTACGACTACGTTAA CCACCGT
CTGTCTCACGACCTGTCTGACGAAGCGCGTGCGCTGCTGCCGAACGTTATCACCAAA GAAGTTT
CTCACGAAATCATCAAAGACCGTCGTTTCACCTCTGACAAATTCTTCTTCCACGTTC CGATCACC
CTGAACTACCAGGCGGCGAACTCTCCGTCTAAATTCAACCAGCGTGTTAACGCGTAC CTGAAAG
AACACCCGGAAACCCCGATCATCGGTATCGACCGTGGTGAACGTAACCTGATCTACA TCACCGT
TATCGACTCTACCGGTAAAATCCTGGAACAGCGTTCTCTGAACACCATCCAGCAGTT CGACTAC
CAGAAAAAACTGGACAACCGTGAAAAAGAACGTGTTGCGGCGCGTCAGGCGTGGTCT GTTGTT
GGTACCATCAAAGACCTGAAACAGGGTTACCTGTCTCAGGTTATCCACGAAATCGTT GACCTGA
TGATCCACTACCAGGCGGTTGTTGTTCTGGAAAACCTGAACTTCGGTTTCAAATCTA AACGTACC
GGTATCGCGGAAAAAGCGGTTTACCAGCAGTTCGAAAAAATGCTGATCGACAAACTG AACTGC
CTGGTTCTGAAAGACTACCCGGCGGAAAAAGTTGGTGGTGTTCTGAACCCGTACCAG CTGACCG
ACCAGTTCACCTCTTTCGCGAAAATGGGTACCCAGTCTGGTTTCCTGTTCTACGTTC CGGCGCCG
TACACCTCTAAAATCGACCCGCTGACCGGTTTCGTTGACCCGTTCGTTTGGAAAACC ATCAAAA
ACCACGAATCTCGTAAACACTTCCTGGAAGGTTTCGACTTCCTGCACTACGACGTTA AAACCGG
TGACTTCATCCTGCACTTCAAAATGAACCGTAACCTGTCTTTCCAGCGTGGTCTGCC GGGTTTCA
TGCCGGCGTGGGACATCGTTTTCGAAAAAAACGAAACCCAGTTCGACGCGAAAGGTA CCCCGTT
CATCGCGGGTAAACGTATCGTTCCGGTTATCGAAAACCACCGTTTCACCGGTCGTTA CCGTGACC
TGTACCCGGCGAACGAACTGATCGCGCTGCTGGAAGAAAAAGGTATCGTTTTCCGTG ACGGTTC
TAACATCCTGCCGAAACTGCTGGAAAACGACGACTCTCACGCGATCGACACCATGGT TGCGCTG
ATCCGTTCTGTTCTGCAGATGCGTAACTCTAACGCGGCGACCGGTGAAGACTACATC AACTCTCC
GGTTCGTGACCTGAACGGTGTTTGCTTCGACTCTCGTTTCCAGAACCCGGAATGGCC GATGGAC
GCGGACGCGAACGGTGCGTACCACATCGCGCTGAAAGGTCAGCTGCTGCTGAACCAC CTGAAA
GAATCTAAAGACCTGAAACTGCAGAACGGTATCTCTAACCAGGACTGGCTGGCGTAC ATCCAGG
AACTGCGTAACTA
SE ATGGCGGTTAAATCTATCAAAGTTAAACTGCGTCTGGACGACATGCCGGAAATCCGTGCG GGTC
Q TGTGGAAACTGCACAAAGAAGTTAACGCGGGTGTTCGTTACTACACCGAATGGCTGTCTC TGCT
no GCGTCAGGAAAACCTGTACCGTCGTTCTCCGAACGGTGACGGTGAACAGGAATGCGACAA AAC
N CGCGGAAGAATGCAAAGCGGAACTGCTGGAACGTCTGCGTGCGCGTCAGGTTGAAAACGG TCA
O: CCGTGGTCCGGCGGGTTCTGACGACGAACTGCTGCAGCTGGCGCGTCAGCTGTACGAACT GCTG
53 GTTCCGCAGGCGATCGGTGCGAAAGGTGACGCGCAGCAGATCGCGCGTAAATTCCTGTCT CCGC
TGGCGGACAAAGACGCGGTTGGTGGTCTGGGTATCGCGAAAGCGGGTAACAAACCGC GTTGGG
TTCGTATGCGTGAAGCGGGTGAACCGGGTTGGGAAGAAGAAAAAGAAAAAGCGGAAA CCCGTA
AATCTGCGGACCGTACCGCGGACGTTCTGCGTGCGCTGGCGGACTTCGGTCTGAAAC CGCTGAT
GCGTGTTTACACCGACTCTGAAATGTCTTCTGTTGAATGGAAACCGCTGCGTAAAGG TCAGGCG
GTTCGTACCTGGGACCGTGACATGTTCCAGCAGGCGATCGAACGTATGATGTCTTGG GAATCTT
GGAACCAGCGTGTTGGTCAGGAATACGCGAAACTGGTTGAACAGAAAAACCGTTTCG AACAGA
AAAACTTCGTTGGTCAGGAACACCTGGTTCACCTGGTTAACCAGCTGCAGCAGGACA TGAAAGA
AGCGTCTCCGGGTCTGGAATCTAAAGAACAGACCGCGCACTACGTTACCGGTCGTGC GCTGCGT
GGTTCTGACAAAGTTTTCGAAAAATGGGGTAAACTGGCGCCGGACGCGCCGTTCGAC CTGTACG
ACGCGGAAATCAAAAACGTTCAGCGTCGTAACACCCGTCGTTTCGGTTCTCACGACC TGTTCGC
GAAACTGGCGGAACCGGAATACCAGGCGCTGTGGCGTGAAGACGCGTCTTTCCTGAC CCGTTAC GCGGTTTACAACTCTATCCTGCGTAAACTGAACCACGCGAAAATGTTCGCGACCTTCACC CTGCC
GGACGCGACCGCGCACCCGATCTGGACCCGTTTCGACAAACTGGGTGGTAACCTGCA CCAGTAC
ACCTTCCTGTTCAACGAATTCGGTGAACGTCGTCACGCGATCCGTTTCCACAAACTG CTGAAAGT
TGAAAACGGTGTTGCGCGTGAAGTTGACGACGTTACCGTTCCGATCTCTATGTCTGA ACAGCTG
GACAACCTGCTGCCGCGTGACCCGAACGAACCGATCGCGCTGTACTTCCGTGACTAC GGTGCGG
AACAGCACTTCACCGGTGAATTCGGTGGTGCGAAAATCCAGTGCCGTCGTGACCAGC TGGCGCA
CATGCACCGTCGTCGTGGTGCGCGTGACGTTTACCTGAACGTTTCTGTTCGTGTTCA GTCTCAGT
CTGAAGCGCGTGGTGAACGTCGTCCGCCGTACGCGGCGGTTTTCCGTCTGGTTGGTG ACAACCA
CCGTGCGTTCGTTCACTTCGACAAACTGTCTGACTACCTGGCGGAACACCCGGACGA CGGTAAA
CTGGGTTCTGAAGGTCTGCTGTCTGGTCTGCGTGTTATGTCTGTTGACCTGGGTCTG CGTACCTCT
GCGTCTATCTCTGTTTTCCGTGTTGCGCGTAAAGACGAACTGAAACCGAACTCTAAA GGTCGTGT
TCCGTTCTTCTTCCCGATCAAAGGTAACGACAACCTGGTTGCGGTTCACGAACGTTC TCAGCTGC
TGAAACTGCCGGGTGAAACCGAATCTAAAGACCTGCGTGCGATCCGTGAAGAACGTC AGCGTA
CCCTGCGTCAGCTGCGTACCCAGCTGGCGTACCTGCGTCTGCTGGTTCGTTGCGGTT CTGAAGAC
GTTGGTCGTCGTGAACGTTCTTGGGCGAAACTGATCGAACAGCCGGTTGACGCGGCG AACCACA
TGACCCCGGACTGGCGTGAAGCGTTCGAAAACGAACTGCAGAAACTGAAATCTCTGC ACGGTAT
CTGCTCTGACAAAGAATGGATGGACGCGGTTTACGAATCTGTTCGTCGTGTTTGGCG TCACATG
GGTAAACAGGTTCGTGACTGGCGTAAAGACGTTCGTTCTGGTGAACGTCCGAAAATC CGTGGTT
ACGCGAAAGACGTTGTTGGTGGTAACTCTATCGAACAGATCGAATACCTGGAACGTC AGTACAA
ATTCCTGAAATCTTGGTCTTTCTTCGGTAAAGTTTCTGGTCAGGTTATCCGTGCGGA AAAAGGTT
CTCGTTTCGCGATCACCCTGCGTGAACACATCGACCACGCGAAAGAAGACCGTCTGA AAAAACT
GGCGGACCGTATCATCATGGAAGCGCTGGGTTACGTTTACGCGCTGGACGAACGTGG TAAAGGT
AAATGGGTTGCGAAATACCCGCCGTGCCAGCTGATCCTGCTGGAAGAACTGTCTGAA TACCAGT
TCAACAACGACCGTCCGCCGTCTGAAAACAACCAGCTGATGCAGTGGTCTCACCGTG GTGTTTT
CCAGGAACTGATCAACCAGGCGCAGGTTCACGACCTGCTGGTTGGTACCATGTACGC GGCGTTC
TCTTCTCGTTTCGACGCGCGTACCGGTGCGCCGGGTATCCGTTGCCGTCGTGTTCCG GCGCGTTG
CACCCAGGAACACAACCCGGAACCGTTCCCGTGGTGGCTGAACAAATTCGTTGTTGA ACACACC
CTGGACGCGTGCCCGCTGCGTGCGGACGACCTGATCCCGACCGGTGAAGGTGAAATC TTCGTTT
CTCCGTTCTCTGCGGAAGAAGGTGACTTCCACCAGATCCACGCGGACCTGAACGCGG CGCAGAA
CCTGCAGCAGCGTCTGTGGTCTGACTTCGACATCTCTCAGATCCGTCTGCGTTGCGA CTGGGGTG
AAGTTGACGGTGAACTGGTTCTGATCCCGCGTCTGACCGGTAAACGTACCGCGGACT CTTACTCT
AACAAAGTTTTCTACACCAACACCGGTGTTACCTACTACGAACGTGAACGTGGTAAA AAACGTC
GTAAAGTTTTCGCGCAGGAAAAACTGTCTGAAGAAGAAGCGGAACTGCTGGTTGAAG CGGACG
AAGCGCGTGAAAAATCTGTTGTTCTGATGCGTGACCCGTCTGGTATCATCAACCGTG GTAACTG
GACCCGTCAGAAAGAATTCTGGTCTATGGTTAACCAGCGTATCGAAGGTTACCTGGT TAAACAG
ATCCGTTCTCGTGTTCCGCTGCAGGACTCTGCGTGCGAAAACACCGGTGACATCTAA
SE ATGGCGACCCGTTCTTTCATCCTGAAAATCGAACCGAACGAAGAAGTTAAAAAAGGTCTG TGGA
Q AAACCCACGAAGTTCTGAACCACGGTATCGCGTACTACATGAACATCCTGAAACTGATCC GTCA
no GGAAGCGATCTACGAACACCACGAACAGGACCCGAAAAACCCGAAAAAAGTTTCTAAAGC GGA
N AATCCAGGCGGAACTGTGGGACTTCGTTCTGAAAATGCAGAAATGCAACTCTTTCACCCA CGAA
O: GTTGACAAAGACGTTGTTTTCAACATCCTGCGTGAACTGTACGAAGAACTGGTTCCGTCT TCTGT 54 TGAAAAAAAAGGTGAAGCGAACCAGCTGTCTAACAAATTCCTGTACCCGCTGGTTGACCC GAAC TCTCAGTCTGGTAAAGGTACCGCGTCTTCTGGTCGTAAACCGCGTTGGTACAACCTGAAA ATCG
CGGGTGACCCGTCTTGGGAAGAAGAAAAAAAAAAATGGGAAGAAGACAAAAAAAAAG ACCCG
CTGGCGAAAATCCTGGGTAAACTGGCGGAATACGGTCTGATCCCGCTGTTCATCCCG TTCACCG
ACTCTAACGAACCGATCGTTAAAGAAATCAAATGGATGGAAAAATCTCGTAACCAGT CTGTTCG
TCGTCTGGACAAAGACATGTTCATCCAGGCGCTGGAACGTTTCCTGTCTTGGGAATC TTGGAACC
TGAAAGTTAAAGAAGAATACGAAAAAGTTGAAAAAGAACACAAAACCCTGGAAGAAC GTATCA
AAGAAGACATCCAGGCGTTCAAATCTCTGGAACAGTACGAAAAAGAACGTCAGGAAC AGCTGC
TGCGTGACACCCTGAACACCAACGAATACCGTCTGTCTAAACGTGGTCTGCGTGGTT GGCGTGA
AATCATCCAGAAATGGCTGAAAATGGACGAAAACGAACCGTCTGAAAAATACCTGGA AGTTTT
CAAAGACTACCAGCGTAAACACCCGCGTGAAGCGGGTGACTACTCTGTTTACGAATT CCTGTCT
AAAAAAGAAAACCACTTCATCTGGCGTAACCACCCGGAATACCCGTACCTGTACGCG ACCTTCT
GCGAAATCGACAAAAAAAAAAAAGACGCGAAACAGCAGGCGACCTTCACCCTGGCGG ACCCGA
TCAACCACCCGCTGTGGGTTCGTTTCGAAGAACGTTCTGGTTCTAACCTGAACAAAT ACCGTATC
CTGACCGAACAGCTGCACACCGAAAAACTGAAAAAAAAACTGACCGTTCAGCTGGAC CGTCTG
ATCTACCCGACCGAATCTGGTGGTTGGGAAGAAAAAGGTAAAGTTGACATCGTTCTG CTGCCGT
CTCGTCAGTTCTACAACCAGATCTTCCTGGACATCGAAGAAAAAGGTAAACACGCGT TCACCTA
CAAAGACGAATCTATCAAATTCCCGCTGAAAGGTACCCTGGGTGGTGCGCGTGTTCA GTTCGAC
CGTGACCACCTGCGTCGTTACCCGCACAAAGTTGAATCTGGTAACGTTGGTCGTATC TACTTCAA
CATGACCGTTAACATCGAACCGACCGAATCTCCGGTTTCTAAATCTCTGAAAATCCA CCGTGAC
GACTTCCCGAAATTCGTTAACTTCAAACCGAAAGAACTGACCGAATGGATCAAAGAC TCTAAAG
GTAAAAAACTGAAATCTGGTATCGAATCTCTGGAAATCGGTCTGCGTGTTATGTCTA TCGACCTG
GGTCAGCGTCAGGCGGCGGCGGCGTCTATCTTCGAAGTTGTTGACCAGAAACCGGAC ATCGAAG
GTAAACTGTTCTTCCCGATCAAAGGTACCGAACTGTACGCGGTTCACCGTGCGTCTT TCAACATC
AAACTGCCGGGTGAAACCCTGGTTAAATCTCGTGAAGTTCTGCGTAAAGCGCGTGAA GACAACC
TGAAACTGATGAACCAGAAACTGAACTTCCTGCGTAACGTTCTGCACTTCCAGCAGT TCGAAGA
CATCACCGAACGTGAAAAACGTGTTACCAAATGGATCTCTCGTCAGGAAAACTCTGA CGTTCCG
CTGGTTTACCAGGACGAACTGATCCAGATCCGTGAACTGATGTACAAACCGTACAAA GACTGGG
TTGCGTTCCTGAAACAGCTGCACAAACGTCTGGAAGTTGAAATCGGTAAAGAAGTTA AACACTG
GCGTAAATCTCTGTCTGACGGTCGTAAAGGTCTGTACGGTATCTCTCTGAAAAACAT CGACGAA
ATCGACCGTACCCGTAAATTCCTGCTGCGTTGGTCTCTGCGTCCGACCGAACCGGGT GAAGTTCG
TCGTCTGGAACCGGGTCAGCGTTTCGCGATCGACCAGCTGAACCACCTGAACGCGCT GAAAGAA
GACCGTCTGAAAAAAATGGCGAACACCATCATCATGCACGCGCTGGGTTACTGCTAC GACGTTC
GTAAAAAAAAATGGCAGGCGAAAAACCCGGCGTGCCAGATCATCCTGTTCGAAGACC TGTCTA
ACTACAACCCGTACGAAGAACGTTCTCGTTTCGAAAACTCTAAACTGATGAAATGGT CTCGTCG
TGAAATCCCGCGTCAGGTTGCGCTGCAGGGTGAAATCTACGGTCTGCAGGTTGGTGA AGTTGGT
GCGCAGTTCTCTTCTCGTTTCCACGCGAAAACCGGTTCTCCGGGTATCCGTTGCTCT GTTGTTACC
AAAGAAAAACTGCAGGACAACCGTTTCTTCAAAAACCTGCAGCGTGAAGGTCGTCTG ACCCTGG
ACAAAATCGCGGTTCTGAAAGAAGGTGACCTGTACCCGGACAAAGGTGGTGAAAAAT TCATCTC
TCTGTCTAAAGACCGTAAACTGGTTACCACCCACGCGGACATCAACGCGGCGCAGAA CCTGCAG
AAACGTTTCTGGACCCGTACCCACGGTTTCTACAAAGTTTACTGCAAAGCGTACCAG GTTGACG
GTCAGACCGTTTACATCCCGGAATCTAAAGACCAGAAACAGAAAATCATCGAAGAAT TCGGTG
AAGGTTACTTCATCCTGAAAGACGGTGTTTACGAATGGGGTAACGCGGGTAAACTGA AAATCAA AAAAGGTTCTTCTAAACAGTCTTCTTCTGAACTGGTTGACTCTGACATCCTGAAAGACTC TTTCG ACCTGGCGTCTGAACTGAAAGGTGAAAAACTGATGCTGTACCGTGACCCGTCTGGTAACG TTTT CCCGTCTGACAAATGGATGGCGGCGGGTGTTTTCTTCGGTAAACTGGAACGTATCCTGAT CTCTA AACTGACCAACCAGTACTCTATCTCTACCATCGAAGACGACTCTTCTAAACAGTCTATGT AA
SE ATGCCGACCCGTACCATCAACCTGAAACTGGTTCTGGGTAAAAACCCGGAAAACGCGACC CTGC
Q GTCGTGCGCTGTTCTCTACCCACCGTCTGGTTAACCAGGCGACCAAACGTATCGAAGAAT TCCTG
no CTGCTGTGCCGTGGTGAAGCGTACCGTACCGTTGACAACGAAGGTAAAGAAGCGGAAATC CCG
N CGTCACGCGGTTCAGGAAGAAGCGCTGGCGTTCGCGAAAGCGGCGCAGCGTCACAACGGT TGC
O: ATCTCTACCTACGAAGACCAGGAAATCCTGGACGTTCTGCGTCAGCTGTACGAACGTCTG GTTC 55 CGTCTGTTAACGAAAACAACGAAGCGGGTGACGCGCAGGCGGCGAACGCGTGGGTTTCTC CGCT
GATGTCTGCGGAATCTGAAGGTGGTCTGTCTGTTTACGACAAAGTTCTGGACCCGCC GCCGGTTT
GGATGAAACTGAAAGAAGAAAAAGCGCCGGGTTGGGAAGCGGCGTCTCAGATCTGGA TCCAGT
CTGACGAAGGTCAGTCTCTGCTGAACAAACCGGGTTCTCCGCCGCGTTGGATCCGTA AACTGCG
TTCTGGTCAGCCGTGGCAGGACGACTTCGTTTCTGACCAGAAAAAAAAACAGGACGA ACTGACC
AAAGGTAACGCGCCGCTGATCAAACAGCTGAAAGAAATGGGTCTGCTGCCGCTGGTT AACCCGT
TCTTCCGTCACCTGCTGGACCCGGAAGGTAAAGGTGTTTCTCCGTGGGACCGTCTGG CGGTTCGT
GCGGCGGTTGCGCACTTCATCTCTTGGGAATCTTGGAACCACCGTACCCGTGCGGAA TACAACT
CTCTGAAACTGCGTCGTGACGAATTCGAAGCGGCGTCTGACGAATTCAAAGACGACT TCACCCT
GCTGCGTCAGTACGAAGCGAAACGTCACTCTACCCTGAAATCTATCGCGCTGGCGGA CGACTCT
AACCCGTACCGTATCGGTGTTCGTTCTCTGCGTGCGTGGAACCGTGTTCGTGAAGAA TGGATCG
ACAAAGGTGCGACCGAAGAACAGCGTGTTACCATCCTGTCTAAACTGCAGACCCAGC TGCGTGG
TAAATTCGGTGACCCGGACCTGTTCAACTGGCTGGCGCAGGACCGTCACGTTCACCT GTGGTCTC
CGCGTGACTCTGTTACCCCGCTGGTTCGTATCAACGCGGTTGACAAAGTTCTGCGTC GTCGTAAA
CCGTACGCGCTGATGACCTTCGCGCACCCGCGTTTCCACCCGCGTTGGATCCTGTAC GAAGCGCC
GGGTGGTTCTAACCTGCGTCAGTACGCGCTGGACTGCACCGAAAACGCGCTGCACAT CACCCTG
CCGCTGCTGGTTGACGACGCGCACGGTACCTGGATCGAAAAAAAAATCCGTGTTCCG CTGGCGC
CGTCTGGTCAGATCCAGGACCTGACCCTGGAAAAACTGGAAAAAAAAAAAAACCGTC TGTACT
ACCGTTCTGGTTTCCAGCAGTTCGCGGGTCTGGCGGGTGGTGCGGAAGTTCTGTTCC ACCGTCCG
TACATGGAACACGACGAACGTTCTGAAGAATCTCTGCTGGAACGTCCGGGTGCGGTT TGGTTCA
AACTGACCCTGGACGTTGCGACCCAGGCGCCGCCGAACTGGCTGGACGGTAAAGGTC GTGTTCG
TACCCCGCCGGAAGTTCACCACTTCAAAACCGCGCTGTCTAACAAATCTAAACACAC CCGTACC
CTGCAGCCGGGTCTGCGTGTTCTGTCTGTTGACCTGGGTATGCGTACCTTCGCGTCT TGCTCTGTT
TTCGAACTGATCGAAGGTAAACCGGAAACCGGTCGTGCGTTCCCGGTTGCGGACGAA CGTTCTA
TGGACTCTCCGAACAAACTGTGGGCGAAACACGAACGTTCTTTCAAACTGACCCTGC CGGGTGA
AACCCCGTCTCGTAAAGAAGAAGAAGAACGTTCTATCGCGCGTGCGGAAATCTACGC GCTGAA
ACGTGACATCCAGCGTCTGAAATCTCTGCTGCGTCTGGGTGAAGAAGACAACGACAA CCGTCGT
GACGCGCTGCTGGAACAGTTCTTCAAAGGTTGGGGTGAAGAAGACGTTGTTCCGGGT CAGGCGT
TCCCGCGTTCTCTGTTCCAGGGTCTGGGTGCGGCGCCGTTCCGTTCTACCCCGGAAC TGTGGCGT
CAGCACTGCCAGACCTACTACGACAAAGCGGAAGCGTGCCTGGCGAAACACATCTCT GACTGGC
GTAAACGTACCCGTCCGCGTCCGACCTCTCGTGAAATGTGGTACAAAACCCGTTCTT ACCACGG
TGGTAAATCTATCTGGATGCTGGAATACCTGGACGCGGTTCGTAAACTGCTGCTGTC TTGGTCTC
TGCGTGGTCGTACCTACGGTGCGATCAACCGTCAGGACACCGCGCGTTTCGGTTCTC TGGCGTCT CGTCTGCTGCACCACATCAACTCTCTGAAAGAAGACCGTATCAAAACCGGTGCGGACTCT ATCG
TTCAGGCGGCGCGTGGTTACATCCCGCTGCCGCACGGTAAAGGTTGGGAACAGCGTT ACGAACC
GTGCCAGCTGATCCTGTTCGAAGACCTGGCGCGTTACCGTTTCCGTGTTGACCGTCC GCGTCGTG
AAAACTCTCAGCTGATGCAGTGGAACCACCGTGCGATCGTTGCGGAAACCACCATGC AGGCGG
AACTGTACGGTCAGATCGTTGAAAACACCGCGGCGGGTTTCTCTTCTCGTTTCCACG CGGCGACC
GGTGCGCCGGGTGTTCGTTGCCGTTTCCTGCTGGAACGTGACTTCGACAACGACCTG CCGAAAC
CGTACCTGCTGCGTGAACTGTCTTGGATGCTGGGTAACACCAAAGTTGAATCTGAAG AAGAAAA
ACTGCGTCTGCTGTCTGAAAAAATCCGTCCGGGTTCTCTGGTTCCGTGGGACGGTGG TGAACAG
TTCGCGACCCTGCACCCGAAACGTCAGACCCTGTGCGTTATCCACGCGGACATGAAC GCGGCGC
AGAACCTGCAGCGTCGTTTCTTCGGTCGTTGCGGTGAAGCGTTCCGTCTGGTTTGCC AGCCGCAC
GGTGACGACGTTCTGCGTCTGGCGTCTACCCCGGGTGCGCGTCTGCTGGGTGCGCTG CAGCAGC
TGGAAAACGGTCAGGGTGCGTTCGAACTGGTTCGTGACATGGGTTCTACCTCTCAGA TGAACCG
TTTCGTTATGAAATCTCTGGGTAAAAAAAAAATCAAACCGCTGCAGGACAACAACGG TGACGAC
GAACTGGAAGACGTTCTGTCTGTTCTGCCGGAAGAAGACGACACCGGTCGTATCACC GTTTTCC
GTGACTCTTCTGGTATCTTCTTCCCGTGCAACGTTTGGATCCCGGCGAAACAGTTCT GGCCGGCG
GTTCGTGCGATGATCTGGAAAGTTATGGCGTCTCACTCTCTGGGTTAA
SE ATGACCAAACTGCGTCACCGTCAGAAAAAACTGACCCACGACTGGGCGGGTTCTAAAAAA CGT
Q GAAGTTCTGGGTTCTAACGGTAAACTGCAGAACCCGCTGCTGATGCCGGTTAAAAAAGGT CAGG
no TTACCGAATTCCGTAAAGCGTTCTCTGCGTACGCGCGTGCGACCAAAGGTGAAATGACCG ACGG
N TCGTAAAAACATGTTCACCCACTCTTTCGAACCGTTCAAAACCAAACCGTCTCTGCACCA GTGCG
O: AACTGGCGGACAAAGCGTACCAGTCTCTGCACTCTTACCTGCCGGGTTCTCTGGCGCACT TCCTG 56 CTGTCTGCGCACGCGCTGGGTTTCCGTATCTTCTCTAAATCTGGTGAAGCGACCGCGTTC CAGGC
GTCTTCTAAAATCGAAGCGTACGAATCTAAACTGGCGTCTGAACTGGCGTGCGTTGA CCTGTCT
ATCCAGAACCTGACCATCTCTACCCTGTTCAACGCGCTGACCACCTCTGTTCGTGGT AAAGGTGA
AGAAACCTCTGCGGACCCGCTGATCGCGCGTTTCTACACCCTGCTGACCGGTAAACC GCTGTCTC
GTGACACCCAGGGTCCGGAACGTGACCTGGCGGAAGTTATCTCTCGTAAAATCGCGT CTTCTTTC
GGTACCTGGAAAGAAATGACCGCGAACCCGCTGCAGTCTCTGCAGTTCTTCGAAGAA GAACTGC
ACGCGCTGGACGCGAACGTTTCTCTGTCTCCGGCGTTCGACGTTCTGATCAAAATGA ACGACCT
GCAGGGTGACCTGAAAAACCGTACCATCGTTTTCGACCCGGACGCGCCGGTTTTCGA ATACAAC
GCGGAAGACCCGGCGGACATCATCATCAAACTGACCGCGCGTTACGCGAAAGAAGCG GTTATC
AAAAACCAGAACGTTGGTAACTACGTTAAAAACGCGATCACCACCACCAACGCGAAC GGTCTG
GGTTGGCTGCTGAACAAAGGTCTGTCTCTGCTGCCGGTTTCTACCGACGACGAACTG CTGGAATT
CATCGGTGTTGAACGTTCTCACCCGTCTTGCCACGCGCTGATCGAACTGATCGCGCA GCTGGAA
GCGCCGGAACTGTTCGAAAAAAACGTTTTCTCTGACACCCGTTCTGAAGTTCAGGGT ATGATCG
ACTCTGCGGTTTCTAACCACATCGCGCGTCTGTCTTCTTCTCGTAACTCTCTGTCTA TGGACTCTG
AAGAACTGGAACGTCTGATCAAATCTTTCCAGATCCACACCCCGCACTGCTCTCTGT TCATCGGT
GCGCAGTCTCTGTCTCAGCAGCTGGAATCTCTGCCGGAAGCGCTGCAGTCTGGTGTT AACTCTGC
GGACATCCTGCTGGGTTCTACCCAGTACATGCTGACCAACTCTCTGGTTGAAGAATC TATCGCGA
CCTACCAGCGTACCCTGAACCGTATCAACTACCTGTCTGGTGTTGCGGGTCAGATCA ACGGTGC
GATCAAACGTAAAGCGATCGACGGTGAAAAAATCCACCTGCCGGCGGCGTGGTCTGA ACTGAT
CTCTCTGCCGTTCATCGGTCAGCCGGTTATCGACGTTGAATCTGACCTGGCGCACCT GAAAAACC
AGTACCAGACCCTGTCTAACGAATTCGACACCCTGATCTCTGCGCTGCAGAAAAACT TCGACCT GAACTTCAACAAAGCGCTGCTGAACCGTACCCAGCACTTCGAAGCGATGTGCCGTTCTAC CAAA
AAAAACGCGCTGTCTAAACCGGAAATCGTTTCTTACCGTGACCTGCTGGCGCGTCTG ACCTCTTG
CCTGTACCGTGGTTCTCTGGTTCTGCGTCGTGCGGGTATCGAAGTTCTGAAAAAACA CAAAATCT
TCGAATCTAACTCTGAACTGCGTGAACACGTTCACGAACGTAAACACTTCGTTTTCG TTTCTCCG
CTGGACCGTAAAGCGAAAAAACTGCTGCGTCTGACCGACTCTCGTCCGGACCTGCTG CACGTTA
TCGACGAAATCCTGCAGCACGACAACCTGGAAAACAAAGACCGTGAATCTCTGTGGC TGGTTCG
TTCTGGTTACCTGCTGGCGGGTCTGCCGGACCAGCTGTCTTCTTCTTTCATCAACCT GCCGATCAT
CACCCAGAAAGGTGACCGTCGTCTGATCGACCTGATCCAGTACGACCAGATCAACCG TGACGCG
TTCGTTATGCTGGTTACCTCTGCGTTCAAATCTAACCTGTCTGGTCTGCAGTACCGT GCGAACAA
ACAGTCTTTCGTTGTTACCCGTACCCTGTCTCCGTACCTGGGTTCTAAACTGGTTTA CGTTCCGAA
AGACAAAGACTGGCTGGTTCCGTCTCAGATGTTCGAAGGTCGTTTCGCGGACATCCT GCAGTCT
GACTACATGGTTTGGAAAGACGCGGGTCGTCTGTGCGTTATCGACACCGCGAAACAC CTGTCTA
ACATCAAAAAATCTGTTTTCTCTTCTGAAGAAGTTCTGGCGTTCCTGCGTGAACTGC CGCACCGT
ACCTTCATCCAGACCGAAGTTCGTGGTCTGGGTGTTAACGTTGACGGTATCGCGTTC AACAACG
GTGACATCCCGTCTCTGAAAACCTTCTCTAACTGCGTTCAGGTTAAAGTTTCTCGTA CCAACACC
TCTCTGGTTCAGACCCTGAACCGTTGGTTCGAAGGTGGTAAAGTTTCTCCGCCGTCT ATCCAGTT
CGAACGTGCGTACTACAAAAAAGACGACCAGATCCACGAAGACGCGGCGAAACGTAA AATCCG
TTTCCAGATGCCGGCGACCGAACTGGTTCACGCGTCTGACGACGCGGGTTGGACCCC GTCTTAC
CTGCTGGGTATCGACCCGGGTGAATACGGTATGGGTCTGTCTCTGGTTTCTATCAAC AACGGTGA
AGTTCTGGACTCTGGTTTCATCCACATCAACTCTCTGATCAACTTCGCGTCTAAAAA ATCTAACC
ACCAGACCAAAGTTGTTCCGCGTCAGCAGTACAAATCTCCGTACGCGAACTACCTGG AACAGTC
TAAAGACTCTGCGGCGGGTGACATCGCGCACATCCTGGACCGTCTGATCTACAAACT GAACGCG
CTGCCGGTTTTCGAAGCGCTGTCTGGTAACTCTCAGTCTGCGGCGGACCAGGTTTGG ACCAAAG
TTCTGTCTTTCTACACCTGGGGTGACAACGACGCGCAGAACTCTATCCGTAAACAGC ACTGGTTC
GGTGCGTCTCACTGGGACATCAAAGGTATGCTGCGTCAGCCGCCGACCGAAAAAAAA CCGAAA
CCGTACATCGCGTTCCCGGGTTCTCAGGTTTCTTCTTACGGTAACTCTCAGCGTTGC TCTTGCTGC
GGTCGTAACCCGATCGAACAGCTGCGTGAAATGGCGAAAGACACCTCTATCAAAGAA CTGAAA
ATCCGTAACTCTGAAATCCAGCTGTTCGACGGTACCATCAAACTGTTCAACCCGGAC CCGTCTAC
CGTTATCGAACGTCGTCGTCACAACCTGGGTCCGTCTCGTATCCCGGTTGCGGACCG TACCTTCA
AAAACATCTCTCCGTCTTCTCTGGAATTCAAAGAACTGATCACCATCGTTTCTCGTT CTATCCGT
CACTCTCCGGAATTCATCGCGAAAAAACGTGGTATCGGTTCTGAATACTTCTGCGCG TACTCTGA
CTGCAACTCTTCTCTGAACTCTGAAGCGAACGCGGCGGCGAACGTTGCGCAGAAATT CCAGAAA
CAGCTGTTCTTCGAACTGTAA
SE ATGAAACGTATCCTGAACTCTCTGAAAGTTGCGGCGCTGCGTCTGCTGTTCCGTGGTAAA GGTTC
Q TGAACTGGTTAAAACCGTTAAATACCCGCTGGTTTCTCCGGTTCAGGGTGCGGTTGAAGA ACTG
no GCGGAAGCGATCCGTCACGACAACCTGCACCTGTTCGGTCAGAAAGAAATCGTTGACCTG ATGG
N AAAAAGACGAAGGTACCCAGGTTTACTCTGTTGTTGACTTCTGGCTGGACACCCTGCGTC TGGG
O: TATGTTCTTCTCTCCGTCTGCGAACGCGCTGAAAATCACCCTGGGTAAATTCAACTCTGA CCAGG
57 TTTCTCCGTTCCGTAAAGTTCTGGAACAGTCTCCGTTCTTCCTGGCGGGTCGTCTGAAAG TTGAA
CCGGCGGAACGTATCCTGTCTGTTGAAATCCGTAAAATCGGTAAACGTGAAAACCGT GTTGAAA
ACTACGCGGCGGACGTTGAAACCTGCTTCATCGGTCAGCTGTCTTCTGACGAAAAAC AGTCTAT
CCAGAAACTGGCGAACGACATCTGGGACTCTAAAGACCACGAAGAACAGCGTATGCT GAAAGC GGACTTCTTCGCGATCCCGCTGATCAAAGACCCGAAAGCGGTTACCGAAGAAGACCCGGA AAA
CGAAACCGCGGGTAAACAGAAACCGCTGGAACTGTGCGTTTGCCTGGTTCCGGAACT GTACACC
CGTGGTTTCGGTTCTATCGCGGACTTCCTGGTTCAGCGTCTGACCCTGCTGCGTGAC AAAATGTC
TACCGACACCGCGGAAGACTGCCTGGAATACGTTGGTATCGAAGAAGAAAAAGGTAA CGGTAT
GAACTCTCTGCTGGGTACCTTCCTGAAAAACCTGCAGGGTGACGGTTTCGAACAGAT CTTCCAG
TTCATGCTGGGTTCTTACGTTGGTTGGCAGGGTAAAGAAGACGTTCTGCGTGAACGT CTGGACCT
GCTGGCGGAAAAAGTTAAACGTCTGCCGAAACCGAAATTCGCGGGTGAATGGTCTGG TCACCGT
ATGTTCCTGCACGGTCAGCTGAAATCTTGGTCTTCTAACTTCTTCCGTCTGTTCAAC GAAACCCG
TGAACTGCTGGAATCTATCAAATCTGACATCCAGCACGCGACCATGCTGATCTCTTA CGTTGAA
GAAAAAGGTGGTTACCACCCGCAGCTGCTGTCTCAGTACCGTAAACTGATGGAACAG CTGCCGG
CGCTGCGTACCAAAGTTCTGGACCCGGAAATCGAAATGACCCACATGTCTGAAGCGG TTCGTTC
TTACATCATGATCCACAAATCTGTTGCGGGTTTCCTGCCGGACCTGCTGGAATCTCT GGACCGTG
ACAAAGACCGTGAATTCCTGCTGTCTATCTTCCCGCGTATCCCGAAAATCGACAAAA AAACCAA
AGAAATCGTTGCGTGGGAACTGCCGGGTGAACCGGAAGAAGGTTACCTGTTCACCGC GAACAA
CCTGTTCCGTAACTTCCTGGAAAACCCGAAACACGTTCCGCGTTTCATGGCGGAACG TATCCCG
GAAGACTGGACCCGTCTGCGTTCTGCGCCGGTTTGGTTCGACGGTATGGTTAAACAG TGGCAGA
AAGTTGTTAACCAGCTGGTTGAATCTCCGGGTGCGCTGTACCAGTTCAACGAATCTT TCCTGCGT
CAGCGTCTGCAGGCGATGCTGACCGTTTACAAACGTGACCTGCAGACCGAAAAATTC CTGAAAC
TGCTGGCGGACGTTTGCCGTCCGCTGGTTGACTTCTTCGGTCTGGGTGGTAACGACA TCATCTTC
AAATCTTGCCAGGACCCGCGTAAACAGTGGCAGACCGTTATCCCGCTGTCTGTTCCG GCGGACG
TTTACACCGCGTGCGAAGGTCTGGCGATCCGTCTGCGTGAAACCCTGGGTTTCGAAT GGAAAAA
CCTGAAAGGTCACGAACGTGAAGACTTCCTGCGTCTGCACCAGCTGCTGGGTAACCT GCTGTTC
TGGATCCGTGACGCGAAACTGGTTGTTAAACTGGAAGACTGGATGAACAACCCGTGC GTTCAGG
AATACGTTGAAGCGCGTAAAGCGATCGACCTGCCGCTGGAAATCTTCGGTTTCGAAG TTCCGAT
CTTCCTGAACGGTTACCTGTTCTCTGAACTGCGTCAGCTGGAACTGCTGCTGCGTCG TAAATCTG
TTATGACCTCTTACTCTGTTAAAACCACCGGTTCTCCGAACCGTCTGTTCCAGCTGG TTTACCTGC
CGCTGAACCCGTCTGACCCGGAAAAAAAAAACTCTAACAACTTCCAGGAACGTCTGG ACACCCC
GACCGGTCTGTCTCGTCGTTTCCTGGACCTGACCCTGGACGCGTTCGCGGGTAAACT GCTGACCG
ACCCGGTTACCCAGGAACTGAAAACCATGGCGGGTTTCTACGACCACCTGTTCGGTT TCAAACT
GCCGTGCAAACTGGCGGCGATGTCTAACCACCCGGGTTCTTCTTCTAAAATGGTTGT TCTGGCGA
AACCGAAAAAAGGTGTTGCGTCTAACATCGGTTTCGAACCGATCCCGGACCCGGCGC ACCCGGT
TTTCCGTGTTCGTTCTTCTTGGCCGGAACTGAAATACCTGGAAGGTCTGCTGTACCT GCCGGAAG
ACACCCCGCTGACCATCGAACTGGCGGAAACCTCTGTTTCTTGCCAGTCTGTTTCTT CTGTTGCG
TTCGACCTGAAAAACCTGACCACCATCCTGGGTCGTGTTGGTGAATTCCGTGTTACC GCGGACC
AGCCGTTCAAACTGACCCCGATCATCCCGGAAAAAGAAGAATCTTTCATCGGTAAAA CCTACCT
GGGTCTGGACGCGGGTGAACGTTCTGGTGTTGGTTTCGCGATCGTTACCGTTGACGG TGACGGTT
ACGAAGTTCAGCGTCTGGGTGTTCACGAAGACACCCAGCTGATGGCGCTGCAGCAGG TTGCGTC
TAAATCTCTGAAAGAACCGGTTTTCCAGCCGCTGCGTAAAGGTACCTTCCGTCAGCA GGAACGT
ATCCGTAAATCTCTGCGTGGTTGCTACTGGAACTTCTACCACGCGCTGATGATCAAA TACCGTGC
GAAAGTTGTTCACGAAGAATCTGTTGGTTCTTCTGGTCTGGTTGGTCAGTGGCTGCG TGCGTTCC
AGAAAGACCTGAAAAAAGCGGACGTTCTGCCGAAAAAAGGTGGTAAAAACGGTGTTG ACAAAA
AAAAACGTGAATCTTCTGCGCAGGACACCCTGTGGGGTGGTGCGTTCTCTAAAAAAG AAGAACA GCAGATCGCGTTCGAAGTTCAGGCGGCGGGTTCTTCTCAGTTCTGCCTGAAATGCGGTTG GTGGT
TCCAGCTGGGTATGCGTGAAGTTAACCGTGTTCAGGAATCTGGTGTTGTTCTGGACT GGAACCGT
TCTATCGTTACCTTCCTGATCGAATCTTCTGGTGAAAAAGTTTACGGTTTCTCTCCG CAGCAGCT
GGAAAAAGGTTTCCGTCCGGACATCGAAACCTTCAAAAAAATGGTTCGTGACTTCAT GCGTCCG
CCGATGTTCGACCGTAAAGGTCGTCCGGCGGCGGCGTACGAACGTTTCGTTCTGGGT CGTCGTC
ACCGTCGTTACCGTTTCGACAAAGTTTTCGAAGAACGTTTCGGTCGTTCTGCGCTGT TCATCTGC
CCGCGTGTTGGTTGCGGTAACTTCGACCACTCTTCTGAACAGTCTGCGGTTGTTCTG GCGCTGAT
CGGTTACATCGCGGACAAAGAAGGTATGTCTGGTAAAAAACTGGTTTACGTTCGTCT GGCGGAA
CTGATGGCGGAATGGAAACTGAAAAAACTGGAACGTTCTCGTGTTGAAGAACAGTCT TCTGCGC
AGTAA
SE ATGGCGGAATCTAAACAGATGCAGTGCCGTAAATGCGGTGCGTCTATGAAATACGAAGTT ATCG
Q GTCTGGGTAAAAAATCTTGCCGTTACATGTGCCCGGACTGCGGTAACCACACCTCTGCGC GTAA
no AATCCAGAACAAAAAAAAACGTGACAAAAAATACGGTTCTGCGTCTAAAGCGCAGTCTCA GCG
N TATCGCGGTTGCGGGTGCGCTGTACCCGGACAAAAAAGTTCAGACCATCAAAACCTACAA ATAC
O: CCGGCGGACCTGAACGGTGAAGTTCACGACTCTGGTGTTGCGGAAAAAATCGCGCAGGCG ATCC 58 AGGAAGACGAAATCGGTCTGCTGGGTCCGTCTTCTGAATACGCGTGCTGGATCGCGTCTC AGAA
ACAGTCTGAACCGTACTCTGTTGTTGACTTCTGGTTCGACGCGGTTTGCGCGGGTGG TGTTTTCG
CGTACTCTGGTGCGCGTCTGCTGTCTACCGTTCTGCAGCTGTCTGGTGAAGAATCTG TTCTGCGT
GCGGCGCTGGCGTCTTCTCCGTTCGTTGACGACATCAACCTGGCGCAGGCGGAAAAA TTCCTGG
CGGTTTCTCGTCGTACCGGTCAGGACAAACTGGGTAAACGTATCGGTGAATGCTTCG CGGAAGG
TCGTCTGGAAGCGCTGGGTATCAAAGACCGTATGCGTGAATTCGTTCAGGCGATCGA CGTTGCG
CAGACCGCGGGTCAGCGTTTCGCGGCGAAACTGAAAATCTTCGGTATCTCTCAGATG CCGGAAG
CGAAACAGTGGAACAACGACTCTGGTCTGACCGTTTGCATCCTGCCGGACTACTACG TTCCGGA
AGAAAACCGTGCGGACCAGCTGGTTGTTCTGCTGCGTCGTCTGCGTGAAATCGCGTA CTGCATG
GGTATCGAAGACGAAGCGGGTTTCGAACACCTGGGTATCGACCCGGGTGCGCTGTCT AACTTCT
CTAACGGTAACCCGAAACGTGGTTTCCTGGGTCGTCTGCTGAACAACGACATCATCG CGCTGGC
GAACAACATGTCTGCGATGACCCCGTACTGGGAAGGTCGTAAAGGTGAACTGATCGA ACGTCTG
GCGTGGCTGAAACACCGTGCGGAAGGTCTGTACCTGAAAGAACCGCACTTCGGTAAC TCTTGGG
CGGACCACCGTTCTCGTATCTTCTCTCGTATCGCGGGTTGGCTGTCTGGTTGCGCGG GTAAACTG
AAAATCGCGAAAGACCAGATCTCTGGTGTTCGTACCGACCTGTTCCTGCTGAAACGT CTGCTGG
ACGCGGTTCCGCAGTCTGCGCCGTCTCCGGACTTCATCGCGTCTATCTCTGCGCTGG ACCGTTTC
CTGGAAGCGGCGGAATCTTCTCAGGACCCGGCGGAACAGGTTCGTGCGCTGTACGCG TTCCACC
TGAACGCGCCGGCGGTTCGTTCTATCGCGAACAAAGCGGTTCAGCGTTCTGACTCTC AGGAATG
GCTGATCAAAGAACTGGACGCGGTTGACCACCTGGAATTCAACAAAGCGTTCCCGTT CTTCTCT
GACACCGGTAAAAAAAAAAAAAAAGGTGCGAACTCTAACGGTGCGCCGTCTGAAGAA GAATAC
ACCGAAACCGAATCTATCCAGCAGCCGGAAGACGCGGAACAGGAAGTTAACGGTCAG GAAGGT
AACGGTGCGTCTAAAAACCAGAAAAAATTCCAGCGTATCCCGCGTTTCTTCGGTGAA GGTTCTC
GTTCTGAATACCGTATCCTGACCGAAGCGCCGCAGTACTTCGACATGTTCTGCAACA ACATGCG
TGCGATCTTCATGCAGCTGGAATCTCAGCCGCGTAAAGCGCCGCGTGACTTCAAATG CTTCCTGC
AGAACCGTCTGCAGAAACTGTACAAACAGACCTTCCTGAACGCGCGTTCTAACAAAT GCCGTGC
GCTGCTGGAATCTGTTCTGATCTCTTGGGGTGAATTCTACACCTACGGTGCGAACGA AAAAAAA
TTCCGTCTGCGTCACGAAGCGTCTGAACGTTCTTCTGACCCGGACTACGTTGTTCAG CAGGCGCT GGAAATCGCGCGTCGTCTGTTCCTGTTCGGTTTCGAATGGCGTGACTGCTCTGCGGGTGA ACGTG
TTGACCTGGTTGAAATCCACAAAAAAGCGATCTCTTTCCTGCTGGCGATCACCCAGG CGGAAGT
TTCTGTTGGTTCTTACAACTGGCTGGGTAACTCTACCGTTTCTCGTTACCTGTCTGT TGCGGGTAC
CGACACCCTGTACGGTACCCAGCTGGAAGAATTCCTGAACGCGACCGTTCTGTCTCA GATGCGT
GGTCTGGCGATCCGTCTGTCTTCTCAGGAACTGAAAGACGGTTTCGACGTTCAGCTG GAATCTTC
TTGCCAGGACAACCTGCAGCACCTGCTGGTTTACCGTGCGTCTCGTGACCTGGCGGC GTGCAAA
CGTGCGACCTGCCCGGCGGAACTGGACCCGAAAATCCTGGTTCTGCCGGTTGGTGCG TTCATCG
CGTCTGTTATGAAAATGATCGAACGTGGTGACGAACCGCTGGCGGGTGCGTACCTGC GTCACCG
TCCGCACTCTTTCGGTTGGCAGATCCGTGTTCGTGGTGTTGCGGAAGTTGGTATGGA CCAGGGTA
CCGCGCTGGCGTTCCAGAAACCGACCGAATCTGAACCGTTCAAAATCAAACCGTTCT CTGCGCA
GTACGGTCCGGTTCTGTGGCTGAACTCTTCTTCTTACTCTCAGTCTCAGTACCTGGA CGGTTTCCT
GTCTCAGCCGAAAAACTGGTCTATGCGTGTTCTGCCGCAGGCGGGTTCTGTTCGTGT TGAACAGC
GTGTTGCGCTGATCTGGAACCTGCAGGCGGGTAAAATGCGTCTGGAACGTTCTGGTG CGCGTGC
GTTCTTCATGCCGGTTCCGTTCTCTTTCCGTCCGTCTGGTTCTGGTGACGAAGCGGT TCTGGCGCC
GAACCGTTACCTGGGTCTGTTCCCGCACTCTGGTGGTATCGAATACGCGGTTGTTGA CGTTCTGG
ACTCTGCGGGTTTCAAAATCCTGGAACGTGGTACCATCGCGGTTAACGGTTTCTCTC AGAAACGT
GGTGAACGTCAGGAAGAAGCGCACCGTGAAAAACAGCGTCGTGGTATCTCTGACATC GGTCGT
AAAAAACCGGTTCAGGCGGAAGTTGACGCGGCGAACGAACTGCACCGTAAATACACC GACGTT
GCGACCCGTCTGGGTTGCCGTATCGTTGTTCAGTGGGCGCCGCAGCCGAAACCGGGT ACCGCGC
CGACCGCGCAGACCGTTTACGCGCGTGCGGTTCGTACCGAAGCGCCGCGTTCTGGTA ACCAGGA
AGACCACGCGCGTATGAAATCTTCTTGGGGTTACACCTGGGGTACCTACTGGGAAAA ACGTAAA
CCGGAAGACATCCTGGGTATCTCTACCCAGGTTTACTGGACCGGTGGTATCGGTGAA TCTTGCCC
GGCGGTTGCGGTTGCGCTGCTGGGTCACATCCGTGCGACCTCTACCCAGACCGAATG GGAAAAA
GAAGAAGTTGTTTTCGGTCGTCTGAAAAAATTCTTCCCGTCTTAA
SE ATGGAAAAACGTATCAACAAAATCCGTAAAAAACTGTCTGCGGACAACGCGACCAAACCG GTT
Q TCTCGTTCTGGTCCGATGAAAACCCTGCTGGTTCGTGTTATGACCGACGACCTGAAAAAA CGTCT
no GGAAAAACGTCGTAAAAAACCGGAAGTTATGCCGCAGGTTATCTCTAACAACGCGGCGAA CAA
N CCTGCGTATGCTGCTGGACGACTACACCAAAATGAAAGAAGCGATCCTGCAGGTTTACTG GCAG
O: GAATTCAAAGACGACCACGTTGGTCTGATGTGCAAATTCGCGCAGCCGGCGTCTAAAAAA ATCG 59 ACCAGAACAAACTGAAACCGGAAATGGACGAAAAAGGTAACCTGACCACCGCGGGTTTCG CGT
GCTCTCAGTGCGGTCAGCCGCTGTTCGTTTACAAACTGGAACAGGTTTCTGAAAAAG GTAAAGC
GTACACCAACTACTTCGGTCGTTGCAACGTTGCGGAACACGAAAAACTGATCCTGCT GGCGCAG
CTGAAACCGGAAAAAGACTCTGACGAAGCGGTTACCTACTCTCTGGGTAAATTCGGT CAGCGTG
CGCTGGACTTCTACTCTATCCACGTTACCAAAGAATCTACCCACCCGGTTAAACCGC TGGCGCA
GATCGCGGGTAACCGTTACGCGTCTGGTCCGGTTGGTAAAGCGCTGTCTGACGCGTG CATGGGT
ACCATCGCGTCTTTCCTGTCTAAATACCAGGACATCATCATCGAACACCAGAAAGTT GTTAAAG
GTAACCAGAAACGTCTGGAATCTCTGCGTGAACTGGCGGGTAAAGAAAACCTGGAAT ACCCGTC
TGTTACCCTGCCGCCGCAGCCGCACACCAAAGAAGGTGTTGACGCGTACAACGAAGT TATCGCG
CGTGTTCGTATGTGGGTTAACCTGAACCTGTGGCAGAAACTGAAACTGTCTCGTGAC GACGCGA
AACCGCTGCTGCGTCTGAAAGGTTTCCCGTCTTTCCCGGTTGTTGAACGTCGTGAAA ACGAAGTT
GACTGGTGGAACACCATCAACGAAGTTAAAAAACTGATCGACGCGAAACGTGACATG GGTCGT
GTTTTCTGGTCTGGTGTTACCGCGGAAAAACGTAACACCATCCTGGAAGGTTACAAC TACCTGC CGAACGAAAACGACCACAAAAAACGTGAAGGTTCTCTGGAAAACCCGAAAAAACCGGCGA AAC
GTCAGTTCGGTGACCTGCTGCTGTACCTGGAAAAAAAATACGCGGGTGACTGGGGTA AAGTTTT
CGACGAAGCGTGGGAACGTATCGACAAAAAAATCGCGGGTCTGACCTCTCACATCGA ACGTGA
AGAAGCGCGTAACGCGGAAGACGCGCAGTCTAAAGCGGTTCTGACCGACTGGCTGCG TGCGAA
AGCGTCTTTCGTTCTGGAACGTCTGAAAGAAATGGACGAAAAAGAATTCTACGCGTG CGAAATC
CAGCTGCAGAAATGGTACGGTGACCTGCGTGGTAACCCGTTCGCGGTTGAAGCGGAA AACCGTG
TTGTTGACATCTCTGGTTTCTCTATCGGTTCTGACGGTCACTCTATCCAGTACCGTA ACCTGCTGG
CGTGGAAATACCTGGAAAACGGTAAACGTGAATTCTACCTGCTGATGAACTACGGTA AAAAAG
GTCGTATCCGTTTCACCGACGGTACCGACATCAAAAAATCTGGTAAATGGCAGGGTC TGCTGTA
CGGTGGTGGTAAAGCGAAAGTTATCGACCTGACCTTCGACCCGGACGACGAACAGCT GATCATC
CTGCCGCTGGCGTTCGGTACCCGTCAGGGTCGTGAATTCATCTGGAACGACCTGCTG TCTCTGGA
AACCGGTCTGATCAAACTGGCGAACGGTCGTGTTATCGAAAAAACCATCTACAACAA AAAAATC
GGTCGTGACGAACCGGCGCTGTTCGTTGCGCTGACCTTCGAACGTCGTGAAGTTGTT GACCCGTC
TAACATCAAACCGGTTAACCTGATCGGTGTTGACCGTGGTGAAAACATCCCGGCGGT TATCGCG
CTGACCGACCCGGAAGGTTGCCCGCTGCCGGAATTCAAAGACTCTTCTGGTGGTCCG ACCGACA
TCCTGCGTATCGGTGAAGGTTACAAAGAAAAACAGCGTGCGATCCAGGCGGCGAAAG AAGTTG
AACAGCGTCGTGCGGGTGGTTACTCTCGTAAATTCGCGTCTAAATCTCGTAACCTGG CGGACGA
CATGGTTCGTAACTCTGCGCGTGACCTGTTCTACCACGCGGTTACCCACGACGCGGT TCTGGTTT
TCGAAAACCTGTCTCGTGGTTTCGGTCGTCAGGGTAAACGTACCTTCATGACCGAAC GTCAGTA
CACCAAAATGGAAGACTGGCTGACCGCGAAACTGGCGTACGAAGGTCTGACCTCTAA AACCTA
CCTGTCTAAAACCCTGGCGCAGTACACCTCTAAAACCTGCTCTAACTGCGGTTTCAC CATCACCA
CCGCGGACTACGACGGTATGCTGGTTCGTCTGAAAAAAACCTCTGACGGTTGGGCGA CCACCCT
GAACAACAAAGAACTGAAAGCGGAAGGTCAGATCACCTACTACAACCGTTACAAACG TCAGAC
CGTTGAAAAAGAACTGTCTGCGGAACTGGACCGTCTGTCTGAAGAATCTGGTAACAA CGACATC
TCTAAATGGACCAAAGGTCGTCGTGACGAAGCGCTGTTCCTGCTGAAAAAACGTTTC TCTCACC
GTCCGGTTCAGGAACAGTTCGTTTGCCTGGACTGCGGTCACGAAGTTCACGCGGACG AACAGGC
GGCGCTGAACATCGCGCGTTCTTGGCTGTTCCTGAACTCTAACTCTACCGAATTCAA ATCTTACA
AATCTGGTAAACAGCCGTTCGTTGGTGCGTGGCAGGCGTTCTACAAACGTCGTCTGA AAGAAGT
TTGGAAACCGAACGCG
SE ATGAAACGTATCAACAAAATCCGTCGTCGTCTGGTTAAAGACTCTAACACCAAAAAAGCG GGTA
Q AAACCGGTCCGATGAAAACCCTGCTGGTTCGTGTTATGACCCCGGACCTGCGTGAACGTC TGGA
no AAACCTGCGTAAAAAACCGGAAAACATCCCGCAGCCGATCTCTAACACCTCTCGTGCGAA CCTG
N AACAAACTGCTGACCGACTACACCGAAATGAAAAAAGCGATCCTGCACGTTTACTGGGAA GAA
O: TTCCAGAAAGACCCGGTTGGTCTGATGTCTCGTGTTGCGCAGCCGGCGCCGAAAAACATC GACC 60 AGCGTAAACTGATCCCGGTTAAAGACGGTAACGAACGTCTGACCTCTTCTGGTTTCGCGT GCTCT
CAGTGCTGCCAGCCGCTGTACGTTTACAAACTGGAACAGGTTAACGACAAAGGTAAA CCGCACA
CCAACTACTTCGGTCGTTGCAACGTTTCTGAACACGAACGTCTGATCCTGCTGTCTC CGCACAAA
CCGGAAGCGAACGACGAACTGGTTACCTACTCTCTGGGTAAATTCGGTCAGCGTGCG CTGGACT
TCTACTCTATCCACGTTACCCGTGAATCTAACCACCCGGTTAAACCGCTGGAACAGA TCGGTGGT
AACTCTTGCGCGTCTGGTCCGGTTGGTAAAGCGCTGTCTGACGCGTGCATGGGTGCG GTTGCGTC
TTTCCTGACCAAATACCAGGACATCATCCTGGAACACCAGAAAGTTATCAAAAAAAA CGAAAA
ACGTCTGGCGAACCTGAAAGACATCGCGTCTGCGAACGGTCTGGCGTTCCCGAAAAT CACCCTG CCGCCGCAGCCGCACACCAAAGAAGGTATCGAAGCGTACAACAACGTTGTTGCGCAGATC GTTA
TCTGGGTTAACCTGAACCTGTGGCAGAAACTGAAAATCGGTCGTGACGAAGCGAAAC CGCTGCA
GCGTCTGAAAGGTTTCCCGTCTTTCCCGCTGGTTGAACGTCAGGCGAACGAAGTTGA CTGGTGG
GACATGGTTTGCAACGTTAAAAAACTGATCAACGAAAAAAAAGAAGACGGTAAAGTT TTCTGG
CAGAACCTGGCGGGTTACAAACGTCAGGAAGCGCTGCTGCCGTACCTGTCTTCTGAA GAAGACC
GTAAAAAAGGTAAAAAATTCGCGCGTTACCAGTTCGGTGACCTGCTGCTGCACCTGG AAAAAAA
ACACGGTGAAGACTGGGGTAAAGTTTACGACGAAGCGTGGGAACGTATCGACAAAAA AGTTGA
AGGTCTGTCTAAACACATCAAACTGGAAGAAGAACGTCGTTCTGAAGACGCGCAGTC TAAAGC
GGCGCTGACCGACTGGCTGCGTGCGAAAGCGTCTTTCGTTATCGAAGGTCTGAAAGA AGCGGAC
AAAGACGAATTCTGCCGTTGCGAACTGAAACTGCAGAAATGGTACGGTGACCTGCGT GGTAAAC
CGTTCGCGATCGAAGCGGAAAACTCTATCCTGGACATCTCTGGTTTCTCTAAACAGT ACAACTGC
GCGTTCATCTGGCAGAAAGACGGTGTTAAAAAACTGAACCTGTACCTGATCATCAAC TACTTCA
AAGGTGGTAAACTGCGTTTCAAAAAAATCAAACCGGAAGCGTTCGAAGCGAACCGTT TCTACAC
CGTTATCAACAAAAAATCTGGTGAAATCGTTCCGATGGAAGTTAACTTCAACTTCGA CGACCCG
AACCTGATCATCCTGCCGCTGGCGTTCGGTAAACGTCAGGGTCGTGAATTCATCTGG AACGACC
TGCTGTCTCTGGAAACCGGTTCTCTGAAACTGGCGAACGGTCGTGTTATCGAAAAAA CCCTGTA
CAACCGTCGTACCCGTCAGGACGAACCGGCGCTGTTCGTTGCGCTGACCTTCGAACG TCGTGAA
GTTCTGGACTCTTCTAACATCAAACCGATGAACCTGATCGGTATCGACCGTGGTGAA AACATCC
CGGCGGTTATCGCGCTGACCGACCCGGAAGGTTGCCCGCTGTCTCGTTTCAAAGACT CTCTGGGT
AACCCGACCCACATCCTGCGTATCGGTGAATCTTACAAAGAAAAACAGCGTACCATC CAGGCGG
CGAAAGAAGTTGAACAGCGTCGTGCGGGTGGTTACTCTCGTAAATACGCGTCTAAAG CGAAAA
ACCTGGCGGACGACATGGTTCGTAACACCGCGCGTGACCTGCTGTACTACGCGGTTA CCCAGGA
CGCGATGCTGATCTTCGAAAACCTGTCTCGTGGTTTCGGTCGTCAGGGTAAACGTAC CTTCATGG
CGGAACGTCAGTACACCCGTATGGAAGACTGGCTGACCGCGAAACTGGCGTACGAAG GTCTGC
CGTCTAAAACCTACCTGTCTAAAACCCTGGCGCAGTACACCTCTAAAACCTGCTCTA ACTGCGGT
TTCACCATCACCTCTGCGGACTACGACCGTGTTCTGGAAAAACTGAAAAAAACCGCG ACCGGTT
GGATGACCACCATCAACGGTAAAGAACTGAAAGTTGAAGGTCAGATCACCTACTACA ACCGTTA
CAAACGTCAGAACGTTGTTAAAGACCTGTCTGTTGAACTGGACCGTCTGTCTGAAGA ATCTGTT
AACAACGACATCTCTTCTTGGACCAAAGGTCGTTCTGGTGAAGCGCTGTCTCTGCTG AAAAAAC
GTTTCTCTCACCGTCCGGTTCAGGAAAAATTCGTTTGCCTGAACTGCGGTTTCGAAA CCCACGCG
GACGAACAGGCGGCGCTGAACATCGCGCGTTCTTGGCTGTTCCTGCGTTCTCAGGAA TACAAAA
AATACCAGACCAACAAAACCACCGGTAACACCGACAAACGTGCGTTCGTTGAAACCT GGCAGT
CTTTCTACCGTAAAAAACTGAAAGAAGTTTGGAAACCG
SE AAAATTCcatGCAAAATGCTCCGGTTTCATGTCATCAAAATGATGACGTAATTAAGCATT GATAAT
Q TGAGATCCCTCTCCCTGACAGGATGATTACATAAATAATAGTGACAAAAATAAATTATTT ATTTA
no TCCAGAAAATGAATTGGAAAATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGA TATG
N TcaaaCAGGTtgccgtcactgcgtcttttactggctcttctcgctaaccaaaccggtaac cccgcttattaaaagcattctgtaacaaagcgggaccaaagc O: catgacaaaaacgcgtaacaaaagtgtctataatcacggcagaaaagtccacattgatta tttgcacggcgtcacactttgctatgccatagcatttttatccataa 61 gattagcggatcctacctgacgctttttatcgcaactctctactgtttctccatacccgt ttttttgggctagcaccgcctatctcgtgtgagataggcggagatacga actttaagAAGGAGatataccATGGGTAAAATGTATTACCTTGGTTTAGACATTGGCACG AATTCCGTGG
GCTACGCGGTGACCGACCCCTCATACCACCTGCTGAAGTTTAAGGGGGAACCAATGT GGGGTGC
GCACGTATTTGCCGCCGGTAATCAGAGCGCGGAACGACGCTCGTTCCGCACATCGCG TCGTCGT TTGGACCGACGCCAACAGCGCGTTAAACTGGTACAGGAGATTTTTGCCCCGGTGATTAGT CCGA
TCGACCCACGCTTCTTCATTCGTCTGCATGAATCCGCCCTGTGGCGCGATGACGTCG CGGAGACG
GATAAACATATCTTTTTCAATGATCCTACCTATACCGATAAGGAATATTATAGCGAT TACCCGAC
TATCCATCACCTGATCGTTGATCTGATGGAAAGCTCTGAGAAACACGATCCGCGGCT GGTGTAC
CTTGCAGTGGCGTGGTTAGTGGCACACCGTGGTCATTTTCTGAACGAGGTGGACAAG GATAATA
TTGGAGATGTGTTGTCGTTCGACGCATTTTATCCGGAGTTTCTCGCGTTCCTGTCGG ACAACGGT
GTATCACCGTGGGTGTGCGAAAGCAAAGCGCTGCAGGCGACCTTGCTGAGCCGTAAC TCAGTGA
ACGACAAATATAAAGCCCTTAAGTCTCTGATCTTCGGATCCCAGAAACCTGAAGATA ACTTCGA
TGCCAATATTTCGGAAGATGGACTCATTCAACTGCTGGCCGGCAAAAAGGTAAAAGT TAACAAA
CTGTTCCCTCAGGAATCGAACGATGCATCCTTCACATTGAATGATAAAGAAGACGCG ATAGAAG
AAATCCTGGGTACGCTTACACCAGATGAATGTGAATGGATTGCGCATATACGCCGCC TTTTTGA
CTGGGCTATCATGAAACATGCTCTGAAAGATGGCAGGACTATTAGCGAGTCAAAAGT CAAACTG
TATGAGCAGCACCATCACGATCTGACCCAACTTAAATACTTCGTGAAAACCTACCTT GCAAAAG
AATACGACGATATTTTCCGCAACGTGGATAGCGAAACAACGAAAAACTATGTAGCGT ATTCCTA
TCATGTGAAAGAGGTGAAAGGCACTCTGCCTAAAAATAAGGCAACGCAAGAAGAGTT TTGTAA
GTATGTCCTGGGCAAGGTTAAAAACATTGAATGCTCTGAAGCAGACAAGGTTGACTT TGATGAG
ATGATTCAGCGTCTTACCGACAACTCTTTTATGCCTAAGCAGGTTTCGGGCGAAAAC CGCGTTAT
TCCTTATCAGTTATATTATTATGAACTGAAGACAATTCTGAATAAAGCAGCCTCGTA CCTGCCTT
TCCTGACGCAGTGTGGAAAAGATGCAATTTCGAACCAGGACAAACTACTGTCGATCA TGACGTT
CCGTATTCCTTACTTCGTCGGACCCTTGCGAAAAGATAATTCGGAACATGCATGGCT CGAACGA
AAGGCCGGTAAGATTTATCCGTGGAACTTTAACGACAAAGTGGACTTGGATAAATCA GAAGAA
GCGTTCATTCGCCGAATGACCAATACCTGTACCTATTATCCCGGCGAAGATGTTTTA CCGTTGGA
TTCGCTGATCTATGAGAAATTTATGATTTTAAATGAAATCAATAATATTCGTATTGA CGGCTACC
CGATTAGTGTTGACGTTAAACAGCAGGTTTTTGGCTTGTTCGAAAAAAAACGACGCG TAACCGT
GAAAGATATTCAGAACCTGCTGCTGTCTCTCGGAGCTCTGGACAAACACGGGAAGCT GACAGGC
ATCGATACCACTATCCACTCAAACTATAATACGTATCACCATTTTAAATCTCTCATG GAACGCGG
CGTCCTGACCCGGGATGACGTGGAACGCATCGTTGAAAGGATGACCTACAGCGACGA TACTAA
GCGTGTGCGTCTGTGGCTGAATAACAACTATGGTACTTTAACCGCCGACGATGTGAA ACACATT
TCGCGTCTGCGCAAACACGATTTTGGCCGTTTATCCAAAATGTTCTTAACAGGTCTG AAGGGTGT
CCATAAGGAGACCGGTGAACGTGCCTCCATACTGGATTTCATGTGGAACACGAACGA TAACCTG
ATGCAGCTCCTTTCCGAATGCTACACGTTCAGTGATGAAATCACAAAGCTGCAAGAG GCGTATT
ATGCAAAAGCCCAGTTGTCTTTAAACGATTTTTTAGACTCGATGTACATCTCTAACG CGGTGAAA
CGTCCGATTTACAGAACTCTGGCAGTGGTGAACGATATTCGAAAAGCATGTGGGACG GCCCCTA
AACGCATTTTCATCGAAATGGCTCGTGATGGTGAATCAAAAAAAAAGAGAAGTGTTA CACGTCG
CGAGCAGATCAAAAACCTGTACCGCTCGATTCGTAAAGATTTCCAGCAGGAAGTTGA TTTTCTG
GAAAAGATCCTGGAAAATAAATCTGATGGTCAACTTCAGTCAGATGCTTTGTATCTT TACTTTGC
ACAATTAGGGCGCGATATGTACACGGGCGATCCAATAAAGCTGGAGCACATCAAAGA TCAGAG
TTTCTATAACATAGACCATATTTACCCGCAGTCTATGGTGAAAGACGATTCCCTAGA TAACAAA
GTGCTGGTGCAAAGCGAAATTAACGGCGAGAAAAGCTCGCGATACCCTTTGGACGCC GCGATCC
GCAATAAAATGAAGCCCCTTTGGGACGCTTACTATAATCATGGCCTGATCTCCTTAA AGAAATA
CCAGCGTCTAACGCGCTCGACCCCGTTTACCGATGATGAAAAATGGGACTTTATTAA TCGCCAG
TTAGTGGAAACCCGTCAATCTACCAAAGCGCTGGCCATTTTGTTGAAGCGTAAGTTT CCAGACA CCGAAATTGTGTATTCGAAGGCGGGGTTATCGTCCGACTTCAGACATGAATTCGGCCTTG TAAA
AAGTCGCAATATTAATGATTTGCACCACGCTAAAGACGCATTCTTGGCTATCGTTAC CGGCAAT
GTGTACCATGAAAGATTCAATCGCAGATGGTTTATGGTGAACCAGCCGTACTCAGTT AAAACTA
AAACTCTTTTTACCCACAGCATAAAGAATGGCAACTTCGTTGCCTGGAACGGCGAAG AAGATCT
CGGTCGTATTGTAAAAATGCTGAAGCAAAACAAAAATACCATTCACTTCACGCGCTT CTCCTTC
GATCGCAAAGAAGGATTATTTGATATCCAACCTCTGAAAGCCAGCACCGGCTTAGTC CCACGAA
AAGCCGGTCTGGATGTCGTTAAATACGGCGGATATGACAAATCTACCGCGGCCTATT ACCTGCT
GGTGAGGTTCACGCTCGAGGACAAGAAAACCCAGCACAAGCTGATGATGATTCCTGT AGAAGG
CCTGTACAAGGCTCGCATTGATCATGACAAGGAATTTCTTACCGATTATGCGCAAAC GACTATA
AGCGAAATCCTACAGAAAGATAAACAGAAAGTGATCAATATTATGTTTCCAATGGGT ACGAGG
CATATAAAACTCAATTCAATGATTAGTATCGATGGCTTCTATCTTAGTATCGGCGGA AAGTCCTC
TAAAGGTAAGTCAGTTCTATGTCACGCAATGGTTCCACTGATCGTCCCTCACAAAAT CGAATGTT
ACATTAAAGCAATGGAAAGCTTCGCCCGGAAGTTTAAAGAAAACAACAAGCTGCGCA TCGTAG
AAAAATTCGATAAAATCACCGTTGAAGACAACCTGAATCTCTACGAGCTCTTTCTCC AAAAACT
GCAGCATAATCCCTATAATAAGTTTTTTTCGACACAGTTTGACGTACTGACGAACGG CCGTTCTA
CTTTCACAAAACTGTCGCCGGAGGAACAGGTACAGACGCTCTTGAACATTTTAAGTA TCTTTAA
AACATGCCGCAGTTCGGGTTGCGACCTGAAATCCATCAACGGCAGTGCCCAGGCAGC GCGCATC
ATGATTAGCGCTGACTTAACTGGACTGTCGAAAAAATATTCAGATATTAGGTTGGTT GAACAGT
CAGCTTCTGGTTTGTTCGTATCCAAAAGTCAGAACTTACTGGAGTATCTCTAAGAAA TCATCCTT
AGCGAAAGCTAAGGATTTTTTTTATCTGAAATTTATTATATCGCGTTGATTATTGAT GCTGTTTTT
AGTTTTAACGGCAATTAATATATGTGTTATTAATTGAATGAATTTTATCATTCATAA TAAGTATG
TGTAGGATCAAGCTCAGGTTAAATATTCACTCAGGAAGTTATTACTCAGGAAGCAAA GAGGATT
ACAGAATTATCTCATAACAAGTGTTAAGGGATGTTATTTCC
SE AAAATTCcatGCAAAATGCTCCGGTTTCATGTCATCAAAATGATGACGTAATTAAGCATT GATAAT
Q TGAGATCCCTCTCCCTGACAGGATGATTACATAAATAATAGTGACAAAAATAAATTATTT ATTTA
no TCCAGAAAATGAATTGGAAAATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGA TATG
N TcaaaCAGGTtgccgtcactgcgtcttttactggctcttctcgctaaccaaaccggtaac cccgcttattaaaagcattctgtaacaaagcgggaccaaagc O: catgacaaaaacgcgtaacaaaagtgtctataatcacggcagaaaagtccacattgatta tttgcacggcgtcacactttgctatgccatagcatttttatccataa 62 gattagcggatcctacctgacgctttttatcgcaactctctactgtttctccatacccgt ttttttgggctagcaccgcctatctcgtgtgagataggcggagatacga actttaagAAGGAGatataccATGTCATCGCTCACGAAATTCACTAACAAATACTCTAAA CAGCTCACCA
TTAAGAATGAACTCATCCCAGTTGGCAAAACACTGGAGAACATCAAAGAGAATGGTC TGATAG
ATGGCGACGAACAGCTGAATGAGAATTATCAGAAGGCGAAAATTATTGTGGATGATT TTCTGCG
GGACTTCATTAATAAAGCACTGAATAATACGCAGATCGGGAACTGGCGCGAACTGGC GGATGC
CCTTAATAAAGAGGATGAAGATAACATCGAGAAATTGCAGGATAAAATTCGGGGAAT CATTGT
ATCCAAATTTGAAACGTTTGATCTGTTTAGCAGCTATTCTATTAAGAAAGATGAAAA GATTATTG
ACGACGACAATGATGTTGAAGAAGAGGAACTGGATCTGGGCAAGAAGACCAGCTCAT TTAAAT
ACATATTTAAAAAAAACCTGTTTAAGTTAGTGTTGCCATCCTACCTGAAAACCACAA ACCAGGA
CAAGCTGAAGATTATTAGCTCGTTTGATAATTTTTCAACGTACTTCCGCGGGTTCTT TGAAAACC
GGAAAAACATTTTTACCAAGAAACCGATCTCCACAAGTATTGCGTATCGCATTGTTC ATGATAA
CTTCCCGAAATTCCTTGATAACATTCGTTGTTTTAATGTGTGGCAGACGGAATGCCC GCAACTAA
TCGTGAAAGCAGATAACTATCTGAAAAGCAAAAATGTTATAGCGAAAGATAAAAGTT TGGCAA
ACTATTTTACCGTGGGCGCGTATGACTATTTCCTGTCTCAGAATGGTATAGATTTTT ACAACAAT ATTATAGGTGGACTGCCAGCGTTCGCCGGCCATGAGAAAATCCAAGGTCTCAATGAATTC ATCA ATCAAGAGTGCCAAAAAGACAGCGAGCTGAAAAGTAAGCTGAAAAACCGTCACGCGTTCA AAA TGGCGGTACTGTTCAAACAGATACTCAGCGATCGTGAAAAAAGTTTTGTAATTGATGAGT TCGA GTCGGATGCTCAAGTTATTGACGCCGTTAAAAACTTTTACGCCGAACAGTGCAAAGATAA CAAT
CATATTCATTGAAGGGAAATACCTGTCGAGCGTTAGTCAAAAACTCTATAGCGATTG GTCAAAA
TTACGTAACGACATTGAGGATTCGGCTAACTCTAAACAAGGCAATAAAGAGCTGGCC AAGAAG
ATCAAAACCAACAAAGGGGATGTAGAAAAAGCGATCTCGAAATATGAGTTCTCGCTG TCGGAA
CTGAACTCGATTGTACATGATAACACCAAGTTTTCTGACCTCCTTAGTTGTACACTG CATAAGGT
GGCTTCTGAGAAACTGGTGAAGGTCAATGAAGGCGACTGGCCGAAACATCTCAAGAA TAATGA
AGAGAAACAAAAAATCAAAGAGCCGCTTGATGCTCTGCTGGAGATCTATAATACACT TCTGATT
TTTAACTGCAAAAGCTTCAATAAAAACGGCAACTTCTATGTCGACTATGATCGTTGC ATCAATG
AACTGAGTTCGGTCGTGTATCTGTATAATAAAACACGTAACTATTGCACTAAAAAAC CCTATAA
CACGGACAAGTTCAAACTCAATTTTAACAGTCCGCAGCTCGGTGAAGGCTTTTCCAA GTCGAAA
GAAAATGACTGTCTGACTCTTTTGTTTAAAAAAGACGACAACTATTATGTAGGCATT ATCCGCA
AAGGTGCAAAAATCAATTTTGATGATACACAAGCAATCGCCGATAACACCGACAATT GCATCTT
TAAAATGAATTATTTCCTACTTAAAGACGCAAAAAAATTTATCCCGAAATGTAGCAT TCAGCTG
AAAGAAGTCAAGGCCCATTTTAAGAAATCTGAAGATGATTACATTTTGTCTGATAAA GAGAAAT
TTGCTAGCCCGCTGGTCATTAAAAAGAGCACATTTTTGCTGGCAACTGCACATGTGA AAGGGAA
AAAAGGCAATATCAAGAAATTTCAGAAAGAATATTCGAAAGAAAACCCCACTGAGTA TCGCAA
TTCTTTAAACGAATGGATTGCTTTTTGTAAAGAGTTCTTAAAAACTTATAAAGCGGC TACCATTT
TTGATATAACCACATTGAAAAAGGCAGAGGAATATGCTGATATTGTAGAATTCTACA AGGATGT
CGATAATCTGTGCTACAAACTGGAGTTCTGCCCGATTAAAACCTCGTTTATAGAAAA CCTGATA
GATAACGGCGACCTGTATCTGTTTCGCATCAATAACAAAGACTTCAGCAGTAAATCG ACCGGCA
CCAAGAACCTTCATACGTTATATTTACAAGCTATATTCGATGAACGTAATCTGAACA ATCCGAC
AATTATGCTGAATGGGGGAGCAGAACTGTTCTATCGTAAAGAAAGTATTGAGCAGAA AAACCG
TATCACACACAAAGCCGGTTCAATTCTCGTGAATAAGGTGTGTAAAGACGGTACAAG CCTGGAT
GATAAGATACGTAATGAAATTTATCAATATGAGAATAAATTTATTGATACCCTGTCT GATGAAG
CTAAAAAGGTGTTACCGAATGTCATTAAAAAGGAAGCTACCCATGACATTACAAAAG ATAAAC
GTTTCACTAGTGACAAATTCTTCTTTCACTGCCCCCTGACAATTAATTATAAGGAAG GCGATACC
AAGCAGTTCAATAACGAAGTGCTGAGTTTTCTGCGTGGAAATCCTGACATCAACATT ATCGGCA
TTGACCGCGGAGAGCGTAATTTAATCTATGTAACGGTTATAAACCAGAAAGGCGAGA TTCTGGA
TTCGGTTTCATTCAATACCGTGACCAACAAGAGTTCAAAAATCGAGCAGACAGTCGA TTATGAA
GAGAAATTGGCAGTCCGCGAGAAAGAGAGGATTGAAGCAAAACGTTCCTGGGACTCT ATCTCA
AAAATTGCGACACTAAAGGAAGGTTATCTGAGCGCAATAGTTCACGAGATCTGTCTG TTAATGA
TTAAACACAACGCGATCGTTGTCTTAGAGAATCTTAATGCAGGCTTTAAGCGTATTC GTGGCGGT
TTATCAGAAAAAAGTGTTTATCAAAAATTCGAAAAAATGTTGATTAACAAACTGAAC TATTTTG
TCAGCAAGAAGGAATCCGACTGGAATAAACCGTCTGGTCTGCTGAATGGACTGCAGC TTTCGGA
TCAGTTTGAAAGCTTCGAAAAACTGGGTATTCAGTCTGGTTTTATTTTTTACGTGCC GGCTGCAT
ATACCTCAAAGATTGATCCGACCACGGGCTTCGCCAATGTTCTGAATCTGTCGAAGG TACGCAA
TGTTGATGCGATCAAAAGCTTTTTTTCTAACTTCAACGAAATTAGTTATAGCAAGAA AGAAGCC
CTTTTCAAATTCTCATTCGATCTGGATTCACTGAGTAAGAAAGGCTTTAGTAGCTTT GTGAAATT TAGTAAGAGTAAATGGAACGTCTACACCTTTGGAGAACGTATCATAAAGCCAAAGAATAA GCA
AGGTTATCGGGAGGACAAAAGAATCAACTTGACCTTCGAGATGAAGAAGTTACTTAA CGAGTAT
AAGGTTTCTTTTGATCTTGAAAATAACTTGATTCCGAATCTCACGAGTGCCAACCTG AAGGATAC
TTTTTGGAAAGAGCTATTCTTTATCTTCAAGACTACGCTGCAGCTCCGTAACAGCGT TACTAACG
GTAAAGAAGATGTGCTCATCTCTCCGGTCAAAAATGCGAAGGGTGAATTCTTCGTTT CGGGAAC
GCATAACAAGACTCTTCCGCAAGATTGCGATGCGAACGGTGCATACCATATTGCGTT GAAAGGT
CTGATGATACTCGAACGTAACAACCTTGTACGTGAGGAGAAAGATACGAAAAAGATT ATGGCG
ATTTCAAACGTGGATTGGTTCGAGTACGTGCAGAAACGTAGAGGCGTTCTGTAAGAA ATCATCC
TTAGCGAAAGCTAAGGATTTTTTTTATCTGAAATTTATTATATCGCGTTGATTATTG ATGCTGTTT
TTAGTTTTAACGGCAATTAATATATGTGTTATTAATTGAATGAATTTTATCATTCAT AATAAGTA
TGTGTAGGATCAAGCTCAGGTTAAATATTCACTCAGGAAGTTATTACTCAGGAAGCA AAGAGGA
TTACAGAATTATCTCATAACAAGTGTTAAGGGATGTTATTTCC
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTGCCG TCACT
Q GCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATTAAAAGCATTC TGTAA
no CAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAATCACGGCAGA AAA
N GTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATTTTTATCCATA AGATT
O: AGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCATACCCGTTTTT TTGGGC
63 TAGCAGTAATACGACTCACTATAGGGGTCTCATCTCGTGTGAGATAGGCGGAGATACGAA CTTT
AAGAGGAGGATATACCATGCACCATCATCATCACCATAACAACTACGACGAATTCAC CAAACTG
TACCCGATCCAGAAAACCATCCGTTTCGAACTGAAACCGCAGGGTCGTACCATGGAA CACCTGG
AAACCTTCAACTTCTTCGAAGAAGACCGTGACCGTGCGGAAAAATACAAAATCCTGA AAGAAG
CGATCGACGAATACCACAAAAAATTCATCGACGAACACCTGACCAACATGTCTCTGG ACTGGAA
CTCTCTGAAACAGATCTCTGAAAAATACTACAAATCTCGTGAAGAAAAAGACAAAAA AGTTTTC
CTGTCTGAACAGAAACGTATGCGTCAGGAAATCGTTTCTGAATTCAAAAAAGACGAC CGTTTCA
AAGACCTGTTCTCTAAAAAACTGTTCTCTGAACTGCTGAAAGAAGAAATCTACAAAA AAGGTAA
CCACCAGGAAATCGACGCGCTGAAATCTTTCGACAAATTCTCTGGTTACTTCATCGG TCTGCACG
AAAACCGTAAAAACATGTACTCTGACGGTGACGAAATCACCGCGATCTCTAACCGTA TCGTTAA
CGAAAACTTCCCGAAATTCCTGGACAACCTGCAGAAATACCAGGAAGCGCGTAAAAA ATACCC
GGAATGGATCATCAAAGCGGAATCTGCGCTGGTTGCGCACAACATCAAAATGGACGA AGTTTTC
TCTCTGGAATACTTCAACAAAGTTCTGAACCAGGAAGGTATCCAGCGTTACAACCTG GCGCTGG
GTGGTTACGTTACCAAATCTGGTGAAAAAATGATGGGTCTGAACGACGCGCTGAACC TGGCGCA
CCAGTCTGAAAAATCTTCTAAAGGTCGTATCCACATGACCCCGCTGTTCAAACAGAT CCTGTCTG
AAAAAGAATCTTTCTCTTACATCCCGGACGTTTTCACCGAAGACTCTCAGCTGCTGC CGTCTATC
GGTGGTTTCTTCGCGCAGATCGAAAACGACAAAGACGGTAACATCTTCGACCGTGCG CTGGAAC
TGATCTCTTCTTACGCGGAATACGACACCGAACGTATCTACATCCGTCAGGCGGACA TCAACCG
TGTTTCTAACGTTATCTTCGGTGAATGGGGTACCCTGGGTGGTCTGATGCGTGAATA CAAAGCG
GACTCTATCAACGACATCAACCTGGAACGTACCTGCAAAAAAGTTGACAAATGGCTG GACTCTA
AAGAATTCGCGCTGTCTGACGTTCTGGAAGCGATCAAACGTACCGGTAACAACGACG CGTTCAA
CGAATACATCTCTAAAATGCGTACCGCGCGTGAAAAAATCGACGCGGCGCGTAAAGA AATGAA
ATTCATCTCTGAAAAAATCTCTGGTGACGAAGAATCTATCCACATCATCAAAACCCT GCTGGAC
TCTGTTCAGCAGTTCCTGCACTTCTTCAACCTGTTCAAAGCGCGTCAGGACATCCCG CTGGACGG
TGCGTTCTACGCGGAATTCGACGAAGTTCACTCTAAACTGTTCGCGATCGTTCCGCT GTACAACA AAGTTCGTAACTACCTGACCAAAAACAACCTGAACACCAAAAAAATCAAACTGAACTTCA AAA
ACCCGACCCTGGCGAACGGTTGGGACCAGAACAAAGTTTACGACTACGCGTCTCTGA TCTTCCT
GCGTGACGGTAACTACTACCTGGGTATCATCAACCCGAAACGTAAAAAAAACATCAA ATTCGAA
CAGGGTTCTGGTAACGGTCCGTTCTACCGTAAAATGGTTTACAAACAGATCCCGGGT CCGAACA
AAAACCTGCCGCGTGTTTTCCTGACCTCTACCAAAGGTAAAAAAGAATACAAACCGT CTAAAGA
AATCATCGAAGGTTACGAAGCGGACAAACACATCCGTGGTGACAAATTCGACCTGGA CTTCTGC
CACAAACTGATCGACTTCTTCAAAGAATCTATCGAAAAACACAAAGACTGGTCTAAA TTCAACT
TCTACTTCTCTCCGACCGAATCTTACGGTGACATCTCTGAATTCTACCTGGACGTTG AAAAACAG
GGTTACCGTATGCACTTCGAAAACATCTCTGCGGAAACCATCGACGAATACGTTGAA AAAGGTG
ACCTGTTCCTGTTCCAGATCTACAACAAAGACTTCGTTAAAGCGGCGACCGGTAAAA AAGACAT
GCACACCATCTACTGGAACGCGGCGTTCTCTCCGGAAAACCTGCAGGACGTTGTTGT TAAACTG
AACGGTGAAGCGGAACTGTTCTACCGTGACAAATCTGACATCAAAGAAATCGTTCAC CGTGAAG
GTGAAATCCTGGTTAACCGTACCTACAACGGTCGTACCCCGGTTCCGGACAAAATCC ACAAAAA
ACTGACCGACTACCACAACGGTCGTACCAAAGACCTGGGTGAAGCGAAAGAATACCT GGACAA
AGTTCGTTACTTCAAAGCGCACTACGACATCACCAAAGACCGTCGTTACCTGAACGA CAAAATC
TACTTCCACGTTCCGCTGACCCTGAACTTCAAAGCGAACGGTAAAAAAAACCTGAAC AAAATGG
TTATCGAAAAATTCCTGTCTGACGAAAAAGCGCACATCATCGGTATCGACCGTGGTG AACGTAA
CCTGCTGTACTACTCTATCATCGACCGTTCTGGTAAAATCATCGACCAGCAGTCTCT GAACGTTA
TCGACGGTTTCGACTACCGTGAAAAACTGAACCAGCGTGAAATCGAAATGAAAGACG CGCGTC
AGTCTTGGAACGCGATCGGTAAAATCAAAGACCTGAAAGAAGGTTACCTGTCTAAAG CGGTTCA
CGAAATCACCAAAATGGCGATCCAGTACAACGCGATCGTTGTTATGGAAGAACTGAA CTACGGT
TTCAAACGTGGTCGTTTCAAAGTTGAAAAACAGATCTACCAGAAATTCGAAAACATG CTGATCG
ACAAAATGAACTACCTGGTTTTCAAAGACGCGCCGGACGAATCTCCGGGTGGTGTTC TGAACGC
GTACCAGCTGACCAACCCGCTGGAATCTTTCGCGAAACTGGGTAAACAGACCGGTAT CCTGTTC
TACGTTCCGGCGGCGTACACCTCTAAAATCGACCCGACCACCGGTTTCGTTAACCTG TTCAACAC
CTCTTCTAAAACCAACGCGCAGGAACGTAAAGAATTCCTGCAGAAATTCGAATCTAT CTCTTAC
TCTGCGAAAGACGGTGGTATCTTCGCGTTCGCGTTCGACTACCGTAAATTCGGTACC TCTAAAAC
CGACCACAAAAACGTTTGGACCGCGTACACCAACGGTGAACGTATGCGTTACATCAA AGAAAA
AAAACGTAACGAACTGTTCGACCCGTCTAAAGAAATCAAAGAAGCGCTGACCTCTTC TGGTATC
AAATACGACGGTGGTCAGAACATCCTGCCGGACATCCTGCGTTCTAACAACAACGGT CTGATCT
ACACCATGTACTCTTCTTTCATCGCGGCGATCCAGATGCGTGTTTACGACGGTAAAG AAGACTA
CATCATCTCTCCGATCAAAAACTCTAAAGGTGAATTCTTCCGTACCGACCCGAAACG TCGTGAA
CTGCCGATCGACGCGGACGCGAACGGTGCGTACAACATCGCGCTGCGTGGTGAACTG ACCATGC
GTGCGATCGCGGAAAAATTCGACCCGGACTCTGAAAAAATGGCGAAACTGGAACTGA AACACA
AAGACTGGTTCGAATTCATGCAGACCCGTGGTGACTAAGAAATCATCCTTAGCGAAA GCTAAGG
ATTTTTTTTATCTGAAATGTAGGGAGACCCTCAGGTTAAATATTCACTCAGGAAGTT ATTACTCA
GGAAGCAAAGAGGATTACA
SE AAAATTCcatGCAAAATGCTCCGGTTTCATGTCATCAAAATGATGACGTAATTAAGCATT GATAAT
Q TGAGATCCCTCTCCCTGACAGGATGATTACATAAATAATAGTGACAAAAATAAATTATTT ATTTA
no TCCAGAAAATGAATTGGAAAATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGA TATG
N TcaaaCAGGTtgccgtcactgcgtcttttactggctcttctcgctaaccaaaccggtaac cccgcttattaaaagcattctgtaacaaagcgggaccaaagc O: catgacaaaaacgcgtaacaaaagtgtctataatcacggcagaaaagtccacattgatta tttgcacggcgtcacactttgctatgccatagcatttttatccataa gattagcggatcctacctgacgctttttatcgcaactctctactgtttctccatacccgt ttttttgggctagcaccgcctatctcgtgtgagataggcggagatacga actttaagAAGGAGatataccATGACTAAAACATTTGATTCAGAGTTTTTTAATTTGTAC TCGCTGCAAAA
AACGGTACGCTTTGAGTTAAAACCCGTGGGAGAAACCGCGTCATTTGTGGAAGACTT TAAAAAC
GAGGGCTTGAAACGTGTTGTGAGCGAAGATGAAAGGCGAGCCGTCGATTACCAGAAA GTTAAG
GAAATAATTGACGATTACCATCGGGATTTCATTGAAGAAAGTTTAAATTATTTTCCG GAACAGG
TGAGTAAAGATGCTCTTGAGCAGGCGTTTCATCTTTATCAGAAACTGAAGGCAGCAA AAGTTGA
GGAAAGGGAAAAAGCGCTGAAAGAATGGGAAGCGCTGCAGAAAAAGCTACGTGAAAA AGTGG
TGAAATGCTTCTCGGACTCGAATAAAGCCCGCTTCTCAAGGATTGATAAAAAGGAAC TGATTAA
GGAAGACCTGATAAATTGGTTGGTCGCCCAGAATCGCGAGGATGATATCCCTACGGT CGAAACG
TTTAACAACTTCACCACATATTTTACCGGCTTCCATGAGAATCGTAAAAATATTTAC TCCAAAGA
TGATCACGCCACCGCTATTAGCTTTCGCCTTATTCATGAAAATCTTCCAAAGTTTTT TGACAACG
TGATTAGCTTCAATAAGTTGAAAGAGGGTTTCCCTGAATTAAAATTTGATAAAGTGA AAGAGGA
TTTAGAAGTAGATTATGATCTGAAGCATGCGTTTGAAATAGAATATTTCGTTAACTT CGTGACCC
AAGCGGGCATAGATCAGTATAATTATCTGTTAGGAGGGAAAACCCTGGAGGACGGGA CGAAAA
AACAAGGGATGAATGAGCAAATTAATCTGTTCAAACAACAGCAAACGCGAGATAAAG CGCGTC
AGATTCCCAAACTGATCCCCCTGTTCAAACAGATTCTTAGCGAAAGGACTGAAAGCC AGTCCTT
TATTCCTAAACAATTTGAAAGTGATCAGGAGTTGTTCGATTCACTGCAGAAGTTACA TAATAACT
GCCAGGATAAATTCACCGTGCTGCAACAAGCCATTCTCGGTCTGGCAGAGGCGGATC TTAAGAA
GGTCTTCATCAAAACCTCTGATTTAAATGCCTTATCTAACACCATTTTCGGGAATTA CAGCGTCT
TTTCCGATGCACTGAACCTGTATAAAGAAAGCCTGAAAACGAAAAAAGCGCAGGAGG CTTTTG
AGAAACTACCGGCCCATTCTATTCACGACCTCATTCAATACTTGGAACAGTTCAATT CCAGCCTG
GACGCGGAAAAACAACAGAGCACCGACACCGTCCTGAACTACTTCATCAAGACCGAT GAATTA
TATTCTCGCTTCATTAAATCCACTAGCGAGGCTTTCACTCAGGTGCAGCCTTTGTTC GAACTGGA
AGCCCTGTCATCTAAGCGCCGCCCACCGGAATCGGAAGATGAAGGGGCAAAAGGGCA GGAAGG
CTTCGAGCAGATCAAGCGTATTAAAGCTTACCTGGATACGCTTATGGAAGCGGTACA CTTTGCA
AAGCCGTTGTATCTTGTTAAGGGTCGTAAAATGATCGAAGGGCTCGATAAAGACCAG TCCTTTT
ATGAAGCGTTTGAAATGGCGTACCAAGAACTTGAATCGTTAATCATTCCTATCTATA ACAAAGC
GCGGAGCTATCTGTCGCGGAAACCTTTCAAGGCCGATAAATTCAAGATTAATTTTGA CAACAAC
ACGCTACTGAGCGGATGGGATGCGAACAAGGAAACTGCTAACGCGTCCATTCTGTTT AAGAAAG
ACGGGTTATATTACCTTGGAATTATGCCGAAAGGTAAGACCTTTCTCTTTGACTACT TTGTATCG
AGCGAGGATTCAGAGAAACTGAAACAGCGTCGCCAGAAGACCGCCGAAGAAGCTCTG GCGCAG
GATGGTGAAAGTTACTTCGAAAAAATTCGTTATAAACTGTTACCAGGGGCTTCAAAG ATGTTAC
CGAAAGTCTTTTTTAGCAACAAAAATATTGGCTTTTACAACCCGTCGGATGACATTT TACGCATT
CGCAACACAGCCTCTCACACCAAAAACGGGACCCCTCAGAAAGGCCACTCAAAAGTT GAGTTTA
ACCTGAATGATTGTCATAAGATGATTGATTTCTTCAAATCATCAATTCAGAAACACC CGGAATG
GGGGTCTTTTGGCTTTACGTTTTCTGATACCAGTGATTTTGAAGACATGAGTGCCTT CTACCGGG
AAGTAGAAAACCAGGGTTACGTAATTAGCTTTGACAAAATCAAAGAGACCTATATAC AGAGCC
AGGTGGAACAGGGTAATCTCTACTTATTCCAGATTTATAACAAGGATTTCTCGCCCT ACAGCAA
AGGCAAACCAAACCTGCATACTCTGTACTGGAAAGCCCTGTTTGAAGAAGCGAACCT GAATAAC
GTAGTGGCGAAGTTGAACGGTGAAGCGGAAATCTTCTTCCGTCGTCACTCCATTAAG GCCTCTG
ATAAAGTTGTCCATCCGGCAAATCAGGCCATTGATAATAAGAATCCACACACGGAAA AAACGC
AGTCAACCTTTGAATATGACCTCGTTAAAGACAAACGCTACACGCAAGATAAGTTCT TTTTCCAC GTCCCAATCAGCCTCAACTTTAAAGCACAAGGGGTTTCAAAGTTTAATGATAAAGTCAAT GGGT
TCCTCAAGGGCAACCCGGATGTCAACATTATAGGTATAGACAGGGGCGAACGCCATC TGCTTTA
CTTTACCGTAGTGAATCAGAAAGGTGAAATACTGGTTCAGGAATCATTAAATACCTT GATGTCG
GACAAAGGGCACGTTAATGATTACCAGCAGAAACTGGATAAAAAAGAACAGGAACGT GATGCT
GCGCGTAAATCGTGGACCACGGTTGAGAACATTAAAGAGCTGAAAGAGGGGTATCTA AGCCAT
GTGGTACACAAACTGGCGCACCTCATCATTAAATATAACGCAATAGTCTGCCTAGAA GACTTGA
ATTTTGGCTTTAAACGCGGCCGCTTCAAAGTGGAAAAACAAGTTTATCAAAAATTTG AAAAGGC
GCTTATAGATAAACTGAATTATCTGGTTTTTAAAGAAAAGGAACTTGGTGAGGTAGG GCACTAC
TTGACAGCTTATCAACTGACGGCCCCGTTCGAATCATTCAAAAAACTGGGCAAACAG TCTGGCA
TTCTGTTTTACGTGCCGGCAGATTATACTTCAAAAATCGATCCAACAACTGGCTTTG TGAACTTC
CTGGACCTGAGATATCAGTCTGTAGAAAAAGCTAAACAACTTCTTAGCGATTTTAAT GCCATTC
GTTTTAACAGCGTTCAGAATTACTTTGAATTCGAAATTGACTATAAAAAACTTACTC CGAAACGT
AAAGTCGGAACCCAAAGTAAATGGGTAATTTGTACGTATGGCGATGTCAGGTATCAG AACCGTC
GGAATCAAAAAGGTCATTGGGAGACCGAAGAAGTGAACGTGACCGAAAAGCTGAAGG CTCTGT
TCGCCAGCGATTCAAAAACTACAACTGTGATCGATTACGCAAATGATGATAACCTGA TAGATGT
GATTTTAGAGCAGGATAAAGCCAGCTTTTTTAAAGAACTGTTGTGGCTCCTGAAACT TACGATG
ACCTTACGACATTCCAAGATCAAATCGGAAGATGATTTTATTCTGTCACCGGTCAAG AATGAGC
AGGGTGAATTCTATGATAGTAGGAAAGCCGGCGAAGTGTGGCCGAAAGACGCCGACG CCAATG
GCGCCTATCATATCGCGCTCAAAGGGCTTTGGAATTTGCAGCAGATTAACCAGTGGG AAAAAGG
TAAAACCCTGAATCTGGCTATCAAAAACCAGGATTGGTTTAGCTTTATCCAAGAGAA ACCGTAT
CAGGAATGAGAAATCATCCTTAGCGAAAGCTAAGGATTTTTTTTATCTGAAATTTAT TATATCGC
TTATCATTCATAATAAGTATGTGTAGGATCAAGCTCAGGTTAAATATTCACTCAGGA AGTTATTA CTCAGGAAGCAAAGAGGATTACAGAATTATCTCATAACAAGTGTTAAGGGATGTTATTTC C
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTGCCG TCACT
Q GCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATTAAAAGCATTC TGTAA
no CAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAATCACGGCAGA AAA
N GTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATTTTTATCCATA AGATT
O: AGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCATACCCGTTTTT TTGGGC 65 TAGCAGTAATACGACTCACTATAGGGGTCTCATCTCGTGTGAGATAGGCGGAGATACGAA CTTT
AAGAGGAGGATATACCATGCACCATCATCATCACCATCATACAGGCGGTCTTCTTAG TATGGAC
GCGAAAGAGTTCACAGGTCAGTATCCGTTGTCGAAAACATTACGATTCGAACTTCGG CCCATCG
GCCGCACGTGGGATAACCTGGAGGCCTCAGGCTACTTAGCGGAAGACCGCCATCGTG CCGAATG
TTATCCTCGTGCGAAAGAGTTATTGGATGACAACCATCGTGCCTTCCTGAATCGTGT GTTGCCAC
AAATCGATATGGATTGGCACCCGATTGCGGAGGCCTTTTGTAAGGTACATAAAAACC CTGGTAA
TAAAGAACTTGCCCAGGATTACAACCTTCAGTTGTCAAAGCGCCGTAAGGAGATCAG CGCATAT
CTTCAGGATGCAGATGGCTATAAAGGCCTGTTCGCGAAGCCCGCCTTAGACGAAGCT ATGAAAA
TTGCGAAAGAAAACGGGAACGAAAGTGATATTGAGGTTCTCGAAGCGTTTAACGGTT TTAGCGT
ATACTTCACCGGTTATCATGAGTCACGCGAGAACATTTATAGCGATGAGGATATGGT GAGCGTA
GCCTACCGAATTACTGAGGATAATTTCCCGCGCTTTGTCTCAAACGCTTTGATCTTT GATAAATT
AAACGAAAGCCATCCGGATATTATCTCTGAAGTATCGGGCAATCTTGGAGTTGATGA CATTGGT
AAGTACTTTGACGTGTCGAACTATAACAATTTTCTTTCCCAGGCCGGTATAGATGAC TACAATCA CATTATTGGCGGCCATACAACCGAAGACGGACTGATACAAGCGTTTAATGTCGTATTGAA CTTA
CGTCACCAAAAAGACCCTGGCTTTGAAAAAATTCAGTTCAAACAGCTCTACAAACAA ATCCTGA
GCGTGCGTACCAGCAAAAGCTACATCCCGAAACAGTTTGACAACTCTAAGGAGATGG TTGACTG
CATTTGCGATTATGTCAGCAAAATAGAGAAATCCGAAACAGTAGAACGGGCCCTGAA ACTAGTC
CGTAATATCAGTTCTTTCGACTTGCGCGGGATCTTTGTCAATAAAAAGAACTTGCGC ATACTGAG
CAACAAACTGATAGGAGATTGGGACGCGATCGAAACCGCATTGATGCATAGTTCTTC ATCAGAA
AACGATAAGAAAAGCGTATATGATAGCGCGGAGGCTTTTACGTTGGATGACATCTTT TCAAGCG
TGAAAAAATTTTCTGATGCCTCTGCCGAAGATATTGGCAACAGGGCGGAAGACATCT GTAGAGT
GATAAGTGAGACGGCCCCTTTTATCAACGATCTGCGAGCGGTGGACCTGGATAGCCT GAACGAC
GATGGTTATGAAGCGGCCGTCTCAAAAATTCGGGAGTCGCTGGAGCCTTATATGGAT CTTTTCC
ATGAACTGGAAATTTTCTCGGTTGGCGATGAGTTCCCAAAATGCGCAGCATTTTACA GCGAACT
GGAGGAAGTCAGCGAACAGCTGATCGAAATTATTCCGTTATTCAACAAGGCGCGTTC GTTCTGC
ACCCGGAAACGCTATAGCACCGATAAGATTAAAGTGAACTTAAAATTCCCGACCTTG GCGGACG
GGTGGGACCTGAACAAAGAGAGAGACAACAAAGCCGCGATTCTGCGGAAAGACGGTA AGTATT
ATCTGGCAATTCTGGATATGAAGAAAGATCTGTCAAGCATTAGGACCAGCGACGAAG ATGAATC
CAGCTTCGAAAAGATGGAGTATAAACTGTTACCGAGTCCAGTAAAAATGCTGCCAAA GATATTC
GTAAAATCGAAAGCCGCTAAGGAAAAATATGGCCTGACAGATCGTATGCTTGAATGC TACGATA
AAGGTATGCATAAGTCGGGTAGTGCGTTTGATCTTGGCTTTTGCCATGAACTCATTG ATTATTAC
AAGCGTTGTATCGCGGAGTACCCAGGCTGGGATGTGTTCGATTTCAAGTTTCGCGAA ACTTCCG
ATTATGGGTCCATGAAAGAGTTCAATGAAGATGTGGCCGGAGCCGGTTACTATATGA GTCTGAG
AAAAATTCCGTGCAGCGAAGTGTACCGTCTGTTAGACGAGAAATCGATTTATCTATT TCAAATTT
ATAACAAAGATTACTCTGAAAATGCACATGGTAATAAGAACATGCATACCATGTACT GGGAGG
GTCTCTTTTCCCCGCAAAACCTGGAGTCGCCCGTTTTCAAGTTGTCGGGTGGGGCAG AACTTTTC
TTTCGAAAATCCTCAATCCCTAACGATGCCAAAACAGTACACCCGAAAGGCTCAGTG CTGGTTC
CACGTAATGATGTTAACGGTCGGCGTATTCCAGATTCAATCTACCGCGAACTGACAC GCTATTTT
AACCGTGGCGATTGCCGAATCAGTGACGAAGCCAAAAGTTATCTTGACAAGGTTAAG ACTAAA
AAAGCGGACCATGACATTGTGAAAGATCGCCGCTTTACCGTGGATAAAATGATGTTC CACGTCC
CGATTGCGATGAACTTTAAGGCGATCAGTAAACCGAACTTAAACAAAAAAGTCATTG ATGGCAT
CATTGATGATCAGGATCTGAAAATCATTGGTATTGATCGTGGCGAGCGGAACTTAAT TTACGTC
ACGATGGTTGACAGAAAAGGGAATATCTTATATCAGGATTCTCTTAACATCCTCAAT GGCTACG
ACTATCGTAAAGCTCTGGATGTGCGCGAATATGACAACAAGGAAGCGCGTCGTAACT GGACTAA
AGTGGAGGGCATTCGCAAAATGAAGGAAGGCTATCTGTCATTAGCGGTCTCGAAATT AGCGGAT
ATGATTATCGAAAATAACGCCATCATCGTTATGGAGGACCTGAACCACGGATTCAAA GCGGGCC
GCTCAAAGATTGAAAAACAAGTTTATCAGAAATTTGAGAGTATGCTGATTAACAAAC TGGGCTA
TATGGTGTTAAAAGACAAGTCAATTGACCAATCAGGTGGCGCGCTGCATGGATACCA GCTGGCG
AACCATGTTACCACCTTAGCATCAGTTGGAAAGCAGTGTGGGGTTATCTTTTATATA CCGGCAGC
GTTCACTAGTAAAATAGATCCGACCACTGGTTTCGCCGATCTCTTTGCCCTGAGTAA CGTTAAAA
ACGTAGCGAGCATGCGTGAATTCTTTTCCAAAATGAAATCTGTCATTTATGATAAAG CTGAAGG
CAAATTCGCATTCACCTTTGATTACTTGGATTACAACGTGAAGAGCGAATGTGGTCG TACGCTGT
GGACCGTTTACACCGTTGGTGAGCGCTTCACCTATTCCCGTGTGAACCGCGAATATG TACGTAA
AGTCCCCACCGATATTATCTATGATGCCCTCCAGAAAGCAGGCATTAGCGTCGAAGG AGACTTA
AGGGACAGAATTGCCGAAAGCGATGGCGATACGCTGAAGTCTATTTTTTACGCATTC AAATACG CGCTAGATATGCGCGTTGAGAATCGCGAGGAAGACTACATTCAATCACCTGTGAAAAATG CCTC
TGGGGAATTTTTTTGTTCAAAAAATGCTGGTAAAAGCCTCCCACAAGATAGCGATGC AAACGGT
GCATATAACATTGCCCTGAAAGGTATTCTTCAATTACGCATGCTGTCTGAGCAGTAC GACCCCA
ACGCGGAATCTATTAGACTTCCGCTGATAACCAATAAAGCCTGGCTGACATTCATGC AGTCTGG
CATGAAGACCTGGAAAAATTAGGAAATCATCCTTAGCGAAAGCTAAGGATTTTTTTT ATCTGAA
ATGTAGGGAGACCCTCAGGTTAAATATTCACTCAGGAAGTTATTACTCAGGAAGCAA AGAGGAT
TACA
SE AAAATTCcatGCAAAATGCTCCGGTTTCATGTCATCAAAATGATGACGTAATTAAGCATT GATAAT
Q TGAGATCCCTCTCCCTGACAGGATGATTACATAAATAATAGTGACAAAAATAAATTATTT ATTTA
no TCCAGAAAATGAATTGGAAAATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGA TATG
N TcaaaCAGGTtgccgtcactgcgtcttttactggctcttctcgctaaccaaaccggtaac cccgcttattaaaagcattctgtaacaaagcgggaccaaagc O: catgacaaaaacgcgtaacaaaagtgtctataatcacggcagaaaagtccacattgatta tttgcacggcgtcacactttgctatgccatagcatttttatccataa
66 gattagcggatcctacctgacgctttttatcgcaactctctactgtttctccatacccgt ttttttgggctagcaccgcctatctcgtgtgagataggcggagatacga actttaagAAGGAGatataccatgGATAGTTTGAAAGATTTCACCAATCTGTACCCTGTC AGTAAGACATTG
AGATTTGAATTAAAGCCCGTTGGAAAGACTTTAGAAAATATCGAGAAAGCAGGTATT TTGAAAG
AGGATGAGCATCGTGCAGAAAGTTATCGGAGGGTGAAGAAAATAATTGATACTTATC ATAAGG
TATTTATCGATTCTTCTCTTGAAAATATGGCTAAAATGGGTATTGAGAATGAAATAA AAGCAAT
GCTCCAAAGTTTCTGCGAATTGTATAAAAAAGATCATCGCACTGAGGGTGAAGACAA GGCATTA
GATAAAATTCGAGCAGTACTTCGTGGCCTGATTGTTGGGGCTTTCACTGGTGTTTGC GGAAGAC
GGGAAAATACAGTCCAAAACGAGAAGTACGAGAGTTTGTTCAAAGAAAAGTTGATAA AAGAAA
TTTTACCTGATTTTGTGCTCTCTACTGAGGCTGAAAGCTTGCCTTTCTCTGTTGAAG AAGCTACG
AGGTCACTGAAGGAGTTTGATAGCTTTACATCCTACTTTGCTGGTTTTTACGAGAAT AGAAAGA
ATATATACTCGACGAAACCTCAATCCACTGCCATTGCTTATCGTCTTATTCATGAGA ACTTGCCG
AAGTTCATTGATAATATTCTTGTTTTTCAGAAGATCAAAGAGCCTATAGCCAAAGAG CTGGAAC
ATATTCGTGCGGACTTTTCTGCCGGGGGGTACATAAAAAAGGATGAGAGATTGGAGG ATATTTT
TTCGTTGAACTATTATATCCACGTGTTATCTCAGGCTGGGATCGAAAAATATAACGC ATTGATTG
GGAAGATTGTGACAGAAGGAGATGGAGAGATGAAAGGGCTCAATGAACACATCAACC TTTACA
ACCAACAAAGAGGCAGAGAGGATCGGCTCCCTCTTTTTAGGCCTCTTTATAAACAGA TATTGAG
TGACAGAGAGCAATTATCATACTTGCCTGAGAGTTTTGAAAAAGATGAGGAGCTCCT CAGGGCT
CTAAAAGAGTTCTATGATCATATCGCAGAAGACATTCTCGGACGTACTCAACAGTTG ATGACTT
CTATTTCAGAATATGATTTATCTCGGATATACGTAAGGAACGATAGCCAATTGACTG ATATATCA
AAAAAAATGTTGGGAGATTGGAATGCTATCTACATGGCTAGAGAACGAGCATATGAC CACGAG
CAGGCTCCCAAAAGAATCACGGCGAAATACGAGAGGGACAGGATTAAAGCTCTTAAA GGAGAA
GAGAGTATAAGTCTGGCAAATCTTAATAGTTGTATTGCCTTTCTGGACAATGTTAGA GATTGCCG
TGTAGATACTTATCTTTCCACACTGGGCCAGAAGGAAGGACCACATGGTCTATCTAA TCTCGTTG
AGAACGTTTTTGCCTCATACCATGAAGCAGAGCAATTGTTGAGCTTTCCATACCCCG AAGAGAA
TAATCTGATTCAGGACAAGGACAATGTGGTGTTAATTAAGAATCTTCTCGACAATAT CAGTGAT
CTGCAGAGGTTCTTGAAACCTCTTTGGGGTATGGGAGACGAACCCGATAAAGATGAA AGATTTT
ATGGAGAGTATAATTATATCCGAGGAGCTCTAGATCAGGTGATCCCTCTGTACAATA AGGTAAG
GAACTACCTCACTCGGAAGCCTTATTCGACCAGAAAAGTAAAACTCAATTTTGGGAA TTCTCAA
TTGCTTAGTGGTTGGGATAGAAATAAGGAAAAGGATAATAGCTGTGTGATTTTGCGT AAGGGGC
AGAACTTCTATTTGGCTATTATGAACAATAGGCACAAAAGAAGTTTCGAAAACAAGG TGTTGCC CGAGTATAAGGAGGGAGAACCTTACTTCGAAAAGATGGATTATAAATTTTTGCCTGATCC TAAT
AAAATGCTTCCTAAGGTTTTTCTTTCGAAAAAAGGAATAGAGATATACAAACCAAGT CCGAAGC
TTTTAGAACAATATGGACATGGAACTCACAAAAAGGGAGATACCTTTAGTATGGATG ATTTGCA
CGAACTGATCGATTTCTTCAAACACTCAATCGAGGCTCATGAAGATTGGAAGCAATT CGGATTC
AAATTTTCTGATACGGCTACTTATGAGAATGTATCTAGTTTCTATAGAGAAGTTGAG GATCAGG
GGTATAAGCTCTCTTTCCGAAAAGTTTCGGAATCTTATGTCTATTCATTAATAGATC AAGGCAAG
TTGTATTTATTTCAGATATACAACAAGGACTTTTCTCCCTGCAGCAAAGGGACACCT AATCTGCA
TACCTTGTATTGGAGAATGCTTTTTGACGAGCGCAATTTGGCAGATGTCATATACAA ACTGGATG
TAAGCCTATCAAAAAGAAAAGTCGACAAAAAAAAGGAGAGGAGAGTCTGTTTGAGTA TGATTT
AGTCAAGGATAGGCACTATACGATGGATAAGTTCCAGTTTCATGTGCCTATTACTAT GAATTTTA
AATGTTCTGCAGGAAGCAAAGTCAATGATATGGTTAATGCTCATATTCGAGAGGCAA AGGATAT
GCATGTCATTGGAATTGATCGTGGAGAACGCAATCTGCTGTATATATGCGTGATAGA TAGTCGA
GGGACGATTTTGGATCAAATTTCTCTGAATACGATTAACGATATAGACTATCATGAT TTATTGGA
GAGTCGAGACAAAGACCGTCAGCAGGAGCGCCGAAACTGGCAAACTATCGAAGGGAT CAAGGA
GCTAAAACAAGGCTACCTTAGTCAGGCGGTTCATCGGATAGCCGAACTGATGGTGGC TTATAAG
GCTGTAGTTGCTTTGGAGGATTTGAATATGGGGTTCAAACGTGGGCGGCAGAAAGTA GAAAGTT
CTGTTTATCAGCAGTTTGAGAAACAGCTGATAGATAAGCTCAACTATCTTGTGGACA AGAAGAA
AAGGCCTGAAGATATTGGAGGATTGTTGAGAGCCTATCAATTTACGGCCCCATTTAA GAGTTTT
AAGGAAATGGGAAAGCAAAACGGCTTCTTGTTTTATATCCCGGCTTGGAACACGAGC AACATAG
ATCCGACTACTGGATTTGTTAATTTATTTCATGCCCAGTATGAAAATGTAGATAAAG CGAAGAG
CTTCTTTCAAAAGTTTGATTCAATTAGTTACAACCCGAAGAAAGACTGGTTTGAGTT TGCATTCG
ATTATAAAAACTTTACTAAAAAGGCTGAAGGAAGTCGTTCTATGTGGATATTATGCA CACATGG
TTCCCGAATAAAGAATTTTAGAAATTCCCAGAAGAATGGTCAATGGGATTCCGAAGA ATTCGCC
TTGACGGAGGCTTTTAAGTCTCTTTTTGTGCGATATGAGATAGATTATACCGCTGAT TTGAAAAC
AGCTATTGTGGACGAAAAGCAAAAAGACTTCTTCGTGGATCTTCTGAAGCTATTCAA ATTGACA
GTACAGATGCGCAACAGCTGGAAAGAGAAGGATTTGGATTATCTAATCTCTCCTGTA GCAGGGG
CTGATGGCCGTTTCTTCGATACAAGAGAGGGAAATAAAAGTCTGCCTAAGGATGCAG ATGCCAA
TGGAGCTTATAATATTGCCCTAAAAGGACTTTGGGCTCTACGCCAGATTCGGCAAAC TTCAGAA
GGCGGTAAACTCAAATTGGCGATTTCCAATAAGGAATGGCTACAGTTTGTGCAAGAG AGATCTT
ACGAGAAAGACtgaGAAATCATCCTTAGCGAAAGCTAAGGATTTTTTTTATCTGAAA TTTATTATA
TCGCGTTGATTATTGATGCTGTTTTTAGTTTTAACGGCAATTAATATATGTGTTATT AATTGAATG
AATTTTATCATTCATAATAAGTATGTGTAGGATCAAGCTCAGGTTAAATATTCACTC AGGAAGTT
ATTACTCAGGAAGCAAAGAGGATTACAGAATTATCTCATAACAAGTGTTAAGGGATG TTATTTC
C
SE AAAATTCcatGCAAAATGCTCCGGTTTCATGTCATCAAAATGATGACGTAATTAAGCATT GATAAT
Q TGAGATCCCTCTCCCTGACAGGATGATTACATAAATAATAGTGACAAAAATAAATTATTT ATTTA
no TCCAGAAAATGAATTGGAAAATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGA TATG
N TcaaaCAGGTtgccgtcactgcgtcttttactggctcttctcgctaaccaaaccggtaac cccgcttattaaaagcattctgtaacaaagcgggaccaaagc O: catgacaaaaacgcgtaacaaaagtgtctataatcacggcagaaaagtccacattgatta tttgcacggcgtcacactttgctatgccatagcatttttatccataa
67 gattagcggatcctacctgacgctttttatcgcaactctctactgtttctccatacccgt ttttttgggctagcaccgcctatctcgtgtgagataggcggagatacga actttaagAAGGAGatataccATGAACAACGGCACAAATAATTTTCAGAACTTCATCGGG ATCTCAAGTT TGCAGAAAACGCTGCGCAATGCTCTGATCCCCACGGAAACCACGCAACAGTTCATCGTCA AGAA
CGGAATAATTAAAGAAGATGAGTTACGTGGCGAGAACCGCCAGATTCTGAAAGATAT CATGGA
TGACTACTACCGCGGATTCATCTCTGAGACTCTGAGTTCTATTGATGACATAGATTG GACTAGCC
TGTTCGAAAAAATGGAAATTCAGCTGAAAAATGGTGATAATAAAGATACCTTAATTA AGGAAC
AGACAGAGTATCGGAAAGCAATCCATAAAAAATTTGCGAACGACGATCGGTTTAAGA ACATGT
TTAGCGCCAAACTGATTAGTGACATATTACCTGAATTTGTCATCCACAACAATAATT ATTCGGCA
TCAGAGAAAGAGGAAAAAACCCAGGTGATAAAATTGTTTTCGCGCTTTGCGACTAGC TTTAAAG
ATTACTTCAAGAACCGTGCAAATTGCTTTTCAGCGGACGATATTTCATCAAGCAGCT GCCATCGC
ATCGTCAACGACAATGCAGAGATATTCTTTTCAAATGCGCTGGTCTACCGCCGGATC GTAAAAT
CGCTGAGCAATGACGATATCAACAAAATTTCGGGCGATATGAAAGATTCATTAAAAG AAATGA
GTCTGGAAGAAATATATTCTTACGAGAAGTATGGGGAATTTATTACCCAGGAAGGCA TTAGCTT
CTATAATGATATCTGTGGGAAAGTGAATTCTTTTATGAACCTGTATTGTCAGAAAAA TAAAGAA
AACAAAAATTTATACAAACTTCAGAAACTTCACAAACAGATTCTATGCATTGCGGAC ACTAGCT
ATGAGGTCCCGTATAAATTTGAAAGTGACGAGGAAGTGTACCAATCAGTTAACGGCT TCCTTGA
TAACATTAGCAGCAAACATATAGTCGAAAGATTACGCAAAATCGGCGATAACTATAA CGGCTAC
AACCTGGATAAAATTTATATCGTGTCCAAATTTTACGAGAGCGTTAGCCAAAAAACC TACCGCG
ACTGGGAAACAATTAATACCGCCCTCGAAATTCATTACAATAATATCTTGCCGGGTA ACGGTAA
AAGTAAAGCCGACAAAGTAAAAAAAGCGGTTAAGAATGATTTACAGAAATCCATCAC CGAAAT
AAATGAACTAGTGTCAAACTATAAGCTGTGCAGTGACGACAACATCAAAGCGGAGAC TTATATA
CATGAGATTAGCCATATCTTGAATAACTTTGAAGCACAGGAATTGAAATACAATCCG GAAATTC
ACCTAGTTGAATCCGAGCTCAAAGCGAGTGAGCTTAAAAACGTGCTGGACGTGATCA TGAATGC
GTTTCATTGGTGTTCGGTTTTTATGACTGAGGAACTTGTTGATAAAGACAACAATTT TTATGCGG
AACTGGAGGAGATTTACGATGAAATTTATCCAGTAATTAGTCTGTACAACCTGGTTC GTAACTA
CGTTACCCAGAAACCGTACAGCACGAAAAAGATTAAATTGAACTTTGGAATACCGAC GTTAGCA
GACGGTTGGTCAAAGTCCAAAGAGTATTCTAATAACGCTATCATACTGATGCGCGAC AATCTGT
ATTATCTGGGCATCTTTAATGCGAAGAATAAACCGGACAAGAAGATTATCGAGGGTA ATACGTC
AGAAAATAAGGGTGACTACAAAAAGATGATTTATAATTTGCTCCCGGGTCCCAACAA AATGATC
CCGAAAGTTTTCTTGAGCAGCAAGACGGGGGTGGAAACGTATAAACCGAGCGCCTAT ATCCTAG
AGGGGTATAAACAGAATAAACATATCAAGTCTTCAAAAGACTTTGATATCACTTTCT GTCATGA
TCTGATCGACTACTTCAAAAACTGTATTGCAATTCATCCCGAGTGGAAAAACTTCGG TTTTGATT
TTAGCGACACCAGTACTTATGAAGACATTTCCGGGTTTTATCGTGAGGTAGAGTTAC AAGGTTA
CAAGATTGATTGGACATACATTAGCGAAAAAGACATTGATCTGCTGCAGGAAAAAGG TCAACT
GTATCTGTTCCAGATATATAACAAAGATTTTTCGAAAAAATCAACCGGGAATGACAA CCTTCAC
ACCATGTACCTGAAAAATCTTTTCTCAGAAGAAAATCTTAAGGATATCGTCCTGAAA CTTAACG
GCGAAGCGGAAATCTTCTTCAGGAAGAGCAGCATAAAGAACCCAATCATTCATAAAA AAGGCT
CGATTTTAGTCAACCGTACCTACGAAGCAGAAGAAAAAGACCAGTTTGGCAACATTC AAATTGT
GCGTAAAAATATTCCGGAAAACATTTATCAGGAGCTGTACAAATACTTCAACGATAA AAGCGAC
AAAGAGCTGTCTGATGAAGCAGCCAAACTGAAGAATGTAGTGGGACACCACGAGGCA GCGACG
AATATAGTCAAGGACTATCGCTACACGTATGATAAATACTTCCTTCATATGCCTATT ACGATCAA
TTTCAAAGCCAATAAAACGGGTTTTATTAATGATAGGATCTTACAGTATATCGCTAA AGAAAAA
GACTTACATGTGATCGGCATTGATCGGGGCGAGCGTAACCTGATCTACGTGTCCGTG ATTGATA
CTTGTGGTAATATAGTTGAACAGAAAAGCTTTAACATTGTAAACGGCTACGACTATC AGATAAA ACTGAAACAACAGGAGGGCGCTAGACAGATTGCGCGGAAAGAATGGAAAGAAATTGGTAA AAT
TAAAGAGATCAAAGAGGGCTACCTGAGCTTAGTAATCCACGAGATCTCTAAAATGGT AATCAAA
TACAATGCAATTATAGCGATGGAGGATTTGTCTTATGGTTTTAAAAAAGGGCGCTTT AAGGTCG
AACGGCAAGTTTACCAGAAATTTGAAACCATGCTCATCAATAAACTCAACTATCTGG TATTTAA
AGATATTTCGATTACCGAGAATGGCGGTCTCCTGAAAGGTTATCAGCTGACATACAT TCCTGAT
AAACTTAAAAACGTGGGTCATCAGTGCGGCTGCATTTTTTATGTGCCTGCTGCATAC ACGAGCA
AAATTGATCCGACCACCGGCTTTGTGAATATCTTTAAATTTAAAGACCTGACAGTGG ACGCAAA
ACGTGAATTCATTAAAAAATTTGACTCAATTCGTTATGACAGTGAAAAAAATCTGTT CTGCTTTA
CATTTGACTACAATAACTTTATTACGCAAAACACGGTCATGAGCAAATCATCGTGGA GTGTGTA
TACATACGGCGTGCGCATCAAACGTCGCTTTGTGAACGGCCGCTTCTCAAACGAAAG TGATACC
ATTGACATAACCAAAGATATGGAGAAAACGTTGGAAATGACGGACATTAACTGGCGC GATGGC
CACGATCTTCGTCAAGACATTATAGATTATGAAATTGTTCAGCACATATTCGAAATT TTCCGTTT
AACAGTGCAAATGCGTAACTCCTTGTCTGAACTGGAGGACCGTGATTACGATCGTCT CATTTCAC
CTGTACTGAACGAAAATAACATTTTTTATGACAGCGCGAAAGCGGGGGATGCACTTC CTAAGGA
TGCCGATGCAAATGGTGCGTATTGTATTGCATTAAAAGGGTTATATGAAATTAAACA AATTACC
GAAAATTGGAAAGAAGATGGTAAATTTTCGCGCGATAAACTCAAAATCAGCAATAAA GATTGG
TTCGACTTTATCCAGAATAAGCGCTATCTCTAAGAAATCATCCTTAGCGAAAGCTAA GGATTTTT
TTTATCTGAAATTTATTATATCGCGTTGATTATTGATGCTGTTTTTAGTTTTAACGG CAATTAATA
TATGTGTTATTAATTGAATGAATTTTATCATTCATAATAAGTATGTGTAGGATCAAG CTCAGGTT
AAATATTCACTCAGGAAGTTATTACTCAGGAAGCAAAGAGGATTACAGAATTATCTC ATAACAA
GTGTTAAGGGATGTTATTTCC
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTGCCG TCACT
Q GCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATTAAAAGCATTC TGTAA
no CAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAATCACGGCAGA AAA
N GTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATTTTTATCCATA AGATT
O: AGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCATACCCGTTTTT TTGGGC 68 TAGCAGTAATACGACTCACTATAGGGGTCTCATCTCGTGTGAGATAGGCGGAGATACGAA CTTT
AAGAGGAGGATATACCATGCACCATCATCATCACCATACCAATAAATTCACTAACCA GTATTCT
CTCTCTAAGACCCTGCGCTTTGAACTGATTCCGCAGGGGAAAACCTTGGAGTTCATT CAAGAAA
AAGGCCTCTTGTCTCAGGATAAACAGAGGGCTGAATCTTACCAAGAAATGAAGAAAA CTATTGA
TAAGTTTCATAAATATTTCATTGATTTAGCCTTGTCTAACGCCAAATTAACTCACTT GGAAACGT
ATCTGGAGTTATACAACAAATCTGCCGAAACTAAGAAAGAACAGAAATTTAAAGACG ATTTGA
AAAAAGTACAGGACAATCTGCGTAAAGAAATTGTCAAATCCTTCAGTGACGGCGATG CTAAAA
GCATTTTTGCCATTCTGGACAAAAAAGAGTTGATTACTGTGGAATTAGAAAAGTGGT TTGAAAA
CAATGAGCAGAAAGACATCTACTTCGATGAGAAATTCAAAACTTTCACCACCTATTT TACAGGA
TTTCATCAAAACCGGAAGAACATGTACTCAGTAGAACCGAACTCCACGGCCATTGCG TATCGTT
TGATCCATGAGAATCTGCCTAAATTTCTGGAGAATGCGAAAGCCTTTGAAAAGATTA AGCAGGT
CGAATCGCTGCAAGTGAATTTTCGTGAACTCATGGGCGAATTTGGTGACGAAGGTCT AATCTTC
GTTAACGAACTGGAAGAAATGTTTCAGATTAATTACTACAATGACGTGCTATCGCAG AACGGTA
TCACAATCTACAATAGTATTATCTCAGGGTTCACAAAAAACGATATAAAATACAAAG GCCTGAA
CGAGTATATCAATAACTACAACCAAACAAAGGACAAAAAGGATAGGCTTCCGAAACT GAAGCA
GTTATACAAACAGATTTTATCTGACAGAATCTCCCTGAGCTTTCTGCCGGATGCTTT CACTGATG GGAAGCAGGTTCTGAAAGCGATTTTCGATTTTTATAAGATTAACTTACTGAGCTACACGA TTGA
AGGTCAAGAAGAATCTCAAAACTTACTGCTCTTGATCCGTCAAACCATTGAAAATCT ATCATCG
TTCGATACGCAGAAAATCTACCTCAAAAACGATACTCACCTGACTACGATCTCTCAG CAGGTTTT
CGGGGATTTTAGTGTATTTTCAACAGCTCTGAACTACTGGTATGAAACCAAAGTCAA TCCGAAA
TTCGAGACGGAATATTCTAAGGCCAACGAAAAAAAACGTGAGATTCTTGATAAAGCT AAAGCC
GTATTTACTAAACAGGATTACTTTTCTATTGCTTTCCTGCAGGAAGTTTTATCGGAG TATATCCTG
ACCCTGGATCATACATCTGATATCGTTAAAAAACACAGCAGCAATTGCATCGCTGAC TATTTCA
AAAACCACTTTGTCGCCAAAAAAGAAAACGAAACAGACAAGACTTTCGATTTCATTG CTAACAT
CACCGCAAAATACCAGTGTATTCAGGGTATCTTGGAAAACGCCGACCAATACGAAGA CGAACT
GAAACAAGATCAGAAGCTGATCGATAATTTAAAATTCTTCTTAGATGCAATCCTGGA GCTGCTG
CACTTCATCAAACCGCTTCATTTAAAGAGCGAGTCCATTACCGAAAAGGACACCGCC TTCTATG
ACGTTTTTGAAAATTATTATGAAGCCCTCTCCTTGCTGACTCCGCTGTATAATATGG TACGCAAT
TACGTAACCCAGAAACCATATTCTACCGAAAAAATTAAACTGAACTTTGAAAACGCA CAGCTGC
TCAACGGTTGGGACGCGAATAAAGAAGGTGACTACCTCACCACCATCCTGAAAAAAG ATGGTA
ACTATTTTCTGGCAATTATGGATAAGAAACATAATAAAGCATTCCAGAAATTTCCTG AAGGGAA
AGAAAATTACGAAAAGATGGTGTACAAACTCTTACCTGGAGTTAACAAAATGTTGCC GAAAGTA
TTTTTTAGTAATAAGAACATCGCGTACTTTAACCCGTCCAAAGAACTGCTGGAAAAT TATAAAA
AGGAGACGCATAAGAAAGGGGATACCTTTAACCTGGAACATTGCCATACCTTAATAG ACTTCTT
CAAGGATTCCCTGAATAAACACGAGGATTGGAAATATTTCGATTTTCAGTTTAGTGA GACCAAG
TCATACCAGGATCTTAGCGGCTTTTATCGCGAAGTAGAACACCAAGGCTATAAAATT AACTTCA
AAAACATCGACAGCGAATACATCGACGGTTTAGTTAACGAGGGCAAACTGTTTCTGT TCCAGAT
CTATTCAAAGGATTTTAGCCCGTTCTCTAAAGGCAAACCAAATATGCATACGTTGTA CTGGAAA
GCACTGTTTGAAGAGCAAAACCTGCAGAATGTGATTTATAAACTGAACGGCCAAGCT GAGATTT
TTTTCCGTAAAGCCTCGATTAAACCGAAAAATATCATCCTTCATAAGAAGAAAATAA AGATCGC
TAAAAAACACTTCATAGATAAAAAAACCAAAACCTCCGAAATAGTGCCTGTTCAAAC AATTAAG
AACTTGAATATGTACTACCAGGGCAAGATATCGGAAAAGGAGTTGACTCAAGACGAT CTTCGCT
ATATCGATAACTTTTCGATTTTTAACGAAAAAAACAAGACGATCGACATCATCAAAG ATAAACG
CTTCACTGTAGATAAGTTCCAGTTTCATGTGCCGATTACTATGAACTTCAAAGCTAC CGGGGGTA
GCTATATCAACCAAACGGTGTTGGAATACCTGCAGAATAACCCGGAAGTCAAAATCA TTGGGCT
GGACCGCGGAGAACGTCACCTTGTGTACTTGACCTTAATCGATCAGCAAGGCAACAT CTTAAAA
CAAGAATCGCTGAATACCATTACGGATTCAAAGATTAGCACCCCGTATCATAAGCTG CTCGATA
ACAAGGAGAATGAGCGCGACCTGGCCCGTAAAAACTGGGGCACGGTGGAAAACATTA AGGAGT
TAAAGGAGGGTTATATTTCCCAGGTAGTGCATAAGATCGCCACTCTCATGCTCGAGG AAAATGC
GATCGTTGTCATGGAAGACTTAAACTTCGGATTTAAACGTGGGCGATTTAAAGTAGA GAAACAA
ATCTACCAGAAGTTAGAAAAAATGCTGATTGACAAATTAAATTACTTGGTCCTAAAA GACAAAC
AGCCGCAAGAATTGGGTGGATTATACAACGCCCTCCAACTTACCAATAAATTCGAAA GTTTTCA
GAAAATGGGTAAACAGTCAGGCTTTCTTTTTTATGTTCCTGCGTGGAACACATCCAA AATCGACC
CTACAACCGGCTTCGTCAATTACTTCTATACTAAATATGAAAACGTCGACAAAGCAA AAGCATT
CTTTGAAAAGTTCGAAGCAATACGTTTTAACGCTGAGAAAAAATATTTCGAGTTCGA AGTCAAG
AAATACTCAGACTTTAACCCCAAAGCTGAGGGCACACAGCAAGCGTGGACAATCTGC ACCTACG
GCGAGCGCATCGAAACGAAGCGTCAAAAAGATCAGAATAACAAATTTGTTTCAACAC CTATCA
ACCTGACCGAGAAGATTGAAGACTTCTTAGGTAAAAATCAGATTGTTTATGGCGACG GTAACTG TATAAAATCTCAAATAGCCTCAAAGGATGATAAAGCATTTTTCGAAACATTATTATATTG GTTCA
AAATGACACTGCAGATGCGCAATAGTGAGACGCGTACAGATATTGATTATCTTATCA GCCCGGT
CATGAACGACAACGGTACTTTTTACAACTCCAGAGACTATGAAAAACTTGAGAATCC AACTCTC
CCCAAAGATGCTGATGCGAACGGTGCTTATCACATCGCGAAAAAAGGTCTGATGCTG CTGAACA
AAATCGACCAAGCCGATCTGACTAAGAAAGTTGACCTAAGCATTTCAAATCGGGACT GGTTACA
GTTTGTTCAAAAGAACAAATGAGAAATCATCCTTAGCGAAAGCTAAGGATTTTTTTT ATCTGAA
ATGTAGGGAGACCCTCAGGTTAAATATTCACTCAGGAAGTTATTACTCAGGAAGCAA AGAGGAT
TACA
SE AAAATTCcatGCAAAATGCTCCGGTTTCATGTCATCAAAATGATGACGTAATTAAGCATT GATAAT
Q TGAGATCCCTCTCCCTGACAGGATGATTACATAAATAATAGTGACAAAAATAAATTATTT ATTTA
no TCCAGAAAATGAATTGGAAAATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGA TATG
N TcaaaCAGGTtgccgtcactgcgtcttttactggctcttctcgctaaccaaaccggtaac cccgcttattaaaagcattctgtaacaaagcgggaccaaagc O: catgacaaaaacgcgtaacaaaagtgtctataatcacggcagaaaagtccacattgatta tttgcacggcgtcacactttgctatgccatagcatttttatccataa
69 gattagcggatcctacctgacgctttttatcgcaactctctactgtttctccatacccgt ttttttgggctagcaccgcctatctcgtgtgagataggcggagatacga actttaagAAGGAGatataccATGGAACAGGAATATTATCTGGGCTTGGACATGGGCACC GGTTCCGTCG
GCTGGGCTGTTACTGACAGTGAATATCACGTTCTAAGAAAGCATGGTAAGGCATTGT GGGGTGT
AAGACTTTTCGAATCTGCTTCCACTGCTGAAGAGCGTAGAATGTTTAGAACGAGTCG ACGTAGG
CTAGACAGGCGCAATTGGAGAATCGAAATTTTACAAGAAATTTTTGCGGAAGAGATA TCTAAGA
AAGACCCAGGCTTTTTCCTGAGAATGAAGGAATCTAAGTATTACCCTGAGGATAAAA GAGATAT
AAATGGTAACTGTCCCGAATTGCCTTACGCATTATTTGTGGACGATGATTTTACCGA TAAGGATT
ACCATAAAAAGTTCCCAACTATCTACCATTTACGCAAAATGTTAATGAATACAGAGG AAACCCC
AGACATAAGACTAGTTTATCTGGCAATACACCATATGATGAAACATAGAGGCCATTT CTTACTTT
CCGGGGATATCAACGAAATCAAAGAGTTTGGTACCACATTTAGTAAGTTACTGGAAA ACATAAA
GAATGAAGAATTGGATTGGAACTTAGAACTCGGAAAAGAAGAATACGCGGTTGTCGA ATCTAT
CCTGAAGGATAATATGCTGAATAGGTCGACCAAAAAAACTAGGCTGATCAAAGCACT GAAAGC
CAAATCTATCTGCGAAAAAGCTGTTTTAAATTTACTTGCTGGTGGCACTGTTAAGTT ATCAGACA
TTTTTGGTTTGGAAGAATTGAACGAAACCGAGCGTCCAAAAATTAGTTTCGCTGATA ATGGCTA
CGATGATTACATTGGTGAGGTGGAAAACGAGTTGGGCGAACAATTTTATATTATAGA GACAGCT
AAGGCAGTCTATGACTGGGCTGTTTTAGTAGAAATCCTTGGTAAATACACATCTATC TCCGAAG
CGAAAGTTGCTACTTACGAAAAGCACAAGTCCGATCTCCAGTTTTTGAAGAAAATTG TCAGGAA
ATATCTGACTAAGGAAGAATATAAAGATATTTTCGTTAGTACCTCTGACAAACTGAA AAATTAC
TCCGCTTACATCGGGATGACCAAGATTAATGGCAAAAAAGTTGATCTGCAAAGCAAA AGGTGTT
CGAAGGAAGAATTTTATGATTTCATTAAAAAGAATGTCTTAAAAAAATTAGAAGGTC AGCCAGA
ATACGAATATTTGAAAGAAGAACTGGAAAGAGAGACATTCTTACCAAAACAAGTCAA CAGAGA
TAATGGGGTAATTCCATATCAAATTCACCTCTACGAATTAAAAAAAATTTTAGGCAA TTTACGC
GATAAAATTGACCTTATCAAAGAAAATGAGGATAAGCTGGTTCAACTCTTTGAATTC AGAATAC
CCTATTATGTGGGCCCACTGAACAAGATTGATGACGGCAAAGAAGGTAAATTCACAT GGGCCGT
CCGCAAATCCAATGAAAAAATTTACCCATGGAACTTTGAAAATGTAGTAGATATTGA AGCGTCT
GCGGAGAAATTTATTCGAAGAATGACTAATAAATGCACTTACTTGATGGGAGAGGAT GTTCTGC
CTAAAGACAGCTTATTATACAGCAAGTACATGGTTCTAAACGAACTTAACAACGTTA AGTTGGA
CGGTGAGAAATTAAGTGTAGAATTGAAACAAAGATTGTATACTGACGTCTTCTGCAA GTACAGA
AAAGTGACAGTTAAAAAAATTAAGAATTACTTGAAGTGCGAAGGTATAATTTCTGGA AACGTAG AGATTACTGGTATTGATGGTGATTTCAAAGCATCCCTAACAGCTTACCACGATTTCAAGG AAAT
CCTGACAGGAACTGAACTCGCAAAAAAAGATAAAGAAAACATTATTACTAATATTGT TCTTTTC
GGTGATGACAAGAAATTGTTGAAGAAAAGACTGAATAGACTTTACCCCCAGATTACT CCCAATC
AACTTAAGAAAATTTGTGCTTTGTCTTACACAGGATGGGGTCGTTTTTCAAAAAAGT TCTTAGAA
GAGATTACCGCACCTGATCCAGAAACAGGCGAAGTATGGAATATAATTACCGCCTTA TGGGAAT
CGAACAATAATCTTATGCAACTTCTGAGCAATGAATATCGTTTCATGGAAGAAGTTG AGACTTA
CAACATGGGCAAACAGACGAAGACTTTATCCTATGAAACTGTGGAAAATATGTATGT ATCACCT
TCTGTCAAGAGACAAATTTGGCAAACCTTAAAAATTGTCAAAGAATTAGAAAAGGTA ATGAAG
GAGTCTCCTAAACGTGTGTTTATTGAAATGGCTAGAGAAAAACAAGAGTCAAAAAGA ACCGAG
TCAAGAAAGAAGCAGTTAATCGATTTATATAAGGCTTGTAAAAACGAAGAGAAAGAT TGGGTT
AAAGAATTGGGGGACCAAGAGGAACAAAAACTACGGTCGGATAAGTTGTATTTATAC TATACG
CAAAAGGGACGATGTATGTATTCCGGCGAGGTAATAGAATTGAAGGATTTATGGGAC AATACA
AAATATGACATAGACCATATATATCCCCAATCAAAAACGATGGACGATAGCTTGAAC AATAGA
GTACTCGTGAAAAAAAAATATAATGCGACCAAATCTGATAAGTATCCTCTGAATGAA AATATCA
GACATGAAAGAAAGGGGTTCTGGAAGTCCTTGTTAGATGGTGGGTTTATAAGCAAAG AAAAGT
ACGAGCGTCTAATAAGAAACACGGAGTTATCGCCAGAAGAACTCGCTGGTTTTATTG AGAGGCA
AATCGTGGAAACGAGACAATCTACCAAAGCCGTTGCTGAGATCCTAAAGCAAGTTTT CCCAGAG
TCGGAGATTGTCTATGTCAAAGCTGGCACAGTGAGCAGGTTTAGGAAAGACTTCGAA CTATTAA
AGGTAAGAGAAGTGAACGATTTACATCACGCAAAGGACGCTTACCTAAATATCGTTG TAGGTAA
CTCATATTATGTTAAATTTACCAAGAACGCCTCTTGGTTTATAAAGGAGAACCCAGG TAGAACA
TATAACCTGAAAAAGATGTTCACCTCTGGTTGGAATATTGAGAGAAACGGAGAAGTC GCATGGG
AAGTTGGTAAGAAAGGGACTATAGTGACAGTAAAGCAAATTATGAACAAAAATAATA TCCTCG
TTACAAGGCAGGTTCATGAAGCAAAGGGCGGCCTTTTTGACCAACAAATTATGAAGA AAGGGA
AAGGTCAAATTGCAATAAAAGAAACCGATGAGAGACTAGCGTCAATAGAAAAGTATG GTGGCT
ATAATAAAGCTGCGGGTGCATACTTTATGCTTGTTGAATCAAAAGACAAGAAAGGTA AGACTAT
TAGAACTATAGAATTTATACCCCTGTACCTTAAAAACAAAATTGAATCGGATGAGTC AATCGCG
TTAAATTTTCTAGAGAAAGGAAGGGGTTTAAAAGAACCAAAGATCCTGTTAAAAAAG ATTAAG
ATTGACACCTTGTTCGATGTAGATGGATTTAAAATGTGGTTATCTGGCAGAACAGGC GATAGAC
TTTTGTTTAAGTGCGCTAATCAATTAATTTTGGATGAGAAAATCATTGTCACAATGA AAAAAATA
GTTAAGTTTATTCAGAGAAGACAAGAAAACAGGGAGTTGAAATTATCTGATAAAGAT GGTATCG
ACAATGAAGTTTTAATGGAAATCTACAATACATTCGTTGATAAACTTGAAAATACCG TATATCG
AATCAGGTTAAGTGAACAAGCCAAAACATTAATTGATAAACAAAAAGAATTTGAAAG GCTATC
ACTGGAAGACAAATCCTCCACCCTATTTGAAATTTTGCATATATTCCAGTGCCAATC TTCAGCAG
CTAATTTAAAAATGATTGGCGGACCTGGGAAAGCCGGCATCCTAGTGATGAACAATA ATATCTC
CAAGTGTAACAAAATATCAATTATTAACCAATCTCCGACAGGTATTTTTGAAAATGA AATAGAC
TTGCTTAAGATATAAGAAATCATCCTTAGCGAAAGCTAAGGATTTTTTTTATCTGAA ATTTATTA
TATCGCGTTGATTATTGATGCTGTTTTTAGTTTTAACGGCAATTAATATATGTGTTA TTAATTGAA
TGAATTTTATCATTCATAATAAGTATGTGTAGGATCAAGCTCAGGTTAAATATTCAC TCAGGAAG
TTATTACTCAGGAAGCAAAGAGGATTACAGAATTATCTCATAACAAGTGTTAAGGGA TGTTATT
TCC
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTGCCG TCACT
Q GCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATTAAAAGCATTC TGTAA E) CAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAATCACGGCAGA AAA N GTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATTTTTATCCATA AGATT
O: AGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCATACCCGTTTTT TTGGGC 70 TAGCAGTAATACGACTCACTATAGGGGTCTCATCTCGTGTGAGATAGGCGGAGATACGAA CTTT AAGAGGAGGATATACCATGCACCATCATCATCACCATTCTTTCGACTCTTTCACCAACCT GTACT CTCTGTCTAAAACCCTGAAATTCGAAATGCGTCCGGTTGGTAACACCCAGAAAATGCTGG ACAA CGCGGGTGTTTTCGAAAAAGACAAACTGATCCAGAAAAAATACGGTAAAACCAAACCGTA CTT CGACCGTCTGCACCGTGAATTCATCGAAGAAGCGCTGACCGGTGTTGAACTGATCGGTCT GGAC GAAAACTTCCGTACCCTGGTTGACTGGCAGAAAGACAAAAAAAACAACGTTGCGATGAAA GCG TACGAAAACTCTCTGCAGCGTCTGCGTACCGAAATCGGTAAAATCTTCAACCTGAAAGCG GAAG ACTGGGTTAAAAACAAATACCCGATCCTGGGTCTGAAAAACAAAAACACCGACATCCTGT TCGA AGAAGCGGTTTTCGGTATCCTGAAAGCGCGTTACGGTGAAGAAAAAGACACCTTCATCGA AGTT GAAGAAATCGACAAAACCGGTAAATCTAAAATCAACCAGATCTCTATCTTCGACTCTTGG AAAG GTTTCACCGGTTACTTCAAAAAATTCTTCGAAACCCGTAAAAACTTCTACAAAAACGACG GTAC CTCTACCGCGATCGCGACCCGTATCATCGACCAGAACCTGAAACGTTTCATCGACAACCT GTCT ATCGTTGAATCTGTTCGTCAGAAAGTTGACCTGGCGGAAACCGAAAAATCTTTCTCTATC TCTCT GTCTCAGTTCTTCTCTATCGACTTCTACAACAAATGCCTGCTGCAGGACGGTATCGACTA CTACA ACAAAATCATCGGTGGTGAAACCCTGAAAAACGGTGAAAAACTGATCGGTCTGAACGAAC TGA TCAACCAGTACCGTCAGAACAACAAAGACCAGAAAATCCCGTTCTTCAAACTGCTGGACA AACA GATCCTGTCTGAAAAAATCCTGTTCCTGGACGAAATCAAAAACGACACCGAACTGATCGA AGCG CTGTCTCAGTTCGCGAAAACCGCGGAAGAAAAAACCAAAATCGTTAAAAAACTGTTCGCG GACT TCGTTGAAAACAACTCTAAATACGACCTGGCGCAGATCTACATCTCTCAGGAAGCGTTCA ACAC CATCTCTAACAAATGGACCTCTGAAACCGAAACCTTCGCGAAATACCTGTTCGAAGCGAT GAAA TCTGGTAAACTGGCGAAATACGAAAAAAAAGACAACTCTTACAAATTCCCGGACTTCATC GCGC TGTCTCAGATGAAATCTGCGCTGCTGTCTATCTCTCTGGAAGGTCACTTCTGGAAAGAAA AATAC TACAAAATCTCTAAATTCCAGGAAAAAACCAACTGGGAACAGTTCCTGGCGATCTTCCTG TACG AATTCAACTCTCTGTTCTCTGACAAAATCAACACCAAAGACGGTGAAACCAAACAGGTTG GTTA CTACCTGTTCGCGAAAGACCTGCACAACCTGATCCTGTCTGAACAGATCGACATCCCGAA AGAC TCTAAAGTTACCATCAAAGACTTCGCGGACTCTGTTCTGACCATCTACCAGATGGCGAAA TACTT CGCGGTTGAAAAAAAACGTGCGTGGCTGGCGGAATACGAACTGGACTCTTTCTACACCCA GCCG GACACCGGTTACCTGCAGTTCTACGACAACGCGTACGAAGACATCGTTCAGGTTTACAAC AAAC TGCGTAACTACCTGACCAAAAAACCGTACTCTGAAGAAAAATGGAAACTGAACTTCGAAA ACTC TACCCTGGCGAACGGTTGGGACAAAAACAAAGAATCTGACAACTCTGCGGTTATCCTGCA GAAA GGTGGTAAATACTACCTGGGTCTGATCACCAAAGGTCACAACAAAATCTTCGACGACCGT TTCC AGGAAAAATTCATCGTTGGTATCGAAGGTGGTAAATACGAAAAAATCGTTTACAAATTCT TCCC GGACCAGGCGAAAATGTTCCCGAAAGTTTGCTTCTCTGCGAAAGGTCTGGAATTCTTCCG TCCGT CTGAAGAAATCCTGCGTATCTACAACAACGCGGAATTCAAAAAAGGTGAAACCTACTCTA TCGA CTCTATGCAGAAACTGATCGACTTCTACAAAGACTGCCTGACCAAATACGAAGGTTGGGC GTGC TACACCTTCCGTCACCTGAAACCGACCGAAGAATACCAGAACAACATCGGTGAATTCTTC CGTG ACGTTGCGGAAGACGGTTACCGTATCGACTTCCAGGGTATCTCTGACCAGTACATCCACG AAAA AAACGAAAAAGGTGAACTGCACCTGTTCGAAATCCACAACAAAGACTGGAACCTGGACAA AGC GCGTGACGGTAAATCTAAAACCACCCAGAAAAACCTGCACACCCTGTACTTCGAATCTCT GTTC TCTAACGACAACGTTGTTCAGAACTTCCCGATCAAACTGAACGGTCAGGCGGAAATCTTC TACC
GTCCGAAAACCGAAAAAGACAAACTGGAATCTAAAAAAGACAAAAAAGGTAACAAAG TTATCG
ACCACAAACGTTACTCTGAAAACAAAATCTTCTTCCACGTTCCGCTGACCCTGAACC GTACCAA
AAACGACTCTTACCGTTTCAACGCGCAGATCAACAACTTCCTGGCGAACAACAAAGA CATCAAC
ATCATCGGTGTTGACCGTGGTGAAAAACACCTGGTTTACTACTCTGTTATCACCCAG GCGTCTGA
CATCCTGGAATCTGGTTCTCTGAACGAACTGAACGGTGTTAACTACGCGGAAAAACT GGGTAAA
AAAGCGGAAAACCGTGAACAGGCGCGTCGTGACTGGCAGGACGTTCAGGGTATCAAA GACCTG
AAAAAAGGTTACATCTCTCAGGTTGTTCGTAAACTGGCGGACCTGGCGATCAAACAC AACGCGA
TCATCATCCTGGAAGACCTGAACATGCGTTTCAAACAGGTTCGTGGTGGTATCGAAA AATCTAT
CTACCAGCAGCTGGAAAAAGCGCTGATCGACAAACTGTCTTTCCTGGTTGACAAAGG TGAAAAA
AACCCGGAACAGGCGGGTCACCTGCTGAAAGCGTACCAGCTGTCTGCGCCGTTCGAA ACCTTCC
AGAAAATGGGTAAACAGACCGGTATCATCTTCTACACCCAGGCGTCTTACACCTCTA AATCTGA
CCCGGTTACCGGTTGGCGTCCGCACCTGTACCTGAAATACTTCTCTGCGAAAAAAGC GAAAGAC
GACATCGCGAAATTCACCAAAATCGAATTCGTTAACGACCGTTTCGAACTGACCTAC GACATCA
AAGACTTCCAGCAGGCGAAAGAATACCCGAACAAAACCGTTTGGAAAGTTTGCTCTA ACGTTGA
ACGTTTCCGTTGGGACAAAAACCTGAACCAGAACAAAGGTGGTTACACCCACTACAC CAACATC
ACCGAAAACATCCAGGAACTGTTCACCAAATACGGTATCGACATCACCAAAGACCTG CTGACCC
AGATCTCTACCATCGACGAAAAACAGAACACCTCTTTCTTCCGTGACTTCATCTTCT ACTTCAAC
CTGATCTGCCAGATCCGTAACACCGACGACTCTGAAATCGCGAAAAAAAACGGTAAA GACGAC
TTCATCCTGTCTCCGGTTGAACCGTTCTTCGACTCTCGTAAAGACAACGGTAACAAA CTGCCGGA
AAACGGTGACGACAACGGTGCGTACAACATCGCGCGTAAAGGTATCGTTATCCTGAA CAAAATC
TCTCAGTACTCTGAAAAAAACGAAAACTGCGAAAAAATGAAATGGGGTGACCTGTAC GTTTCTA
ACATCGACTGGGACAACTTCGTTGAAATCATCCTTAGCGAAAGCTAAGGATTTTTTT TATCTGAA
ATGTAGGGAGACCCTCAGGTTAAATATTCACTCAGGAAGTTATTACTCAGGAAGCAA AGAGGAT
TACA
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTGCCG TCACT
Q GCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATTAAAAGCATTC TGTAA
no CAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAATCACGGCAGA AAA
N GTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATTTTTATCCATA AGATT
O: AGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCATACCCGTTTTT TTGGGC 71 TAGCAGTAATACGACTCACTATAGGGGTCTCATCTCGTGTGAGATAGGCGGAGATACGAA CTTT
AAGAGGAGGATATACCATGCACCATCATCATCACCATAACAAATTCGAAAACTTCAC CGGTCTG
TACCCGATCTCTAAAACCCTGCGTTTCGAACTGATCCCGCAGGGTAAAACCCTGGAA TACATCG
AAAAATCTGAAATCCTGGAAAACGACAACTACCGTGCGGAAAAATACGAAGAAGTTA AAGACA
TCATCGACGGTTACCACAAATGGTTCATCAACGAAACCCTGCACGACCTGCACATCA ACTGGTC
TGAACTGAAAGTTGCGCTGGAAAACAACCGTATCGAAAAATCTGACGCGTCTAAAAA AGAACT
GCAGCGTGTTCAGAAAATCAAACGTGAAGAAATCTACAACGCGTTCATCGAACACGA AGCGTTC
CAGTACCTGTTCAAAGAAAACCTGCTGTCTGACCTGCTGCCGATCCAGATCGAACAG TCTGAAG
ACCTGGACGCGGAAAAAAAAAAACAGGCGGTTGAAACCTTCAACCGTTTCTCTACCT ACTTCAC
CGGTTTCCACGAAAACCGTAAAAACATCTACTCTAAAGAAGGTATCTCTACCTCTGT TACCTACC
GTATCGTTCACGACAACTTCCCGAAATTCCTGGAAAACATGAAAGTTTTCGAAATCC TGCGTAA
CGAATGCCCGGAAGTTATCTCTGACACCGCGAACGAACTGGCGCCGTTCATCGACGG TGTTCGT ATCGAAGACATCTTCCTGATCGACTTCTTCAACTCTACCTTCTCTCAGAACGGTATCGAC TACTA
CAACCGTATCCTGGGTGGTGTTACCACCGAAACCGGTGAAAAATACCGTGGTATCAA CGAATTC
ACCAACCTGTACCGTCAGCAGCACCCGGAATTCGGTAAATCTAAAAAAGCGACCAAA ATGGTTG
TTCTGTTCAAACAGATCCTGTCTGACCGTGACACCCTGTCTTTCATCCCGGAAATGT TCGGTAAC
GACAAACAGGTTCAGAACTCTATCCAGCTGTTCTACAACCGTGAAATCTCTCAGTTC GAAAACG
AAGGTGTTAAAACCGACGTTTGCACCGCGCTGGCGACCCTGACCTCTAAAATCGCGG AATTCGA
CACCGAAAAAATCTACATCCAGCAGCCGGAACTGCCGAACGTTTCTCAGCGTCTGTT CGGTTCTT
GGAACGAACTGAACGCGTGCCTGTTCAAATACGCGGAACTGAAATTCGGTACCGCGG AAAAAG
TTGCGAACCGTAAAAAAATCGACAAATGGCTGAAATCTGACCTGTTCTCTTTCACCG AACTGAA
CAAAGCGCTGGAATTCTCTGGTAAAGACGAACGTATCGAAAACTACTTCTCTGAAAC CGGTATC
TTCGCGCAGCTGGTTAAAACCGGTTTCGACGAAGCGCAGTCTATCCTGGAAACCGAA TACACCT
CTGAAGTTCACCTGAAAGACCAGCAGACCGACATCGAAAAAATCAAAACCTTCCTGG ACGCGCT
GCAGAACCTGATGCACCTGCTGAAATCTCTGTGCGTTTCTGAAGAAGCGGACCGTGA CGCGGCG
TTCTACAACGAATTCGACATGCTGTACAACCAGCTGAAACTGGTTGTTCCGCTGTAC AACAAAG
TTCGTAACTACATCACCCAGAAACTGTTCCGTTCTGACAAAATCAAAATCTACTTCG AAAACAA
AGGTCAGTTCCTGGGTGGTTGGGTTGACTCTCAGACCGAAAACTCTGACAACGGTAC CCAGGCG
GGTGGTTACATCTTCCGTAAAGAAAACGTTATCAACGAATACGACTACTACCTGGGT ATCTGCT
CTGACCCGAAACTGTTCCGTCGTACCACCATCGTTTCTGAAAACGACCGTTCTTCTT TCGAACGT
CTGGACTACTACCAGCTGAAAACCGCGTCTGTTTACGGTAACTCTTACTGCGGTAAA CACCCGT
ACACCGAAGACAAAAACGAACTGGTTAACTCTATCGACCGTTTCGTTCACCTGTCTG GTAACAA
CATCCTGATCGAAAAAATCGCGAAAGACAAAGTTAAATCTAACCCGACCACCAACAC CCCGTCT
GGTTACCTGAACTTCATCCACCGTGAAGCGCCGAACACCTACGAATGCCTGCTGCAG GACGAAA
ACTTCGTTTCTCTGAACCAGCGTGTTGTTTCTGCGCTGAAAGCGACCCTGGCGACCC TGGTTCGT
GTTCCGAAAGCGCTGGTTTACGCGAAAAAAGACTACCACCTGTTCTCTGAAATCATC AACGACA
TCGACGAACTGTCTTACGAAAAAGCGTTCTCTTACTTCCCGGTTTCTCAGACCGAAT TCGAAAAC
TCTTCTAACCGTACCATCAAACCGCTGCTGCTGTTCAAAATCTCTAACAAAGACCTG TCTTTCGC
GGAAAACTTCGAAAAAGGTAACCGTCAGAAAATCGGTAAAAAAAACCTGCACACCCT GTACTT
CGAAGCGCTGATGAAAGGTAACCAGGACACCATCGACATCGGTACCGGTATGGTTTT CCACCGT
GTTAAATCTCTGAACTACAACGAAAAAACCCTGAAATACGGTCACCACTCTACCCAG CTGAACG
AAAAATTCTCTTACCCGATCATCAAAGACAAACGTTTCGCGTCTGACAAATTCCTGT TCCACCTG
TCTACCGAAATCAACTACAAAGAAAAACGTAAACCGCTGAACAACTCTATCATCGAA TTCCTGA
CCAACAACCCGGACATCAACATCATCGGTCTGGACCGTGGTGAACGTCACCTGATCT ACCTGAC
CCTGATCAACCAGAAAGGTGAAATCCTGCGTCAGAAAACCTTCAACATCGTTGGTAA CACCAAC
TACCACGAAAAACTGAACCAGCGTGAAAAAGAACGTGACAACGCGCGTAAATCTTGG GCGACC
ATCGGTAAAATCAAAGAACTGAAAGAAGGTTTCCTGTCTCTGGTTATCCACGAAATC GCGAAAA
TCATGGTTGAAAACAACGCGATCGTTGTTCTGGAAGACCTGAACTTCGGTTTCAAAC GTGGTCG
TTTCAAAGTTGAAAAACAGATCTACCAGAAATTCGAAAAAATGCTGATCGACAAACT GAACTAC
CTGGTTTTCAAAGACAAAAAAGCGAACGAAGCGGGTGGTGTTCTGAAAGGTTACCAG CTGGCG
GAAAAATTCGAATCTTTCCAGAAAATGGGTAAACAGTCTGGTTTCCTGTTCTACGTT CCGGCGGC
GTACACCTCTAAAATCGACCCGACCACCGGTTTCGTTAACATGCTGAACCTGAACTA CACCAAC
ATGAAAGACGCGCAGACCCTGCTGTCTGGTATGGACAAAATCTCTTTCAACGCGGAC GCGAACT
ACTTCGAATTCGAACTGGACTACGAAAAATTCAAAACCAACCAGACCGACCACACCA ACAAAT GGACCATCTGCACCGTTGGTGAAAAACGTTTCACCTACAACTCTGCGACCAAAGAAACCA CCAC
CGTTAACGTTACCGAAGACCTGAAAAAACTGCTGGACAAATTCGAAGTTAAATACTC TAACGGT
GACAACATCAAAGACGAAATCTGCCGTCAGACCGACGCGAAATTCTTCGAAATCATC CTGTGGC
TGCTGAAACTGACCATGCAGATGCGTAACTCTAACACCAAAACCGAAGAAGACTTCA TCCTGTC
TCCGGTTAAAAACTCTAACGGTGAATTCTTCCGTTCTAACGACGACGCGAACGGTAT CTGGCCG
GCGGACGCGGACGCGAACGGTGCGTACCACATCGCGCTGAAAGGTCTGTACCTGGTT AAAGAA
TGCTTCAACAAAAACGAAAAATCTCTGAAAATCGAACACAAAAACTGGTTCAAATTC GCGCAG
ACCCGTTTCAACGGTTCTCTGACCAAAAACGGTTAAGAAATCATCCTTAGCGAAAGC TAAGGAT
TTTTTTTATCTGAAATGTAGGGAGACCCTCAGGTTAAATATTCACTCAGGAAGTTAT TACTCAGG
AAGCAAAGAGGATTACA
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTGCCG TCACT
Q GCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATTAAAAGCATTC TGTAA
no CAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAATCACGGCAGA AAA
N GTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATTTTTATCCATA AGATT
O: AGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCATACCCGTTTTT TTGGGC
72 TAGCAGTAATACGACTCACTATAGGGGTCTCATCTCGTGTGAGATAGGCGGAGATACGAA CTTT
AAGAGGAGGATATACCATGCACCATCATCATCACCATACCCAGTTCGAAGGTTTCAC CAACCTG
TACCAGGTTTCTAAAACCCTGCGTTTCGAACTGATCCCGCAGGGTAAAACCCTGAAA CACATCC
AGGAACAGGGTTTCATCGAAGAAGACAAAGCGCGTAACGACCACTACAAAGAACTGA AACCGA
TCATCGACCGTATCTACAAAACCTACGCGGACCAGTGCCTGCAGCTGGTTCAGCTGG ACTGGGA
AAACCTGTCTGCGGCGATCGACTCTTACCGTAAAGAAAAAACCGAAGAAACCCGTAA CGCGCT
GATCGAAGAACAGGCGACCTACCGTAACGCGATCCACGACTACTTCATCGGTCGTAC CGACAAC
CTGACCGACGCGATCAACAAACGTCACGCGGAAATCTACAAAGGTCTGTTCAAAGCG GAACTGT
TCAACGGTAAAGTTCTGAAACAGCTGGGTACCGTTACCACCACCGAACACGAAAACG CGCTGCT
GCGTTCTTTCGACAAATTCACCACCTACTTCTCTGGTTTCTACGAAAACCGTAAAAA CGTTTTCT
CTGCGGAAGACATCTCTACCGCGATCCCGCACCGTATCGTTCAGGACAACTTCCCGA AATTCAA
AGAAAACTGCCACATCTTCACCCGTCTGATCACCGCGGTTCCGTCTCTGCGTGAACA CTTCGAAA
ACGTTAAAAAAGCGATCGGTATCTTCGTTTCTACCTCTATCGAAGAAGTTTTCTCTT TCCCGTTCT
ACAACCAGCTGCTGACCCAGACCCAGATCGACCTGTACAACCAGCTGCTGGGTGGTA TCTCTCG
TGAAGCGGGTACCGAAAAAATCAAAGGTCTGAACGAAGTTCTGAACCTGGCGATCCA GAAAAA
CGACGAAACCGCGCACATCATCGCGTCTCTGCCGCACCGTTTCATCCCGCTGTTCAA ACAGATCC
TGTCTGACCGTAACACCCTGTCTTTCATCCTGGAAGAATTCAAATCTGACGAAGAAG TTATCCAG
TCTTTCTGCAAATACAAAACCCTGCTGCGTAACGAAAACGTTCTGGAAACCGCGGAA GCGCTGT
TCAACGAACTGAACTCTATCGACCTGACCCACATCTTCATCTCTCACAAAAAACTGG AAACCAT
CTCTTCTGCGCTGTGCGACCACTGGGACACCCTGCGTAACGCGCTGTACGAACGTCG TATCTCTG
AACTGACCGGTAAAATCACCAAATCTGCGAAAGAAAAAGTTCAGCGTTCTCTGAAAC ACGAAG
ACATCAACCTGCAGGAAATCATCTCTGCGGCGGGTAAAGAACTGTCTGAAGCGTTCA AACAGAA
AACCTCTGAAATCCTGTCTCACGCGCACGCGGCGCTGGACCAGCCGCTGCCGACCAC CCTGAAA
AAACAGGAAGAAAAAGAAATCCTGAAATCTCAGCTGGACTCTCTGCTGGGTCTGTAC CACCTGC
TGGACTGGTTCGCGGTTGACGAATCTAACGAAGTTGACCCGGAATTCTCTGCGCGTC TGACCGG
TATCAAACTGGAAATGGAACCGTCTCTGTCTTTCTACAACAAAGCGCGTAACTACGC GACCAAA
AAACCGTACTCTGTTGAAAAATTCAAACTGAACTTCCAGATGCCGACCCTGGCGTCT GGTTGGG ACGTTAACAAAGAAAAAAACAACGGTGCGATCCTGTTCGTTAAAAACGGTCTGTACTACC TGGG
TATCATGCCGAAACAGAAAGGTCGTTACAAAGCGCTGTCTTTCGAACCGACCGAAAA AACCTCT
GAAGGTTTCGACAAAATGTACTACGACTACTTCCCGGACGCGGCGAAAATGATCCCG AAATGCT
CTACCCAGCTGAAAGCGGTTACCGCGCACTTCCAGACCCACACCACCCCGATCCTGC TGTCTAA
CAACTTCATCGAACCGCTGGAAATCACCAAAGAAATCTACGACCTGAACAACCCGGA AAAAGA
ACCGAAAAAATTCCAGACCGCGTACGCGAAAAAAACCGGTGACCAGAAAGGTTACCG TGAAGC
GCTGTGCAAATGGATCGACTTCACCCGTGACTTCCTGTCTAAATACACCAAAACCAC CTCTATCG
ACCTGTCTTCTCTGCGTCCGTCTTCTCAGTACAAAGACCTGGGTGAATACTACGCGG AACTGAAC
CCGCTGCTGTACCACATCTCTTTCCAGCGTATCGCGGAAAAAGAAATCATGGACGCG GTTGAAA
CCGGTAAACTGTACCTGTTCCAGATCTACAACAAAGACTTCGCGAAAGGTCACCACG GTAAACC
GAACCTGCACACCCTGTACTGGACCGGTCTGTTCTCTCCGGAAAACCTGGCGAAAAC CTCTATC
AAACTGAACGGTCAGGCGGAACTGTTCTACCGTCCGAAATCTCGTATGAAACGTATG GCGCACC
GTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCCGATCCCGG ACACCC
TGTACCAGGAACTGTACGACTACGTTAACCACCGTCTGTCTCACGACCTGTCTGACG AAGCGCG
TGCGCTGCTGCCGAACGTTATCACCAAAGAAGTTTCTCACGAAATCATCAAAGACCG TCGTTTC
ACCTCTGACAAATTCTTCTTCCACGTTCCGATCACCCTGAACTACCAGGCGGCGAAC TCTCCGTC
TAAATTCAACCAGCGTGTTAACGCGTACCTGAAAGAACACCCGGAAACCCCGATCAT CGGTATC
GACCGTGGTGAACGTAACCTGATCTACATCACCGTTATCGACTCTACCGGTAAAATC CTGGAAC
AGCGTTCTCTGAACACCATCCAGCAGTTCGACTACCAGAAAAAACTGGACAACCGTG AAAAAG
AACGTGTTGCGGCGCGTCAGGCGTGGTCTGTTGTTGGTACCATCAAAGACCTGAAAC AGGGTTA
CCTGTCTCAGGTTATCCACGAAATCGTTGACCTGATGATCCACTACCAGGCGGTTGT TGTTCTGG
AAAACCTGAACTTCGGTTTCAAATCTAAACGTACCGGTATCGCGGAAAAAGCGGTTT ACCAGCA
GTTCGAAAAAATGCTGATCGACAAACTGAACTGCCTGGTTCTGAAAGACTACCCGGC GGAAAA
AGTTGGTGGTGTTCTGAACCCGTACCAGCTGACCGACCAGTTCACCTCTTTCGCGAA AATGGGT
ACCCAGTCTGGTTTCCTGTTCTACGTTCCGGCGCCGTACACCTCTAAAATCGACCCG CTGACCGG
TTTCGTTGACCCGTTCGTTTGGAAAACCATCAAAAACCACGAATCTCGTAAACACTT CCTGGAA
GGTTTCGACTTCCTGCACTACGACGTTAAAACCGGTGACTTCATCCTGCACTTCAAA ATGAACCG
TAACCTGTCTTTCCAGCGTGGTCTGCCGGGTTTCATGCCGGCGTGGGACATCGTTTT CGAAAAAA
ACGAAACCCAGTTCGACGCGAAAGGTACCCCGTTCATCGCGGGTAAACGTATCGTTC CGGTTAT
CGAAAACCACCGTTTCACCGGTCGTTACCGTGACCTGTACCCGGCGAACGAACTGAT CGCGCTG
CTGGAAGAAAAAGGTATCGTTTTCCGTGACGGTTCTAACATCCTGCCGAAACTGCTG GAAAACG
ACGACTCTCACGCGATCGACACCATGGTTGCGCTGATCCGTTCTGTTCTGCAGATGC GTAACTCT
AACGCGGCGACCGGTGAAGACTACATCAACTCTCCGGTTCGTGACCTGAACGGTGTT TGCTTCG
ACTCTCGTTTCCAGAACCCGGAATGGCCGATGGACGCGGACGCGAACGGTGCGTACC ACATCGC
GCTGAAAGGTCAGCTGCTGCTGAACCACCTGAAAGAATCTAAAGACCTGAAACTGCA GAACGG
TATCTCTAACCAGGACTGGCTGGCGTACATCCAGGAACTGCGTAACTAGAAATCATC CTTAGCG
AAAGCTAAGGATTTTTTTTATCTGAAATGTAGGGAGACCCTCAGGTTAAATATTCAC TCAGGAA
GTTATTACTCAGGAAGCAAAGAGGATTACA
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTGCCG TCACT
Q GCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATTAAAAGCATTC TGTAA
no CAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAATCACGGCAGA AAA
N GTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATTTTTATCCATA AGATT O: AGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCATACCCGTTTTT TTGGGC
73 TAGCAGTAATACGACTCACTATAGGGGTCTCATCTCGTGTGAGATAGGCGGAGATACGAA CTTT
AAGAGGAGGATATACCATGCACCATCATCATCACCATGCGGTTAAATCTATCAAAGT TAAACTG
CGTCTGGACGACATGCCGGAAATCCGTGCGGGTCTGTGGAAACTGCACAAAGAAGTT AACGCG
GGTGTTCGTTACTACACCGAATGGCTGTCTCTGCTGCGTCAGGAAAACCTGTACCGT CGTTCTCC
GAACGGTGACGGTGAACAGGAATGCGACAAAACCGCGGAAGAATGCAAAGCGGAACT GCTGG
AACGTCTGCGTGCGCGTCAGGTTGAAAACGGTCACCGTGGTCCGGCGGGTTCTGACG ACGAACT
GCTGCAGCTGGCGCGTCAGCTGTACGAACTGCTGGTTCCGCAGGCGATCGGTGCGAA AGGTGAC
GCGCAGCAGATCGCGCGTAAATTCCTGTCTCCGCTGGCGGACAAAGACGCGGTTGGT GGTCTGG
GTATCGCGAAAGCGGGTAACAAACCGCGTTGGGTTCGTATGCGTGAAGCGGGTGAAC CGGGTT
GGGAAGAAGAAAAAGAAAAAGCGGAAACCCGTAAATCTGCGGACCGTACCGCGGACG TTCTGC
GTGCGCTGGCGGACTTCGGTCTGAAACCGCTGATGCGTGTTTACACCGACTCTGAAA TGTCTTCT
GTTGAATGGAAACCGCTGCGTAAAGGTCAGGCGGTTCGTACCTGGGACCGTGACATG TTCCAGC
AGGCGATCGAACGTATGATGTCTTGGGAATCTTGGAACCAGCGTGTTGGTCAGGAAT ACGCGAA
ACTGGTTGAACAGAAAAACCGTTTCGAACAGAAAAACTTCGTTGGTCAGGAACACCT GGTTCAC
CTGGTTAACCAGCTGCAGCAGGACATGAAAGAAGCGTCTCCGGGTCTGGAATCTAAA GAACAG
ACCGCGCACTACGTTACCGGTCGTGCGCTGCGTGGTTCTGACAAAGTTTTCGAAAAA TGGGGTA
AACTGGCGCCGGACGCGCCGTTCGACCTGTACGACGCGGAAATCAAAAACGTTCAGC GTCGTAA
CACCCGTCGTTTCGGTTCTCACGACCTGTTCGCGAAACTGGCGGAACCGGAATACCA GGCGCTG
TGGCGTGAAGACGCGTCTTTCCTGACCCGTTACGCGGTTTACAACTCTATCCTGCGT AAACTGAA
CCACGCGAAAATGTTCGCGACCTTCACCCTGCCGGACGCGACCGCGCACCCGATCTG GACCCGT
TTCGACAAACTGGGTGGTAACCTGCACCAGTACACCTTCCTGTTCAACGAATTCGGT GAACGTC
GTCACGCGATCCGTTTCCACAAACTGCTGAAAGTTGAAAACGGTGTTGCGCGTGAAG TTGACGA
CGTTACCGTTCCGATCTCTATGTCTGAACAGCTGGACAACCTGCTGCCGCGTGACCC GAACGAA
CCGATCGCGCTGTACTTCCGTGACTACGGTGCGGAACAGCACTTCACCGGTGAATTC GGTGGTG
CGAAAATCCAGTGCCGTCGTGACCAGCTGGCGCACATGCACCGTCGTCGTGGTGCGC GTGACGT
TTACCTGAACGTTTCTGTTCGTGTTCAGTCTCAGTCTGAAGCGCGTGGTGAACGTCG TCCGCCGT
ACGCGGCGGTTTTCCGTCTGGTTGGTGACAACCACCGTGCGTTCGTTCACTTCGACA AACTGTCT
GACTACCTGGCGGAACACCCGGACGACGGTAAACTGGGTTCTGAAGGTCTGCTGTCT GGTCTGC
GTGTTATGTCTGTTGACCTGGGTCTGCGTACCTCTGCGTCTATCTCTGTTTTCCGTG TTGCGCGTA
AAGACGAACTGAAACCGAACTCTAAAGGTCGTGTTCCGTTCTTCTTCCCGATCAAAG GTAACGA
CAACCTGGTTGCGGTTCACGAACGTTCTCAGCTGCTGAAACTGCCGGGTGAAACCGA ATCTAAA
GACCTGCGTGCGATCCGTGAAGAACGTCAGCGTACCCTGCGTCAGCTGCGTACCCAG CTGGCGT
ACCTGCGTCTGCTGGTTCGTTGCGGTTCTGAAGACGTTGGTCGTCGTGAACGTTCTT GGGCGAAA
CTGATCGAACAGCCGGTTGACGCGGCGAACCACATGACCCCGGACTGGCGTGAAGCG TTCGAA
AACGAACTGCAGAAACTGAAATCTCTGCACGGTATCTGCTCTGACAAAGAATGGATG GACGCG
GTTTACGAATCTGTTCGTCGTGTTTGGCGTCACATGGGTAAACAGGTTCGTGACTGG CGTAAAG
ACGTTCGTTCTGGTGAACGTCCGAAAATCCGTGGTTACGCGAAAGACGTTGTTGGTG GTAACTC
TATCGAACAGATCGAATACCTGGAACGTCAGTACAAATTCCTGAAATCTTGGTCTTT CTTCGGTA
AAGTTTCTGGTCAGGTTATCCGTGCGGAAAAAGGTTCTCGTTTCGCGATCACCCTGC GTGAACAC
ATCGACCACGCGAAAGAAGACCGTCTGAAAAAACTGGCGGACCGTATCATCATGGAA GCGCTG
GGTTACGTTTACGCGCTGGACGAACGTGGTAAAGGTAAATGGGTTGCGAAATACCCG CCGTGCC AGCTGATCCTGCTGGAAGAACTGTCTGAATACCAGTTCAACAACGACCGTCCGCCGTCTG AAAA
CAACCAGCTGATGCAGTGGTCTCACCGTGGTGTTTTCCAGGAACTGATCAACCAGGC GCAGGTT
CACGACCTGCTGGTTGGTACCATGTACGCGGCGTTCTCTTCTCGTTTCGACGCGCGT ACCGGTGC
GCCGGGTATCCGTTGCCGTCGTGTTCCGGCGCGTTGCACCCAGGAACACAACCCGGA ACCGTTC
CCGTGGTGGCTGAACAAATTCGTTGTTGAACACACCCTGGACGCGTGCCCGCTGCGT GCGGACG
ACCTGATCCCGACCGGTGAAGGTGAAATCTTCGTTTCTCCGTTCTCTGCGGAAGAAG GTGACTTC
CACCAGATCCACGCGGACCTGAACGCGGCGCAGAACCTGCAGCAGCGTCTGTGGTCT GACTTCG
ACATCTCTCAGATCCGTCTGCGTTGCGACTGGGGTGAAGTTGACGGTGAACTGGTTC TGATCCCG
CGTCTGACCGGTAAACGTACCGCGGACTCTTACTCTAACAAAGTTTTCTACACCAAC ACCGGTGT
TACCTACTACGAACGTGAACGTGGTAAAAAACGTCGTAAAGTTTTCGCGCAGGAAAA ACTGTCT
GAAGAAGAAGCGGAACTGCTGGTTGAAGCGGACGAAGCGCGTGAAAAATCTGTTGTT CTGATG
CGTGACCCGTCTGGTATCATCAACCGTGGTAACTGGACCCGTCAGAAAGAATTCTGG TCTATGG
TTAACCAGCGTATCGAAGGTTACCTGGTTAAACAGATCCGTTCTCGTGTTCCGCTGC AGGACTCT
GCGTGCGAAAACACCGGTGACATCTAAGAAATCATCCTTAGCGAAAGCTAAGGATTT TTTTTAT
CTGAAATGTAGGGAGACCCTCAGGTTAAATATTCACTCAGGAAGTTATTACTCAGGA AGCAAAG
AGGATTACA
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTGCCG TCACT
Q GCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATTAAAAGCATTC TGTAA
no CAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAATCACGGCAGA AAA
N GTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATTTTTATCCATA AGATT
O: AGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCATACCCGTTTTT TTGGGC
74 TAGCAGTAATACGACTCACTATAGGGGTCTCATCTCGTGTGAGATAGGCGGAGATACGAA CTTT
AAGAGGAGGATATACCATGCACCATCATCATCACCATGCGACCCGTTCTTTCATCCT GAAAATC
GAACCGAACGAAGAAGTTAAAAAAGGTCTGTGGAAAACCCACGAAGTTCTGAACCAC GGTATC
GCGTACTACATGAACATCCTGAAACTGATCCGTCAGGAAGCGATCTACGAACACCAC GAACAG
GACCCGAAAAACCCGAAAAAAGTTTCTAAAGCGGAAATCCAGGCGGAACTGTGGGAC TTCGTT
CTGAAAATGCAGAAATGCAACTCTTTCACCCACGAAGTTGACAAAGACGTTGTTTTC AACATCC
TGCGTGAACTGTACGAAGAACTGGTTCCGTCTTCTGTTGAAAAAAAAGGTGAAGCGA ACCAGCT
GTCTAACAAATTCCTGTACCCGCTGGTTGACCCGAACTCTCAGTCTGGTAAAGGTAC CGCGTCTT
CTGGTCGTAAACCGCGTTGGTACAACCTGAAAATCGCGGGTGACCCGTCTTGGGAAG AAGAAA
AAAAAAAATGGGAAGAAGACAAAAAAAAAGACCCGCTGGCGAAAATCCTGGGTAAAC TGGCG
GAATACGGTCTGATCCCGCTGTTCATCCCGTTCACCGACTCTAACGAACCGATCGTT AAAGAAA
TCAAATGGATGGAAAAATCTCGTAACCAGTCTGTTCGTCGTCTGGACAAAGACATGT TCATCCA
GGCGCTGGAACGTTTCCTGTCTTGGGAATCTTGGAACCTGAAAGTTAAAGAAGAATA CGAAAAA
GTTGAAAAAGAACACAAAACCCTGGAAGAACGTATCAAAGAAGACATCCAGGCGTTC AAATCT
CTGGAACAGTACGAAAAAGAACGTCAGGAACAGCTGCTGCGTGACACCCTGAACACC AACGAA
TACCGTCTGTCTAAACGTGGTCTGCGTGGTTGGCGTGAAATCATCCAGAAATGGCTG AAAATGG
ACGAAAACGAACCGTCTGAAAAATACCTGGAAGTTTTCAAAGACTACCAGCGTAAAC ACCCGC
GTGAAGCGGGTGACTACTCTGTTTACGAATTCCTGTCTAAAAAAGAAAACCACTTCA TCTGGCG
TAACCACCCGGAATACCCGTACCTGTACGCGACCTTCTGCGAAATCGACAAAAAAAA AAAAGA
CGCGAAACAGCAGGCGACCTTCACCCTGGCGGACCCGATCAACCACCCGCTGTGGGT TCGTTTC
GAAGAACGTTCTGGTTCTAACCTGAACAAATACCGTATCCTGACCGAACAGCTGCAC ACCGAAA AACTGAAAAAAAAACTGACCGTTCAGCTGGACCGTCTGATCTACCCGACCGAATCTGGTG GTTG
GGAAGAAAAAGGTAAAGTTGACATCGTTCTGCTGCCGTCTCGTCAGTTCTACAACCA GATCTTC
CTGGACATCGAAGAAAAAGGTAAACACGCGTTCACCTACAAAGACGAATCTATCAAA TTCCCGC
TGAAAGGTACCCTGGGTGGTGCGCGTGTTCAGTTCGACCGTGACCACCTGCGTCGTT ACCCGCA
CAAAGTTGAATCTGGTAACGTTGGTCGTATCTACTTCAACATGACCGTTAACATCGA ACCGACC
GAATCTCCGGTTTCTAAATCTCTGAAAATCCACCGTGACGACTTCCCGAAATTCGTT AACTTCAA
ACCGAAAGAACTGACCGAATGGATCAAAGACTCTAAAGGTAAAAAACTGAAATCTGG TATCGA
ATCTCTGGAAATCGGTCTGCGTGTTATGTCTATCGACCTGGGTCAGCGTCAGGCGGC GGCGGCG
TCTATCTTCGAAGTTGTTGACCAGAAACCGGACATCGAAGGTAAACTGTTCTTCCCG ATCAAAG
GTACCGAACTGTACGCGGTTCACCGTGCGTCTTTCAACATCAAACTGCCGGGTGAAA CCCTGGT
TAAATCTCGTGAAGTTCTGCGTAAAGCGCGTGAAGACAACCTGAAACTGATGAACCA GAAACTG
AACTTCCTGCGTAACGTTCTGCACTTCCAGCAGTTCGAAGACATCACCGAACGTGAA AAACGTG
TTACCAAATGGATCTCTCGTCAGGAAAACTCTGACGTTCCGCTGGTTTACCAGGACG AACTGAT
CCAGATCCGTGAACTGATGTACAAACCGTACAAAGACTGGGTTGCGTTCCTGAAACA GCTGCAC
AAACGTCTGGAAGTTGAAATCGGTAAAGAAGTTAAACACTGGCGTAAATCTCTGTCT GACGGTC
GTAAAGGTCTGTACGGTATCTCTCTGAAAAACATCGACGAAATCGACCGTACCCGTA AATTCCT
GCTGCGTTGGTCTCTGCGTCCGACCGAACCGGGTGAAGTTCGTCGTCTGGAACCGGG TCAGCGT
TTCGCGATCGACCAGCTGAACCACCTGAACGCGCTGAAAGAAGACCGTCTGAAAAAA ATGGCG
AACACCATCATCATGCACGCGCTGGGTTACTGCTACGACGTTCGTAAAAAAAAATGG CAGGCGA
AAAACCCGGCGTGCCAGATCATCCTGTTCGAAGACCTGTCTAACTACAACCCGTACG AAGAACG
TTCTCGTTTCGAAAACTCTAAACTGATGAAATGGTCTCGTCGTGAAATCCCGCGTCA GGTTGCGC
TGCAGGGTGAAATCTACGGTCTGCAGGTTGGTGAAGTTGGTGCGCAGTTCTCTTCTC GTTTCCAC
GCGAAAACCGGTTCTCCGGGTATCCGTTGCTCTGTTGTTACCAAAGAAAAACTGCAG GACAACC
GTTTCTTCAAAAACCTGCAGCGTGAAGGTCGTCTGACCCTGGACAAAATCGCGGTTC TGAAAGA
AGGTGACCTGTACCCGGACAAAGGTGGTGAAAAATTCATCTCTCTGTCTAAAGACCG TAAACTG
GTTACCACCCACGCGGACATCAACGCGGCGCAGAACCTGCAGAAACGTTTCTGGACC CGTACCC
ACGGTTTCTACAAAGTTTACTGCAAAGCGTACCAGGTTGACGGTCAGACCGTTTACA TCCCGGA
ATCTAAAGACCAGAAACAGAAAATCATCGAAGAATTCGGTGAAGGTTACTTCATCCT GAAAGA
CGGTGTTTACGAATGGGGTAACGCGGGTAAACTGAAAATCAAAAAAGGTTCTTCTAA ACAGTCT
TCTTCTGAACTGGTTGACTCTGACATCCTGAAAGACTCTTTCGACCTGGCGTCTGAA CTGAAAGG
TGAAAAACTGATGCTGTACCGTGACCCGTCTGGTAACGTTTTCCCGTCTGACAAATG GATGGCG
GCGGGTGTTTTCTTCGGTAAACTGGAACGTATCCTGATCTCTAAACTGACCAACCAG TACTCTAT
CTCTACCATCGAAGACGACTCTTCTAAACAGTCTATGTAAGAAATCATCCTTAGCGA AAGCTAA
CAGGAAGCAAAGAGGATTACA
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTGCCG TCACT
Q GCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATTAAAAGCATTC TGTAA
no CAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAATCACGGCAGA AAA
N GTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATTTTTATCCATA AGATT
O: AGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCATACCCGTTTTT TTGGGC
75 TAGCAGTAATACGACTCACTATAGGGGTCTCATCTCGTGTGAGATAGGCGGAGATACGAA CTTT
AAGAGGAGGATATACCATGCACCATCATCATCACCATCCGACCCGTACCATCAACCT GAAACTG GTTCTGGGTAAAAACCCGGAAAACGCGACCCTGCGTCGTGCGCTGTTCTCTACCCACCGT CTGG
TTAACCAGGCGACCAAACGTATCGAAGAATTCCTGCTGCTGTGCCGTGGTGAAGCGT ACCGTAC
CGTTGACAACGAAGGTAAAGAAGCGGAAATCCCGCGTCACGCGGTTCAGGAAGAAGC GCTGGC
GTTCGCGAAAGCGGCGCAGCGTCACAACGGTTGCATCTCTACCTACGAAGACCAGGA AATCCTG
GACGTTCTGCGTCAGCTGTACGAACGTCTGGTTCCGTCTGTTAACGAAAACAACGAA GCGGGTG
ACGCGCAGGCGGCGAACGCGTGGGTTTCTCCGCTGATGTCTGCGGAATCTGAAGGTG GTCTGTC
TGTTTACGACAAAGTTCTGGACCCGCCGCCGGTTTGGATGAAACTGAAAGAAGAAAA AGCGCC
GGGTTGGGAAGCGGCGTCTCAGATCTGGATCCAGTCTGACGAAGGTCAGTCTCTGCT GAACAAA
CCGGGTTCTCCGCCGCGTTGGATCCGTAAACTGCGTTCTGGTCAGCCGTGGCAGGAC GACTTCGT
TTCTGACCAGAAAAAAAAACAGGACGAACTGACCAAAGGTAACGCGCCGCTGATCAA ACAGCT
GAAAGAAATGGGTCTGCTGCCGCTGGTTAACCCGTTCTTCCGTCACCTGCTGGACCC GGAAGGT
AAAGGTGTTTCTCCGTGGGACCGTCTGGCGGTTCGTGCGGCGGTTGCGCACTTCATC TCTTGGGA
ATCTTGGAACCACCGTACCCGTGCGGAATACAACTCTCTGAAACTGCGTCGTGACGA ATTCGAA
GCGGCGTCTGACGAATTCAAAGACGACTTCACCCTGCTGCGTCAGTACGAAGCGAAA CGTCACT
CTACCCTGAAATCTATCGCGCTGGCGGACGACTCTAACCCGTACCGTATCGGTGTTC GTTCTCTG
CGTGCGTGGAACCGTGTTCGTGAAGAATGGATCGACAAAGGTGCGACCGAAGAACAG CGTGTT
ACCATCCTGTCTAAACTGCAGACCCAGCTGCGTGGTAAATTCGGTGACCCGGACCTG TTCAACT
GGCTGGCGCAGGACCGTCACGTTCACCTGTGGTCTCCGCGTGACTCTGTTACCCCGC TGGTTCGT
ATCAACGCGGTTGACAAAGTTCTGCGTCGTCGTAAACCGTACGCGCTGATGACCTTC GCGCACC
CGCGTTTCCACCCGCGTTGGATCCTGTACGAAGCGCCGGGTGGTTCTAACCTGCGTC AGTACGC
GCTGGACTGCACCGAAAACGCGCTGCACATCACCCTGCCGCTGCTGGTTGACGACGC GCACGGT
ACCTGGATCGAAAAAAAAATCCGTGTTCCGCTGGCGCCGTCTGGTCAGATCCAGGAC CTGACCC
TGGAAAAACTGGAAAAAAAAAAAAACCGTCTGTACTACCGTTCTGGTTTCCAGCAGT TCGCGGG
TCTGGCGGGTGGTGCGGAAGTTCTGTTCCACCGTCCGTACATGGAACACGACGAACG TTCTGAA
GAATCTCTGCTGGAACGTCCGGGTGCGGTTTGGTTCAAACTGACCCTGGACGTTGCG ACCCAGG
CGCCGCCGAACTGGCTGGACGGTAAAGGTCGTGTTCGTACCCCGCCGGAAGTTCACC ACTTCAA
AACCGCGCTGTCTAACAAATCTAAACACACCCGTACCCTGCAGCCGGGTCTGCGTGT TCTGTCTG
TTGACCTGGGTATGCGTACCTTCGCGTCTTGCTCTGTTTTCGAACTGATCGAAGGTA AACCGGAA
ACCGGTCGTGCGTTCCCGGTTGCGGACGAACGTTCTATGGACTCTCCGAACAAACTG TGGGCGA
AACACGAACGTTCTTTCAAACTGACCCTGCCGGGTGAAACCCCGTCTCGTAAAGAAG AAGAAGA
ACGTTCTATCGCGCGTGCGGAAATCTACGCGCTGAAACGTGACATCCAGCGTCTGAA ATCTCTG
CTGCGTCTGGGTGAAGAAGACAACGACAACCGTCGTGACGCGCTGCTGGAACAGTTC TTCAAAG
GTTGGGGTGAAGAAGACGTTGTTCCGGGTCAGGCGTTCCCGCGTTCTCTGTTCCAGG GTCTGGGT
GCGGCGCCGTTCCGTTCTACCCCGGAACTGTGGCGTCAGCACTGCCAGACCTACTAC GACAAAG
CGGAAGCGTGCCTGGCGAAACACATCTCTGACTGGCGTAAACGTACCCGTCCGCGTC CGACCTC
TCGTGAAATGTGGTACAAAACCCGTTCTTACCACGGTGGTAAATCTATCTGGATGCT GGAATAC
CTGGACGCGGTTCGTAAACTGCTGCTGTCTTGGTCTCTGCGTGGTCGTACCTACGGT GCGATCAA
CCGTCAGGACACCGCGCGTTTCGGTTCTCTGGCGTCTCGTCTGCTGCACCACATCAA CTCTCTGA
AAGAAGACCGTATCAAAACCGGTGCGGACTCTATCGTTCAGGCGGCGCGTGGTTACA TCCCGCT
GCCGCACGGTAAAGGTTGGGAACAGCGTTACGAACCGTGCCAGCTGATCCTGTTCGA AGACCTG
GCGCGTTACCGTTTCCGTGTTGACCGTCCGCGTCGTGAAAACTCTCAGCTGATGCAG TGGAACC
ACCGTGCGATCGTTGCGGAAACCACCATGCAGGCGGAACTGTACGGTCAGATCGTTG AAAACAC CGCGGCGGGTTTCTCTTCTCGTTTCCACGCGGCGACCGGTGCGCCGGGTGTTCGTTGCCG TTTCC
TGCTGGAACGTGACTTCGACAACGACCTGCCGAAACCGTACCTGCTGCGTGAACTGT CTTGGAT
GCTGGGTAACACCAAAGTTGAATCTGAAGAAGAAAAACTGCGTCTGCTGTCTGAAAA AATCCGT
CCGGGTTCTCTGGTTCCGTGGGACGGTGGTGAACAGTTCGCGACCCTGCACCCGAAA CGTCAGA
CCCTGTGCGTTATCCACGCGGACATGAACGCGGCGCAGAACCTGCAGCGTCGTTTCT TCGGTCG
TTGCGGTGAAGCGTTCCGTCTGGTTTGCCAGCCGCACGGTGACGACGTTCTGCGTCT GGCGTCTA
CCCCGGGTGCGCGTCTGCTGGGTGCGCTGCAGCAGCTGGAAAACGGTCAGGGTGCGT TCGAACT
GGTTCGTGACATGGGTTCTACCTCTCAGATGAACCGTTTCGTTATGAAATCTCTGGG TAAAAAAA
AAATCAAACCGCTGCAGGACAACAACGGTGACGACGAACTGGAAGACGTTCTGTCTG TTCTGCC
GGAAGAAGACGACACCGGTCGTATCACCGTTTTCCGTGACTCTTCTGGTATCTTCTT CCCGTGCA
ACGTTTGGATCCCGGCGAAACAGTTCTGGCCGGCGGTTCGTGCGATGATCTGGAAAG TTATGGC
GTCTCACTCTCTGGGTTAAGAAATCATCCTTAGCGAAAGCTAAGGATTTTTTTTATC TGAAATGT
AGGGAGACCCTCAGGTTAAATATTCACTCAGGAAGTTATTACTCAGGAAGCAAAGAG GATTACA
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTGCCG TCACT
Q GCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATTAAAAGCATTC TGTAA
no CAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAATCACGGCAGA AAA
N GTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATTTTTATCCATA AGATT
O: AGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCATACCCGTTTTT TTGGGC
76 TAGCAGTAATACGACTCACTATAGGGGTCTCATCTCGTGTGAGATAGGCGGAGATACGAA CTTT
AAGAGGAGGATATACCATGCACCATCATCATCACCATACCAAACTGCGTCACCGTCA GAAAAA
ACTGACCCACGACTGGGCGGGTTCTAAAAAACGTGAAGTTCTGGGTTCTAACGGTAA ACTGCAG
AACCCGCTGCTGATGCCGGTTAAAAAAGGTCAGGTTACCGAATTCCGTAAAGCGTTC TCTGCGT
ACGCGCGTGCGACCAAAGGTGAAATGACCGACGGTCGTAAAAACATGTTCACCCACT CTTTCGA
ACCGTTCAAAACCAAACCGTCTCTGCACCAGTGCGAACTGGCGGACAAAGCGTACCA GTCTCTG
CACTCTTACCTGCCGGGTTCTCTGGCGCACTTCCTGCTGTCTGCGCACGCGCTGGGT TTCCGTAT
CTTCTCTAAATCTGGTGAAGCGACCGCGTTCCAGGCGTCTTCTAAAATCGAAGCGTA CGAATCT
AAACTGGCGTCTGAACTGGCGTGCGTTGACCTGTCTATCCAGAACCTGACCATCTCT ACCCTGTT
CAACGCGCTGACCACCTCTGTTCGTGGTAAAGGTGAAGAAACCTCTGCGGACCCGCT GATCGCG
CGTTTCTACACCCTGCTGACCGGTAAACCGCTGTCTCGTGACACCCAGGGTCCGGAA CGTGACC
TGGCGGAAGTTATCTCTCGTAAAATCGCGTCTTCTTTCGGTACCTGGAAAGAAATGA CCGCGAA
CCCGCTGCAGTCTCTGCAGTTCTTCGAAGAAGAACTGCACGCGCTGGACGCGAACGT TTCTCTGT
CTCCGGCGTTCGACGTTCTGATCAAAATGAACGACCTGCAGGGTGACCTGAAAAACC GTACCAT
CGTTTTCGACCCGGACGCGCCGGTTTTCGAATACAACGCGGAAGACCCGGCGGACAT CATCATC
AAACTGACCGCGCGTTACGCGAAAGAAGCGGTTATCAAAAACCAGAACGTTGGTAAC TACGTT
AAAAACGCGATCACCACCACCAACGCGAACGGTCTGGGTTGGCTGCTGAACAAAGGT CTGTCTC
TGCTGCCGGTTTCTACCGACGACGAACTGCTGGAATTCATCGGTGTTGAACGTTCTC ACCCGTCT
TGCCACGCGCTGATCGAACTGATCGCGCAGCTGGAAGCGCCGGAACTGTTCGAAAAA AACGTTT
TCTCTGACACCCGTTCTGAAGTTCAGGGTATGATCGACTCTGCGGTTTCTAACCACA TCGCGCGT
CTGTCTTCTTCTCGTAACTCTCTGTCTATGGACTCTGAAGAACTGGAACGTCTGATC AAATCTTTC
CAGATCCACACCCCGCACTGCTCTCTGTTCATCGGTGCGCAGTCTCTGTCTCAGCAG CTGGAATC
TCTGCCGGAAGCGCTGCAGTCTGGTGTTAACTCTGCGGACATCCTGCTGGGTTCTAC CCAGTACA
TGCTGACCAACTCTCTGGTTGAAGAATCTATCGCGACCTACCAGCGTACCCTGAACC GTATCAA CTACCTGTCTGGTGTTGCGGGTCAGATCAACGGTGCGATCAAACGTAAAGCGATCGACGG TGAA
AAAATCCACCTGCCGGCGGCGTGGTCTGAACTGATCTCTCTGCCGTTCATCGGTCAG CCGGTTAT
CGACGTTGAATCTGACCTGGCGCACCTGAAAAACCAGTACCAGACCCTGTCTAACGA ATTCGAC
ACCCTGATCTCTGCGCTGCAGAAAAACTTCGACCTGAACTTCAACAAAGCGCTGCTG AACCGTA
CCCAGCACTTCGAAGCGATGTGCCGTTCTACCAAAAAAAACGCGCTGTCTAAACCGG AAATCGT
TTCTTACCGTGACCTGCTGGCGCGTCTGACCTCTTGCCTGTACCGTGGTTCTCTGGT TCTGCGTCG
TGCGGGTATCGAAGTTCTGAAAAAACACAAAATCTTCGAATCTAACTCTGAACTGCG TGAACAC
GTTCACGAACGTAAACACTTCGTTTTCGTTTCTCCGCTGGACCGTAAAGCGAAAAAA CTGCTGC
GTCTGACCGACTCTCGTCCGGACCTGCTGCACGTTATCGACGAAATCCTGCAGCACG ACAACCT
GGAAAACAAAGACCGTGAATCTCTGTGGCTGGTTCGTTCTGGTTACCTGCTGGCGGG TCTGCCG
GACCAGCTGTCTTCTTCTTTCATCAACCTGCCGATCATCACCCAGAAAGGTGACCGT CGTCTGAT
CGACCTGATCCAGTACGACCAGATCAACCGTGACGCGTTCGTTATGCTGGTTACCTC TGCGTTCA
AATCTAACCTGTCTGGTCTGCAGTACCGTGCGAACAAACAGTCTTTCGTTGTTACCC GTACCCTG
TCTCCGTACCTGGGTTCTAAACTGGTTTACGTTCCGAAAGACAAAGACTGGCTGGTT CCGTCTCA
GATGTTCGAAGGTCGTTTCGCGGACATCCTGCAGTCTGACTACATGGTTTGGAAAGA CGCGGGT
CGTCTGTGCGTTATCGACACCGCGAAACACCTGTCTAACATCAAAAAATCTGTTTTC TCTTCTGA
AGAAGTTCTGGCGTTCCTGCGTGAACTGCCGCACCGTACCTTCATCCAGACCGAAGT TCGTGGTC
TGGGTGTTAACGTTGACGGTATCGCGTTCAACAACGGTGACATCCCGTCTCTGAAAA CCTTCTCT
AACTGCGTTCAGGTTAAAGTTTCTCGTACCAACACCTCTCTGGTTCAGACCCTGAAC CGTTGGTT
CGAAGGTGGTAAAGTTTCTCCGCCGTCTATCCAGTTCGAACGTGCGTACTACAAAAA AGACGAC
CAGATCCACGAAGACGCGGCGAAACGTAAAATCCGTTTCCAGATGCCGGCGACCGAA CTGGTTC
ACGCGTCTGACGACGCGGGTTGGACCCCGTCTTACCTGCTGGGTATCGACCCGGGTG AATACGG
TATGGGTCTGTCTCTGGTTTCTATCAACAACGGTGAAGTTCTGGACTCTGGTTTCAT CCACATCA
ACTCTCTGATCAACTTCGCGTCTAAAAAATCTAACCACCAGACCAAAGTTGTTCCGC GTCAGCA
GTACAAATCTCCGTACGCGAACTACCTGGAACAGTCTAAAGACTCTGCGGCGGGTGA CATCGCG
CACATCCTGGACCGTCTGATCTACAAACTGAACGCGCTGCCGGTTTTCGAAGCGCTG TCTGGTA
ACTCTCAGTCTGCGGCGGACCAGGTTTGGACCAAAGTTCTGTCTTTCTACACCTGGG GTGACAAC
GACGCGCAGAACTCTATCCGTAAACAGCACTGGTTCGGTGCGTCTCACTGGGACATC AAAGGTA
TGCTGCGTCAGCCGCCGACCGAAAAAAAACCGAAACCGTACATCGCGTTCCCGGGTT CTCAGGT
TTCTTCTTACGGTAACTCTCAGCGTTGCTCTTGCTGCGGTCGTAACCCGATCGAACA GCTGCGTG
AAATGGCGAAAGACACCTCTATCAAAGAACTGAAAATCCGTAACTCTGAAATCCAGC TGTTCGA
CGGTACCATCAAACTGTTCAACCCGGACCCGTCTACCGTTATCGAACGTCGTCGTCA CAACCTG
GGTCCGTCTCGTATCCCGGTTGCGGACCGTACCTTCAAAAACATCTCTCCGTCTTCT CTGGAATT
CAAAGAACTGATCACCATCGTTTCTCGTTCTATCCGTCACTCTCCGGAATTCATCGC GAAAAAAC
GTGGTATCGGTTCTGAATACTTCTGCGCGTACTCTGACTGCAACTCTTCTCTGAACT CTGAAGCG
AACGCGGCGGCGAACGTTGCGCAGAAATTCCAGAAACAGCTGTTCTTCGAACTGTAA GAAATCA
TCCTTAGCGAAAGCTAAGGATTTTTTTTATCTGAAATGTAGGGAGACCCTCAGGTTA AATATTCA
CTCAGGAAGTTATTACTCAGGAAGCAAAGAGGATTACA
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTGCCG TCACT
Q GCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATTAAAAGCATTC TGTAA
no CAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAATCACGGCAGA AAA
N GTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATTTTTATCCATA AGATT O: AGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCATACCCGTTTTT TTGGGC
77 TAGCAGTAATACGACTCACTATAGGGGTCTCATCTCGTGTGAGATAGGCGGAGATACGAA CTTT
AAGAGGAGGATATACCATGCACCATCATCATCACCATAAACGTATCCTGAACTCTCT GAAAGTT
GCGGCGCTGCGTCTGCTGTTCCGTGGTAAAGGTTCTGAACTGGTTAAAACCGTTAAA TACCCGCT
GGTTTCTCCGGTTCAGGGTGCGGTTGAAGAACTGGCGGAAGCGATCCGTCACGACAA CCTGCAC
CTGTTCGGTCAGAAAGAAATCGTTGACCTGATGGAAAAAGACGAAGGTACCCAGGTT TACTCTG
TTGTTGACTTCTGGCTGGACACCCTGCGTCTGGGTATGTTCTTCTCTCCGTCTGCGA ACGCGCTG
AAAATCACCCTGGGTAAATTCAACTCTGACCAGGTTTCTCCGTTCCGTAAAGTTCTG GAACAGTC
TCCGTTCTTCCTGGCGGGTCGTCTGAAAGTTGAACCGGCGGAACGTATCCTGTCTGT TGAAATCC
GTAAAATCGGTAAACGTGAAAACCGTGTTGAAAACTACGCGGCGGACGTTGAAACCT GCTTCAT
CGGTCAGCTGTCTTCTGACGAAAAACAGTCTATCCAGAAACTGGCGAACGACATCTG GGACTCT
AAAGACCACGAAGAACAGCGTATGCTGAAAGCGGACTTCTTCGCGATCCCGCTGATC AAAGAC
CCGAAAGCGGTTACCGAAGAAGACCCGGAAAACGAAACCGCGGGTAAACAGAAACCG CTGGA
ACTGTGCGTTTGCCTGGTTCCGGAACTGTACACCCGTGGTTTCGGTTCTATCGCGGA CTTCCTGG
TTCAGCGTCTGACCCTGCTGCGTGACAAAATGTCTACCGACACCGCGGAAGACTGCC TGGAATA
CGTTGGTATCGAAGAAGAAAAAGGTAACGGTATGAACTCTCTGCTGGGTACCTTCCT GAAAAAC
CTGCAGGGTGACGGTTTCGAACAGATCTTCCAGTTCATGCTGGGTTCTTACGTTGGT TGGCAGGG
TAAAGAAGACGTTCTGCGTGAACGTCTGGACCTGCTGGCGGAAAAAGTTAAACGTCT GCCGAAA
CCGAAATTCGCGGGTGAATGGTCTGGTCACCGTATGTTCCTGCACGGTCAGCTGAAA TCTTGGTC
TTCTAACTTCTTCCGTCTGTTCAACGAAACCCGTGAACTGCTGGAATCTATCAAATC TGACATCC
AGCACGCGACCATGCTGATCTCTTACGTTGAAGAAAAAGGTGGTTACCACCCGCAGC TGCTGTC
TCAGTACCGTAAACTGATGGAACAGCTGCCGGCGCTGCGTACCAAAGTTCTGGACCC GGAAATC
GAAATGACCCACATGTCTGAAGCGGTTCGTTCTTACATCATGATCCACAAATCTGTT GCGGGTTT
CCTGCCGGACCTGCTGGAATCTCTGGACCGTGACAAAGACCGTGAATTCCTGCTGTC TATCTTCC
CGCGTATCCCGAAAATCGACAAAAAAACCAAAGAAATCGTTGCGTGGGAACTGCCGG GTGAAC
CGGAAGAAGGTTACCTGTTCACCGCGAACAACCTGTTCCGTAACTTCCTGGAAAACC CGAAACA
CGTTCCGCGTTTCATGGCGGAACGTATCCCGGAAGACTGGACCCGTCTGCGTTCTGC GCCGGTTT
GGTTCGACGGTATGGTTAAACAGTGGCAGAAAGTTGTTAACCAGCTGGTTGAATCTC CGGGTGC
GCTGTACCAGTTCAACGAATCTTTCCTGCGTCAGCGTCTGCAGGCGATGCTGACCGT TTACAAAC
GTGACCTGCAGACCGAAAAATTCCTGAAACTGCTGGCGGACGTTTGCCGTCCGCTGG TTGACTT
CTTCGGTCTGGGTGGTAACGACATCATCTTCAAATCTTGCCAGGACCCGCGTAAACA GTGGCAG
ACCGTTATCCCGCTGTCTGTTCCGGCGGACGTTTACACCGCGTGCGAAGGTCTGGCG ATCCGTCT
GCGTGAAACCCTGGGTTTCGAATGGAAAAACCTGAAAGGTCACGAACGTGAAGACTT CCTGCGT
CTGCACCAGCTGCTGGGTAACCTGCTGTTCTGGATCCGTGACGCGAAACTGGTTGTT AAACTGG
AAGACTGGATGAACAACCCGTGCGTTCAGGAATACGTTGAAGCGCGTAAAGCGATCG ACCTGC
CGCTGGAAATCTTCGGTTTCGAAGTTCCGATCTTCCTGAACGGTTACCTGTTCTCTG AACTGCGT
CAGCTGGAACTGCTGCTGCGTCGTAAATCTGTTATGACCTCTTACTCTGTTAAAACC ACCGGTTC
TCCGAACCGTCTGTTCCAGCTGGTTTACCTGCCGCTGAACCCGTCTGACCCGGAAAA AAAAAAC
TCTAACAACTTCCAGGAACGTCTGGACACCCCGACCGGTCTGTCTCGTCGTTTCCTG GACCTGAC
CCTGGACGCGTTCGCGGGTAAACTGCTGACCGACCCGGTTACCCAGGAACTGAAAAC CATGGCG
GGTTTCTACGACCACCTGTTCGGTTTCAAACTGCCGTGCAAACTGGCGGCGATGTCT AACCACCC
GGGTTCTTCTTCTAAAATGGTTGTTCTGGCGAAACCGAAAAAAGGTGTTGCGTCTAA CATCGGTT TCGAACCGATCCCGGACCCGGCGCACCCGGTTTTCCGTGTTCGTTCTTCTTGGCCGGAAC TGAAA
TACCTGGAAGGTCTGCTGTACCTGCCGGAAGACACCCCGCTGACCATCGAACTGGCG GAAACCT
CTGTTTCTTGCCAGTCTGTTTCTTCTGTTGCGTTCGACCTGAAAAACCTGACCACCA TCCTGGGTC
GTGTTGGTGAATTCCGTGTTACCGCGGACCAGCCGTTCAAACTGACCCCGATCATCC CGGAAAA
AGAAGAATCTTTCATCGGTAAAACCTACCTGGGTCTGGACGCGGGTGAACGTTCTGG TGTTGGT
TTCGCGATCGTTACCGTTGACGGTGACGGTTACGAAGTTCAGCGTCTGGGTGTTCAC GAAGACA
CCCAGCTGATGGCGCTGCAGCAGGTTGCGTCTAAATCTCTGAAAGAACCGGTTTTCC AGCCGCT
GCGTAAAGGTACCTTCCGTCAGCAGGAACGTATCCGTAAATCTCTGCGTGGTTGCTA CTGGAAC
TTCTACCACGCGCTGATGATCAAATACCGTGCGAAAGTTGTTCACGAAGAATCTGTT GGTTCTTC
TGGTCTGGTTGGTCAGTGGCTGCGTGCGTTCCAGAAAGACCTGAAAAAAGCGGACGT TCTGCCG
AAAAAAGGTGGTAAAAACGGTGTTGACAAAAAAAAACGTGAATCTTCTGCGCAGGAC ACCCTG
TGGGGTGGTGCGTTCTCTAAAAAAGAAGAACAGCAGATCGCGTTCGAAGTTCAGGCG GCGGGTT
CTTCTCAGTTCTGCCTGAAATGCGGTTGGTGGTTCCAGCTGGGTATGCGTGAAGTTA ACCGTGTT
CAGGAATCTGGTGTTGTTCTGGACTGGAACCGTTCTATCGTTACCTTCCTGATCGAA TCTTCTGG
TGAAAAAGTTTACGGTTTCTCTCCGCAGCAGCTGGAAAAAGGTTTCCGTCCGGACAT CGAAACC
TTCAAAAAAATGGTTCGTGACTTCATGCGTCCGCCGATGTTCGACCGTAAAGGTCGT CCGGCGG
CGGCGTACGAACGTTTCGTTCTGGGTCGTCGTCACCGTCGTTACCGTTTCGACAAAG TTTTCGAA
GAACGTTTCGGTCGTTCTGCGCTGTTCATCTGCCCGCGTGTTGGTTGCGGTAACTTC GACCACTC
TTCTGAACAGTCTGCGGTTGTTCTGGCGCTGATCGGTTACATCGCGGACAAAGAAGG TATGTCT
GGTAAAAAACTGGTTTACGTTCGTCTGGCGGAACTGATGGCGGAATGGAAACTGAAA AAACTG
GAACGTTCTCGTGTTGAAGAACAGTCTTCTGCGCAGTAAGAAATCATCCTTAGCGAA AGCTAAG
AGGAAGCAAAGAGGATTACA
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTGCCG TCACT
Q GCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATTAAAAGCATTC TGTAA
no CAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAATCACGGCAGA AAA
N GTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATTTTTATCCATA AGATT
O: AGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCATACCCGTTTTT TTGGGC
78 TAGCAGTAATACGACTCACTATAGGGGTCTCATCTCGTGTGAGATAGGCGGAGATACGAA CTTT
AAGAGGAGGATATACCATGCACCATCATCATCACCATGCGGAATCTAAACAGATGCA GTGCCGT
AAATGCGGTGCGTCTATGAAATACGAAGTTATCGGTCTGGGTAAAAAATCTTGCCGT TACATGT
GCCCGGACTGCGGTAACCACACCTCTGCGCGTAAAATCCAGAACAAAAAAAAACGTG ACAAAA
AATACGGTTCTGCGTCTAAAGCGCAGTCTCAGCGTATCGCGGTTGCGGGTGCGCTGT ACCCGGA
CAAAAAAGTTCAGACCATCAAAACCTACAAATACCCGGCGGACCTGAACGGTGAAGT TCACGA
CTCTGGTGTTGCGGAAAAAATCGCGCAGGCGATCCAGGAAGACGAAATCGGTCTGCT GGGTCCG
TCTTCTGAATACGCGTGCTGGATCGCGTCTCAGAAACAGTCTGAACCGTACTCTGTT GTTGACTT
CTGGTTCGACGCGGTTTGCGCGGGTGGTGTTTTCGCGTACTCTGGTGCGCGTCTGCT GTCTACCG
TTCTGCAGCTGTCTGGTGAAGAATCTGTTCTGCGTGCGGCGCTGGCGTCTTCTCCGT TCGTTGAC
GACATCAACCTGGCGCAGGCGGAAAAATTCCTGGCGGTTTCTCGTCGTACCGGTCAG GACAAAC
TGGGTAAACGTATCGGTGAATGCTTCGCGGAAGGTCGTCTGGAAGCGCTGGGTATCA AAGACCG
TATGCGTGAATTCGTTCAGGCGATCGACGTTGCGCAGACCGCGGGTCAGCGTTTCGC GGCGAAA
CTGAAAATCTTCGGTATCTCTCAGATGCCGGAAGCGAAACAGTGGAACAACGACTCT GGTCTGA CCGTTTGCATCCTGCCGGACTACTACGTTCCGGAAGAAAACCGTGCGGACCAGCTGGTTG TTCT
GCTGCGTCGTCTGCGTGAAATCGCGTACTGCATGGGTATCGAAGACGAAGCGGGTTT CGAACAC
CTGGGTATCGACCCGGGTGCGCTGTCTAACTTCTCTAACGGTAACCCGAAACGTGGT TTCCTGGG
TCGTCTGCTGAACAACGACATCATCGCGCTGGCGAACAACATGTCTGCGATGACCCC GTACTGG
GAAGGTCGTAAAGGTGAACTGATCGAACGTCTGGCGTGGCTGAAACACCGTGCGGAA GGTCTG
TACCTGAAAGAACCGCACTTCGGTAACTCTTGGGCGGACCACCGTTCTCGTATCTTC TCTCGTAT
CGCGGGTTGGCTGTCTGGTTGCGCGGGTAAACTGAAAATCGCGAAAGACCAGATCTC TGGTGTT
CGTACCGACCTGTTCCTGCTGAAACGTCTGCTGGACGCGGTTCCGCAGTCTGCGCCG TCTCCGGA
CTTCATCGCGTCTATCTCTGCGCTGGACCGTTTCCTGGAAGCGGCGGAATCTTCTCA GGACCCGG
CGGAACAGGTTCGTGCGCTGTACGCGTTCCACCTGAACGCGCCGGCGGTTCGTTCTA TCGCGAA
CAAAGCGGTTCAGCGTTCTGACTCTCAGGAATGGCTGATCAAAGAACTGGACGCGGT TGACCAC
CTGGAATTCAACAAAGCGTTCCCGTTCTTCTCTGACACCGGTAAAAAAAAAAAAAAA GGTGCGA
ACTCTAACGGTGCGCCGTCTGAAGAAGAATACACCGAAACCGAATCTATCCAGCAGC CGGAAG
ACGCGGAACAGGAAGTTAACGGTCAGGAAGGTAACGGTGCGTCTAAAAACCAGAAAA AATTCC
AGCGTATCCCGCGTTTCTTCGGTGAAGGTTCTCGTTCTGAATACCGTATCCTGACCG AAGCGCCG
CAGTACTTCGACATGTTCTGCAACAACATGCGTGCGATCTTCATGCAGCTGGAATCT CAGCCGC
GTAAAGCGCCGCGTGACTTCAAATGCTTCCTGCAGAACCGTCTGCAGAAACTGTACA AACAGAC
CTTCCTGAACGCGCGTTCTAACAAATGCCGTGCGCTGCTGGAATCTGTTCTGATCTC TTGGGGTG
AATTCTACACCTACGGTGCGAACGAAAAAAAATTCCGTCTGCGTCACGAAGCGTCTG AACGTTC
TTCTGACCCGGACTACGTTGTTCAGCAGGCGCTGGAAATCGCGCGTCGTCTGTTCCT GTTCGGTT
TCGAATGGCGTGACTGCTCTGCGGGTGAACGTGTTGACCTGGTTGAAATCCACAAAA AAGCGAT
CTCTTTCCTGCTGGCGATCACCCAGGCGGAAGTTTCTGTTGGTTCTTACAACTGGCT GGGTAACT
CTACCGTTTCTCGTTACCTGTCTGTTGCGGGTACCGACACCCTGTACGGTACCCAGC TGGAAGAA
TTCCTGAACGCGACCGTTCTGTCTCAGATGCGTGGTCTGGCGATCCGTCTGTCTTCT CAGGAACT
GAAAGACGGTTTCGACGTTCAGCTGGAATCTTCTTGCCAGGACAACCTGCAGCACCT GCTGGTT
TACCGTGCGTCTCGTGACCTGGCGGCGTGCAAACGTGCGACCTGCCCGGCGGAACTG GACCCGA
AAATCCTGGTTCTGCCGGTTGGTGCGTTCATCGCGTCTGTTATGAAAATGATCGAAC GTGGTGAC
GAACCGCTGGCGGGTGCGTACCTGCGTCACCGTCCGCACTCTTTCGGTTGGCAGATC CGTGTTCG
TGGTGTTGCGGAAGTTGGTATGGACCAGGGTACCGCGCTGGCGTTCCAGAAACCGAC CGAATCT
GAACCGTTCAAAATCAAACCGTTCTCTGCGCAGTACGGTCCGGTTCTGTGGCTGAAC TCTTCTTC
TTACTCTCAGTCTCAGTACCTGGACGGTTTCCTGTCTCAGCCGAAAAACTGGTCTAT GCGTGTTC
TGCCGCAGGCGGGTTCTGTTCGTGTTGAACAGCGTGTTGCGCTGATCTGGAACCTGC AGGCGGG
TAAAATGCGTCTGGAACGTTCTGGTGCGCGTGCGTTCTTCATGCCGGTTCCGTTCTC TTTCCGTCC
GTCTGGTTCTGGTGACGAAGCGGTTCTGGCGCCGAACCGTTACCTGGGTCTGTTCCC GCACTCTG
GTGGTATCGAATACGCGGTTGTTGACGTTCTGGACTCTGCGGGTTTCAAAATCCTGG AACGTGGT
ACCATCGCGGTTAACGGTTTCTCTCAGAAACGTGGTGAACGTCAGGAAGAAGCGCAC CGTGAAA
AACAGCGTCGTGGTATCTCTGACATCGGTCGTAAAAAACCGGTTCAGGCGGAAGTTG ACGCGGC
GAACGAACTGCACCGTAAATACACCGACGTTGCGACCCGTCTGGGTTGCCGTATCGT TGTTCAG
TGGGCGCCGCAGCCGAAACCGGGTACCGCGCCGACCGCGCAGACCGTTTACGCGCGT GCGGTTC
GTACCGAAGCGCCGCGTTCTGGTAACCAGGAAGACCACGCGCGTATGAAATCTTCTT GGGGTTA
CACCTGGGGTACCTACTGGGAAAAACGTAAACCGGAAGACATCCTGGGTATCTCTAC CCAGGTT
TACTGGACCGGTGGTATCGGTGAATCTTGCCCGGCGGTTGCGGTTGCGCTGCTGGGT CACATCC GTGCGACCTCTACCCAGACCGAATGGGAAAAAGAAGAAGTTGTTTTCGGTCGTCTGAAAA AATT CTTCCCGTCTTAAGAAATCATCCTTAGCGAAAGCTAAGGATTTTTTTTATCTGAAATGTA GGGAG ACCCTCAGGTTAAATATTCACTCAGGAAGTTATTACTCAGGAAGCAAAGAGGATTACA
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTGCCG TCACT
Q GCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATTAAAAGCATTC TGTAA
no CAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAATCACGGCAGA AAA
N GTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATTTTTATCCATA AGATT
O: AGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCATACCCGTTTTT TTGGGC
79 TAGCAGTAATACGACTCACTATAGGGGTCTCATCTCGTGTGAGATAGGCGGAGATACGAA CTTT
AAGAGGAGGATATACCATGCACCATCATCATCACCATGAAAAACGTATCAACAAAAT CCGTAA
AAAACTGTCTGCGGACAACGCGACCAAACCGGTTTCTCGTTCTGGTCCGATGAAAAC CCTGCTG
GTTCGTGTTATGACCGACGACCTGAAAAAACGTCTGGAAAAACGTCGTAAAAAACCG GAAGTT
ATGCCGCAGGTTATCTCTAACAACGCGGCGAACAACCTGCGTATGCTGCTGGACGAC TACACCA
AAATGAAAGAAGCGATCCTGCAGGTTTACTGGCAGGAATTCAAAGACGACCACGTTG GTCTGAT
GTGCAAATTCGCGCAGCCGGCGTCTAAAAAAATCGACCAGAACAAACTGAAACCGGA AATGGA
CGAAAAAGGTAACCTGACCACCGCGGGTTTCGCGTGCTCTCAGTGCGGTCAGCCGCT GTTCGTT
TACAAACTGGAACAGGTTTCTGAAAAAGGTAAAGCGTACACCAACTACTTCGGTCGT TGCAACG
TTGCGGAACACGAAAAACTGATCCTGCTGGCGCAGCTGAAACCGGAAAAAGACTCTG ACGAAG
CGGTTACCTACTCTCTGGGTAAATTCGGTCAGCGTGCGCTGGACTTCTACTCTATCC ACGTTACC
AAAGAATCTACCCACCCGGTTAAACCGCTGGCGCAGATCGCGGGTAACCGTTACGCG TCTGGTC
CGGTTGGTAAAGCGCTGTCTGACGCGTGCATGGGTACCATCGCGTCTTTCCTGTCTA AATACCAG
GACATCATCATCGAACACCAGAAAGTTGTTAAAGGTAACCAGAAACGTCTGGAATCT CTGCGTG
AACTGGCGGGTAAAGAAAACCTGGAATACCCGTCTGTTACCCTGCCGCCGCAGCCGC ACACCAA
AGAAGGTGTTGACGCGTACAACGAAGTTATCGCGCGTGTTCGTATGTGGGTTAACCT GAACCTG
TGGCAGAAACTGAAACTGTCTCGTGACGACGCGAAACCGCTGCTGCGTCTGAAAGGT TTCCCGT
CTTTCCCGGTTGTTGAACGTCGTGAAAACGAAGTTGACTGGTGGAACACCATCAACG AAGTTAA
AAAACTGATCGACGCGAAACGTGACATGGGTCGTGTTTTCTGGTCTGGTGTTACCGC GGAAAAA
CGTAACACCATCCTGGAAGGTTACAACTACCTGCCGAACGAAAACGACCACAAAAAA CGTGAA
GGTTCTCTGGAAAACCCGAAAAAACCGGCGAAACGTCAGTTCGGTGACCTGCTGCTG TACCTGG
AAAAAAAATACGCGGGTGACTGGGGTAAAGTTTTCGACGAAGCGTGGGAACGTATCG ACAAAA
AAATCGCGGGTCTGACCTCTCACATCGAACGTGAAGAAGCGCGTAACGCGGAAGACG CGCAGT
CTAAAGCGGTTCTGACCGACTGGCTGCGTGCGAAAGCGTCTTTCGTTCTGGAACGTC TGAAAGA
AATGGACGAAAAAGAATTCTACGCGTGCGAAATCCAGCTGCAGAAATGGTACGGTGA CCTGCG
TGGTAACCCGTTCGCGGTTGAAGCGGAAAACCGTGTTGTTGACATCTCTGGTTTCTC TATCGGTT
CTGACGGTCACTCTATCCAGTACCGTAACCTGCTGGCGTGGAAATACCTGGAAAACG GTAAACG
TGAATTCTACCTGCTGATGAACTACGGTAAAAAAGGTCGTATCCGTTTCACCGACGG TACCGAC
ATCAAAAAATCTGGTAAATGGCAGGGTCTGCTGTACGGTGGTGGTAAAGCGAAAGTT ATCGACC
TGACCTTCGACCCGGACGACGAACAGCTGATCATCCTGCCGCTGGCGTTCGGTACCC GTCAGGG
TCGTGAATTCATCTGGAACGACCTGCTGTCTCTGGAAACCGGTCTGATCAAACTGGC GAACGGT
CGTGTTATCGAAAAAACCATCTACAACAAAAAAATCGGTCGTGACGAACCGGCGCTG TTCGTTG
CGCTGACCTTCGAACGTCGTGAAGTTGTTGACCCGTCTAACATCAAACCGGTTAACC TGATCGGT
GTTGACCGTGGTGAAAACATCCCGGCGGTTATCGCGCTGACCGACCCGGAAGGTTGC CCGCTGC CGGAATTCAAAGACTCTTCTGGTGGTCCGACCGACATCCTGCGTATCGGTGAAGGTTACA AAGA
AAAACAGCGTGCGATCCAGGCGGCGAAAGAAGTTGAACAGCGTCGTGCGGGTGGTTA CTCTCG
TAAATTCGCGTCTAAATCTCGTAACCTGGCGGACGACATGGTTCGTAACTCTGCGCG TGACCTGT
TCTACCACGCGGTTACCCACGACGCGGTTCTGGTTTTCGAAAACCTGTCTCGTGGTT TCGGTCGT
CAGGGTAAACGTACCTTCATGACCGAACGTCAGTACACCAAAATGGAAGACTGGCTG ACCGCG
AAACTGGCGTACGAAGGTCTGACCTCTAAAACCTACCTGTCTAAAACCCTGGCGCAG TACACCT
CTAAAACCTGCTCTAACTGCGGTTTCACCATCACCACCGCGGACTACGACGGTATGC TGGTTCGT
CTGAAAAAAACCTCTGACGGTTGGGCGACCACCCTGAACAACAAAGAACTGAAAGCG GAAGGT
CAGATCACCTACTACAACCGTTACAAACGTCAGACCGTTGAAAAAGAACTGTCTGCG GAACTGG
ACCGTCTGTCTGAAGAATCTGGTAACAACGACATCTCTAAATGGACCAAAGGTCGTC GTGACGA
AGCGCTGTTCCTGCTGAAAAAACGTTTCTCTCACCGTCCGGTTCAGGAACAGTTCGT TTGCCTGG
ACTGCGGTCACGAAGTTCACGCGGACGAACAGGCGGCGCTGAACATCGCGCGTTCTT GGCTGTT
CCTGAACTCTAACTCTACCGAATTCAAATCTTACAAATCTGGTAAACAGCCGTTCGT TGGTGCGT
GGCAGGCGTTCTACAAACGTCGTCTGAAAGAAGTTTGGAAACCGAACGCGTAAGAAA TCATCCT
TAGCGAAAGCTAAGGATTTTTTTTATCTGAAATGTAGGGAGACCCTCAGGTTAAATA TTCACTCA
GGAAGTTATTACTCAGGAAGCAAAGAGGATTACA
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTGCCG TCACT
Q GCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATTAAAAGCATTC TGTAA
no CAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAATCACGGCAGA AAA
N GTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATTTTTATCCATA AGATT
O: AGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCATACCCGTTTTT TTGGGC 80 TAGCAGTAATACGACTCACTATAGGGGTCTCATCTCGTGTGAGATAGGCGGAGATACGAA CTTT
AAGAGGAGGATATACCATGCACCATCATCATCACCATAAACGTATCAACAAAATCCG TCGTCGT
CTGGTTAAAGACTCTAACACCAAAAAAGCGGGTAAAACCGGTCCGATGAAAACCCTG CTGGTTC
GTGTTATGACCCCGGACCTGCGTGAACGTCTGGAAAACCTGCGTAAAAAACCGGAAA ACATCCC
GCAGCCGATCTCTAACACCTCTCGTGCGAACCTGAACAAACTGCTGACCGACTACAC CGAAATG
AAAAAAGCGATCCTGCACGTTTACTGGGAAGAATTCCAGAAAGACCCGGTTGGTCTG ATGTCTC
GTGTTGCGCAGCCGGCGCCGAAAAACATCGACCAGCGTAAACTGATCCCGGTTAAAG ACGGTA
ACGAACGTCTGACCTCTTCTGGTTTCGCGTGCTCTCAGTGCTGCCAGCCGCTGTACG TTTACAAA
CTGGAACAGGTTAACGACAAAGGTAAACCGCACACCAACTACTTCGGTCGTTGCAAC GTTTCTG
AACACGAACGTCTGATCCTGCTGTCTCCGCACAAACCGGAAGCGAACGACGAACTGG TTACCTA
CTCTCTGGGTAAATTCGGTCAGCGTGCGCTGGACTTCTACTCTATCCACGTTACCCG TGAATCTA
ACCACCCGGTTAAACCGCTGGAACAGATCGGTGGTAACTCTTGCGCGTCTGGTCCGG TTGGTAA
AGCGCTGTCTGACGCGTGCATGGGTGCGGTTGCGTCTTTCCTGACCAAATACCAGGA CATCATC
CTGGAACACCAGAAAGTTATCAAAAAAAACGAAAAACGTCTGGCGAACCTGAAAGAC ATCGCG
TCTGCGAACGGTCTGGCGTTCCCGAAAATCACCCTGCCGCCGCAGCCGCACACCAAA GAAGGTA
TCGAAGCGTACAACAACGTTGTTGCGCAGATCGTTATCTGGGTTAACCTGAACCTGT GGCAGAA
ACTGAAAATCGGTCGTGACGAAGCGAAACCGCTGCAGCGTCTGAAAGGTTTCCCGTC TTTCCCG
CTGGTTGAACGTCAGGCGAACGAAGTTGACTGGTGGGACATGGTTTGCAACGTTAAA AAACTGA
TCAACGAAAAAAAAGAAGACGGTAAAGTTTTCTGGCAGAACCTGGCGGGTTACAAAC GTCAGG
AAGCGCTGCTGCCGTACCTGTCTTCTGAAGAAGACCGTAAAAAAGGTAAAAAATTCG CGCGTTA
CCAGTTCGGTGACCTGCTGCTGCACCTGGAAAAAAAACACGGTGAAGACTGGGGTAA AGTTTAC GACGAAGCGTGGGAACGTATCGACAAAAAAGTTGAAGGTCTGTCTAAACACATCAAACTG GAA
GAAGAACGTCGTTCTGAAGACGCGCAGTCTAAAGCGGCGCTGACCGACTGGCTGCGT GCGAAA
GCGTCTTTCGTTATCGAAGGTCTGAAAGAAGCGGACAAAGACGAATTCTGCCGTTGC GAACTGA
AACTGCAGAAATGGTACGGTGACCTGCGTGGTAAACCGTTCGCGATCGAAGCGGAAA ACTCTAT
CCTGGACATCTCTGGTTTCTCTAAACAGTACAACTGCGCGTTCATCTGGCAGAAAGA CGGTGTTA
AAAAACTGAACCTGTACCTGATCATCAACTACTTCAAAGGTGGTAAACTGCGTTTCA AAAAAAT
CAAACCGGAAGCGTTCGAAGCGAACCGTTTCTACACCGTTATCAACAAAAAATCTGG TGAAATC
GTTCCGATGGAAGTTAACTTCAACTTCGACGACCCGAACCTGATCATCCTGCCGCTG GCGTTCGG
TAAACGTCAGGGTCGTGAATTCATCTGGAACGACCTGCTGTCTCTGGAAACCGGTTC TCTGAAA
CTGGCGAACGGTCGTGTTATCGAAAAAACCCTGTACAACCGTCGTACCCGTCAGGAC GAACCGG
CGCTGTTCGTTGCGCTGACCTTCGAACGTCGTGAAGTTCTGGACTCTTCTAACATCA AACCGATG
AACCTGATCGGTATCGACCGTGGTGAAAACATCCCGGCGGTTATCGCGCTGACCGAC CCGGAAG
GTTGCCCGCTGTCTCGTTTCAAAGACTCTCTGGGTAACCCGACCCACATCCTGCGTA TCGGTGAA
TCTTACAAAGAAAAACAGCGTACCATCCAGGCGGCGAAAGAAGTTGAACAGCGTCGT GCGGGT
GGTTACTCTCGTAAATACGCGTCTAAAGCGAAAAACCTGGCGGACGACATGGTTCGT AACACCG
CGCGTGACCTGCTGTACTACGCGGTTACCCAGGACGCGATGCTGATCTTCGAAAACC TGTCTCGT
GGTTTCGGTCGTCAGGGTAAACGTACCTTCATGGCGGAACGTCAGTACACCCGTATG GAAGACT
GGCTGACCGCGAAACTGGCGTACGAAGGTCTGCCGTCTAAAACCTACCTGTCTAAAA CCCTGGC
GCAGTACACCTCTAAAACCTGCTCTAACTGCGGTTTCACCATCACCTCTGCGGACTA CGACCGTG
TTCTGGAAAAACTGAAAAAAACCGCGACCGGTTGGATGACCACCATCAACGGTAAAG AACTGA
AAGTTGAAGGTCAGATCACCTACTACAACCGTTACAAACGTCAGAACGTTGTTAAAG ACCTGTC
TGTTGAACTGGACCGTCTGTCTGAAGAATCTGTTAACAACGACATCTCTTCTTGGAC CAAAGGTC
GTTCTGGTGAAGCGCTGTCTCTGCTGAAAAAACGTTTCTCTCACCGTCCGGTTCAGG AAAAATTC
GTTTGCCTGAACTGCGGTTTCGAAACCCACGCGGACGAACAGGCGGCGCTGAACATC GCGCGTT
CTTGGCTGTTCCTGCGTTCTCAGGAATACAAAAAATACCAGACCAACAAAACCACCG GTAACAC
CGACAAACGTGCGTTCGTTGAAACCTGGCAGTCTTTCTACCGTAAAAAACTGAAAGA AGTTTGG
AAACCGGAAATCATCCTTAGCGAAAGCTAAGGATTTTTTTTATCTGAAATGTAGGGA GACCCTC
AGGTTAAATATTCACTCAGGAAGTTATTACTCAGGAAGCAAAGAGGATTACA
SE tgccgtcactgcgtcttttactggctcttctcgctaaccaaaccggtaaccccgcttatt aaaagcattctgtaacaaagcgggaccaaagccatgacaaaaacg
Q cgtaacaaaagtgtctataatcacggcagaaaagtccacattgattatttgcacggcgtc acactttgctatgccatagcatttttatccataagattagcggatcct no acctgacgctttttatcgcaactctctactgtttctccatacccgtttttttgggctagc accgcctatctcgtgtgagataggcggagatacgaactttaagAAG
N GAGatatacc
O:
81
SE TGCCGTCACTGCGTCTTTTACTGGCTCTTCTCGCTAACCAAACCGGTAACCCCGCTTATT AAAAG Q CATTCTGTAACAAAGCGGGACCAAAGCCATGACAAAAACGCGTAACAAAAGTGTCTATAA TCA
ID CGGCAGAAAAGTCCACATTGATTATTTGCACGGCGTCACACTTTGCTATGCCATAGCATT TTTAT N CCATAAGATTAGCGGATCCTACCTGACGCTTTTTATCGCAACTCTCTACTGTTTCTCCAT ACCCGT
O: TTTTTTGGGTAGCGGATCCTACCTGAC
82
SE AATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGATATGTCAAACAGGTTTCTA GAGC
Q ACAGCTAACACCACGTCGTCCCTATCTGCTGCCCTAGGTCTATGAGTGGTTGCTGGATAA CTTTA no CGGGCATGCATAAGGCTCGTAATATATATTCAGGGAGACCACAACGGTTTCCCTCTACAA ATAA
N TTTTGTTTAACTTTTACTAGAGCTAGCAGTAATACGACTCACTATAGGGGTCTCATCTCG TGTGA
0: GATAGGCGGAGATACGAACTTTAAGAGGAGGATATACCA
83
SE GTTTGAGAGATATGTAAATTCAAAGGATAATCAAAC
Q
no
N
0:
84
SE actacattttttaagacctaattttgagt
Q
no
N
0:
85
SE ctcaaaactcattcgaatctctactctttgtagat
Q
no
N
0:
86
SE CTCTAGCAGGCCTGGCAAATTTCTACTGTTGTAGAT
Q
no
N
0:
87
SE CCGTCTAAAACTCATTCAGAATTTCTACTAGTGTAGAT
Q
no
N
0:
88
SE GTCTAGGTACTCTCTTTAATTTCTACTATTGT
Q
no
N
0:
89
SE gttaagttatatagaataatttctactgttgtaga Q
no
N
0:
90
SE gtttaaaaccactttaaaatttctactattgta
Q
no
N
0:
91
SE GTTTGAGAATGATGTAAAAATGTATGGTACACAGAAATGTTTTAATACCATATTTTTACA TCACT
Q CTCAAACATACATCTCTTGTTACTGTTTATCGTATCCAGATTAAATTTCACGTTTTT
no
N
0:
92
SE CTCTACAACTGATAAAGAATTTCTACTTTTGTAGAT
Q
no
N
0:
93
SE GTCTGGCCCCAAATTTTAATTTCTACTGTTGTAGAT
Q
no
N
0:
94
SE GTCAAAAGACCTTTTTAATTTCTACTCTTGTAGAT
Q
no
N
0:
95
SE GTCTAGAGGACAGAATTTTTCAACGGGTGTGCCAATGGCCACTTTCCAGGTGGCAAAGCC CGTT
Q GAGCTTCTACGGAAGTGGCAC
no
N
0:
96 SE CGAGGTTCTGTCTTTTGGTCAGGACAACCGTCTAGCTATAAGTGCTGCAGGGGTGTGAGA AACT
Q CCTATTGCTGGACGATGTCTCTTTTAACGAGGCATTAGCAC
no
N
0:
97
SE GAACGAGGGACGTTTTGTCTCCAATGATTTTGCTATGACGACCTCGAACTGTGCCTTCAA GTCTG
Q AGGCGAAAAAGAAATGGAAAAAAGTGTCTCATCGCTCTACCTCGTAGTTAGAGG
no
N
0:
98
SE AATTACTGATGTTGTGATGAAGG
Q
no
N
0:
99
SE TATACCATAAGGATTTAAAGACT
Q
no
N
0:
10
0
SE GTCTTTACTCTCACCTTTCCACCTG
Q
no
N
0:
10
1
SE ATTTGAAGGTATCTCCGATAAGTAAAACGCATCAAAG
Q
no
N
0:
10
2
SE GTTTGAAGATATCTCCGATAAATAAGAAGCATCAAAG
Q
no N
0:
10
3
SE
Q
ID
N
0:
10
4
SE AAAGAACGCTCGCTCAGTGTTCTGACCTTTCGAGCGCCTGTTCAGGGCGAAAACCCTGGG AGGC
Q GCTCGAATCATAGGTGGGACAAGGGATTCGCGGCGAAAA
ID
N
0:
10
5
SE GTTTGAGAATGATGTAAAAATGTATGGTACACAGAAATGTTTTAATACCATATTTTTACA TCACT
Q CTCAAACATACATCTCTTGTTACTGTTTATCGTATCCAGATTAAATTTCACGTTTTT
ID
N
0:
10
6
SE GTCTAGAGGACAGAATTTTTCAACGGGTGTGCCAATGGCCACTTTCCAGGTGGCAAAGCC CGTT
Q GAGCTTCTACGGAAGTGGCAC
ID
N
0:
10
7
SE MSIYQEFVNKYSLSKTLRFELIPQGKTLENIKARGLILDDEKRAKDYKKAKQIIDKYHQF FIEEILSSVC
Q ISEDLLQNYSDWFKLKKSDDDNLQKDFKSAKDTIKKQISEYIKDSEKFKNLFNQNLIDAK KGQESDL
ID IL N WLKQSKDNGIELFKANSDITDIDEALEIIKSFKGWTTYFKGFHENRKNVYSSNDIPTSII YRIVDDNLPK
0: FLENKAKYESLKDKAPEAINYEQIKKDLAEELTFDIDYKTSEVNQRVFSLDEVFEIANFN YLNQSGI 10 TK
8 FNTIIGGKFWGENTKRKGINEYINLYSQQINDKTLKKYKMSVLFKQILSDTESKSFVIDK LEDDSDV VT
TMQSFYEQIAAFKTVEEKSIKETLSLLFDDLKAQKLDLSKIYFKNDKSLTDLSQQVF DDYSVIGTAVL EY ITQQIAPKNLDNPSKKEQELIAKKTEKAKYLSLETI^
EIAQNKDNLAQISIKYQNQGKKDLLQASAEDDVKAIKDLLDQTNNLLHKLKIFHISQSED KANILDK DEH
FYL EECYFELAMWLYNKIPJvTYITQKPYSDEKFKLNFENSTLANGWDKNKEPDNTAILFIKD DKY YL
GVMNKKNNKIFDDKAIKENKGEGYKKIW TKN
GSPQKGYEKFEFNIEDCRKFIDFYKQSISKHPEWKDFGFRFSDTQRYNSIDEFYREV ENQGYKLTFENI S
ESYIDSVVNQGKLYLFQIYN DFSAYSKGPJ'NLHTLYWKALFDERNLQDVVYKLNGEAELFYRKQS IPKK
ITFffAKEAIANKNKDNPKKES EYDLIKD
D
VHILSIDRGEPJiLAYYTLVDGKGNIIKQDTFNIIGNDPJVKTNYHDKLAAIEKDRD SAPJ DWKKINNI KEM
KEGYLSQVVHEIAKLVIEYNAIV EDLNFGFKRGRFKVEKQWQKLEKMLIEKLNYL KDNEFDK TGG
VLRAYQLTAPFETFKKMGKQTGIIYYVPAGFTSKICPVTGFVNQLYPKYESVSKSQE FFSKFDKICYN LD
KGYFEFSFDYKNFGDKAAKGKWTIASFGSRLINFRNSDKNHNWDTREVYPTKELEKL LKDYSIEYG HGEC
IKAAICGESDKKFFAKLTSVLNTILQMRNSKTGTELDYLISPVADVNGNFFDSRQAP KNMPQDADAN GAY
HIGLKGLMLLGRIKNNQEGKKLNLVIKNEEYFEFVQNRNN
SE MSIYQEFVNKYSLSKTLRFELIPQGKTLENIKARGLILDDEKRAKDYKKAKQIIDKYHQF FIEEILSSVC
Q ISEDLLQNYSDWFKLKKSDDDNLQKDFKSAKDTIKKQISEYIKDSEKFKNLFNQNLIDAK KGQESDL
no IL
N WLKQSKDNGIELFKANSDITDIDEALEIIKSFKGWTTYFKGFHENRKNVYSSDDIPTSII YRIVDDNLPK
0: FLENKAKYESLKDKAPEAINYEQIKKDLAEELTFDIDYKTSEVNQRVFSLDEVFEIANFN YLNQSGI 10 TK
9 FNTIIGGKFWGENTKRKGINEYINLYSQQINDKTLKKYKMSVLFKQILSDTESKSFVIDK LEDDSDV VT
TMQSFYEQIAAFKTVEEKSIKETLSLLFDDLKAQKLDLSKIYFKNDKSLTDLSQQVF DDYSVIGTAVL EY
ITQQVAPKNLDNPSKKEQDLIAKKTEKAKYLSLETIKLALEEFN HRDIDKQCRFEEILA FAAIPMIF D
EIAQNKDNLAQISLKYQNQGKKDLLQASAEEDVKAIKDLLDQTN LLHRLKIFHISQSEDKANILDK DEH
FYL EECYFELAMWLYNKIR YITQKPYSDEKFKLNFENSTLANGWDKNKEPDNTAILFIKDDKY YL
GVMNKKNNKIFDDKAIKENKGEGYKKIW TKN GNPQKGYEKFEFNIEDCRKFIDFYKESISKHPEWKDFGFRFSDTQRYNSIDEFYREVENQ GYKLTFENI S
ESYIDSVVNQGKLYLFQIYN DFSAYSKGPJ'NLHTLYWKALFDERNLQDVWKLNGEAELFYRKQS IPKK
ITHPAKEAIANKN DNPKKES EYDLIKDKJ FTEDKFFFHCPITINFKSSGAN F D
VHILSIDRGERHLAYYTLVDGKGNIIKQDTFNIIGNDRMKTNYHDKLAAIEKDRDSA RKDWKKINNI KEM
KEGYLSQVVHEIAKLVIEHNAIV EDLNFGFKRGRFKVEKQWQKLEKMLIEKLNYLVFKDNEFDK TGG
VLRAYQLTAPFETFKKMGKQTGIIYYVPAGFTSKICPVTGFVNQLYPKYESVSKSQE FFSKFDKICYN LD
KGYFEFSFDYKNFGDKAAKGKWTIASFGSRLINFRNSDKNHNWDTREVYPTKELEKL LKDYSIEYG HGEC
IKAAICGESDKKFFAKLTSVLNTILQMRNSKTGTELDYLISPVADVNGNFFDSRQAP KNMPQDADAN GAY
HIGLKGLMLLDRIKNNQEGKKLNLVIKNEEYFEFVQNRNN
SE MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAE ATRLKRT
Q ARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVA YHEKYPTI
no YHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQL FEENPINA
N SGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDLAEDAK LQLSKDTY
O: DDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQD LTLLKAL 11 WQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLL RKQRTF
0 DNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWM TRKSEETITP
WNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTWNELTKVKYVTEG MRKPAFLS
GEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLL KIIKDKDFLDN
EENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLSRKL INGIRDKQSG
KTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAI KKGILQTVKVV
DELVKVMGRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPV ENTQLQNEKL
YLYYLQNGRDMYVDQELDINRLSDYDVDHIWQSFLKDDSIDNKVLTRSDKNRGKSDN VPSEEVVK
KMKNY WRQLLN AKLITQRKFDNLTK AERGGL SELDK AGFIKRQL VETRQITKH V AQILD SRMNTKY
DENDKLIREVKVITLKSKLVSDFRKDFQFYKVREIN YHHAHDAYLNAVVGTALIKKYPKLESEFVY
GDYKWDVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGE TGEIVWDKGR
DFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFD SPTVAYSVL
VVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKY SLFELENGRKR
MLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEI IEQISEFSKR
VILADANLDKVLSAYN HRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLDATL
IHQSITGLYETRIDLSQLGGD
SE PKKKRKV
Q
ID
N 0:
11
1
SE KRPAATKKAGQAKKKK
Q
ID
N
0:
11
2
SE PAAKRVKLD
Q
ID
N
0:
11
3
SE RQRRNELKRSP
Q
ID
N
0:
11
4
SE NQSSNFGPMKGGNFGGRSSGPYGGGGQYFAKPRNQGGY
Q
ID
N
0:
11
5
SE RMRIZFKNKGKDTAELRRRRVEVSVELRKAKKDEQILKRRNV
Q
ID
N
0:
11
6
SE VSRKRPRP
Q
ID
N 0:
11
7
SE PPKKARED
Q
ID
N
0:
11
8
SE PQPKKKPL
Q
ID
N
0:
11
9
SE SALIKKKKKMAP
Q
ID
N
0:
12
0
SE DRLRR
Q
ID
N
0:
12
1
SE PKQKKRK
Q
ID
N
0:
12
2
SE RKLKKKIKKL
Q
ID
N 0:
12
3
SE REKKKFLKRR
Q
ID
N
0:
12
4
SE KRKGDEVDGVDEVAKKKSKK
Q
ID
N
0:
12
5
SE RKCLQAGMNLEARKTKK
Q
ID
N
0:
12
6
SE ATGGGTAAGATGTATTATCTGGGTTTGGATATAGGCACTAACTCTGTGGGATATGCAGTA ACTG
Q ATCCCTCGTATCACTTGTTAAAGTTCAAAGGCGAACCCATGTGGGGAGCACATGTATTTG CTGC
ID GGGTAATCAGAGTGCCGAAAGGCGATCTTTCAGAACATCCAGGAGGCGATTAGATAGGAG ACA N GCAAAGAGTAAAGCTTGTGCAAGAGATCTTTGCTCCTGTCATTTCACCTATAGACCCTCG TTTTT
0: TTATAAGATTGCACGAATCGGCTCTATGGAGAGACGATGTTGCCGAAACAGATAAACATA TCTT 12 TTTCAATGATCCCACTTATACAGACAAGGAATACTACTCCGACTACCCGACAATTCATCA TTTGA
7 TCGTCGATCTTATGGAGAGCTCTGAAAAGCATGACCCCCGACTTGTCTATTTGGCTGTAG CTTGG
TTAGTTGCTCATAGAGGTCATTTCTTGAATGAAGTAGATAAAGACAATATAGGTGAT GTACTTTC
TTTTGATGCTTTCTACCCGGAATTTTTGGCCTTTTTGTCAGACAATGGCGTCAGTCC CTGGGTCTG
TGAGTCGAAGGCCCTTCAAGCTACTCTGCTGTCTAGGAATAGCGTCAACGACAAATA TAAAGCA
TTAAAATCGCTGATATTCGGATCGCAAAAACCGGAAGATAACTTTGACGCTAACATC TCTGAAG
ATGGTTTAATCCAATTGCTGGCGGGTAAGAAAGTTAAAGTAAACAAACTATTCCCAC AAGAGTC
CAACGATGCTAGCTTTACGTTGAATGATAAAGAAGACGCTATTGAAGAAATTCTAGG TACTTTA
ACGCCTGACGAGTGCGAATGGATCGCTCATATTCGCAGATTGTTCGATTGGGCCATC ATGAAAC
ACGCGCTAAAGGATGGCAGGACGATATCTGAATCAAAAGTGAAGCTATACGAGCAGC ATCATC
ATGACTTGACTCAGTTAAAGTACTTTGTGAAGACCTACCTAGCTAAAGAGTATGATG ATATCTTC
AGAAACGTAGACTCCGAGACAACTAAAAATTATGTAGCTTATTCTTACCATGTGAAG GAAGTGA
AAGGCACATTACCAAAAAATAAAGCAACGCAAGAAGAATTTTGTAAATACGTCCTTG GCAAAG TCAAAAACATTGAATGTTCCGAAGCAGACAAGGTTGATTTTGATGAAATGATACAACGAC TTAC
GGACAATTCTTTTATGCCAAAGCAAGTCTCAGGTGAAAATAGAGTAATACCATACCA GTTGTAC
TACTATGAATTAAAGACAATTTTAAACAAAGCCGCCTCATATCTACCTTTTTTGACA CAATGCGG
TAAAGATGCTATTTCTAACCAAGACAAATTACTGTCTATAATGACATTTCGCATACC ATATTTCG
TCGGCCCTTTAAGGAAAGATAATTCAGAACATGCCTGGTTGGAACGTAAAGCGGGTA AAATTTA
CCCGTGGAACTTTAATGATAAAGTAGATCTTGATAAATCGGAGGAAGCCTTTATCCG TAGGATG
ACCAATACTTGCACGTATTACCCAGGAGAAGACGTGTTACCATTAGATTCACTTATC TATGAAA
AGTTTATGATCTTGAATGAGATAAACAATATTAGGATTGACGGATACCCCATTTCTG TTGATGTG
AAACAACAAGTATTTGGTTTATTTGAGAAGAAAAGGCGAGTAACAGTTAAGGATATT CAAAATC
TACT ATT ATCTCTTGGAGCGTTGGATAAACACGGTAAGCTGACTGGTATTGACACGACAATACA
CTCTAATTATAACACTTATCATCATTTTAAATCTCTTATGGAGCGGGGAGTATTGAC CAGAGATG
ATGTGGAAAGAATAGTGGAAAGAATGACATATTCTGACGATACTAAGAGGGTCAGAC TGTGGT
TAAATAATAATTATGGAACTCTAACAGCTGACGATGTTAAGCATATCTCAAGACTCA GAAAACA
CGATTTCGGCCGTTTGTCTAAAATGTTTTTGACAGGATTGAAAGGTGTTCATAAGGA GACAGGC
GAGAGAGCAAGTATACTGGATTTTATGTGGAATACTAACGACAATTTAATGCAACTA CTGTCCG
AATGTTACACATTCTCGGATGAGATCACCAAATTACAAGAGGCCTACTACGCAAAAG CTCAATT
ATCGCTAAATGACTTCTTGGACTCTATGTATATATCAAACGCCGTTAAGAGACCTAT TTATCGGA
CCTTAGCGGTAGTAAATGATATTAGAAAGGCATGCGGGACGGCACCTAAAAGAATTT TCATCGA
GATGGCGCGAGATGGAGAGTCTAAGAAGAAAAGATCTGTGACTCGTAGAGAGCAAAT TAAAAA
TCTCTATAGATCAATTCGTAAAGACTTTCAACAAGAAGTTGATTTTCTGGAAAAGAT ATTGGAA
AATAAGAGTGACGGGCAGCTTCAGTCTGACGCTTTATATTTGTATTTTGCTCAATTA GGCAGAGA
CATGTACACAGGTGATCCAATCAAATTAGAACATATTAAAGACCAATCTTTTTACAA CATTGAT
CATATTTATCCTCAATCGATGGTGAAAGATGACAGTTTGGATAACAAGGTACTAGTC CAAAGCG
AAATCAATGGCGAAAAGAGTTCGCGCTATCCATTAGACGCAGCCATTAGAAACAAAA TGAAGC
CGTTGTGGGATGCCTACTATAATCATGGATTAATTTCTCTTAAGAAATACCAGCGTT TGACGAGA
TCTACTCCATTTACGGACGACGAGAAGTGGGATTTTATCAATCGTCAGCTAGTTGAA ACTAGGC
AATCTACTAAAGCTTTAGCAATATTGTTAAAGCGTAAGTTTCCAGATACTGAAATAG TTTACTCA
AAGGCTGGACTATCCAGCGATTTTAGACATGAATTCGGCCTGGTTAAGAGTAGGAAT ATTAATG
ATCTACACCATGCTAAAGATGCCTTTCTCGCAATAGTTACTGGGAACGTTTATCATG AAAGATTT
AATAGAAGATGGTTTATGGTTAACCAGCCATACTCTGTGAAAACTAAGACATTGTTT ACCCATTC
AATTAAGAATGGCAACTTTGTCGCTTGGAATGGAGAAGAAGATCTTGGACGTATCGT AAAGATG
TTGAAACAAAACAAGAACACAATCCACTTCACCAGGTTTTCCTTTGATAGGAAGGAG GGATTGT
TCGATATTCAACCTCTCAAAGCTTCTACCGGATTGGTTCCACGAAAAGCAGGGTTGG ATGTTGTT
AAATATGGAGGATACGATAAAAGCACTGCCGCGTATTATTTATTAGTACGTTTTACA CTCGAGG
ATAAGAAGACTCAACACAAATTGATGATGATTCCTGTTGAAGGTCTCTACAAAGCAC GTATTGA
CCATGATAAAGAGTTTTTAACAGATTATGCTCAGACCACGATCAGCGAAATTCTTCA AAAGGAC
AAGCAGAAAGTGATCAACATCATGTTCCCTATGGGCACGAGACATATCAAACTGAAT TCGATGA
TTTCTATTGATGGATTCTATCTTTCTATTGGTGGGAAGAGTAGCAAAGGTAAGTCAG TACTATGT
CATGCTATGGTGCCATTAATCGTCCCACACAAGATAGAATGTTATATCAAGGCTATG GAATCGT
TTGCAAGAAAATTCAAAGAAAATAATAAATTGAGGATCGTTGAAAAGTTTGATAAAA TAACTGT
TGAAGATAACTTGAACTTATACGAGCTTTTTCTACAAAAGTTGCAACATAACCCATA TAATAAA
TTTTTCTCTACACAATTTGATGTGTTGACGAACGGTAGAAGTACATTCACCAAATTG TCTCCAGA GGAGCAAGTCCAGACTTTACTTAATATACTGAGTATATTTAAAACTTGTCGTTCTTCTGG GTGTG ATTTAAAATCAATAAATGGTTCCGCTCAAGCGGCTAGAATTATGATATCCGCTGATTTAA CTGGC TTATCAAAAAAGTATTCAGATATTAGATTAGTTGAGCAAAGCGCATCAGGTCTATTTGTT TCAAA ATCTCAAAATCTCTTGGAATACTTGCCAAAAAAGAAAAGGAAAGTTTAG
SE ATGAGTAGTTTAACAAAGTTTACCAATAAATATAGTAAGCAACTAACTATAAAGAACGAA TTGA
Q TACCGGTCGGTAAGACTTTGGAAAACATAAAAGAAAATGGGTTGATTGATGGAGACGAGC AAT
no TGAATGAGAATTATCAAAAAGCAAAGATAATAGTAGATGATTTTTTGAGAGACTTTATTA ATAA
N AGCTCTAAATAACACTCAAATTGGTAACTGGAGAGAGCTAGCCGACGCCTTGAACAAGGA AGA
O: TGAGGATAATATTGAGAAATTACAAGATAAGATTAGAGGGATTATCGTGTCTAAGTTTGA GACT 12 TTTGATCTGTTCAGTTCGTATTCGATTAAAAAGGACGAGAAAATCATCGATGATGATAAC GATG 8 TGGAAGAAGAGGAGCTAGACCTTGGGAAGAAGACATCTAGCTTCAAATACATATTCAAGA AAA
ATTTGTTCAAACTTGTCCTTCCTTCATATTTAAAAACAACAAATCAAGATAAGTTAA AAATCATT
TCTTCCTTCGATAATTTTAGTACTTATTTTCGTGGTTTTTTCGAAAACAGGAAAAAT ATATTCACT
AAAAAGCCTATATCTACCTCTATAGCTTATAGAATTGTTCACGATAATTTCCCAAAA TTTCTAGA
TAATATCAGGTGTTTTAATGTTTGGCAAACCGAGTGTCCTCAGTTAATAGTCAAGGC CGACAACT
ACCTTAAAAGCAAGAATGTGATTGCAAAAGATAAGTCTTTGGCTAACTATTTTACAG TCGGTGC
CTATGATTATTTTCTGAGTCAAAATGGTATCGATTTCTATAACAACATTATTGGCGG CTTACCAG
CTTTTGCCGGGCATGAGAAGATTCAGGGTTTGAACGAATTTATCAATCAAGAATGTC AAAAGGA
TTCTGAATTAAAGTCTAAGCTCAAGAATAGGCACGCTTTCAAAATGGCAGTCTTATT CAAACAA
ATCCTTTCAGACAGAGAAAAGTCATTTGTGATTGACGAGTTCGAATCAGACGCTCAG GTAATTG
ATGCTGTTAAAAATTTTTACGCGGAACAATGCAAAGATAATAACGTCATATTTAATT TATTGAAT
CTGATCAAGAATATTGCTTTTTTGTCGGATGATGAGTTAGACGGCATTTTCATAGAG GGTAAATA
CCTGTCCTCTGTGTCTCAAAAATTGTATAGTGATTGGTCAAAGTTGAGAAATGATAT TGAAGATT
CGGCTAATTCTAAACAGGGTAACAAAGAATTAGCGAAGAAAATCAAAACTAACAAGG GTGATG
TTGAAAAGGCTATAAGTAAGTACGAGTTCAGTTTATCTGAACTAAATTCAATTGTTC ATGATAAC
ACAAAATTTTCCGATCTTTTATCATGCACATTACATAAAGTTGCAAGTGAAAAATTA GTCAAAGT
AAACGAAGGTGATTGGCCAAAACATCTAAAAAACAACGAGGAAAAACAGAAGATAAA AGAAC
CTCTTGACGCTTTATTGGAAATATACAATACTCTATTAATATTTAACTGTAAAAGTT TTAACAAA
AATGGTAATTTCTATGTCGACTACGATCGCTGCATTAATGAGTTGTCCAGTGTTGTG TACTTGTA
TAATAAAACTCGTAATTATTGTACGAAAAAGCCGTACAACACTGACAAATTTAAGTT GAATTTC
AACTCCCCACAACTGGGTGAGGGCTTCTCTAAAAGTAAAGAGAATGATTGCCTTACA TTATTAT
TTAAAAAAGATGATAATTATTATGTCGGAATCATAAGAAAGGGGGCAAAGATCAACT TCGATG
ACACTCAGGCCATAGCAGACAACACAGATAACTGTATATTCAAAATGAATTATTTTT TGCTGAA
GGATGCTAAAAAATTTATCCCCAAATGTTCAATACAATTAAAAGAGGTTAAGGCCCA TTTCAAA
AAGTCGGAAGATGACTATATTTTGTCCGATAAGGAAAAATTCGCTAGTCCGCTTGTT ATTAAAA
AATCCACATTTCTTCTCGCTACGGCTCATGTGAAAGGAAAGAAGGGCAATATTAAGA AATTTCA
GAAAGAATACTCCAAAGAAAATCCTACGGAGTATAGAAATAGTCTGAACGAATGGAT AGCATT
CTGCAAAGAGTTCTTGAAGACCTATAAAGCTGCCACCATCTTTGATATTACAACTTT GAAAAAG
GCCGAGGAATACGCTGACATTGTGGAATTCTATAAGGATGTAGATAATCTTTGTTAC AAGTTAG
AATTTTGCCCTATCAAAACTTCTTTTATCGAAAATCTTATAGATAATGGCGATTTAT ACCTGTTTA
GAATTAATAACAAGGACTTTTCTTCAAAAAGTACAGGCACGAAAAACTTACACACAT TATACTT
GCAGGCTATATTTGACGAGCGAAACTTAAACAACCCCACGATAATGTTGAATGGAGG TGCAGA GTTATTCTACAGAAAAGAATCTATAGAACAGAAAAATCGGATCACGCACAAAGCCGGTAG TAT
CTTAGTGAATAAAGTGTGCAAAGATGGTACAAGTCTAGATGACAAAATCCGTAACGA AATTTAC
CAGTATGAAAACAAATTCATTGATACTCTTTCGGACGAAGCTAAAAAGGTTCTGCCA AACGTTA
TTAAGAAAGAGGCTACGCATGATATAACAAAAGATAAACGTTTCACTAGCGACAAAT TCTTCTT
TCATTGTCCTTTAACAATCAACTACAAGGAAGGTGACACCAAACAATTTAATAATGA AGTGCTC
TCATTCCTTAGAGGTAACCCCGATATCAATATTATCGGCATTGATAGAGGAGAAAGA AACCTAA
TCTATGTAACAGTCATTAACCAAAAAGGCGAAATATTGGATAGCGTCTCCTTCAATA CTGTCAC
CAATAAGTCATCGAAGATAGAACAAACTGTTGATTACGAAGAAAAATTGGCCGTTAG AGAAAA
GGAACGTATCGAAGCGAAGAGATCTTGGGATAGCATATCCAAGATTGCCACCTTGAA GGAGGG
TTATCTAAGCGCGATCGTACATGAAATCTGCTTATTAATGATTAAGCATAATGCTAT TGTCGTGT
TAGAAAACCTGAATGCCGGTTTTAAAAGGATTAGAGGTGGTTTGTCAGAAAAGTCAG TATATCA
AAAGTTTGAAAAGATGCTTATTAATAAACTCAACTACTTCGTTAGCAAGAAAGAAAG TGATTGG
AATAAACCGTCAGGTTTGCTCAATGGTCTTCAGTTAAGTGATCAATTTGAGTCTTTC GAAAAATT
CCGGATTTGCCAACGTCTTGAATTTGTCCAAGGTCAGAAATGTTGACGCCATCAAAA GTTTTTTT
AGCAACTTCAATGAAATCTCTTATTCCAAAAAGGAAGCCCTTTTCAAGTTTTCTTTT GACCTAGA
CTCGTTATCGAAGAAAGGATTTTCATCTTTCGTAAAGTTTAGCAAGTCCAAGTGGAA TGTATACA
CATTCGGCGAGAGAATTATCAAGCCCAAGAACAAACAGGGCTATAGAGAAGACAAGA GAATCA
ACTTGACTTTTGAGATGAAAAAATTACTCAACGAATACAAGGTTTCATTTGATTTGG AGAACAA
CTTGATTCCCAATTTGACATCAGCTAACTTGAAGGATACGTTCTGGAAGGAGTTATT CTTTATAT
TCAAAACGACATTACAACTGCGTAATAGTGTTACAAACGGTAAAGAAGATGTATTAA TCTCACC
TGTAAAGAATGCCAAAGGAGAATTTTTCGTATCCGGTACTCACAATAAGACACTACC ACAGGAT
TGCGACGCTAACGGTGCGTATCATATTGCGTTGAAAGGATTAATGATACTTGAAAGA AATAACC
TTGTTCGCGAAGAAAAAGACACCAAGAAGATCATGGCTATTAGCAATGTTGATTGGT TTGAATA
CGTGCAAAAGAGGAGAGGTGTTTTGTAA
SE ATGAACAATTATGACGAGTTCACAAAGCTATACCCTATCCAAAAAACTATCAGGTTCGAA TTGA
Q AACCACAAGGGAGAACAATGGAACATCTGGAGACATTCAACTTTTTTGAAGAGGACAGAG ACA
no GAGCGGAGAAATACAAAATTTTAAAAGAGGCCATCGATGAATATCACAAAAAGTTTATCG ACG
N AGCATTTAACAAACATGTCTTTGGACTGGAATTCACTTAAACAAATTTCTGAGAAATATT ATAA
O: GTCTCGGGAGGAAAAAGACAAAAAGGTCTTTTTGTCCGAGCAAAAGAGAATGAGACAAGA AAT 12 TGTCTCGGAGTTTAAAAAAGATGATCGGTTCAAAGATTTGTTTAGCAAGAAATTGTTTTC TGAAT
9 TGTTGAAGGAGGAGATATACAAGAAAGGCAACCATCAAGAAATAGATGCTTTGAAATCGT TTG
ACAAGTTCAGCGGTTACTTCATTGGTTTACATGAAAATAGGAAGAACATGTATAGCG ACGGCGA
TGAGATCACCGCTATATCGAATAGAATCGTTAACGAAAATTTTCCGAAATTTTTGGA TAATTTGC
AAAAATACCAGGAAGCTAGGAAAAAGTACCCTGAATGGATAATAAAGGCGGAATCAG CTTTGG
TGGCTCACAACATAAAGATGGATGAAGTCTTCTCGCTGGAATATTTTAACAAAGTAT TAAATCA
GGAAGGAATCCAAAGATACAACTTAGCCTTGGGTGGATACGTAACCAAATCAGGTGA GAAAAT
GATGGGCTTAAATGATGCACTTAATCTAGCTCACCAATCCGAAAAGTCCTCTAAAGG GAGGATA
CACATGACACCATTGTTTAAGCAAATCCTTTCGGAGAAAGAATCTTTTTCATATATC CCCGATGT
TTTCACTGAGGATAGTCAATTGTTGCCCAGCATTGGTGGATTTTTTGCACAAATAGA AAATGATA
AAGATGGTAACATCTTCGATAGAGCCTTGGAATTGATAAGCTCCTATGCAGAATACG ATACGGA
ACGAATATACATTAGACAAGCTGACATCAACAGAGTAAGCAATGTTATTTTTGGTGA GTGGGGA ACTTTAGGTGGATTAATGCGGGAGTACAAAGCTGACTCAATCAATGATATTAATTTGGAA CGTA
CGTGCAAAAAAGTCGATAAGTGGCTTGATAGTAAGGAGTTTGCTCTGTCGGATGTAC TAGAAGC
AATTAAGAGAACAGGAAACAATGATGCATTTAATGAATATATTAGTAAAATGAGGAC GGCTAG
AGAAAAGATAGACGCCGCACGTAAGGAAATGAAGTTTATTTCCGAGAAAATATCTGG CGATGA
AGAGTCGATTCACATCATCAAGACCCTACTCGATTCTGTTCAGCAATTTCTCCATTT TTTTAACCT
CTTCAAAGCAAGACAAGACATTCCCTTAGATGGGGCTTTTTATGCCGAATTTGATGA AGTTCATT
CAAAGTTGTTTGCTATTGTTCCTCTTTACAATAAGGTCCGTAATTACCTTACTAAAA ATAACTTG
AACACCAAGAAAATAAAGTTAAACTTCAAGAATCCGACTCTTGCCAACGGGTGGGAT CAGAAT
AAAGTTTATGATTATGCTAGCTTAATATTTCTAAGAGATGGGAATTATTACTTAGGA ATCATCAA
TCCAAAGCGTAAGAAAAACATTAAATTTGAACAAGGGTCAGGCAATGGCCCATTCTA TAGAAA
AATGGTGTATAAGCAAATACCAGGACCTAACAAGAACTTGCCTCGCGTATTTTTAAC TTCAACA
AAGGGTAAAAAAGAATATAAACCAAGCAAAGAAATTATTGAAGGTTACGAAGCAGAT AAACAC
ATCAGAGGTGATAAGTTCGATCTGGATTTCTGCCATAAATTGATTGACTTTTTTAAG GAATCTAT
AGAAAAACATAAGGACTGGTCCAAATTTAATTTCTACTTCTCACCTACAGAAAGTTA TGGTGAC
ATTTCAGAATTTTATTTAGACGTTGAGAAACAAGGATATAGGATGCATTTTGAAAAT ATTTCAGC
GGAAACCATCGACGAATACGTTGAGAAGGGTGATTTATTCTTGTTCCAAATTTACAA TAAAGAC
TTCGTTAAAGCTGCAACCGGAAAGAAGGATATGCATACCATATATTGGAACGCTGCA TTCTCGC
CAGAAAACTTACAAGATGTCGTTGTAAAGCTTAATGGAGAAGCTGAGCTGTTCTATA GAGACAA
GAGTGATATAAAAGAGATTGTGCATCGGGAAGGTGAAATTCTGGTGAACAGAACTTA CAATGG
TCGTACACCCGTTCCAGACAAAATACATAAAAAACTGACCGATTATCATAATGGTAG GACAAAG
GACTTGGGCGAGGCCAAGGAGTACCTCGATAAAGTTAGATATTTCAAGGCACACTAT GATATTA
CGAAAGACAGGAGATATTTAAACGATAAAATTTACTTTCATGTCCCTTTGACCCTTA ACTTTAAA
GCTAATGGTAAAAAGAATTTGAACAAAATGGTAATTGAGAAGTTTTTATCGGACGAA AAAGCTC
ACATAATCGGAATCGACCGCGGAGAGAGAAATTTACTGTATTATAGTATCATCGACA GAAGTGG
AAAGATTATTGATCAGCAATCTTTGAACGTCATTGATGGGTTTGACTATCGGGAAAA GTTAAAT
CAAAGGGAAATTGAAATGAAGGATGCGAGACAATCATGGAATGCCATTGGTAAAATT AAAGAT
CTCAAGGAGGGGTACTTATCAAAAGCTGTACACGAGATAACTAAAATGGCTATCCAA TATAATG
CAATTGTTGTAATGGAAGAATTGAATTATGGTTTTAAACGCGGCAGGTTTAAAGTCG AAAAACA
AATATACCAAAAGTTTGAAAACATGTTAATTGATAAGATGAACTATCTTGTTTTCAA AGATGCA
CCTGATGAGAGTCCTGGCGGTGTGCTGAACGCCTATCAATTAACAAACCCATTAGAG TCCTTTG
CTAAACTGGGTAAACAAACTGGCATTCTATTTTATGTTCCAGCCGCTTACACCTCAA AGATCGAT
CCAACGACCGGTTTTGTAAACTTATTTAATACTTCTTCCAAAACAAACGCGCAAGAA CGCAAAG
AATTCCTACAAAAATTTGAATCAATATCCTATAGCGCAAAAGATGGAGGTATATTCG CTTTCGCT
TTTGACTACAGAAAGTTTGGCACTTCCAAGACAGATCATAAAAATGTGTGGACCGCT TATACCA
ACGGAGAAAGGATGCGTTATATTAAAGAAAAAAAGAGGAACGAACTATTTGATCCAT CGAAAG
AAATTAAAGAAGCTTTGACAAGCAGCGGAATCAAATATGATGGAGGTCAAAACATAC TTCCAG
ATATTCTCAGATCTAATAATAACGGTCTTATTTACACGATGTATTCATCTTTTATCG CTGCCATCC
AAATGCGTGTGTATGATGGCAAGGAAGATTATATTATATCTCCTATTAAAAATTCAA AGGGTGA
ATTTTTTCGCACGGATCCAAAAAGAAGAGAGCTTCCAATTGACGCCGATGCTAACGG TGCTTAC
AATATTGCATTGCGTGGTGAACTTACTATGAGAGCCATCGCCGAAAAGTTTGATCCG GACAGTG
AAAAAATGGCGAAATTGGAGCTAAAGCACAAGGATTGGTTTGAATTCATGCAGACCC GTGGCG
ATTGA SE ATGACTAAAACGTTCGACTCCGAGTTTTTTAATCTCTATTCCTTGCAAAAGACCGTTAGG TTTGA
Q ATTGAAACCAGTTGGTGAAACTGCCTCATTTGTCGAAGACTTTAAAAACGAGGGATTGAA AAGA
no GTGGTTAGTGAAGATGAAAGAAGGGCAGTAGACTATCAAAAGGTTAAAGAAATCATTGAC GAT
N TACCACAGAGATTTTATAGAAGAATCTCTGAACTATTTTCCAGAGCAGGTTTCAAAAGAT GCTCT
O: AGAGCAAGCGTTTCATTTGTATCAAAAGTTGAAAGCAGCGAAGGTGGAAGAAAGGGAAAA AGC 13 TTTAAAAGAATGGGAAGCATTACAGAAAAAATTGCGAGAAAAAGTCGTCAAATGTTTCAG CGA 0 CTCTAATAAAGCTCGCTTTTCTAGAATCGATAAAAAAGAATTGATTAAGGAAGATTTAAT AAAT
TGGCTGGTAGCACAAAACAGAGAGGATGATATTCCTACTGTTGAAACGTTCAATAAT TTTACTA
CTTACTTCACTGGTTTCCATGAGAACAGGAAGAATATTTACTCTAAAGATGATCACG CTACTGCT
ATAAGTTTTAGGTTGATTCACGAAAACTTGCCTAAATTTTTTGACAATGTCATCAGT TTTAACAA
GTTGAAAGAAGGTTTCCCGGAATTAAAATTCGACAAAGTTAAAGAAGATTTAGAAGT AGATTAC
GACTTGAAGCATGCGTTTGAAATTGAATATTTCGTTAATTTCGTCACACAAGCTGGT ATCGACCA
ATATAATTACCTGCTTGGAGGCAAAACTCTAGAAGACGGTACGAAGAAACAAGGAAT GAATGA
ACAGATTAATTTATTTAAGCAACAACAAACTCGCGATAAAGCTAGACAGATTCCAAA ACTGATT
CCACTTTTCAAACAGATTCTATCTGAGAGAACTGAATCTCAGAGTTTTATCCCTAAG CAGTTCGA
GTCTGATCAGGAACTATTCGATTCCCTGCAGAAATTGCATAACAACTGTCAAGATAA GTTTACC
GTTTTGCAACAGGCGATCTTGGGATTGGCTGAGGCAGATCTTAAAAAGGTCTTTATT AAAACTA
GTGATCTAAACGCATTGTCTAACACTATTTTTGGAAATTATTCTGTGTTCTCAGACG CGCTCAAT
TTATATAAAGAGTCGCTAAAAACTAAAAAGGCTCAAGAAGCTTTTGAAAAGTTGCCT GCACATA
GTATTCATGATTTAATCCAATACTTAGAACAATTTAATTCGTCTCTCGATGCTGAAA AGCAACAG
TCTACCGATACTGTATTAAACTACTTTATTAAAACCGACGAATTATATAGTCGTTTC ATTAAATC
CACCTCTGAGGCATTCACCCAAGTACAACCTCTCTTTGAACTGGAAGCTTTGAGCTC CAAAAGA
AGACCCCCAGAAAGTGAAGATGAGGGGGCTAAAGGCCAAGAAGGTTTCGAACAAATT AAGAGA
ATCAAAGCTTATCTAGACACTCTAATGGAGGCTGTCCACTTTGCTAAGCCTTTGTAT CTTGTCAA
GGGTAGAAAGATGATAGAGGGTCTAGACAAGGATCAAAGCTTCTACGAAGCGTTTGA AATGGC
CTACCAGGAGTTGGAGTCTTTAATCATCCCCATTTACAATAAGGCCAGATCTTACCT GTCTAGGA
AGCCATTTAAAGCGGATAAATTCAAAATTAATTTTGACAATAATACACTTCTATCTG GGTGGGA
TGCTAACAAGGAGACGGCTAACGCCAGCATATTGTTTAAGAAGGATGGTTTATACTA CCTGGGA
ATCATGCCAAAAGGCAAAACTTTCTTGTTCGATTATTTCGTTAGTTCAGAAGATTCT GAAAAGTT
GAAACAACGGAGACAGAAAACCGCAGAGGAAGCGCTCGCACAGGATGGAGAATCCTA TTTTGA
AAAAATACGGTATAAACTCCTACCAGGTGCTAGTAAGATGTTGCCAAAGGTATTTTT TAGCAAT
AAAAATATTGGGTTTTACAATCCCTCAGATGATATTCTACGAATTCGGAATACGGCC TCTCATAC
TAAGAATGGTACTCCCCAGAAGGGTCATTCCAAGGTAGAATTTAACTTGAATGACTG TCACAAA
TCTGATACGTCGGACTTTGAAGATATGAGTGCTTTCTACCGAGAAGTTGAAAATCAA GGTTACG
TTATAAGTTTTGATAAAATAAAAGAAACTTACATTCAGTCTCAAGTTGAGCAAGGTA ACTTATA
TTTATTTCAAATTTACAACAAAGATTTTAGTCCGTATTCAAAGGGAAAGCCAAACCT GCACACTT
TATACTGGAAAGCTCTGTTTGAAGAGGCTAATTTGAATAACGTAGTGGCTAAGCTAA ACGGCGA
AGCAGAAATCTTTTTCAGAAGACACAGTATCAAAGCATCTGATAAAGTGGTACATCC TGCTAAT
CAAGCTATAGATAATAAGAATCCCCATACTGAGAAGACGCAGTCCACATTTGAATAT GACTTGG
GCTCAGGGCGTTTCAAAGTTTAATGATAAGGTAAATGGATTCTTAAAGGGCAATCCC GACGTTA ATATAATCGGTATAGATCGAGGTGAGAGACATCTTTTATACTTTACCGTGGTGAATCAAA AAGG
AGAAATATTAGTGCAAGAGTCCTTGAATACATTAATGTCTGACAAGGGTCATGTCAA CGATTAT
CAACAGAAATTGGACAAGAAGGAACAGGAAAGGGACGCTGCCAGGAAGTCCTGGACG ACAGT
AGAAAATATTAAAGAATTAAAAGAAGGTTATTTATCACATGTGGTTCATAAACTTGC ACATTTA
ATCATCAAATATAACGCAATAGTGTGCTTGGAAGATCTTAATTTTGGCTTCAAGAGG GGTAGGT
TCAAGGTCGAAAAACAGGTCTACCAGAAGTTCGAGAAAGCTCTGATCGATAAATTGA ATTATCT
TGTTTTCAAAGAAAAAGAATTAGGAGAAGTTGGTCATTATCTTACAGCATACCAACT CACTGCA
CCATTTGAAAGCTTCAAAAAGCTAGGCAAGCAATCTGGGATTTTGTTCTATGTTCCG GCTGATTA
TACATCAAAGATAGATCCTACCACAGGCTTTGTAAATTTTTTAGATCTTAGGTACCA ATCCGTTG
AAAAAGCTAAACAGTTGCTGTCCGATTTTAATGCGATAAGATTTAATAGTGTTCAGA ATTATTTT
GAGTTCGAAATTGATTATAAAAAATTGACACCAAAACGTAAAGTAGGAACACAATCT AAATGG
GTTATTTGTACCTATGGAGATGTTAGATACCAAAACAGAAGAAATCAGAAAGGTCAC TGGGAA
ACTGAAGAAGTTAACGTTACTGAAAAACTTAAAGCTCTATTTGCGAGCGATTCAAAA ACGACGA
CGGTGATCGATTATGCAAATGATGATAACCTTATTGATGTAATTCTGGAACAAGATA AGGCATC
ATTTTTTAAAGAACTACTATGGTTGTTAAAGCTAACCATGACCCTAAGGCACTCCAA GATAAAG
TCAGAGGATGATTTTATCCTCTCTCCAGTGAAAAACGAACAAGGTGAGTTTTACGAC TCAAGAA
AGGCGGGTGAAGTCTGGCCTAAGGATGCTGATGCCAATGGAGCTTATCACATCGCTC TGAAGGG
GCTATGGAACTTACAGCAAATTAACCAATGGGAAAAAGGTAAAACTTTAAACCTCGC CATAAA
GAACCAGGATTGGTTCAGCTTTATCCAAGAAAAACCATATCAAGAATAA
SE ATGCACACAGGAGGTCTACTCTCGATGGATGCTAAGGAATTTACCGGTCAATATCCGCTG TCCA
Q AAACTTTGCGTTTTGAGCTTAGACCTATTGGCCGAACGTGGGATAACCTAGAGGCTTCTG GTTAT
no TTGGCGGAAGATAGACATAGAGCTGAGTGTTATCCCCGAGCTAAAGAATTGCTGGATGAT AACC
N ACAGGGCGTTCCTGAATAGAGTTCTACCGCAAATCGATATGGATTGGCATCCAATTGCTG AAGC
O: TTTCTGCAAGGTGCACAAAAATCCAGGTAATAAAGAATTGGCTCAGGATTATAATTTGCA GCTT 13 AGTAAGAGAAGAAAAGAAATTTCCGCTTATTTGCAGGATGCTGATGGATACAAGGGGTTG TTCG 1 CGAAACCTGCCCTGGACGAAGCTATGAAAATAGCTAAGGAAAACGGCAATGAATCTGATA TTG
AAGTTTTGGAAGCCTTCAATGGATTTTCCGTTTATTTCACTGGTTATCATGAGAGTA GGGAGAAT
ATATACTCAGACGAAGATATGGTATCCGTCGCCTATCGCATAACTGAAGATAATTTT CCAAGGT
TCGTGTCGAACGCGTTAATTTTTGATAAACTAAATGAATCGCACCCGGATATTATTT CGGAAGTG
TCCGGTAATCTGGGGGTAGACGATATTGGTAAATATTTTGATGTGTCCAACTACAAT AATTTCCT
TAGTCAAGCAGGAATTGATGACTACAACCATATTATAGGAGGGCATACAACTGAAGA CGGTCTC
ATTCAAGCTTTTAACGTAGTGTTAAACCTAAGGCACCAAAAAGACCCAGGTTTTGAG AAAATTC
AATTTAAGCAACTCTACAAGCAGATACTGAGCGTTAGGACTAGTAAGTCATATATCC CAAAGCA
ATTCGATAACTCAAAGGAAATGGTCGACTGTATATGCGACTACGTCTCAAAAATAGA AAAATCT
GAAACAGTAGAAAGAGCTCTGAAATTGGTAAGAAATATATCTTCTTTTGATTTAAGA GGTATTT
TCGTAAATAAAAAAAACCTTCGAATTTTGTCTAATAAGTTAATTGGAGACTGGGACG CAATAGA
GACAGCTTTGATGCACAGTTCCAGCAGTGAAAACGATAAGAAATCAGTGTATGACTC TGCAGAG
GCATTCACCCTTGATGATATCTTCAGTTCTGTGAAAAAGTTCAGCGACGCCTCCGCT GAGGATAT
AGGAAACCGCGCTGAAGACATATGTCGTGTTATCTCAGAAACAGCTCCTTTCATTAA CGACTTA
AGGGCTGTAGATTTGGATTCTTTAAATGATGACGGCTATGAAGCGGCCGTGTCTAAA ATACGGG
AATCTCTTGAACCCTACATGGATCTATTTCACGAATTGGAGATCTTTAGCGTGGGTG ATGAGTTT
CCTAAATGTGCTGCCTTTTATAGCGAGTTGGAAGAGGTCTCAGAACAACTGATTGAA ATCATTC CTTTATTTAACAAAGCAAGAAGTTTTTGCACAAGGAAAAGGTATTCAACCGACAAAATCA AAGT
CAATTTAAAATTCCCTACTCTGGCAGATGGATGGGATCTAAATAAAGAAAGGGATAA CAAAGCC
GCAATTCTAAGAAAAGACGGTAAATACTACCTGGCAATTTTAGACATGAAGAAAGAT CTCAGTA
GTATTCGTACGAGCGATGAGGACGAGTCTTCTTTTGAAAAGATGGAATATAAATTGC TCCCTTCT
CCTGTGAAAATGCTTCCAAAAATTTTTGTTAAATCGAAAGCCGCCAAAGAAAAGTAC GGGTTGA
CCGATAGAATGTTAGAATGCTACGATAAAGGTATGCATAAGTCGGGTAGTGCTTTTG ATTTGGG
TTTTTGTCATGAATTGATCGATTACTATAAGCGCTGCATTGCCGAGTACCCAGGCTG GGATGTTT
TCGACTTTAAATTTCGTGAGACAAGCGATTACGGATCCATGAAAGAATTTAATGAAG ACGTCGC
TGGCGCAGGTTACTATATGTCACTTAGAAAGATTCCATGTTCCGAAGTTTATCGTTT ACTGGACG
AGAAGTCAATTTACTTGTTTCAAATATATAATAAGGATTATAGCGAAAACGCACATG GGAATAA
GAATATGCATACGATGTATTGGGAGGGCTTGTTCTCACCACAAAATTTGGAATCACC AGTCTTC
AAATTGTCCGGAGGCGCAGAACTTTTTTTCAGAAAGTCATCTATTCCTAATGACGCT AAAACGG
TACATCCGAAAGGTTCAGTTCTTGTTCCCAGAAACGACGTCAATGGTAGAAGAATAC CAGACTC
GATCTACAGAGAGTTGACAAGGTATTTTAACCGTGGGGATTGCAGGATCAGTGATGA AGCTAAG
TCTTACCTGGACAAGGTCAAGACAAAAAAAGCGGACCATGACATTGTTAAGGATAGA AGATTT
ACTGTAGATAAGATGATGTTCCATGTTCCGATTGCCATGAATTTTAAAGCTATAAGT AAACCAA
ATCTTAATAAGAAAGTTATTGATGGCATAATAGATGATCAAGATTTGAAAATCATCG GTATCGA
TCGTGGTGAGAGAAATCTTATTTATGTGACCATGGTCGATAGGAAGGGGAATATATT GTATCAA
GACAGTCTTAATATTTTAAATGGATACGATTACCGCAAAGCTTTAGACGTGAGGGAA TATGATA
ACAAAGAAGCTAGAAGGAATTGGACTAAAGTAGAAGGTATTAGAAAAATGAAAGAAG GTTATT
TATCTTTAGCTGTTAGTAAATTGGCCGATATGATCATCGAAAATAATGCTATAATCG TAATGGAA
GATTTGAATCACGGGTTTAAGGCAGGTCGTTCCAAAATTGAAAAGCAGGTGTATCAA AAATTCG
AATCAATGTTAATCAACAAGTTAGGATACATGGTGCTAAAAGACAAGTCCATTGACC AGTCTGG
TGGAGCCCTTCATGGTTACCAATTAGCCAATCATGTTACGACCTTAGCTAGCGTGGG TAAACAA
TGATTTATTCGCTCTCTCTAATGTGAAGAATGTCGCTTCTATGAGAGAGTTCTTCTC CAAAATGA
AGTCAGTAATATATGACAAGGCGGAAGGCAAATTCGCCTTTACATTTGATTATTTGG ATTATAA
CGTTAAAAGCGAATGTGGACGTACCTTATGGACTGTGTATACAGTTGGTGAACGCTT CACCTAC
TCTAGAGTAAACCGAGAGTATGTTCGGAAAGTCCCAACAGATATCATCTATGATGCA TTACAAA
AAGCTGGTATTAGCGTCGAAGGTGACCTTAGAGATAGAATCGCGGAAAGCGACGGTG ACACAT
TAAAGTCTATATTCTACGCTTTTAAATACGCGTTGGATATGAGAGTCGAAAACAGAG AGGAAGA
CTATATACAGTCACCTGTGAAGAATGCTTCTGGTGAGTTCTTTTGTTCAAAAAACGC CGGAAAGT
CTTTGCCGCAGGATTCAGATGCAAATGGTGCCTATAATATAGCTCTGAAAGGGATCC TACAACT
CAGAATGTTGAGCGAACAATACGATCCAAATGCAGAATCGATTAGATTGCCACTTAT AACTAAC
AAGGCATGGTTAACTTTTATGCAATCCGGTATGAAAACTTGGAAGAATTAA
SE ATGGATTCTCTTAAGGATTTCACTAATTTATATCCAGTCTCGAAAACATTGCGGTTCGAA TTGAA
Q ACCAGTTGGGAAAACTCTAGAAAACATTGAAAAAGCCGGTATATTGAAAGAAGATGAACA CAG
no AGCGGAATCCTACCGCCGGGTAAAAAAGATAATTGACACATACCATAAAGTGTTTATTGA CAGC
N TCCTTAGAGAACATGGCTAAAATGGGGATAGAAAATGAAATCAAGGCTATGCTGCAGTCT TTTT
O: GTGAACTCTATAAGAAAGACCACAGGACAGAAGGAGAAGATAAAGCTCTTGATAAAATTA GAG 13 CTGTTCTTAGAGGTTTAATCGTTGGGGCTTTCACTGGTGTATGTGGAAGACGAGAAAACA CAGT 2 ACAAAATGAAAAGTACGAGAGTTTGTTCAAAGAAAAATTGATAAAGGAAATTTTGCCAGA TTTC GTGTTGTCCACCGAGGCTGAGTCTCTTCCATTCAGCGTTGAAGAAGCAACAAGGAGCTTA AAAG
AGTTTGACTCATTCACTTCTTATTTTGCTGGTTTTTACGAAAATAGAAAGAATATTT ATTCCACG
AAACCGCAAAGTACTGCGATAGCCTACAGATTAATTCATGAAAACTTGCCTAAATTT ATAGATA
ATATTTTGGTCTTCCAGAAGATTAAAGAACCAATCGCTAAAGAACTTGAGCACATAA GAGCAGA
TTTTAGCGCAGGCGGATATATCAAAAAAGATGAACGGCTAGAAGACATATTCTCATT AAATTAC
TACATTCATGTCCTTTCTCAAGCTGGTATAGAAAAATATAATGCTTTAATCGGGAAG ATAGTGAC
GGAAGGTGATGGTGAAATGAAAGGTCTTAATGAACATATTAACTTATATAACCAACA GAGGGG
TCGAGAGGATAGGTTGCCCTTGTTTAGGCCTCTATACAAGCAAATCCTGTCCGATAG AGAGCAA
TTGTCTTATTTACCTGAATCATTTGAAAAAGATGAAGAGCTGCTTAGAGCACTTAAG GAATTTTA
CGATCACATCGCCGAAGACATCTTGGGTAGAACACAGCAATTGATGACTTCAATTTC TGAATAC
GACTTGTCCCGTATTTATGTCAGAAATGATTCTCAACTTACAGACATCTCGAAGAAA ATGCTAG
GAGATTGGAACGCCATTTATATGGCTAGAGAACGAGCCTACGACCACGAACAGGCTC CTAAAC
GTATTACTGCTAAATACGAACGTGATAGAATCAAGGCCTTAAAAGGTGAAGAGTCAA TTTCATT
GGCGAATCTGAACAGCTGTATAGCTTTCTTGGACAATGTAAGGGATTGTCGAGTTGA CACATAC
CTATCAACTTTGGGGCAGAAAGAGGGTCCTCATGGCTTAAGTAACTTGGTGGAAAAC GTCTTCG
CCTCATATCATGAAGCAGAACAGTTATTGTCGTTTCCTTACCCCGAAGAGAACAACC TTATTCAG
GACAAAGACAATGTAGTTTTGATCAAAAACCTATTGGATAATATAAGTGATTTACAA CGTTTCC
TTAAACCTTTGTGGGGAATGGGCGATGAACCTGACAAAGACGAAAGGTTTTACGGTG AATACAA
CTATATTAGAGGAGCGCTTGACCAGGTAATACCTTTGTACAATAAAGTAAGGAACTA CTTGACT
CGTAAACCATATTCTACTAGAAAAGTTAAATTGAACTTTGGTAATTCACAGCTGCTG AGTGGTTG
GGATCGTAATAAAGAAAAAGATAACTCCTGTGTTATCTTGCGAAAAGGACAAAACTT TTACTTG
GCAATTATGAACAACCGTCACAAAAGGTCCTTCGAGAACAAAGTTCTGCCTGAATAC AAAGAA
GGTGAACCATATTTTGAAAAAATGGACTATAAATTCCTGCCAGATCCTAATAAAATG TTGCCTA
AGGTCTTCTTGTCTAAAAAAGGTATAGAAATATATAAACCATCCCCGAAGTTGCTGG AGCAATA
TGGTCATGGAACGCACAAAAAAGGTGACACTTTTAGTATGGATGACTTGCACGAGTT GATTGAT
TTTTTTAAACATTCCATTGAAGCGCACGAAGATTGGAAACAATTTGGTTTCAAGTTC TCTGACAC
AGCCACTTACGAAAATGTATCGTCCTTTTATAGAGAAGTGGAAGATCAGGGTTATAA ACTGTCA
TTCCGTAAGGTTAGTGAAAGCTATGTGTACTCGTTGATCGATCAAGGGAAGCTTTAT CTTTTTCA
AATCTATAATAAAGATTTCTCTCCTTGTTCAAAGGGCACACCTAATCTTCATACACT ATACTGGA
GAATGCTTTTCGATGAAAGAAATTTGGCTGATGTGATCTATAAATTAGACGGTAAAG CTGAGAT
TTTTTTCAGAGAGAAATCCCTGAAAAACGACCATCCAACTCATCCGGCAGGTAAACC GATTAAA
AAGAAATCCCGGCAAAAAAAGGGCGAAGAGAGTTTATTCGAGTATGATTTAGTTAAG GACAGA
CATTATACAATGGACAAATTTCAATTTCATGTGCCCATTACTATGAACTTTAAGTGT AGTGCAGG
GTCTAAGGTTAATGATATGGTAAACGCACATATTAGAGAAGCTAAAGATATGCACGT CATCGGT
ATTGATCGCGGAGAAAGAAATTTACTTTACATTTGCGTTATCGATTCTAGGGGCACC ATCTTGGA
TCAAATCTCTTTGAACACTATAAATGATATTGACTATCATGATCTACTAGAGAGTCG GGATAAA
GACAGGCAACAAGAAAGAAGAAATTGGCAAACAATTGAAGGTATTAAAGAATTAAAG CAAGG
CTATCTAAGCCAGGCTGTACACAGAATTGCCGAATTAATGGTAGCATATAAAGCTGT CGTAGCT
CTAGAAGACTTGAACATGGGTTTCAAAAGAGGGCGCCAGAAGGTCGAAAGTAGTGTT TATCAA
CAATTTGAAAAACAGTTAATAGATAAGTTGAATTATCTAGTGGATAAAAAAAAGCGT CCTGAGG
ACATTGGCGGTTTATTAAGAGCCTACCAATTCACTGCGCCATTTAAATCGTTCAAAG AAATGGG
TAAACAAAACGGTTTTCTATTCTACATCCCCGCATGGAATACCTCAAATATAGATCC AACTACCG GTTTCGTCAACTTATTTCATGCTCAATATGAGAATGTGGACAAAGCAAAATCATTCTTTC AAAAA
TTTGATAGCATTAGCTACAATCCTAAAAAAGATTGGTTTGAATTTGCGTTCGATTAT AAAAATTT
CACCAAGAAGGCTGAAGGTTCCAGATCTATGTGGATATTGTGCACCCACGGAAGTAG AATTAAG
AACTTCCGTAATTCACAGAAAAACGGCCAGTGGGACAGCGAAGAATTCGCCCTAACC GAAGCTT
TCAAAAGTCTTTTCGTAAGATACGAGATAGACTATACAGCTGATCTAAAGACAGCTA TTGTGGA
TGAGAAGCAAAAAGACTTCTTTGTCGACCTTCTTAAGTTGTTCAAGTTAACTGTGCA GATGAGA
AATAGTTGGAAGGAAAAAGACCTAGATTACTTGATTAGCCCAGTCGCTGGTGCAGAT GGCAGAT
TTTTTGATACACGTGAAGGCAATAAATCACTACCAAAAGACGCGGACGCTAATGGCG CATACAA
CATCGCATTGAAGGGTTTGTGGGCTCTCAGGCAGATTAGGCAGACAAGTGAGGGTGG TAAGCTT
AAGCTGGCGATTTCTAATAAGGAATGGTTACAGTTTGTTCAAGAAAGATCCTACGAA AAAGATT
AA
SE ATGAACAATGGTACTAATAATTTTCAAAACTTCATAGGGATTTCTAGCCTTCAAAAGACA TTGA
Q GAAATGCTTTAATTCCAACAGAAACGACTCAACAATTCATAGTGAAAAATGGTATTATAA AAGA
no AGACGAGTTGCGTGGCGAGAATAGACAAATTTTGAAAGATATCATGGATGACTACTACAG AGG
N GTTCATCTCCGAAACATTGTCTTCTATTGACGACATTGACTGGACCAGCTTATTCGAAAA AATGG
O: AAATACAGCTGAAGAACGGAGATAACAAGGACACTCTTATAAAGGAGCAAACGGAATATA GAA 13 AGGCTATACACAAAAAGTTTGCTAATGACGATAGATTTAAAAACATGTTTAGTGCGAAGT TAAT
3 TTCTGATATTCTACCCGAGTTTGTCATTCATAATAATAACTACTCTGCATCTGAAAAAGA GGAGA
AGACCCAGGTTATAAAGTTGTTTTCAAGATTTGCCACATCATTTAAAGACTACTTCA AGAACAG
GGCGAATTGCTTCTCTGCTGATGATATTAGCTCTTCCAGCTGTCATAGAATTGTTAA CGATAATG
ATAAACAAGATTAGTGGTGATATGAAAGATAGCCTTAAAGAAATGAGCCTTGAAGAG ATATATT
CATATGAGAAGTACGGTGAATTTATAACTCAAGAAGGAATTTCTTTTTATAACGATA TTTGTGGT
AAGGTTAATTCTTTTATGAATTTGTATTGCCAGAAGAACAAGGAAAATAAGAATCTA TATAAAC
TACAAAAGTTGCATAAACAGATTTTGTGTATAGCTGATACATCCTACGAAGTTCCGT ATAAATTT
GAATCTGATGAGGAAGTTTATCAATCGGTAAACGGTTTTCTTGACAACATTTCCAGC AAACATA
TCGTTGAGAGACTACGTAAAATTGGAGACAACTATAATGGTTACAATCTAGATAAAA TATACAT
AGTGTCCAAGTTTTATGAGTCTGTCTCTCAAAAGACATATCGTGATTGGGAGACCAT TAATACTG
CACTTGAAATTCATTATAACAACATATTGCCTGGTAACGGGAAGAGTAAAGCTGATA AGGTTAA
AAAGGCCGTCAAAAACGACTTGCAAAAGTCTATTACCGAGATAAATGAATTAGTGTC AAACTAC
AAACTATGCTCAGATGATAATATTAAAGCGGAAACATACATCCACGAAATTTCCCAC ATACTGA
ATAACTTTGAAGCTCAGGAGCTTAAATATAACCCGGAAATACACTTGGTTGAGAGCG AGTTAAA
AGCATCTGAGTTGAAAAATGTATTAGACGTCATCATGAATGCGTTTCATTGGTGTTC AGTTTTCA
TGACTGAAGAATTAGTCGACAAAGATAACAATTTTTATGCCGAATTAGAGGAAATAT ATGATGA
AATTTATCCCGTAATTAGTTTATACAATCTAGTTAGAAATTATGTTACACAAAAGCC GTATAGTA
CCAAGAAAATAAAGCTTAATTTCGGAATACCTACGCTTGCTGATGGTTGGTCAAAAA GTAAAGA
ATATAGCAATAATGCAATAATTTTAATGAGAGATAACCTATATTATTTGGGTATTTT TAACGCTA
AGAACAAACCAGACAAGAAAATAATTGAAGGTAATACATCTGAAAACAAGGGCGACT ATAAAA
AGATGATATACAATTTGCTCCCAGGTCCTAATAAAATGATTCCTAAGGTTTTCCTGA GTAGCAAG
ACTGGCGTTGAAACTTACAAGCCTAGTGCGTATATCCTGGAGGGTTATAAACAGAAC AAGCATA
TCAAATCCTCTAAGGACTTCGATATCACCTTTTGCCATGACTTAATCGATTATTTTA AAAATTGT
ATCGCAATTCATCCAGAATGGAAAAATTTCGGATTTGATTTTAGTGATACCAGCACT TACGAGG ATATCTCTGGGTTCTACAGAGAAGTGGAGTTGCAGGGCTACAAAATCGATTGGACTTACA TATC
TGAAAAGGACATAGATTTGCTGCAGGAGAAAGGTCAGCTATATTTGTTTCAAATCTA CAACAAA
GACTTTTCTAAAAAGTCTACCGGTAATGACAATCTGCACACAATGTACTTGAAGAAC TTATTCTC
CGAGGAGAACTTAAAGGACATTGTACTCAAGTTGAATGGAGAAGCCGAGATTTTTTT TAGAAAG
AGCAGTATAAAGAATCCTATAATCCACAAGAAGGGCTCAATTCTCGTGAATAGGACG TATGAGG
CAGAAGAAAAGGACCAATTTGGGAATATACAAATTGTAAGAAAAAACATCCCAGAAA ATATCT
ACCAGGAATTATATAAGTATTTTAATGACAAATCTGATAAGGAACTGTCTGACGAAG CCGCTAA
GCTCAAGAATGTTGTGGGCCACCATGAAGCTGCTACTAATATAGTGAAGGACTACAG ATATACC
TACGATAAATATTTCCTGCATATGCCAATTACTATAAACTTCAAAGCAAATAAAACA GGTTTTAT
AAATGATAGAATCCTGCAGTATATTGCTAAAGAAAAGGATTTACATGTAATTGGGAT TGATAGA
GGTGAACGCAATCTGATCTATGTCAGCGTAATAGATACTTGTGGTAATATTGTGGAA CAAAAGT
CCTTTAATATTGTGAACGGATATGATTACCAAATCAAGTTGAAACAACAAGAGGGAG CACGCCA
AATTGCCCGTAAGGAATGGAAAGAGATAGGTAAGATCAAGGAAATTAAGGAAGGTTA TCTTTC
ATTAGTTATTCACGAAATTTCGAAGATGGTAATCAAATACAACGCAATAATTGCTAT GGAGGAC
CTGTCATATGGATTTAAGAAAGGTAGATTCAAGGTTGAGAGACAGGTATACCAGAAA TTTGAAA
CTATGTTGATCAACAAATTAAATTACTTAGTCTTTAAGGACATATCAATAACGGAAA ACGGCGG
GCTTTTAAAAGGGTATCAACTTACATACATACCTGATAAGTTGAAAAATGTGGGTCA TCAGTGT
GGGTGCATCTTTTATGTTCCAGCCGCTTACACATCAAAAATCGATCCTACTACTGGG TTCGTAAA
CATATTTAAATTTAAAGATCTAACCGTTGATGCAAAAAGAGAGTTTATCAAGAAATT TGATAGC
ATTAGGTACGATTCAGAAAAAAATCTATTCTGTTTTACTTTTGACTACAACAACTTT ATAACGCA
GAATACAGTGATGTCAAAATCGTCCTGGTCAGTGTATACTTATGGTGTTAGAATTAA GAGACGT
TTCGTAAACGGTCGTTTTTCTAACGAGTCCGATACAATCGACATCACTAAAGATATG GAAAAAA
CTTTGGAAATGACAGATATAAACTGGAGAGATGGTCACGACCTTAGACAAGATATAA TCGATTA
TGAAATCGTACAGCATATTTTTGAAATTTTTCGCTTAACAGTTCAGATGCGTAACTC TCTTAGTG
AGCTAGAAGATAGAGATTATGATAGACTTATCTCGCCTGTTCTTAACGAAAATAATA TCTTCTAT
GACTCGGCAAAAGCCGGTGATGCACTTCCAAAAGATGCTGATGCAAATGGCGCGTAC TGCATCG
CATTGAAGGGGCTCTACGAGATTAAACAAATCACCGAAAACTGGAAAGAAGATGGTA AATTTT
CTAGGGATAAGTTGAAAATCAGTAATAAAGATTGGTTCGATTTTATACAAAATAAGC GATACTT
ATAG
SE ATGACCAATAAGTTTACTAATCAATACTCATTGTCTAAAACGTTAAGATTCGAGTTAATT CCCCA
Q GGGAAAGACACTAGAATTTATTCAAGAAAAAGGTCTTCTCTCTCAGGATAAACAAAGAGC AGA
no ATCATACCAGGAGATGAAAAAAACCATAGATAAATTTCATAAGTACTTCATCGACTTGGC ACTA
N TCGAACGCCAAGCTAACACATTTGGAAACCTACCTGGAGTTGTATAATAAATCGGCAGAG ACGA
O: AAAAGGAACAAAAATTCAAGGATGACCTGAAGAAGGTTCAAGATAATCTGCGAAAGGAAA TAG 13 TGAAGTCGTTTAGTGATGGTGATGCAAAGTCAATCTTTGCTATTTTAGACAAGAAGGAAT TAAT 4 AACCGTGGAACTTGAAAAGTGGTTTGAAAATAACGAACAGAAAGATATTTACTTCGACGA AAA
ATTTAAAACGTTTACTACGTACTTTACAGGGTTCCATCAGAACCGCAAAAACATGTA CTCCGTTG
AACCAAACTCTACTGCAATCGCCTACAGATTAATACACGAAAATTTGCCTAAGTTTT TAGAAAA
TGCAAAGGCTTTTGAAAAGATAAAGCAAGTCGAATCGTTACAGGTAAACTTTCGCGA ATTAATG
GGCGAATTTGGAGATGAAGGTCTTATTTTTGTCAATGAATTAGAGGAAATGTTTCAA ATTAATTA
TTATAACGATGTCTTGAGTCAGAACGGCATTACTATCTACAACTCAATTATCAGTGG TTTCACTA
AGAATGATATAAAATATAAAGGTTTGAATGAATACATTAATAATTATAATCAAACTA AAGATAA GAAGGACAGGCTTCCGAAATTGAAGCAATTGTACAAGCAGATTCTAAGTGATAGGATTAG TTTG
TCTTTCTTGCCAGACGCATTTACTGATGGCAAGCAAGTCTTAAAGGCTATATTCGAT TTCTACAA
GATTAACCTACTTTCGTACACAATTGAAGGTCAAGAAGAATCTCAAAATCTGCTGCT TTTGATTA
GGCAAACTATAGAAAATTTGTCGTCCTTTGACACTCAAAAAATTTACCTGAAGAATG ATACACA
CCTGACTACAATATCACAGCAGGTCTTTGGGGATTTTTCTGTCTTCTCCACGGCCCT AAACTATT
GGTATGAGACAAAAGTTAATCCAAAATTTGAAACAGAATATAGTAAGGCGAATGAAA AAAAGA
GAGAAATTTTGGATAAAGCGAAGGCAGTATTCACAAAACAAGACTATTTTTCTATCG CATTTCT
CCAAGAAGTCTTATCCGAATATATTTTGACACTCGATCACACCTCTGATATAGTTAA GAAACATT
CGTCCAACTGCATCGCAGATTACTTCAAGAATCACTTCGTGGCTAAGAAAGAAAACG AAACGGA
TAAAACTTTTGACTTCATTGCTAACATAACCGCTAAATACCAATGTATTCAGGGCAT ATTAGAAA
ATGCAGACCAGTACGAAGACGAGTTAAAACAGGACCAAAAGTTAATAGATAATCTAA AGTTTTT
CTTAGATGCTATACTTGAGTTATTACATTTTATAAAGCCATTGCATCTAAAATCGGA AAGTATTA
CTGAAAAAGACACTGCGTTCTATGATGTGTTCGAAAATTATTATGAGGCTTTATCTT TATTGACC
CCCCTTTACAACATGGTCCGCAATTATGTTACTCAGAAGCCTTACTCTACTGAAAAG ATCAAATT
AAACTTTGAAAATGCTCAGTTGCTGAATGGTTGGGATGCCAATAAGGAAGGTGACTA CCTGACG
ACTATTCTAAAAAAAGACGGTAATTATTTCTTAGCAATCATGGATAAAAAACATAAC AAGGCAT
TTCAAAAATTTCCAGAAGGAAAAGAAAACTATGAAAAGATGGTTTATAAATTGTTGC CTGGAGT
TAATAAAATGTTGCCAAAAGTTTTTTTTAGCAATAAGAACATAGCTTACTTTAATCC ATCTAAGG
AACTGCTCGAGAACTACAAGAAGGAAACACATAAAAAAGGTGATACATTTAATTTGG AACATT
GCCATACTCTGATTGATTTTTTTAAGGACTCTCTTAATAAACATGAAGACTGGAAAT ATTTTGAT
TTTCAATTTTCGGAAACTAAATCATACCAAGATCTAAGTGGATTTTACAGAGAAGTT GAACACC
AAGGTTATAAGATTAACTTCAAGAATATAGATTCTGAATACATTGATGGTCTTGTAA ACGAGGG
TAAACTATTCCTGTTCCAAATCTACTCTAAGGACTTCTCACCTTTTTCCAAAGGAAA ACCTAATA
TGCATACGTTGTACTGGAAGGCTCTATTTGAAGAACAAAATTTGCAAAATGTAATCT ACAAACT
GAACGGCCAAGCTGAAATATTCTTCAGAAAAGCCTCAATTAAGCCAAAAAACATTAT TCTTCAT
AAAAAGAAGATCAAGATTGCGAAGAAACATTTTATTGATAAGAAGACCAAGACTTCC GAAATT
GTACCAGTACAAACAATCAAGAATCTCAATATGTATTATCAAGGCAAGATAAGTGAG AAAGAG
TTAACCCAGGATGATTTACGTTATATAGACAATTTCTCTATATTCAACGAGAAGAAC AAAACAA
TAGACATTATCAAAGATAAAAGGTTTACTGTTGACAAATTTCAATTTCATGTGCCTA TCACAATG
AACTTTAAGGCCACAGGTGGTTCGTACATTAATCAAACTGTTTTAGAATATCTGCAA AATAACC
CAGAGGTCAAGATCATCGGTCTTGATAGGGGTGAGAGACATCTGGTGTATCTAACAC TCATTGA
TCAACAAGGCAACATCTTGAAGCAAGAATCATTGAACACTATCACAGACTCCAAGAT CTCGACT
CCATATCACAAACTCCTTGACAATAAAGAAAACGAAAGGGATCTTGCCAGAAAAAAT TGGGGT
ACAGTTGAAAATATTAAGGAACTAAAAGAAGGTTACATTTCGCAAGTAGTTCACAAG ATTGCAA
CACTCATGTTGGAAGAAAACGCAATCGTTGTCATGGAAGATTTAAATTTCGGATTTA AGAGAGG
AAGATTTAAAGTAGAAAAGCAAATCTACCAGAAGTTGGAGAAGATGTTAATTGACAA ATTGAA
CTACTTAGTGCTGAAAGACAAACAGCCTCAAGAATTGGGCGGTCTATACAACGCTTT ACAACTG
ACAAATAAATTTGAGTCATTCCAAAAGATGGGTAAGCAGAGTGGTTTTTTGTTTTAT GTTCCGGC
ATGGAACACATCCAAAATCGATCCAACTACAGGCTTCGTGAATTATTTCTACACTAA ATATGAA
AATGTGGATAAAGCAAAAGCTTTCTTTGAGAAGTTCGAGGCGATCCGTTTTAACGCT GAAAAGA
AGTACTTCGAGTTCGAGGTCAAAAAGTATTCAGATTTTAACCCCAAGGCTGAAGGCA CCCAGCA
AGCATGGACTATTTGCACGTACGGTGAGCGAATCGAAACTAAAAGGCAAAAGGATCA AAATAA TAAGTTTGTAAGCACACCCATTAACTTGACAGAAAAGATAGAAGATTTTCTTGGAAAAAA CCAA ATTGTATATGGTGACGGTAACTGTATCAAGTCACAAATTGCTTCTAAAGACGATAAGGCC TTCTT CGAAACTCTGCTATACTGGTTTAAAATGACGTTGCAAATGAGAAACAGTGAAACTAGAAC TGAT ATCGACTATTTAATATCACCCGTGATGAACGATAATGGTACCTTTTACAATTCAAGAGAT TACGA GAAATTGGAGAACCCCACACTACCAAAAGACGCAGACGCTAATGGTGCCTACCATATTGC TAAA AAGGGACTGATGTTGTTGAACAAGATAGATCAAGCCGACTTAACTAAAAAAGTTGATTTG TCAA TTTCGAATAGAGATTGGTTGCAATTCGTCCAGAAAAATAAGTAA
SE ATGGAACAGGAATACTACTTGGGTTTGGATATGGGAACTGGTTCAGTCGGTTGGGCTGTT ACGG
Q ACTCCGAGTACCACGTGTTGAGAAAACACGGAAAGGCTTTATGGGGTGTCAGACTATTCG AATC
no AGCATCGACCGCGGAAGAGAGAAGAATGTTTAGAACTTCAAGAAGAAGGCTGGATCGTAG GAA
N TTGGCGGATAGAAATTTTACAAGAAATATTCGCCGAAGAAATCTCTAAAAAAGATCCAGG ATTT
O: TTTCTACGTATGAAGGAATCCAAATACTATCCGGAAGATAAACGTGATATTAATGGCAAT TGTC 13 CAGAGTTACCCTATGCTTTATTTGTGGACGACGATTTCACCGATAAAGATTACCATAAGA AGTTC 5 CCAACAATTTACCATCTGAGAAAGATGTTAATGAACACTGAAGAAACCCCGGATATAAGA CTGG
TCTATCTAGCCATTCATCATATGATGAAACACAGGGGACACTTCTTGCTATCAGGGG ATATAAA
TGAAATTAAAGAATTTGGTACAACATTTTCTAAATTATTGGAAAATATTAAAAACGA AGAATTA
GATTGGAATTTAGAATTAGGCAAGGAGGAATACGCAGTTGTCGAATCGATTCTGAAA GATAACA
TGTTGAACAGATCAACGAAAAAAACAAGGCTGATCAAGGCTTTAAAAGCGAAATCAA TATGCG
AAAAAGCAGTATTGAATTTGTTAGCTGGGGGGACTGTCAAGTTGTCTGATATTTTCG GATTGGA
AGAATTGAATGAAACAGAGAGACCGAAGATATCCTTCGCCGATAATGGCTACGATGA TTATATA
GGCGAAGTCGAAAATGAGCTGGGCGAACAATTCTACATTATCGAGACTGCCAAGGCT GTTTATG
ATTGGGCGGTGTTAGTCGAAATCCTTGGCAAATACACTTCCATCTCCGAAGCTAAGG TGGCAAC
CTACGAAAAGCATAAAAGTGATTTGCAATTCCTTAAGAAAATTGTCCGAAAGTACTT GACCAAA
GAAGAGTACAAGGATATTTTCGTATCAACATCGGACAAACTGAAGAATTATTCAGCT TATATTG
GCATGACGAAAATTAATGGTAAGAAAGTTGATTTGCAATCCAAGAGATGTTCTAAAG AAGAATT
TTACGATTTCATTAAAAAAAATGTCCTAAAAAAGTTGGAGGGACAACCTGAATATGA GTATTTA
AAGGAAGAACTGGAAAGAGAAACTTTCCTACCAAAGCAAGTTAATCGTGATAATGGC GTTATTC
CATACCAAATACACTTGTACGAATTAAAGAAGATCTTGGGTAACTTGAGGGACAAAA TTGATTT
AATCAAGGAAAATGAAGACAAACTGGTACAATTATTTGAATTTAGAATACCTTACTA CGTGGGC
CCTTTAAACAAAATAGACGATGGTAAGGAAGGGAAGTTCACATGGGCAGTCAGAAAG TCCAAT
GAAAAAATTTACCCATGGAATTTCGAAAACGTTGTAGATATTGAAGCTTCTGCTGAG AAATTTA
TTAGGAGAATGACAAATAAATGCACTTATCTTATGGGGGAAGACGTGTTGCCTAAAG ATAGTTT
ATTATATTCAAAGTATATGGTCTTAAATGAATTAAACAATGTTAAATTAGATGGTGA AAAACTTT
CCGTCGAATTGAAACAAAGATTGTATACAGATGTATTCTGCAAATATAGAAAAGTAA CTGTAAA
GAAGATTAAAAACTACCTTAAATGTGAAGGCATTATCAGCGGAAATGTTGAGATCAC TGGTATC
GATGGTGATTTTAAGGCATCTTTAACCGCATATCACGACTTTAAGGAAATATTGACG GGTACTG
AGCTTGCTAAAAAAGACAAAGAGAACATTATCACCAATATCGTGCTCTTCGGAGACG ACAAGA
AATTATTGAAAAAGAGATTGAACCGCCTATACCCTCAGATTACCCCTAACCAATTGA AGAAAAT
CTGCGCTCTGTCTTATACTGGATGGGGTCGTTTTAGCAAGAAGTTTCTAGAAGAAAT TACTGCTC
CGGATCCTGAAACTGGGGAAGTCTGGAATATAATTACCGCGCTATGGGAATCGAATA ATAATTT
AATGCAATTACTATCTAATGAATACAGATTTATGGAAGAAGTCGAAACTTACAATAT GGGAAAA
CAAACAAAAACTTTGAGCTACGAAACAGTAGAGAATATGTATGTCTCACCATCTGTA AAGCGGC AGATCTGGCAAACCTTGAAGATAGTTAAAGAATTAGAAAAAGTGATGAAGGAAAGTCCAA AAA
AACTTATAGATCTATATAAAGCCTGCAAAAATGAAGAAAAAGATTGGGTAAAGGAAT TAGGTG
ACCAGGAAGAGCAAAAATTGAGATCTGACAAGCTGTACTTGTATTATACGCAAAAGG GCCGGT
GTATGTATTCGGGTGAGGTAATAGAATTGAAAGATTTATGGGATAACACTAAGTATG ACATTGA
CCATATTTACCCCCAGTCTAAGACAATGGACGATTCATTAAATAACCGAGTTCTTGT CAAAAAG
AAGTACAATGCCACAAAGAGCGATAAGTACCCATTGAACGAAAATATAAGACATGAA CGAAAA
GGTTTCTGGAAATCATTGTTGGACGGTGGATTTATTTCCAAAGAAAAATACGAGAGA TTGATTA
GAAACACTGAACTATCTCCAGAGGAGTTAGCTGGCTTTATCGAAAGACAAATTGTTG AAACTAG
ACAGTCTACAAAAGCAGTTGCAGAAATCTTAAAACAAGTATTTCCAGAATCCGAAAT TGTGTAC
GTCAAAGCCGGAACAGTAAGTAGATTTAGAAAAGACTTTGAATTATTGAAAGTACGA GAGGTT
AACGACCTACATCATGCTAAGGATGCTTATTTAAATATAGTCGTTGGTAATTCGTAT TACGTGAA
ATTCACAAAAAACGCATCTTGGTTCATCAAGGAGAATCCTGGTAGGACATACAACTT GAAAAAG
ATGTTTACATCAGGATGGAATATCGAAAGAAATGGTGAGGTTGCGTGGGAGGTAGGC AAGAAG
GGAACCATTGTTACTGTAAAGCAAATTATGAATAAAAACAATATACTTGTTACGAGA CAGGTGC
ACGAAGCCAAAGGAGGGTTGTTTGACCAGCAAATCATGAAGAAAGGTAAAGGTCAGA TAGCAA
TAAAAGAGACTGATGAGCGTTTAGCTAGTATAGAAAAATATGGGGGCTACAATAAGG CAGCTG
GTGCTTACTTCATGTTGGTCGAATCAAAGGATAAAAAAGGGAAGACGATCCGGACCA TAGAGTT
TATCCCTCTGTACTTGAAGAATAAGATTGAGTCTGACGAAAGCATCGCATTGAATTT CTTGGAA
AAGGGGCGCGGTCTAAAGGAGCCAAAAATATTGTTAAAGAAAATTAAAATAGACACC CTATTC
GACGTCGATGGGTTTAAGATGTGGCTTAGTGGTCGTACTGGGGACAGATTATTATTC AAGTGTG
CCAATCAGTTAATCCTTGACGAGAAAATCATTGTTACAATGAAAAAAATTGTTAAGT TTATTCA
AAGGCGACAAGAAAATAGAGAACTAAAGTTGAGTGATAAGGATGGAATCGATAATGA AGTGTT
AATGGAGATTTATAACACTTTTGTCGACAAATTGGAGAATACGGTGTACAGAATTAG GCTATCT
GAACAGGCTAAAACCCTAATTGATAAACAGAAGGAGTTTGAGCGACTTTCTCTTGAA GACAAAT
CTTCAACTCTTTTCGAGATCCTACATATCTTTCAGTGTCAATCTTCTGCAGCTAATT TGAAAATGA
TTGGAGGTCCTGGTAAGGCTGGTATATTAGTCATGAACAACAACATATCTAAGTGTA ATAAGAT
TAGTATAATTAACCAATCACCGACAGGTATCTTTGAAAATGAAATTGATTTACTTAA A
SE ATGAAATCATTCGACTCGTTCACCAACTTGTACTCCCTGTCTAAAACATTGAAATTTGAA ATGCG
Q ACCTGTTGGTAACACCCAAAAGATGTTAGATAATGCAGGAGTTTTCGAAAAGGATAAACT GATC
no CAGAAAAAATACGGTAAAACGAAACCATATTTCGATAGGTTGCATCGGGAATTTATAGAA GAA
N GCTTTGACTGGTGTAGAATTAATTGGCTTAGATGAGAATTTCCGTACTCTAGTCGATTGG CAAAA
O: AGATAAAAAGAACAATGTTGCCATGAAGGCATACGAAAATAGTCTACAAAGACTAAGAAC AGA 13 GATCGGGAAAATTTTCAATTTGAAGGCAGAAGACTGGGTGAAGAACAAATATCCAATATT GGGT 6 CTTAAGAATAAGAATACTGATATATTGTTCGAGGAGGCCGTTTTCGGTATTCTTAAGGCA AGAT
ATGGTGAAGAGAAAGACACGTTTATTGAAGTTGAGGAGATTGATAAAACCGGTAAGT CCAAAA
TCAACCAGATCTCTATCTTCGACAGTTGGAAGGGCTTCACTGGTTATTTTAAGAAGT TCTTCGAA
ACTAGGAAGAACTTCTATAAAAACGATGGTACTTCCACGGCTATTGCTACAAGAATT ATCGACC
AAAACCTTAAGCGTTTTATTGATAACCTATCAATTGTTGAAAGTGTTCGACAGAAAG TAGATTTG
GCTGAAACTGAAAAATCTTTTAGTATCTCCTTATCCCAGTTTTTCTCTATAGATTTT TATAATAAA
TGTTTGCTGCAAGATGGCATTGACTACTATAATAAAATAATTGGTGGAGAGACATTG AAAAACG
GAGAGAAGCTGATTGGCCTTAATGAGTTGATAAATCAATATAGACAAAATAATAAGG ACCAGA AAATCCCTTTCTTTAAATTGCTAGACAAACAGATTTTGTCTGAAAAGATCCTATTCTTGG ATGAA
ATAAAGAACGATACTGAATTGATTGAAGCTTTGTCCCAGTTTGCTAAAACAGCTGAA GAAAAGA
CAAAGATTGTGAAAAAATTGTTTGCTGATTTCGTAGAAAACAATTCTAAATATGATC TAGCCCA
GATTTATATAAGTCAAGAAGCTTTCAATACAATAAGTAATAAGTGGACAAGTGAAAC AGAAACT
TTTGCTAAGTATTTATTCGAAGCCATGAAGTCTGGTAAACTTGCCAAATACGAAAAA AAAGATA
ACAGTTATAAATTTCCAGACTTTATAGCCCTTTCACAGATGAAGTCTGCCTTATTGT CGATATCC
TTAGAAGGTCATTTTTGGAAGGAAAAATATTATAAGATAAGCAAGTTCCAAGAAAAG ACTAATT
GGGAACAATTTTTGGCTATATTTCTATATGAGTTCAATTCATTATTTTCCGATAAAA TCAACACT
AAGGATGGAGAGACTAAGCAAGTTGGCTACTATTTGTTCGCAAAAGATCTGCACAAT TTGATTC
TATCAGAACAAATAGATATACCAAAAGATTCAAAGGTAACTATAAAGGATTTCGCAG ATTCCGT
CCTCACCATTTATCAAATGGCTAAATATTTTGCCGTTGAAAAAAAGAGAGCGTGGTT AGCAGAA
TACGAGTTGGACTCGTTTTATACTCAGCCAGATACTGGATACTTGCAATTCTACGAT AATGCATA
CGAAGACATTGTACAGGTATACAATAAACTTAGAAATTACTTAACCAAGAAGCCCTA CAGTGAA
GAAAAATGGAAGCTGAACTTTGAAAATTCGACTTTGGCAAATGGTTGGGATAAAAAT AAAGAA
AGTGACAACTCCGCAGTGATTTTGCAAAAGGGTGGGAAATATTACTTGGGTTTAATC ACAAAAG
GCCACAATAAGATTTTTGATGATAGATTTCAAGAAAAATTCATAGTTGGTATAGAAG GTGGCAA
ATACGAGAAAATTGTCTATAAATTCTTCCCTGATCAAGCCAAAATGTTCCCAAAAGT TTGCTTTT
CTGCTAAAGGATTGGAGTTTTTCCGGCCTAGCGAGGAGATCCTTCGTATCTACAACA ATGCTGA
ATTCAAAAAAGGAGAAACCTATAGCATAGATTCTATGCAAAAACTGATAGATTTTTA TAAGGAT
TGTTTAACAAAGTACGAAGGCTGGGCCTGCTATACATTTAGACATTTAAAGCCCACA GAAGAAT
ACCAAAATAACATTGGTGAATTCTTTCGGGACGTTGCCGAAGACGGCTATAGGATCG ATTTTCA
AGGTATCTCAGATCAATATATCCACGAAAAGAACGAGAAGGGTGAGCTGCACCTTTT CGAAATT
CATAATAAGGACTGGAATTTGGATAAGGCGAGAGATGGTAAATCGAAGACCACTCAA AAGAAC
TTGCATACTTTATATTTTGAGTCCTTGTTTTCTAATGATAACGTCGTCCAAAATTTT CCAATAAAG
TTGAATGGACAAGCGGAAATTTTCTATCGGCCTAAGACAGAGAAAGACAAATTAGAA TCAAAG
AAAGATAAAAAGGGAAATAAAGTCATTGATCACAAACGATACTCTGAGAATAAAATA TTTTTCC
ACGTACCATTGACACTCAACAGGACTAAGAATGACTCTTATAGATTTAATGCTCAGA TTAATAA
TTTTTTGGCAAATAACAAGGATATTAACATAATTGGGGTGGATAGAGGTGAAAAGCA CTTGGTA
TATTACTCTGTCATCACTCAGGCTTCTGATATATTGGAAAGCGGGTCTCTAAATGAA TTGAACGG
TGTTAACTACGCCGAAAAGCTAGGTAAAAAAGCTGAAAACAGAGAGCAGGCTCGGCG CGATTG
GCAAGATGTTCAAGGAATTAAAGACCTTAAAAAAGGCTACATTAGTCAAGTAGTTAG AAAGTTA
GCCGATCTTGCTATTAAACATAACGCAATCATTATTCTGGAGGACCTAAATATGCGT TTTAAGCA
AGTTAGGGGTGGCATAGAAAAAAGTATTTATCAGCAGCTTGAGAAGGCTTTGATAGA TAAGTTA
TCGTTCCTAGTTGACAAAGGTGAAAAAAATCCTGAACAAGCTGGTCATCTGTTGAAA GCTTATC
AGCTGAGCGCACCTTTTGAAACATTTCAAAAAATGGGAAAACAAACAGGTATTATTT TCTATAC
TCAAGCGAGTTATACAAGTAAATCTGACCCAGTGACAGGATGGAGACCACACCTTTA TCTAAAA
ATAGATTTGAATTGACTTACGATATTAAAGATTTTCAGCAAGCAAAAGAATACCCAA ATAAGAC AGTGTGGAAAGTATGCTCCAATGTGGAGAGATTTAGATGGGATAAAAATCTCAATCAAAA CAA GGGTGGTTACACACATTATACTAATATAACTGAAAATATTCAAGAATTGTTTACTAAGTA CGGA ATTGACATAACCAAAGACTTACTAACTCAGATTTCAACTATTGACGAAAAACAAAATACC TCAT TTGCCAAGAAGAACGGAAAAGATGATTTCATCCTATCTCCAGTGGAACCATTTTTTGACT CAAG
AAAAGATAATGGTAATAAGTTGCCTGAGAACGGAGATGATAACGGCGCTTATAATAT CGCTCGG
AAGGGTATTGTAATTCTTAATAAAATATCTCAGTACTCTGAAAAGAACGAAAACTGC GAGAAAA
TGAAGTGGGGCGACTTGTATGTATCTAATATAGATTGGGATAATTTCGTTACTCAAG CCAACGC
GAGACATTGA
SE ATGGAAAATTTTAAAAACCTATATCCAATTAATAAGACACTTAGATTCGAGCTTAGGCCA TACG
Q GCAAAACACTAGAAAATTTTAAGAAGTCAGGCCTATTAGAAAAAGACGCCTTTAAGGCAA ATTC
no CAGAAGATCAATGCAGGCAATTATTGATGAGAAATTTAAAGAGACTATCGAGGAAAGGTT GAA
N ATACACTGAATTCTCTGAGTGCGATCTGGGAAACATGACTTCCAAGGATAAAAAGATTAC CGAT
O: AAGGCTGCTACCAACCTCAAAAAGCAAGTCATCTTATCGTTTGATGATGAAATTTTTAAT AACTA 13 CTTAAAGCCGGACAAAAACATTGACGCCCTATTCAAAAATGATCCGTCCAACCCCGTAAT TTCA
7 ACTTTTAAGGGTTTTACCACGTACTTTGTAAATTTTTTTGAGATTCGTAAACATATCTTC AAAGG
AGAATCGTCGGGTTCCATGGCCTATAGGATAATTGATGAAAATCTTACGACTTACTT AAACAAT
ATCGAAAAGATAAAAAAGTTACCAGAAGAATTAAAGTCTCAATTGGAAGGTATTGAC CAAATA
GACAAATTAAATAACTATAATGAGTTCATAACTCAAAGCGGTATCACACATTACAAT GAAATTA
TCGGTGGTATATCTAAAAGTGAGAACGTAAAAATACAGGGAATAAACGAGGGGATCA ATCTAT
ACTGTCAGAAGAATAAAGTAAAATTACCAAGACTAACGCCATTATACAAAATGATTC TGTCTGA
TAGAGTTTCCAACTCGTTCGTGCTTGATACTATAGAAAATGATACTGAATTAATTGA GATGATTA
GCGACTTGATTAATAAAACAGAAATATCTCAAGACGTAATAATGTCAGACATTCAGA ACATTTT
CATAAAATATAAACAGCTTGGTAATTTACCGGGGATAAGTTACTCTAGCATCGTGAA TGCTATTT
GCTCCGATTATGACAATAATTTTGGTGACGGAAAAAGAAAAAAATCATATGAGAACG ATAGGA
AGAAACACCTTGAAACAAACGTATACTCAATTAACTATATATCGGAACTGTTAACAG ACACCGA
TGTATCATCTAATATAAAAATGAGATATAAGGAACTTGAACAAAATTACCAGGTGTG TAAGGAG
AATTTCAATGCTACCAACTGGATGAACATTAAGAATATTAAACAGAGTGAAAAGACA AACTTGA
TTAAAGATCTACTAGATATACTGAAATCAATACAGAGATTCTACGATCTGTTTGATA TAGTTGAT
GAAGACAAAAATCCTAGTGCTGAGTTTTACACGTGGCTAAGTAAAAATGCGGAAAAG TTAGATT
TCGAGTTCAACTCTGTTTATAATAAATCTAGGAATTATTTAACTAGAAAGCAGTATT CTGATAAA
AAGATAAAATTGAACTTCGACTCCCCTACGTTGGCAAAGGGTTGGGATGCAAACAAA GAAATC
GATAACTCCACCATAATAATGCGTAAGTTTAACAATGATAGGGGGGATTACGATTAT TTTTTGG
GAATTTGGAACAAATCTACCCCAGCGAATGAAAAAATTATTCCCCTTGAAGACAATG GTCTTTT
TGAAAAAATGCAGTATAAATTATATCCAGACCCATCCAAGATGCTTCCAAAGCAATT TCTGTCA
AAAATTTGGAAGGCTAAACACCCTACTACTCCTGAATTTGATAAGAAGTATAAGGAG GGCCGAC
ACAAAAAGGGTCCAGATTTTGAAAAAGAATTCCTGCATGAATTGATAGATTGTTTTA AGCATGG
TTTGGTAAATCATGATGAAAAATATCAGGATGTCTTTGGATTCAATTTGAGAAATAC AGAGGAT
TACAACTCATATACAGAATTTCTCGAGGACGTCGAACGTTGCAATTATAATCTCAGT TTCAACAA
GATCGCAGACACTTCAAACTTAATTAACGACGGAAAATTGTACGTTTTTCAAATCTG GTCGAAA
GACTTTAGTATTGATTCAAAGGGTACAAAAAACCTAAATACAATATATTTCGAAAGT CTATTCTC
GGAAGAAAACATGATCGAAAAAATGTTCAAACTGTCAGGCGAAGCTGAAATATTCTA CCGTCCC
GCAAGCCTTAATTATTGTGAGGATATCATTAAAAAAGGACATCACCATGCAGAGTTA AAAGATA
AATTCGATTACCCAATAATTAAAGATAAAAGATACTCCCAGGATAAGTTCTTTTTCC ATGTACCT
ATGGTTATTAACTACAAGTCGGAAAAACTAAACTCGAAGTCATTAAATAATAGAACT AACGAGA
ACTTGGGACAATTCACACATATAATTGGTATTGATCGTGGCGAAAGACATTTAATAT ATCTGACT GTTGTTGATGTTTCAACAGGAGAAATTGTTGAACAGAAACATCTTGATGAAATTATAAAC ACAG
ATACAAAAGGCGTTGAGCATAAAACTCATTATCTAAATAAATTGGAGGAAAAGTCGA AGACTC
GCGATAACGAGAGAAAGAGTTGGGAAGCAATTGAAACCATAAAAGAGCTTAAAGAAG GTTACA
TTAGTCACGTCATCAATGAAATACAAAAGTTACAAGAAAAGTATAACGCTTTGATTG TAATGGA
AAATCTAAATTATGGTTTTAAGAATTCAAGAATCAAAGTCGAAAAGCAGGTCTATCA GAAATTT
GAAACGGCACTTATTAAAAAGTTTAACTACATTATTGATAAAAAGGACCCAGAAACT TATATTC
ATGGTTACCAACTGACGAACCCAATCACAACATTGGACAAAATTGGAAACCAAAGTG GAATTGT
TTTATACATTCCAGCTTGGAATACATCCAAAATAGACCCTGTCACGGGGTTTGTCAA CTTGTTAT
ATGCCGACGATTTAAAGTATAAAAACCAAGAACAAGCAAAGTCTTTTATTCAAAAGA TTGATAA
TATTTATTTCGAAAACGGTGAATTTAAATTCGACATAGATTTTTCTAAATGGAACAA CCGTTATT
CAATAAGTAAAACTAAATGGACACTCACCTCATACGGCACTCGTATCCAAACCTTTC GGAATCC
CCAAAAAAATAACAAATGGGATTCTGCAGAATACGACTTGACCGAGGAATTTAAATT AATTCTT
AATATAGACGGTACACTCAAAAGTCAAGACGTGGAGACATACAAGAAGTTTATGTCG TTATTCA
AGCTTATGCTTCAGTTGAGGAACTCCGTTACAGGCACTGATATTGATTACATGATTT CACCAGTA
ACGGATAAGACTGGGACTCATTTCGATTCTAGGGAAAATATTAAAAATTTACCTGCT GACGCAG
ACGCAAACGGCGCATACAATATAGCAAGAAAAGGGATTATGGCCATTGAGAATATTA TGAATG
GCATATCAGATCCATTAAAGATAAGCAATGAAGACTACTTAAAATACATTCAGAATC AGCAAGA
ATAA
SE ATGACCCAGTTTGAAGGTTTCACCAATTTGTACCAAGTAAGTAAAACCTTGAGGTTCGAA TTGA
Q TCCCACAGGGCAAGACATTGAAGCATATTCAAGAGCAAGGATTTATAGAAGAAGATAAAG CGA
no GAAACGATCACTATAAAGAGTTAAAACCCATTATTGACAGGATCTATAAAACATACGCCG ATCA
N ATGCCTTCAATTAGTGCAATTAGATTGGGAAAACTTGAGCGCTGCCATCGATTCCTACAG GAAG
O: GAAAAAACAGAAGAAACAAGAAATGCCTTAATCGAGGAACAAGCAACCTATAGAAACGCT ATA 13 CACGATTACTTCATCGGTAGAACTGATAATCTAACAGATGCAATAAATAAGAGACATGCT GAGA 8 TATATAAAGGACTATTTAAAGCAGAATTATTCAACGGAAAGGTGTTGAAACAGTTAGGTA CCGT
TACAACTACTGAGCATGAAAATGCCTTGCTGAGAAGCTTTGACAAGTTTACTACCTA CTTTTCGG
GTTTCTACGAAAATCGCAAAAATGTATTTTCTGCGGAAGATATTTCAACTGCAATCC CTCATAGG
ATTGTTCAAGATAATTTCCCTAAGTTTAAAGAGAACTGTCACATTTTTACAAGGTTA ATTACTGC
GGTTCCAAGTCTAAGAGAACATTTTGAGAATGTAAAAAAAGCGATTGGTATATTTGT ATCCACT
GTACAACCAATTGTTAGGTGGTATATCGAGGGAGGCTGGTACGGAAAAGATTAAAGG ATTAAA
TGAAGTTCTTAATTTGGCCATACAAAAAAATGATGAAACCGCGCACATTATCGCATC TTTACCA
CATAGGTTTATACCGTTATTCAAGCAAATATTATCTGATCGTAATACCTTATCGTTC ATATTAGA
GGAGTTTAAATCTGACGAAGAAGTTATACAATCTTTTTGCAAGTATAAGACGCTATT GAGAAAC
GAAAACGTTCTGGAAACAGCCGAAGCACTGTTCAATGAATTAAACAGTATCGACTTG ACTCATA
TTTTTATATCGCATAAAAAGTTGGAGACAATTTCTTCAGCATTGTGCGATCACTGGG ACACTTTA
AGGAACGCACTATATGAACGTAGGATCTCAGAATTGACAGGTAAGATAACGAAGTCT GCTAAA
GAGAAAGTGCAGAGATCCCTAAAACACGAGGATATAAATTTGCAGGAGATAATTTCA GCTGCA
GGTAAAGAGTTGTCTGAAGCGTTCAAGCAAAAGACTTCCGAAATCTTGTCACACGCA CACGCCG
CATTAGATCAACCTTTACCCACTACTTTGAAAAAACAAGAAGAGAAGGAGATATTAA AATCACA
ACTTGATTCTTTACTTGGCCTTTATCATCTTTTAGATTGGTTCGCTGTTGACGAGAG CAATGAAGT
GGATCCAGAGTTTTCCGCAAGATTGACCGGTATAAAGTTGGAAATGGAACCTTCGTT ATCATTTT ACAACAAAGCTAGGAACTATGCTACAAAAAAACCTTATTCTGTCGAAAAATTTAAACTGA ACTT
CCAAATGCCTACTCTAGCAAGTGGCTGGGATGTTAATAAAGAAAAGAACAATGGCGC TATTTTG
TTTGTAAAAAATGGCCTATACTATCTTGGAATTATGCCTAAACAAAAAGGTCGCTAC AAGGCTT
TGTCATTTGAACCTACTGAAAAGACTAGCGAAGGTTTCGATAAGATGTATTACGATT ATTTCCCG
GATGCCGCTAAAATGATCCCCAAGTGCTCTACTCAATTGAAGGCAGTAACTGCTCAT TTCCAAA
CGCATACCACGCCAATACTGCTTTCTAACAACTTTATAGAACCACTAGAAATAACGA AAGAAAT
TTACGACCTAAATAACCCAGAGAAAGAACCAAAAAAGTTCCAGACGGCCTACGCCAA AAAGAC
AGGGGACCAAAAAGGTTACCGCGAGGCGTTATGTAAATGGATTGATTTTACTAGGGA CTTTTTA
TCAAAATACACTAAAACGACGTCTATTGATCTTAGCTCCTTACGCCCGTCCTCCCAA TACAAGGA
TCTAGGTGAGTATTACGCAGAGTTGAACCCGCTATTATACCATATTTCCTTCCAAAG GATTGCTG
AAAAGGAAATTATGGACGCTGTTGAAACTGGGAAATTGTACCTGTTTCAGATTTATA ATAAGGA
CTTCGCAAAGGGTCACCATGGTAAGCCTAACCTTCACACTTTGTACTGGACCGGACT ATTCTCGC
CTGAAAATTTGGCTAAAACAAGTATCAAGTTAAACGGTCAGGCCGAGTTATTTTATA GACCCAA
ATCTAGAATGAAAAGAATGGCCCATAGATTAGGCGAAAAGATGTTAAACAAGAAATT AAAGGA
CCAAAAAACCCCGATACCAGACACTCTATACCAAGAACTGTACGACTATGTGAATCA CAGGCTT
AGTCACGATTTATCAGATGAAGCGAGGGCTTTATTGCCAAATGTCATCACCAAGGAA GTATCAC
ATGAAATAATTAAGGATAGAAGGTTCACATCTGATAAATTCTTTTTTCATGTCCCAA TTACATTG
AATTATCAAGCAGCGAACTCACCATCTAAATTTAATCAGCGCGTCAACGCCTATTTG AAAGAAC
ATCCCGAAACACCAATCATCGGCATAGATCGAGGTGAGAGAAACTTAATATATATAA CTGTGAT
TGATTCTACAGGAAAAATCCTGGAGCAACGATCTTTAAATACCATACAACAGTTTGA TTATCAA
AAAAAGTTGGATAACAGAGAAAAAGAACGTGTTGCCGCTAGGCAGGCTTGGTCTGTG GTAGGA
ACAATTAAGGACTTAAAGCAGGGCTATCTGTCCCAAGTTATTCATGAAATAGTCGAT CTGATGA
TACATTATCAGGCAGTTGTCGTGTTGGAAAATTTGAATTTTGGCTTTAAATCAAAAA GAACTGGC
ATAGCAGAAAAAGCTGTGTACCAGCAGTTTGAAAAGATGTTAATCGATAAGCTAAAC TGCCTTG
TTCTTAAAGATTACCCCGCAGAAAAAGTAGGTGGTGTTCTTAATCCATATCAGTTGA CAGACCA
ATTTACATCCTTTGCGAAAATGGGTACGCAAAGCGGGTTCTTATTCTACGTACCGGC CCCCTATA
CTTCTAAGATCGACCCACTAACAGGTTTTGTGGACCCTTTTGTTTGGAAGACGATAA AGAACCA
CGAGTCACGCAAACATTTCTTAGAGGGCTTTGATTTCTTGCACTACGACGTGAAAAC TGGTGATT
TTATCTTACACTTTAAAATGAACAGAAATCTCTCTTTCCAACGTGGACTGCCCGGAT TCATGCCG
GCTTGGGACATCGTTTTTGAAAAGAATGAAACGCAGTTTGACGCCAAAGGTACACCA TTTATAG
CGGGTAAGAGAATTGTGCCGGTCATAGAAAACCATAGATTTACAGGTAGATATAGGG ATCTGTA
CCCTGCTAATGAATTGATTGCATTACTCGAAGAGAAAGGAATTGTGTTTCGAGATGG ATCGAAT
ATTTTACCTAAGTTGTTGGAAAATGATGATTCACACGCAATTGATACTATGGTTGCC CTCATAAG
ATCGGTATTGCAAATGAGAAACTCAAATGCTGCTACGGGAGAGGATTATATAAACAG CCCCGTT
CGCGATCTTAATGGTGTTTGTTTTGATTCACGTTTTCAGAACCCCGAATGGCCAATG GATGCCGA
CGCAAACGGAGCATATCATATTGCTCTTAAAGGCCAACTACTATTAAATCACTTAAA GGAATCC
AAAGACCTAAAATTGCAAAACGGGATATCTAATCAGGATTGGCTGGCTTACATACAA GAACTAC
GTAACTAG
SE ATGGCCGTTAAGTCAATCAAAGTGAAACTTAGACTGGATGACATGCCAGAGATTCGTGCG GGGT
Q TATGGAAACTTCATAAGGAAGTTAACGCAGGGGTAAGATATTATACCGAATGGTTATCAT TACT
no TCGACAAGAGAATTTGTACAGAAGGTCCCCGAACGGCGACGGTGAGCAAGAATGCGATAA GAC
N GGCTGAAGAATGTAAGGCAGAACTTTTGGAGCGCCTGAGAGCCCGTCAGGTTGAAAATGG CCA TAGAGGTCCTGCGGGATCTGATGATGAGCTTTTACAGCTAGCTAGACAATTGTATGAATT GTTG
GTCCCTCAGGCTATTGGGGCTAAAGGAGACGCTCAACAAATCGCCAGAAAGTTCTTG TCACCTC
TGGCTGACAAAGATGCCGTGGGAGGATTAGGTATCGCTAAAGCAGGTAATAAACCAA GATGGG
TTAGAATGAGAGAAGCAGGCGAACCTGGTTGGGAAGAAGAGAAAGAAAAGGCCGAAA CTAGA
AAAAGCGCTGACAGAACCGCAGATGTTTTACGGGCCTTGGCTGATTTTGGACTGAAG CCTTTGA
TGAGAGTGTATACTGATTCAGAAATGTCTTCCGTTGAATGGAAGCCCCTAAGGAAGG GACAAGC
GGTCAGAACCTGGGATAGGGATATGTTTCAACAGGCTATTGAAAGGATGATGTCATG GGAATCC
TGGAATCAAAGAGTAGGTCAAGAATACGCTAAACTGGTCGAACAAAAGAATAGATTT GAACAA
AAAAATTTTGTAGGTCAAGAACATTTAGTACATTTGGTTAATCAACTTCAACAAGAT ATGAAAG
AGGCATCTCCTGGTTTGGAATCAAAAGAACAAACAGCACACTATGTTACCGGCCGAG CTTTGCG
AGGTTCTGACAAAGTATTTGAAAAGTGGGGGAAATTAGCTCCCGATGCCCCCTTTGA TCTATAT
GATGCTGAAATTAAAAACGTTCAAAGAAGGAACACTAGACGTTTTGGATCCCATGAT CTTTTTG
CAAAGCTAGCTGAGCCAGAATACCAGGCTCTATGGCGTGAAGACGCCTCGTTTTTGA CTAGATA
CGCAGTATACAATTCAATACTCAGAAAACTAAACCATGCCAAGATGTTTGCTACATT CACCCTG
CCCGATGCTACCGCTCATCCTATTTGGACTAGATTTGACAAGTTGGGGGGGAATCTA CATCAGT
ACACATTTTTATTTAATGAATTCGGTGAAAGAAGACACGCTATTAGATTCCACAAGC TCCTAAA
GGTTGAAAACGGCGTTGCGAGAGAAGTTGATGATGTAACAGTTCCCATTTCTATGTC GGAGCAA
TTGGATAATCTATTGCCTAGAGACCCTAATGAACCAATTGCTTTGTACTTTCGTGAC TACGGTGC
AGAACAACACTTTACAGGTGAATTCGGCGGAGCCAAGATTCAATGTAGACGTGATCA ACTCGCA
CACATGCATAGAAGAAGAGGCGCTCGTGATGTTTATTTAAATGTGTCTGTTAGAGTT CAATCCC
AATCGGAGGCTAGAGGTGAAAGAAGGCCACCATACGCAGCAGTTTTTAGGTTAGTAG GTGATA
ATCATAGGGCATTTGTCCACTTCGACAAATTAAGTGATTATTTAGCAGAGCACCCTG ATGATGG
AAAGTTGGGCAGTGAGGGATTATTAAGTGGGTTGAGGGTAATGTCTGTAGATCTTGG TCTTCGT
ACTTCTGCGAGTATCTCTGTCTTTAGAGTAGCACGTAAGGATGAGTTGAAACCTAAT AGCAAAG
CAACTTTTGAAATTGCCAGGAGAAACGGAGTCCAAGGACTTGAGGGCAATTAGAGAG GAACGT
CAGCGTACATTGCGACAGCTGAGAACTCAATTGGCTTATTTGAGGTTGTTGGTTAGG TGTGGTTC
CGAGGATGTTGGCAGAAGAGAAAGGTCTTGGGCCAAATTGATAGAACAACCAGTGGA CGCCGC
AAATCACATGACACCAGATTGGAGAGAAGCTTTCGAAAATGAACTCCAGAAATTAAA GAGCCT
ACATGGCATATGCTCTGATAAAGAGTGGATGGATGCCGTATACGAATCCGTTCGTAG AGTCTGG
CGCCACATGGGTAAGCAAGTACGGGACTGGAGAAAGGATGTTCGTTCCGGCGAAAGA CCGAAG
ATAAGGGGGTATGCAAAGGACGTTGTAGGCGGTAATTCTATTGAACAGATTGAGTAT TTGGAAA
GGCAGTACAAATTTCTTAAATCCTGGAGCTTCTTCGGCAAAGTGTCAGGACAAGTCA TCAGGGC
TGAAAAAGGTTCCAGATTTGCTATTACGCTAAGGGAACATATTGATCATGCGAAAGA AGATAGA
CTGAAAAAACTAGCAGATAGAATAATTATGGAAGCACTTGGTTACGTCTATGCACTT GATGAAA
GAGGCAAGGGGAAATGGGTAGCTAAATACCCGCCTTGTCAACTTATTTTATTAGAAG AATTAAG
CGAGTACCAATTTAACAACGATAGACCTCCATCCGAAAATAATCAGCTGATGCAATG GTCCCAT
AGGGGTGTTTTTCAAGAATTGATAAATCAAGCTCAAGTACACGATTTGCTGGTAGGT ACTATGT
ACGCAGCGTTTTCGAGCCGTTTTGATGCAAGAACTGGTGCCCCAGGTATCAGATGTC GACGTGT
TCCGGCCAGATGTACACAGGAACATAACCCTGAGCCATTTCCGTGGTGGCTTAATAA GTTTGTT
GTCGAGCACACATTAGACGCATGCCCTCTGAGAGCAGATGACCTTATACCCACTGGA GAAGGCG
AAATATTTGTTAGTCCATTCTCTGCAGAAGAAGGTGACTTTCACCAGATACATGCAG ACTTAAAT GCAGCACAGAATCTCCAACAAAGGTTGTGGTCGGATTTTGATATTTCGCAAATAAGACTA AGAT
GCGATTGGGGAGAGGTTGATGGAGAATTGGTGCTGATTCCAAGATTAACCGGAAAGC GAACTG
CCGATTCCTATTCTAACAAGGTGTTTTACACAAATACTGGTGTTACCTATTACGAAA GAGAAAG
GGGTAAGAAGAGACGTAAAGTATTTGCTCAAGAAAAATTGTCAGAAGAGGAGGCAGA ACTGTT
AGTAGAAGCAGACGAAGCCAGAGAAAAATCAGTTGTGCTTATGCGTGACCCTTCCGG CATTATA
AATCGTGGTAATTGGACACGACAAAAAGAATTTTGGTCTATGGTCAATCAACGTATC GAAGGCT
ACCTAGTTAAGCAAATCAGGTCTAGGGTTCCACTACAAGATAGCGCATGTGAAAATA CGGGTGA
TATATAA
SE ATGGCTACTAGATCTTTCATTTTAAAAATTGAACCTAATGAAGAAGTGAAGAAGGGTCTC TGGA
Q AAACTCACGAAGTACTTAATCATGGCATTGCCTATTATATGAATATCCTGAAGCTTATTC GTCAA
no GAAGCTATATACGAGCATCATGAGCAAGATCCTAAGAACCCTAAGAAAGTAAGCAAAGCG GAA
N ATTCAGGCTGAATTGTGGGACTTCGTCTTGAAGATGCAGAAGTGTAACAGTTTTACGCAC GAAG
O: TTGATAAAGATGTGGTGTTTAATATTTTGAGGGAGCTATATGAGGAGTTGGTGCCCTCGA GTGTC 14 GAAAAAAAAGGAGAAGCTAATCAGCTGTCAAATAAATTTTTATATCCTCTGGTGGATCCA AACT 0 CTCAATCAGGTAAAGGCACTGCCAGTAGTGGTCGAAAACCGAGATGGTATAATTTGAAAA TCGC
AGGTGATCCATCGTGGGAAGAAGAAAAAAAAAAATGGGAAGAAGATAAAAAAAAAGA TCCCC
TTGCCAAAATACTAGGTAAGCTAGCCGAGTATGGACTTATACCATTATTCATTCCTT TCACGGAC
TCTAATGAACCAATTGTGAAGGAAATCAAATGGATGGAAAAATCACGTAATCAGTCT GTTAGGA
GGTTGGACAAAGATATGTTTATACAGGCTCTTGAGAGGTTTTTGTCGTGGGAGTCCT GGAATTTG
AAAGTGAAAGAAGAATATGAAAAAGTGGAAAAGGAGCATAAGACGTTGGAAGAAAGG ATTAA
GGAAGATATTCAGGCCTTTAAGAGTCTGGAACAGTACGAAAAAGAAAGACAGGAACA GTTATT
GAGAGATACTCTAAACACTAATGAATATAGGCTTTCCAAGAGGGGCTTGCGAGGATG GAGAGA
GATAATTCAGAAATGGTTGAAAATGGATGAGAACGAGCCATCGGAGAAATATCTAGA GGTGTT
TAAAGATTACCAAAGAAAGCACCCTCGCGAAGCTGGTGATTACTCTGTTTATGAATT CCTTTCGA
AGAAGGAAAATCACTTCATCTGGCGAAATCATCCAGAGTACCCATATTTATATGCTA CATTTTGC
GAAATTGACAAGAAAAAAAAAGATGCTAAACAGCAAGCGACATTCACCCTCGCTGAT CCCATC
AACCACCCATTATGGGTCAGGTTCGAAGAGAGATCAGGCTCGAACCTGAATAAGTAC AGGATCT
TGACTGAGCAATTGCATACTGAGAAGTTAAAAAAGAAATTGACGGTCCAACTTGACA GATTGAT
TTATCCCACTGAATCTGGTGGATGGGAGGAGAAAGGTAAGGTTGATATTGTCCTATT GCCTTCTC
GTCAATTTTACAACCAAATATTTCTGGACATCGAAGAGAAGGGTAAACATGCTTTTA CCTATAA
GGATGAGAGTATTAAATTTCCATTGAAGGGAACGCTTGGCGGCGCTAGAGTTCAGTT CGATAGA
GATCATTTGAGAAGATACCCGCATAAAGTGGAATCTGGTAATGTAGGTCGGATCTAC TTTAACA
TGACGGTAAATATTGAACCTACCGAGTCACCAGTCAGTAAGTCTTTAAAGATTCATA GGGATGA
TTTCCCTAAATTTGTCAACTTCAAGCCTAAGGAACTAACCGAGTGGATCAAAGACAG TAAAGGC
AAAAAGTTAAAGAGCGGTATTGAGTCCCTGGAGATAGGTCTTAGAGTCATGTCTATC GATTTGG
GTCAAAGACAAGCAGCCGCAGCATCTATTTTCGAAGTTGTTGACCAAAAACCGGATA TCGAGGG
AACTGCCAGGAGAAACACTAGTAAAATCTAGAGAGGTCTTGCGTAAAGCACGTGAGG ACAATC
TCAAATTAATGAATCAGAAGTTAAATTTCCTTAGGAACGTGTTGCATTTCCAACAGT TCGAGGA
CATAACTGAACGCGAGAAAAGAGTCACTAAGTGGATCTCAAGACAAGAAAATAGTGA TGTGCC
ATTAGTGTATCAAGACGAACTTATTCAAATAAGAGAGCTAATGTATAAACCATATAA AGACTGG
GTGGCATTCTTAAAACAATTACACAAGCGGCTTGAAGTAGAAATAGGAAAAGAAGTA AAGCAT TGGAGGAAGAGTCTGTCCGATGGTCGCAAAGGCCTGTACGGGATATCACTTAAAAATATT GATG
AAATTGACAGAACACGAAAATTTTTGTTAAGATGGTCATTGAGACCAACCGAACCAG GTGAGGT
TAGAAGGTTGGAACCAGGCCAAAGGTTTGCCATCGATCAATTAAACCATCTTAACGC ACTGAAA
GAAGATAGATTGAAGAAGATGGCGAACACTATTATTATGCACGCTCTAGGTTATTGC TATGATG
TGAGAAAGAAAAAATGGCAAGCCAAGAACCCTGCATGCCAAATTATTTTGTTTGAAG ATCTTTC
TAATTACAATCCATACGAAGAGCGTTCACGTTTTGAAAACTCTAAATTGATGAAATG GTCTAGA
AGAGAGATTCCGAGACAGGTCGCTCTACAAGGGGAGATTTACGGTCTTCAAGTCGGT GAGGTTG
GTGCTCAATTTTCTTCCAGATTTCATGCAAAAACTGGGTCTCCAGGCATTAGGTGTT CGGTCGTT
ACTAAGGAAAAGTTACAGGACAACCGTTTCTTCAAAAATTTGCAACGTGAAGGCCGT TTAACAC
TTGATAAGATAGCTGTCCTTAAGGAAGGCGATCTGTACCCAGATAAAGGTGGTGAGA AATTCAT
ATCTTTGAGTAAAGACAGGAAACTGGTTACAACACACGCCGACATTAACGCAGCTCA GAACTTG
CAAAAGAGATTCTGGACAAGGACCCACGGCTTCTATAAGGTGTACTGTAAAGCTTAT CAAGTAG
ATGGACAAACGGTTTATATTCCTGAATCAAAGGACCAGAAACAAAAAATTATAGAAG AATTTG
GTGAAGGATACTTTATCTTGAAGGATGGAGTTTATGAGTGGGGCAATGCAGGTAAGT TAAAGAT
AAAGAAAGGTTCATCAAAGCAATCAAGTAGCGAACTGGTCGATTCGGATATTTTAAA GGATAGC
TTTGATCTAGCTAGTGAATTGAAGGGAGAAAAGTTAATGTTATACAGAGATCCCAGT GGGAATG
TATTTCCATCTGATAAGTGGATGGCCGCCGGAGTGTTTTTTGGCAAATTAGAGAGAA TCTTGATT
TCTAAACTGACCAATCAATACTCAATTTCGACCATCGAAGACGACTCTTCAAAACAA TCCATGT
GA
SE ATGCCTACTCGCACCATCAATCTGAAGTTAGTTTTGGGGAAGAACCCAGAAAATGCGACT CTAA
Q GACGGGCACTATTCTCTACACATAGACTTGTCAACCAAGCGACTAAGAGAATTGAAGAAT TTTT
no ACTGTTGTGTAGAGGAGAAGCTTATCGTACCGTAGATAATGAAGGTAAAGAAGCTGAGAT CCCA
N CGCCATGCTGTTCAAGAAGAGGCGCTTGCTTTTGCAAAAGCTGCACAACGACATAACGGC TGTA
O: TCTCCACATATGAGGACCAGGAAATCTTGGATGTGCTTAGACAATTGTATGAAAGATTAG TACC 14 TAGCGTCAATGAAAACAACGAGGCTGGGGATGCCCAAGCCGCTAACGCTTGGGTGAGTCC ATTA 1 ATGAGTGCAGAGTCCGAAGGTGGACTATCGGTCTATGATAAAGTGTTAGACCCGCCGCCA GTAT
GGATGAAACTCAAAGAAGAGAAAGCGCCTGGTTGGGAAGCTGCTTCTCAGATTTGGA TACAGTC
CGACGAAGGTCAATCGCTGCTAAATAAACCGGGTAGCCCACCACGTTGGATTAGAAA ACTTAGA
TCTGGTCAACCGTGGCAAGATGACTTCGTTTCAGACCAAAAAAAAAAGCAAGATGAA CTAACG
AAAGGTAACGCACCACTCATAAAACAATTGAAAGAGATGGGCCTCTTGCCTTTAGTT AATCCCT
TTTTTAGACATTTGTTGGATCCCGAGGGTAAGGGTGTATCCCCATGGGACAGATTGG CCGTAAG
GGCCGCGGTGGCGCACTTCATCTCTTGGGAAAGTTGGAACCACAGAACAAGAGCTGA GTATAAC
AGTTTGAAACTGCGAAGAGATGAATTTGAGGCCGCATCTGATGAATTCAAGGACGAT TTTACAT
TGCTACGACAATATGAGGCTAAGCGACATAGTACGCTTAAGTCAATTGCCTTAGCTG ATGACTC
TAACCCGTACCGAATTGGTGTAAGGTCCTTGAGAGCCTGGAATAGGGTTAGAGAAGA ATGGATT
GACAAAGGCGCAACCGAGGAACAAAGGGTTACCATCCTTAGTAAGCTTCAAACACAA TTACGG
GGTAAATTCGGTGATCCAGACCTATTTAATTGGCTAGCCCAAGATAGACACGTACAC CTGTGGT
CCCCGAGAGATTCCGTCACGCCCCTCGTAAGGATTAATGCCGTCGACAAAGTGCTTA GAAGACG
TAAGCCTTATGCACTGATGACTTTTGCACATCCGAGATTCCATCCAAGATGGATTCT ATACGAAG
CGCCTGGTGGTTCTAACTTGCGACAATACGCTTTAGATTGTACTGAAAATGCTCTGC ATATTACA
CTTCCATTACTCGTCGACGACGCCCATGGTACATGGATTGAGAAAAAAATCCGCGTA CCACTCG
CTCCTAGTGGACAAATACAAGATTTAACTTTAGAAAAACTTGAAAAGAAAAAAAACA GATTAT ACTATAGATCAGGATTCCAACAATTTGCTGGATTAGCCGGTGGTGCTGAGGTGTTGTTTC ATAGG
CCGTATATGGAACATGATGAGAGATCAGAAGAATCTCTGTTGGAAAGGCCAGGCGCT GTGTGGT
TCAAATTAACCTTAGATGTTGCTACCCAAGCACCACCTAACTGGTTAGATGGTAAAG GCAGAGT
TAGGACACCTCCAGAAGTTCATCATTTCAAAACCGCTCTGTCAAATAAATCTAAACA TACGAGA
ACCTTGCAACCAGGATTGAGAGTCCTTTCTGTTGATTTGGGTATGAGAACATTTGCT TCTTGTTC
TGTTTTCGAATTGATCGAAGGTAAACCTGAAACAGGTAGAGCATTCCCTGTTGCTGA CGAAAGA
TCAATGGATAGTCCAAATAAGTTATGGGCCAAGCACGAGAGAAGCTTTAAACTAACT CTGCCTG
GAGAAACACCGAGCAGAAAGGAGGAAGAAGAGAGAAGCATTGCTAGGGCAGAGATTT ACGCG
CTGAAAAGAGATATTCAAAGACTGAAATCACTCCTAAGATTAGGTGAGGAAGATAAT GATAAT
AGAAGAGATGCTTTGTTAGAGCAATTCTTTAAAGGATGGGGTGAAGAGGACGTAGTT CCTGGTC
AAGCTTTCCCTAGAAGCCTCTTTCAGGGATTAGGCGCTGCACCCTTTAGGTCAACAC CCGAATTG
TGGAGACAGCACTGTCAGACGTATTACGACAAAGCGGAAGCTTGCCTGGCAAAGCAT ATTTCCG
ACTGGAGGAAGAGAACTAGACCTCGTCCGACTTCGAGAGAGATGTGGTATAAGACAA GATCTT
ACCATGGTGGCAAAAGTATTTGGATGCTAGAATACTTAGATGCTGTCCGCAAATTAC TACTTTCA
TGGTCGTTAAGAGGTCGTACTTACGGAGCTATTAATAGACAAGACACCGCTCGTTTT GGTTCCTT
AGCTTCTAGATTGTTGCATCATATCAACTCTTTAAAGGAAGACCGCATCAAAACCGG TGCAGAT
AGTATTGTGCAGGCCGCAAGGGGCTATATTCCTCTCCCACATGGCAAGGGTTGGGAA CAGCGTT
ATGAACCCTGTCAGTTGATATTATTTGAAGATCTAGCTAGGTACAGATTTCGTGTAG ACAGACCT
CGGAGAGAGAATTCGCAATTGATGCAGTGGAATCATCGAGCTATAGTAGCAGAAACG ACGATG
CAAGCTGAACTATACGGTCAAATAGTCGAAAATACCGCTGCTGGTTTCTCCTCAAGA TTTCATGC
TGCAACTGGTGCTCCTGGTGTCAGATGTCGCTTTTTGTTAGAACGAGATTTCGATAA TGACCTAC
CAAAGCCGTACTTACTGAGAGAACTAAGTTGGATGTTAGGTAACACAAAGGTTGAAT CAGAGG
AAGAAAAATTGCGTCTTCTAAGCGAGAAAATTAGACCAGGTTCATTAGTCCCTTGGG ATGGGGG
TGAACAATTCGCGACATTACACCCGAAAAGACAAACTCTTTGTGTCATTCACGCAGA TATGAAC
GCTGCTCAAAACCTGCAACGCAGATTTTTCGGAAGGTGTGGGGAAGCCTTTCGCCTT GTGTGTC
AGCCACATGGTGATGATGTTTTGAGGCTAGCGTCTACACCAGGTGCAAGACTTTTGG GTGCATT
ACAACAACTGGAAAATGGTCAGGGAGCTTTCGAATTAGTTCGTGATATGGGTAGCAC ATCACAA
ATGAATCGTTTCGTCATGAAGTCGTTGGGCAAAAAAAAGATCAAGCCATTACAAGAC AATAACG
GGGATGATGAACTAGAAGACGTGCTATCTGTTTTACCTGAAGAAGATGATACCGGAC GAATTAC
TGTATTTCGGGACTCTTCGGGTATATTCTTCCCTTGTAACGTTTGGATCCCGGCAAA ACAGTTCT
GGCCTGCGGTCCGTGCTATGATTTGGAAGGTTATGGCATCACATTCATTGGGTTAG
SE ATGACAAAGTTAAGGCATAGACAGAAGAAGTTAACTCACGATTGGGCGGGGTCTAAAAAG AGA
Q GAAGTTCTAGGGAGCAATGGTAAATTACAGAATCCATTGCTAATGCCCGTCAAAAAAGGT CAGG
no TGACAGAATTTCGAAAAGCATTTTCCGCATACGCCCGAGCAACCAAAGGGGAAATGACGG ATG
N GCAGAAAAAATATGTTTACTCACTCATTTGAACCATTCAAGACCAAGCCTTCGTTACATC AGTGC
O: GAACTGGCTGACAAAGCCTACCAGAGCTTGCATTCATATTTACCGGGTTCTTTGGCGCAT TTTCT 14 TTTATCTGCCCATGCACTTGGTTTTAGGATTTTTAGCAAATCAGGGGAAGCCACTGCATT CCAAG 2 CGTCCTCAAAGATTGAAGCTTACGAAAGCAAGTTAGCTAGCGAGCTTGCTTGTGTTGATT TGTCT
ATTCAGAACTTGACTATTTCAACTTTGTTCAACGCATTAACGACTTCCGTAAGAGGT AAAGGTGA
GGAGACATCGGCAGATCCACTGATAGCTAGATTTTACACCTTACTTACCGGTAAACC ACTAAGC
AGAGACACTCAGGGCCCAGAACGAGATTTAGCCGAGGTGATAAGCAGAAAAATTGCA AGTTCT
TTTGGAACTTGGAAGGAGATGACTGCCAATCCACTTCAATCTCTTCAATTTTTTGAA GAGGAGTT GCATGCGCTAGATGCAAATGTTAGTTTGTCACCTGCCTTCGATGTTCTGATTAAGATGAA CGACC
TGCAGGGTGACTTGAAGAACAGAACGATAGTTTTTGATCCAGATGCTCCTGTGTTTG AATATAA
TGCTGAGGATCCTGCTGACATCATCATTAAACTGACAGCTAGATATGCGAAAGAAGC AGTGATT
AAAAATCAAAATGTCGGGAATTATGTTAAGAACGCTATTACGACAACTAACGCAAAC GGACTA
GGTTGGTTGCTGAACAAAGGCCTTTCCTTATTGCCTGTCTCCACTGATGACGAACTA TTGGAGTT
TATTGGGGTCGAGAGATCCCATCCTAGCTGTCATGCGTTGATAGAACTTATCGCTCA GTTAGAA
GCACCTGAACTGTTCGAAAAAAATGTTTTTTCTGATACTCGTTCCGAGGTTCAAGGT ATGATAGA
TTCAGCTGTAAGCAATCATATCGCCAGGCTGTCAAGCTCTCGTAATTCATTGAGCAT GGACTCAG
AGGAACTTGAGAGATTGATAAAATCTTTTCAAATTCATACACCACATTGTTCATTAT TTATAGGG
GCTCAATCCTTATCTCAACAATTGGAAAGCCTACCCGAAGCATTGCAGTCAGGAGTG AACAGTG
CTGATATTCTGCTCGGCTCAACCCAATACATGTTGACAAATTCTTTGGTCGAGGAGT CAATCGCT
ACGTATCAGAGAACCTTAAATAGAATTAACTACCTGTCCGGCGTTGCAGGACAGATT AACGGTG
CTATTAAGAGGAAAGCTATTGATGGTGAGAAGATACATTTACCCGCTGCTTGGTCAG AGTTAAT
TTCTTTACCCTTTATTGGGCAACCAGTGATTGATGTTGAATCAGATTTAGCCCACTT AAAGAACC
AATACCAGACATTGTCTAACGAATTTGATACGCTGATTTCCGCACTGCAAAAGAATT TCGACTTA
AATTTTAATAAAGCCTTGCTTAATCGAACACAACATTTCGAGGCTATGTGTAGATCA ACAAAAA
AGAATGCCCTTTCTAAGCCTGAGATCGTTAGTTATAGAGATTTGCTAGCCAGGTTGA CTTCTTGT
CTTTATAGGGGCTCTCTAGTCTTGAGGAGGGCGGGTATAGAAGTACTGAAAAAGCAC AAGATAT
TTGAGTCCAACTCTGAATTAAGAGAGCACGTTCATGAAAGAAAACACTTCGTATTTG TTTCTCCG
CTCGATAGAAAAGCCAAGAAGCTCCTACGTTTGACTGACTCTAGGCCTGATTTATTG CACGTAA
TTGATGAAATACTACAACATGATAATTTAGAGAACAAGGATAGAGAATCTTTGTGGT TAGTTCG
ATCTGGTTATTTACTGGCCGGCCTACCAGACCAACTCTCCTCTTCCTTTATAAATCT TCCAATCAT
TACTCAAAAAGGCGATCGTCGCTTGATAGATCTCATTCAATACGACCAAATTAATAG AGATGCT
TTTGTGATGTTGGTAACTTCCGCTTTTAAGTCGAACTTAAGTGGGCTGCAGTACAGA GCAAACA
AACAATCTTTTGTGGTTACGCGCACTTTGTCACCATATTTGGGATCTAAATTGGTTT ATGTGCCC
AAAGATAAAGATTGGCTGGTCCCTTCCCAAATGTTCGAGGGGAGATTTGCGGACATT TTGCAAT
CCGATTATATGGTGTGGAAGGACGCTGGAAGATTGTGTGTTATTGACACAGCTAAGC ATTTGTC
TAACATTAAAAAATCTGTATTCTCAAGTGAAGAAGTCCTCGCGTTTTTAAGAGAATT GCCACAC
CGTACGTTTATCCAAACTGAGGTCAGGGGTTTAGGGGTGAATGTGGACGGTATTGCA TTTAATA
ACGGGGATATACCCTCTCTGAAGACGTTTAGCAATTGCGTGCAAGTCAAAGTGAGTC GGACAAA
CACTAGTCTGGTCCAAACATTAAATAGATGGTTTGAAGGCGGTAAGGTCTCGCCGCC TAGCATC
CAATTTGAGAGAGCATATTACAAAAAAGATGATCAAATCCACGAGGACGCTGCAAAA AGGAAG
ATAAGGTTTCAAATGCCAGCTACAGAGTTGGTACACGCGTCAGACGACGCAGGATGG ACCCCCT
CCTATTTACTTGGTATCGATCCCGGTGAATATGGTATGGGTTTGTCATTGGTCTCAA TAAATAAT
GGCGAAGTTTTAGATAGCGGATTTATACACATAAATTCATTGATAAATTTCGCTTCT AAGAAATC
AAATCATCAAACCAAAGTTGTTCCGAGGCAGCAATACAAGTCACCATACGCCAACTA TCTAGAA
CAATCTAAAGATTCTGCAGCAGGAGACATAGCTCATATTTTGGATAGACTTATCTAC AAGTTGA
ACGCCCTACCCGTTTTCGAAGCTCTATCTGGCAATAGTCAAAGCGCAGCGGATCAGG TTTGGAC
AAAAGTCCTCAGCTTCTACACCTGGGGAGATAATGATGCACAAAATTCAATTCGTAA GCAACAT
TGGTTCGGTGCTTCACACTGGGACATTAAAGGCATGTTGAGGCAACCGCCAACAGAA AAAAAG
CCCAAACCATACATTGCCTTTCCCGGTTCACAAGTTTCTTCTTATGGTAATTCTCAA AGGTGTTC
ATGTTGTGGACGTAACCCAATTGAACAATTGCGCGAAATGGCGAAGGACACATCCAT TAAGGA GTTGAAGATTAGAAATTCAGAAATTCAATTGTTCGACGGTACTATAAAGTTATTTAATCC AGAC
CCGTCAACGGTCATAGAAAGAAGAAGACATAATTTAGGGCCATCAAGAATTCCTGTA GCTGATA
GAACTTTCAAAAATATAAGTCCAAGCTCACTAGAATTCAAAGAACTAATAACGATTG TGTCACG
GTCTATACGTCATTCCCCAGAATTTATTGCTAAAAAAAGAGGTATAGGTAGTGAGTA CTTTTGTG
CTTATAGTGATTGTAATTCCTCCTTAAATTCAGAAGCAAATGCGGCTGCGAACGTTG CCCAAAA
GTTCCAAAAGCAATTGTTTTTCGAATTATAG
SE ATGAAAAGAATCTTGAACTCTTTAAAGGTTGCCGCCCTGCGTTTGTTATTTAGAGGTAAA GGATC
Q TGAACTTGTCAAGACTGTTAAATACCCTTTGGTCTCGCCGGTTCAGGGTGCAGTTGAGGA GTTAG
no CTGAGGCGATCCGCCATGATAACCTACATCTGTTTGGTCAAAAAGAAATTGTTGACCTTA TGGA
N AAAGGATGAAGGTACGCAAGTTTACTCAGTGGTTGATTTCTGGTTAGATACCCTTCGTTT GGGG
O: ATGTTTTTCAGTCCATCAGCAAACGCATTAAAAATCACGCTGGGTAAGTTTAATTCTGAT CAGGT 14 TAGCCCTTTTAGGAAAGTGTTAGAGCAGTCTCCATTCTTCTTGGCTGGTAGGCTGAAGGT TGAAC
3 CGGCAGAACGTATATTATCTGTCGAGATCCGTAAGATTGGGAAGAGGGAAAACAGAGTTG AGA
ACTATGCTGCTGACGTAGAAACGTGTTTTATAGGCCAATTAAGTTCAGATGAGAAAC AGTCAAT
ACAAAAATTAGCTAATGATATCTGGGATAGTAAAGATCATGAAGAGCAAAGAATGTT AAAGGC
AGATTTCTTCGCTATCCCTTTGATTAAGGATCCAAAGGCTGTGACCGAAGAGGATCC TGAAAAT
GAAACTGCTGGTAAACAAAAACCCTTGGAGTTGTGTGTCTGCCTTGTCCCAGAACTT TACACAA
GAGGATTCGGGTCAATAGCCGATTTTTTGGTTCAACGCTTAACTCTTTTAAGGGATA AAATGTCT
ACAGATACTGCAGAAGATTGTTTAGAATATGTCGGGATTGAGGAGGAAAAAGGTAAC GGCATG
AACTCATTGTTGGGAACGTTCTTAAAGAATTTGCAAGGCGATGGATTTGAGCAGATT TTCCAATT
TATGTTAGGGAGCTATGTCGGTTGGCAAGGGAAGGAAGATGTTTTAAGAGAGAGATT AGACTTA
TTGGCTGAAAAAGTGAAGAGGTTACCGAAACCAAAATTTGCTGGCGAATGGTCTGGT CATAGGA
TGTTCTTGCATGGCCAATTGAAGTCTTGGTCTTCAAATTTTTTTAGACTATTTAACG AGACAAGG
GAACTTCTAGAGTCTATTAAGTCAGATATACAGCATGCCACAATGCTAATATCATAT GTAGAAG
AAAAAGGTGGTTATCATCCTCAATTACTTAGTCAATATAGAAAACTTATGGAACAAC TACCAGC
TTTGCGTACCAAGGTATTGGACCCTGAGATTGAAATGACACATATGTCCGAAGCAGT TCGCTCTT
ATATAATGATACATAAATCTGTTGCGGGTTTTTTACCGGATTTATTAGAATCATTAG ATAGAGAC
AAGGATCGTGAGTTTCTGCTTAGTATTTTTCCAAGAATCCCAAAAATTGATAAAAAA ACCAAGG
AAATTGTAGCTTGGGAACTGCCGGGAGAACCAGAAGAAGGTTATTTATTTACTGCTA ATAACTT
GTTCAGAAACTTCTTAGAGAATCCGAAACATGTCCCGAGATTTATGGCCGAAAGGAT CCCAGAA
GATTGGACTCGATTACGCTCTGCTCCTGTCTGGTTCGATGGAATGGTAAAACAATGG CAAAAAG
TCGTTAACCAGTTAGTAGAATCACCAGGTGCTTTATATCAATTTAACGAATCCTTCT TGAGACAA
AGGTTACAGGCCATGTTAACTGTGTATAAGAGGGACTTACAAACTGAAAAATTTCTT AAACTTT
TGGCGGATGTTTGTAGGCCTCTTGTAGATTTTTTTGGTTTGGGTGGAAATGATATTA TTTTTAAG
AGCTGTCAAGACCCAAGAAAACAATGGCAAACCGTTATTCCTCTCTCTGTTCCGGCA GATGTCT
ATACTGCTTGCGAAGGTTTGGCGATTAGACTAAGGGAGACATTAGGATTCGAATGGA AGAATTT
GAAAGGTCACGAGAGAGAAGATTTCTTAAGATTGCACCAGTTATTGGGCAATTTACT TTTCTGG
ATTCGTGATGCTAAATTGGTAGTAAAATTAGAGGATTGGATGAACAACCCATGTGTT CAGGAAT
ATGTAGAAGCCCGGAAAGCTATCGATCTTCCACTAGAAATATTCGGTTTTGAAGTGC CTATCTTC
CTGAATGGCTATCTATTTTCGGAGTTGAGACAATTAGAACTTTTGCTTAGGAGAAAA AGTGTGA
TGACTAGCTACAGTGTAAAGACTACTGGATCTCCTAATAGGCTATTTCAGCTAGTTT ATTTACCT
CTAAACCCTAGTGACCCCGAAAAGAAGAACTCAAATAACTTTCAAGAACGTTTGGAT ACCCCAA CTGGTTTGTCCCGTCGTTTCCTAGACCTAACCCTTGATGCATTCGCAGGTAAGTTACTTA CCGAT
CCAGTTACACAAGAATTGAAGACAATGGCAGGTTTTTACGATCATCTTTTTGGATTC AAATTGCC
ATGTAAACTCGCCGCCATGTCGAATCATCCAGGTTCTTCTTCAAAGATGGTTGTGTT AGCGAAAC
CCAAAAAAGGTGTTGCTTCTAATATAGGGTTTGAACCGATCCCAGATCCCGCTCATC CCGTATTT
AGGGTTAGATCCAGTTGGCCAGAGTTGAAGTACCTCGAGGGGCTATTGTATTTGCCA GAAGACA
CACCTTTGACCATCGAATTAGCAGAGACCTCCGTATCGTGCCAAAGTGTCTCGTCAG TTGCATTC
GATTTGAAAAACTTGACAACGATCTTAGGTCGTGTGGGAGAATTTAGGGTCACAGCT GATCAAC
CCTTTAAACTAACGCCTATAATCCCGGAGAAAGAAGAATCTTTTATTGGTAAAACTT ATTTGGGT
CTCGACGCGGGTGAAAGGAGCGGCGTCGGTTTCGCTATTGTTACAGTGGACGGAGAT GGGTACG
AAGTGCAAAGATTGGGGGTCCACGAGGATACACAGCTTATGGCCTTGCAGCAAGTTG CTAGTAA
ATCCTTAAAAGAGCCAGTATTTCAGCCTCTAAGAAAAGGCACCTTTAGACAACAAGA AAGAATA
CGGAAATCCTTACGTGGTTGCTACTGGAATTTTTATCATGCCTTGATGATAAAATAT AGGGCCAA
AGTAGTACATGAGGAATCTGTCGGAAGTAGTGGTCTTGTGGGTCAATGGTTGAGGGC TTTTCAG
AAGGATTTGAAGAAAGCCGATGTTCTCCCCAAGAAGGGCGGTAAAAACGGTGTAGAT AAGAAG
AAGAGAGAGTCCTCAGCTCAAGACACTCTTTGGGGTGGTGCTTTCTCTAAAAAGGAG GAGCAAC
AGATTGCGTTTGAGGTGCAAGCTGCAGGTTCTTCGCAATTTTGTTTGAAGTGCGGAT GGTGGTTC
CAACTAGGCATGCGTGAAGTAAACAGGGTACAAGAATCGGGCGTCGTGTTAGATTGG AATAGA
AGCATAGTTACCTTTTTAATAGAATCATCCGGCGAAAAAGTTTATGGTTTCTCCCCA CAGCAATT
AGAGAAGGGTTTCAGACCAGACATCGAAACTTTTAAAAAGATGGTAAGAGACTTTAT GAGACCT
CCTATGTTTGATAGAAAAGGCAGACCGGCCGCAGCTTACGAGAGATTTGTTTTAGGA AGGAGAC
ATCGAAGGTACAGGTTTGATAAAGTATTTGAGGAAAGATTTGGGAGGTCTGCTCTTT TCATTTGT
CCTAGAGTAGGTTGTGGAAATTTTGACCACAGCTCCGAACAGTCCGCGGTTGTTTTG GCCTTGAT
CGGATATATTGCCGATAAGGAGGGAATGTCAGGTAAGAAGTTGGTTTATGTACGGCT GGCCGAA
CTTATGGCCGAATGGAAACTAAAAAAATTAGAAAGATCCAGAGTTGAAGAACAATCA TCCGCT
CAATAA
SE ATGGCAGAAAGCAAACAAATGCAGTGTAGGAAATGTGGAGCTAGTATGAAGTACGAAGTC ATC
Q GGTTTGGGTAAAAAGTCATGTAGATACATGTGTCCCGATTGTGGCAACCATACCTCGGCA AGAA
no AGATACAAAACAAAAAAAAAAGAGATAAAAAATATGGGTCAGCCAGTAAAGCCCAATCTC AAA
N GAATTGCTGTAGCAGGTGCTCTTTACCCTGACAAAAAAGTACAAACTATCAAAACCTATA AATA
O: TCCAGCAGACTTGAATGGTGAGGTGCATGATAGCGGTGTTGCCGAGAAAATCGCACAAGC AAT 14 ACAAGAGGACGAGATTGGACTTTTGGGACCAAGCTCAGAATATGCATGCTGGATTGCATC TCAA 4 AAACAGTCTGAGCCTTACAGTGTAGTCGATTTCTGGTTTGATGCAGTGTGCGCAGGGGGA GTCT
TCGCCTACTCTGGCGCTAGATTATTGAGTACAGTTTTACAGTTATCCGGTGAGGAAT CGGTGCTT
AGAGCTGCCTTAGCCTCGTCTCCATTCGTTGACGATATAAACTTAGCGCAAGCCGAA AAGTTTTT
GGCGGTTAGCAGGCGTACAGGTCAAGATAAGTTAGGTAAGAGAATTGGGGAGTGCTT TGCAGA
AGGAAGATTGGAAGCTTTAGGGATAAAAGATAGAATGAGGGAATTTGTTCAAGCTAT CGATGTT
GCACAGACCGCCGGACAACGTTTCGCTGCCAAATTGAAGATATTCGGTATAAGTCAG ATGCCAG
AAGCTAAGCAATGGAATAACGATTCCGGACTGACTGTCTGTATACTACCTGATTATT ATGTTCCC
GAAGAGAATCGCGCGGACCAACTTGTAGTGTTGTTAAGAAGACTTCGCGAGATTGCA TATTGCA
TGGGTATTGAAGATGAAGCGGGTTTCGAACATCTTGGAATAGATCCTGGTGCTCTTT CGAATTTT
TCAAACGGTAACCCTAAGAGAGGATTTCTAGGGAGGCTGTTAAATAACGATATTATT GCGTTGG
CAAACAATATGAGTGCGATGACTCCATATTGGGAAGGGCGTAAGGGTGAACTCATAG AAAGGC TTGCGTGGTTAAAGCACAGGGCAGAAGGGCTGTATCTTAAAGAACCTCATTTCGGTAACT CCTG
GGCCGATCATAGGTCACGAATTTTCTCAAGGATCGCAGGCTGGTTATCTGGTTGCGC TGGCAAG
TTGAAAATTGCGAAAGACCAAATTTCTGGAGTACGTACAGATCTATTTCTGCTAAAA AGACTGC
TGGACGCAGTTCCGCAATCGGCGCCATCCCCCGATTTTATTGCGTCAATTTCGGCAC TTGACAGG
TTTTTAGAAGCTGCAGAATCGAGCCAGGACCCTGCTGAACAAGTGAGGGCTCTCTAC GCTTTTC
ACTTGAACGCACCTGCAGTCCGAAGTATAGCCAATAAAGCAGTGCAAAGGTCCGACA GCCAAG
AATGGCTGATAAAAGAACTAGACGCTGTTGACCATTTAGAATTTAACAAAGCGTTCC CATTTTTC
TCTGACACAGGAAAAAAAAAAAAAAAAGGTGCTAATAGCAACGGTGCTCCATCGGAA GAAGAG
TACACTGAAACGGAATCAATACAACAACCTGAGGACGCGGAACAGGAAGTAAACGGA CAAGA
AGGGAACGGAGCGTCTAAAAATCAAAAGAAATTTCAAAGAATACCTAGATTCTTCGG TGAAGG
CTCCAGATCTGAATACAGAATTTTAACGGAAGCTCCACAGTATTTCGATATGTTTTG TAATAACA
TGAGGGCTATATTTATGCAGTTAGAAAGTCAACCCCGTAAAGCTCCCAGAGATTTTA AATGTTTC
CTACAAAATCGATTACAAAAATTATACAAACAGACTTTCTTGAATGCACGAAGCAAC AAGTGTC
GCGCTCTGCTTGAGTCAGTTTTAATCTCTTGGGGAGAATTTTATACATACGGTGCCA ACGAAAAG
AAATTTAGATTAAGACATGAAGCTTCAGAACGCAGCAGTGACCCAGATTACGTAGTT CAGCAAG
CCTTGGAAATCGCGCGTCGTCTATTCCTTTTTGGCTTCGAATGGAGAGATTGCTCCG CTGGTGAA
AGAGTGGATTTGGTTGAAATTCACAAAAAGGCTATCAGTTTTTTGTTGGCTATTACT CAAGCTGA
GGTCTCTGTTGGTTCATACAATTGGCTTGGCAACTCAACAGTATCGAGATATTTATC CGTTGCGG
GAACTGATACCTTATACGGTACCCAATTGGAAGAATTCCTGAACGCTACAGTGTTGA GTCAAAT
GCGTGGTCTGGCCATTAGATTGAGTTCTCAAGAACTTAAGGACGGTTTTGATGTGCA GCTCGAG
TCTTCCTGCCAGGACAATCTGCAACACCTATTGGTGTATAGGGCTTCGAGAGATTTG GCGGCTTG
CAAGCGCGCTACTTGTCCAGCCGAACTCGATCCTAAGATTTTAGTTTTACCGGTAGG TGCATTCA
TCGCTTCCGTAATGAAAATGATAGAAAGAGGTGACGAACCTTTAGCTGGTGCTTATT TACGGCA
TAGGCCACACTCTTTCGGATGGCAAATTAGGGTCCGCGGTGTTGCTGAGGTAGGGAT GGATCAG
GGTACAGCATTGGCCTTTCAAAAGCCAACAGAGTCAGAACCTTTTAAAATTAAGCCC TTCTCTG
CACAGTATGGACCAGTTCTGTGGTTGAACAGTAGTAGTTATTCTCAATCACAATATT TGGACGGT
TTTCTATCTCAACCAAAAAATTGGAGTATGAGGGTGTTGCCTCAGGCGGGTTCAGTT CGCGTCG
AACAACGAGTTGCTTTGATATGGAACTTACAAGCAGGCAAGATGAGACTAGAACGCT CCGGTGC
GAGGGCCTTTTTCATGCCTGTACCGTTTTCATTTAGGCCATCCGGCAGTGGGGACGA AGCAGTTT
TGGCGCCCAACCGGTACTTGGGTCTGTTCCCTCATTCCGGAGGTATAGAATACGCTG TAGTGGAT
GTCCTGGATTCTGCTGGATTTAAAATTCTTGAAAGAGGCACTATTGCTGTCAATGGT TTCTCTCA
GAAAAGGGGAGAGCGCCAAGAAGAAGCCCATCGTGAAAAACAAAGAAGGGGGATAAG TGATA
TAGGGCGAAAGAAGCCTGTGCAGGCAGAAGTCGATGCGGCGAACGAATTGCATAGAA AGTACA
CTGATGTTGCCACAAGATTAGGTTGTAGAATCGTCGTTCAATGGGCACCACAACCTA AACCAGG
GACAGCACCGACAGCGCAAACTGTTTACGCGAGGGCTGTTAGGACAGAAGCTCCGAG GAGCGG
CAACCAAGAAGATCATGCAAGAATGAAAAGTTCTTGGGGTTACACCTGGGGTACGTA TTGGGA
GAAACGAAAACCAGAAGATATTTTAGGGATTTCTACACAGGTGTATTGGACAGGAGG TATAGG
CGAATCCTGTCCTGCTGTAGCAGTCGCTTTATTAGGTCATATTAGAGCAACTTCAAC ACAAACGG
AGTGGGAAAAGGAAGAAGTTGTCTTTGGAAGACTGAAGAAGTTCTTTCCGAGTTAA
SE ATGGAGAAGAGAATTAATAAGATACGGAAAAAATTATCTGCGGATAATGCAACAAAGCCA GTC
Q TCTCGTTCAGGCCCCATGAAAACCCTGCTTGTAAGAGTAATGACGGATGATTTAAAAAAG AGGT
no TGGAAAAGCGTAGAAAAAAACCAGAAGTGATGCCGCAAGTGATCTCAAATAACGCAGCTA ATA N ATCTAAGGATGCTACTTGATGATTATACAAAAATGAAAGAAGCAATCCTGCAAGTTTACT GGCA O: GGAATTCAAGGATGACCATGTTGGACTAATGTGCAAATTCGCACAACCAGCGTCTAAGAA AATT 14 GACCAAAATAAATTGAAACCCGAAATGGACGAAAAAGGGAATTTAACAACTGCCGGGTTT GCC 5 TGCTCGCAATGTGGGCAACCATTATTTGTTTATAAATTAGAGCAGGTTTCGGAAAAAGGA AAGG CTTACACAAATTACTTCGGCAGATGTAATGTTGCCGAACACGAAAAACTCATATTGTTAG CTCA GTTGAAGCCTGAGAAAGACTCTGATGAGGCCGTTACTTACTCGTTGGGGAAGTTTGGTCA AAGA GCTCTCGATTTTTATTCTATTCATGTGACAAAGGAGTCCACACATCCCGTCAAGCCCTTG GCACA AATTGCGGGTAATAGATACGCTTCGGGTCCAGTTGGGAAGGCCCTTTCTGATGCATGTAT GGGC ACAATTGCTAGCTTTCTTAGTAAATACCAGGATATCATAATAGAGCATCAAAAAGTTGTA AAGG GTAACCAAAAGAGATTAGAATCGCTGCGTGAGTTGGCGGGTAAAGAAAACTTGGAATATC CAT CTGTCACTCTGCCTCCTCAACCTCATACTAAGGAAGGTGTAGATGCGTACAATGAAGTTA TCGCT AGAGTCCGTATGTGGGTGAATTTAAATTTGTGGCAAAAATTGAAGTTATCGCGTGATGAT GCAA AACCTCTTCTTAGACTAAAGGGCTTTCCTAGCTTCCCTGTAGTGGAAAGACGCGAAAATG AAGT CGATTGGTGGAATACAATTAACGAAGTCAAAAAACTGATCGATGCAAAGCGAGATATGGG TCG AGTTTTTTGGTCTGGTGTTACAGCTGAAAAAAGGAATACGATCTTAGAAGGTTACAACTA CTTG CCAAATGAGAACGATCATAAAAAAAGAGAAGGCAGTTTAGAAAATCCAAAAAAGCCAGCT AAG AGACAATTTGGTGATTTGCTACTTTACCTAGAAAAAAAGTACGCCGGAGATTGGGGGAAA GTCT TTGACGAAGCTTGGGAGAGAATAGATAAAAAAATAGCAGGATTGACGTCACACATTGAAA GAG AAGAGGCGAGAAATGCAGAAGATGCTCAGTCCAAAGCTGTCCTCACCGACTGGTTGAGAG CCA AAGCGTCCTTTGTTCTCGAACGCCTAAAAGAAATGGATGAGAAGGAATTTTATGCCTGCG AAAT CCAGCTACAAAAATGGTACGGAGACTTGAGAGGTAACCCCTTTGCCGTGGAAGCAGAGAA CCG TGTTGTAGATATCTCCGGTTTCTCAATCGGTAGCGATGGACACTCCATTCAGTATCGCAA CTTGT TGGCCTGGAAATATTTGGAAAACGGTAAGAGGGAATTCTATTTACTTATGAATTATGGCA AGAA AGGTAGAATCAGGTTTACTGACGGAACAGACATTAAAAAGAGTGGTAAGTGGCAAGGCCT TTT GTACGGTGGTGGCAAGGCCAAAGTAATAGACTTAACATTTGACCCCGACGACGAACAACT GAT AATACTGCCTTTAGCTTTTGGTACTCGACAGGGGCGAGAGTTCATTTGGAATGATCTTTT GTCAC TCGAGACTGGTTTGATAAAACTTGCAAATGGAAGAGTCATCGAGAAGACAATTTACAACA AAA AGATAGGTCGCGATGAGCCTGCACTATTTGTGGCCTTGACCTTTGAGAGAAGGGAAGTTG TCGA CCCATCCAATATTAAACCAGTCAACCTAATCGGTGTAGATAGAGGTGAAAACATCCCAGC TGTT ATCGCTCTGACAGACCCTGAAGGTTGCCCTTTGCCAGAATTTAAAGATTCGTCTGGTGGA CCAA CAGATATATTACGTATTGGGGAAGGCTATAAAGAGAAACAACGTGCTATTCAGGCTGCAA AAG AAGTTGAACAGAGGAGAGCTGGAGGTTACAGTAGAAAATTCGCCAGTAAAAGTAGAAACT TAG CAGATGACATGGTTAGAAACTCTGCCCGGGATTTGTTCTATCATGCGGTTACTCACGATG CAGTC TTAGTCTTTGAAAATCTATCGCGCGGTTTTGGTAGGCAAGGCAAGAGGACTTTTATGACA GAGA GACAATATACAAAAATGGAAGATTGGTTAACCGCGAAGCTCGCATATGAAGGTCTTACTT CGAA AACGTACCTCAGCAAAACGCTGGCTCAATATACTTCTAAAACTTGTTCAAATTGTGGTTT TACTA TTACCACGGCAGACTACGACGGGATGTTGGTGAGATTGAAGAAGACGAGCGATGGTTGGG CAA CAACATTGAATAATAAGGAATTAAAAGCAGAAGGACAGATTACGTATTACAATCGTTATA AAC GCCAAACGGTTGAGAAAGAGTTGTCAGCCGAGTTGGATAGACTAAGTGAAGAGAGCGGTA ACA ATGATATCTCAAAGTGGACTAAAGGGAGGCGGGATGAAGCCCTCTTTTTACTAAAGAAGA GATT CTCACATAGACCTGTGCAAGAACAATTCGTTTGTTTAGATTGTGGCCATGAGGTTCATGC AGAC GAACAGGCTGCGTTAAATATTGCGAGAAGCTGGCTATTTCTAAATTCTAATTCAACAGAG TTCA AGAGCTATAAATCCGGAAAACAACCTTTCGTAGGCGCGTGGCAAGCCTTCTATAAAAGGA GATT AAAAGAGGTTTGGAAACCAAATGCA
SE ATGAAAAGAATTAACAAAATTAGAAGGAGGCTGGTCAAAGATTCTAATACCAAGAAAGCT GGT
Q AAGACTGGTCCGATGAAAACCCTATTAGTCAGAGTTATGACCCCAGATTTGAGAGAAAGA TTGG
no AGAACCTCAGGAAAAAGCCCGAAAACATCCCACAACCCATTAGTAACACATCAAGAGCTA ATT
N TAAACAAGTTATTAACTGACTACACTGAAATGAAAAAAGCAATATTGCATGTTTACTGGG AAGA
O: GTTCCAGAAAGATCCTGTTGGGTTGATGTCTAGAGTTGCTCAACCGGCCCCAAAGAATAT AGAT 14 CAAAGGAAACTTATTCCTGTGAAGGACGGCAATGAAAGATTAACCAGCTCCGGTTTCGCT TGCT
6 CCCAGTGCTGCCAACCCCTGTATGTATACAAACTGGAACAAGTAAATGATAAAGGTAAGC CACA
TACTAACTACTTTGGTAGGTGTAATGTATCCGAGCATGAAAGATTGATCTTGTTAAG TCCCCATA
AACCAGAAGCTAATGATGAGTTAGTAACTTATAGTTTAGGTAAGTTCGGACAACGAG CTTTAGA
TTTCTATAGCATCCATGTTACAAGAGAAAGCAATCACCCCGTCAAACCACTGGAACA AATCGGT
GGTAATAGTTGTGCGTCAGGTCCAGTAGGCAAAGCTTTATCAGACGCTTGCATGGGT GCCGTGG
AAAGAGACTCGCTAACTTAAAAGATATTGCAAGTGCCAATGGTTTAGCTTTTCCTAA AATTACCT
TGCCACCTCAGCCACATACAAAGGAGGGAATTGAAGCTTACAATAATGTAGTAGCCC AAATAGT
TATTTGGGTGAACCTTAACCTATGGCAAAAGTTAAAAATTGGTAGAGACGAAGCCAA ACCCCTG
CAGAGGCTGAAGGGTTTTCCCTCCTTCCCCTTAGTAGAGAGACAAGCTAATGAAGTG GACTGGT
GGGATATGGTGTGCAATGTTAAAAAATTGATTAATGAGAAGAAAGAGGATGGTAAAG TGTTTTG
GCAGAATCTTGCTGGCTACAAGAGACAGGAAGCTTTACTGCCTTATTTATCTTCTGA GGAAGAT
AGGAAAAAAGGTAAAAAATTTGCTAGATATCAATTCGGAGACCTACTTCTGCATTTA GAAAAAA
AACATGGCGAAGATTGGGGTAAAGTTTATGATGAAGCCTGGGAAAGAATTGATAAGA AGGTAG
AAGGTCTCTCCAAACATATTAAATTAGAGGAAGAACGTAGGTCCGAAGACGCTCAAT CAAAGG
CAGCATTAACTGATTGGTTGAGAGCAAAAGCCTCTTTCGTTATTGAAGGATTAAAAG AAGCCGA
CAAAGATGAATTTTGTAGATGTGAGTTAAAGTTGCAAAAGTGGTATGGAGACCTCCG TGGTAAA
CCTTTTGCTATTGAGGCTGAAAATTCTATACTCGATATCTCTGGATTTTCAAAACAA TATAACTG
CGCATTTATATGGCAGAAAGATGGTGTTAAAAAGCTAAATCTATACTTAATTATCAA TTACTTTA
AAGGTGGTAAATTGCGTTTTAAGAAGATAAAGCCTGAAGCCTTTGAGGCAAACCGTT TTTACAC
TGTTATCAATAAAAAATCTGGGGAAATCGTACCAATGGAAGTTAATTTCAATTTCGA TGATCCT
AATCTTATTATTTTACCTCTTGCTTTCGGCAAAAGGCAAGGTAGGGAGTTTATTTGG AATGATTT
ATTGTCGCTGGAAACGGGGTCTCTCAAACTCGCAAACGGTAGGGTGATAGAAAAAAC ATTATAC
AACAGGAGAACTCGGCAGGATGAGCCAGCTCTTTTTGTGGCTCTGACATTCGAGAGA AGGGAA
GTTTTAGATTCATCTAACATCAAACCAATGAATTTAATAGGTATTGACCGGGGTGAA AATATAC
CTGCAGTTATTGCTTTAACTGATCCTGAGGGATGTCCTCTTAGCAGATTCAAGGACT CGTTGGGT
AACCCTACTCACATCTTAAGGATTGGAGAAAGTTACAAGGAGAAACAAAGGACAATA CAAGCT
GCTAAAGAAGTAGAACAAAGGAGGGCGGGTGGATATAGTCGGAAATATGCCAGCAAG GCCAA
GAATTTAGCTGACGACATGGTTAGGAATACAGCTAGAGACCTTTTATACTATGCCGT CACCCAG
GATGCCATGTTGATATTTGAAAATTTAAGTAGAGGCTTCGGTAGACAAGGTAAGCGC ACCTTCA
TGGCAGAGAGACAATATACTAGAATGGAAGATTGGTTGACTGCCAAATTGGCATACG AAGGTCT
ACCTAGTAAGACGTACTTATCTAAAACACTAGCGCAGTATACTTCCAAGACATGCAG TAATTGT
GGTTTCACAATCACTTCTGCCGATTACGATCGCGTCTTGGAAAAACTAAAAAAAACA GCGACAG
GTTGGATGACTACTATTAATGGGAAAGAATTGAAGGTCGAAGGACAAATAACTTACT ATAATAG ATATAAACGGCAAAACGTTGTAAAAGACCTGTCAGTCGAACTCGATCGACTTAGTGAAGA ATCT
GTTAATAATGATATTAGTTCGTGGACAAAAGGTAGATCCGGTGAAGCTTTGAGCCTC CTGAAAA
AACGTTTTAGCCATAGGCCTGTCCAAGAAAAGTTTGTATGTTTAAACTGTGGTTTTG AGACCCAT
GCAGACGAGCAGGCCGCTCTTAATATTGCTAGATCATGGTTATTTTTAAGATCTCAG GAATACA
AGAAGTACCAGACTAACAAGACAACAGGCAACACAGATAAGCGAGCATTCGTTGAGA CTTGGC
AATCTTTTTATAGAAAGAAATTGAAGGAAGTCTGGAAACCA
SE ATGGGAAAAATGTATTATCTAGGCCTGGACATAGGGACCAATTCAGTAGGCTACGCTGTC ACTG
Q ACCCCTCCTACCATTTGCTGAAGTTCAAGGGGGAACCCATGTGGGGAGCACACGTGTTTG CGGC
no CGGCAACCAGAGCGCAGAGCGGAGAAGCTTCCGCACCTCCAGGAGAAGGCTGGATCGCAG GCA
N GCAGCGTGTGAAGCTGGTCCAAGAGATATTTGCCCCAGTGATTTCCCCCATCGATCCGCG CTTCT
O: TTATTAGGCTCCACGAGTCCGCTCTCTGGCGCGACGACGTGGCCGAAACTGATAAACATA TTTTC 14 TTTAATGACCCAACATACACTGACAAGGAGTACTATTCAGATTACCCAACAATTCACCAT TTGAT
7 CGTGGACCTTATGGAAAGTTCGGAGAAGCATGATCCTCGACTTGTCTATTTGGCCGTGGC GTGG
CTCGTGGCACATAGGGGCCACTTCTTGAACGAGGTGGACAAGGATAACATCGGGGAT GTGTTAT
CTTTCGACGCTTTCTATCCTGAATTCCTTGCTTTTCTGTCTGACAATGGCGTCAGCC CGTGGGTCT
GCGAATCCAAGGCCCTCCAGGCTACGCTATTGTCAAGAAATAGCGTGAACGACAAGT ACAAGG
GGACGGGCTGATTCAGCTCCTCGCTGGGAAAAAGGTCAAGGTCAATAAGCTGTTTCC ACAGGAG
TCAAATGACGCGAGCTTCACCCTTAACGACAAAGAGGATGCCATTGAAGAGATCCTG GGGACA
CTCACCCCAGACGAGTGCGAGTGGATAGCCCATATTAGGCGCCTCTTTGATTGGGCC ATAATGA
AACATGCGCTTAAGGACGGGCGCACGATATCCGAAAGCAAGGTCAAATTGTACGAGC AGCACC
ACCATGATCTGACCCAGCTAAAATATTTTGTAAAAACATATCTGGCCAAGGAGTACG ATGATAT
CTTCCGCAACGTGGATAGTGAGACCACCAAAAACTACGTCGCGTACTCATACCACGT GAAAGAA
GTTAAGGGCACGCTGCCTAAGAACAAGGCAACACAAGAGGAGTTCTGCAAGTACGTT CTCGGG
AAAGTTAAAAATATAGAGTGCAGCGAGGCCGACAAAGTGGATTTTGACGAGATGATT CAACGC
CTGACCGACAATTCGTTTATGCCTAAACAGGTGAGTGGAGAGAATCGCGTGATTCCA TATCAGC
TCTATTACTATGAACTCAAGACTATTCTGAATAAGGCCGCTAGCTATTTACCCTTCC TTACGCAG
TGCGGGAAGGATGCCATTTCTAACCAGGATAAACTCTTGAGTATAATGACATTTCGA ATTCCCT
ATTTCGTGGGTCCGCTTCGTAAGGATAACAGTGAGCACGCTTGGCTGGAGCGGAAGG CTGGCAA
AATTTATCCATGGAATTTCAACGACAAGGTGGATCTGGACAAATCCGAAGAAGCCTT TATCCGC
AGGATGACCAATACTTGCACATACTATCCTGGGGAGGATGTCCTTCCACTGGACTCT CTGATCTA
CGAAAAGTTCATGATTTTGAATGAAATTAACAACATAAGGATCGATGGGTATCCTAT TTCCGTC
GACGTGAAGCAGCAGGTGTTCGGGCTCTTTGAGAAGAAGCGACGGGTGACCGTGAAG GATATT
CAGAATCTTCTCTTATCGCTGGGAGCCCTGGATAAACACGGAAAACTGACCGGGATA GATACTA
CGATTCATTCTAATTACAACACGTATCACCATTTTAAGTCACTGATGGAGAGGGGCG TCCTAAC
AAGAGATGACGTGGAGAGAATAGTGGAACGAATGACATATTCTGATGACACCAAGAG AGTGCG
GCTTTGGCTGAATAACAACTACGGCACTCTGACGGCGGATGATGTAAAGCATATTTC CCGACTC
CGTAAGCATGACTTCGGGCGGCTGTCTAAGATGTTTCTAACAGGCCTCAAGGGTGTG CATAAGG
AAACTGGGGAGCGCGCTAGCATCCTGGATTTTATGTGGAACACCAATGATAACCTGA TGCAGCT
CCTGTCAGAATGCTACACATTTTCGGACGAAATCACCAAGCTGCAGGAGGCTTACTA TGCCAAG
GCCCAACTAAGCTTGAATGATTTCCTGGATTCTATGTACATCAGCAACGCCGTAAAA CGACCAA
TTTATAGGACACTGGCAGTGGTTAACGACATTAGGAAAGCATGCGGAACAGCTCCCA AGCGAAT CTTTATCGAGATGGCCCGCGACGGCGAGAGTAAGAAGAAAAGGTCAGTGACTAGGCGGGA GCA
GATCAAGAACCTTTACCGCTCTATCCGAAAAGACTTCCAGCAAGAGGTTGATTTCCT TGAGAAG
ATCTTAGAGAACAAGTCAGATGGACAGCTCCAATCCGATGCTCTGTATCTGTACTTC GCTCAGCT
GGGACGAGATATGTACACTGGCGACCCCATTAAACTAGAACATATCAAGGACCAATC GTTTTAT
AATATCGACCACATCTACCCTCAGTCCATGGTGAAAGACGATAGTCTGGACAATAAG GTGCTCG
TCCAAAGTGAGATTAACGGAGAAAAGTCGAGCAGATATCCTTTGGACGCTGCGATCC GCAACA
AGATGAAGCCCCTGTGGGATGCTTACTACAATCATGGACTGATCAGCCTGAAGAAGT ATCAGAG
ACTGACCCGGAGTACCCCTTTCACAGACGATGAGAAGTGGGATTTTATCAATAGACA ACTGGTG
GAAACCAGGCAGTCCACGAAAGCTCTGGCCATTCTTCTGAAGAGAAAGTTTCCAGAC ACAGAG
ATCGTCTATTCAAAGGCCGGCCTCAGTTCCGACTTTAGACATGAGTTCGGACTCGTT AAATCACG
AAATATAAACGATCTCCACCATGCAAAGGACGCATTCCTCGCGATTGTGACTGGAAA TGTCTAT
CACGAAAGATTTAATAGGCGGTGGTTCATGGTTAACCAGCCATACTCAGTGAAGACC AAGACCC
TTTTCACTCACTCTATTAAAAATGGCAACTTCGTGGCTTGGAATGGTGAGGAGGATC TTGGAAG
AATTGTGAAGATGTTAAAACAGAATAAGAATACCATCCACTTTACTAGATTCAGCTT TGACCGA
AAAGAGGGGCTATTCGATATTCAACCGTTAAAGGCTTCAACAGGTCTCGTTCCACGA AAGGCCG
GACTGGACGTAGTGAAATACGGCGGCTATGATAAGAGCACCGCAGCTTACTACCTCC TTGTGCG
ATTTACGCTCGAGGATAAGAAGACCCAACACAAGCTGATGATGATTCCCGTGGAGGG ACTGTAC
AAAGCTCGAATTGACCATGATAAAGAGTTTCTCACAGATTACGCACAAACCACCATC TCTGAGA
TTCTCCAGAAAGACAAACAAAAAGTTATAAACATAATGTTTCCAATGGGTACAAGGC ATATTAA
ACTGAACAGCATGATCTCCATTGATGGCTTTTATTTGTCCATTGGAGGAAAGTCTAG TAAAGGC
AAGTCTGTCCTCTGCCATGCCATGGTACCCCTAATCGTCCCACACAAGATTGAATGC TACATCAA
GGCTATGGAGAGTTTTGCTCGGAAATTTAAAGAGAATAATAAGCTGCGTATTGTGGA AAAATTC
GACAAGATAACCGTTGAAGACAATCTGAATCTGTACGAGCTCTTTCTGCAGAAGCTG CAGCATA
ACCCCTATAATAAGTTCTTCTCCACACAGTTCGATGTACTGACCAACGGGCGATCAA CTTTCACA
GATCTTCAGGATGCGACTTGAAGAGCATTAACGGGAGCGCACAGGCAGCTAGGATCA TGATCTC AGCTGACCTGACAGGGCTGAGTAAAAAATACTCCGACATTCGGCTTGTAGAGCAAAGCGC CAGT GGGTTGTTCGTTAGTAAGTCGCAGAACCTGCTGGAATACCTGTAA
SE ATGTCTTCTTTGACGAAGTTTACAAACAAATACTCTAAGCAGCTTACAATTAAGAACGAA CTGA
Q TTCCCGTAGGAAAGACTCTGGAAAACATCAAAGAGAATGGGCTGATAGACGGCGACGAAC AAC
no TGAATGAGAACTATCAGAAGGCCAAAATTATCGTGGATGACTTCCTGAGGGATTTTATTA ACAA
N GGCCCTGAATAATACCCAGATCGGCAATTGGCGGGAACTGGCCGACGCTCTGAACAAAGA AGA
O: TGAGGACAATATCGAAAAATTACAAGACAAAATCAGGGGCATTATTGTCAGTAAGTTCGA GAC 14 ATTCGATCTGTTCTCTTCGTACTCCATTAAGAAGGACGAGAAAATCATCGATGATGACAA TGAC 8 GTTGAGGAAGAAGAACTGGACTTGGGTAAAAAGACCTCATCCTTCAAGTATATTTTTAAA AAAA
ATCTGTTTAAATTAGTGCTCCCCAGTTATTTAAAGACAACTAACCAGGACAAGCTTA AGATTATC
TCCTCTTTTGACAACTTTAGCACCTATTTTAGAGGCTTCTTTGAAAATCGCAAGAAT ATTTTCACT
AAGAAGCCCATAAGCACCTCTATTGCCTACAGAATCGTACATGATAACTTCCCAAAA TTTTTGG
ATAACATTAGATGTTTTAATGTATGGCAGACCGAATGTCCTCAGTTAATTGTGAAGG CGGATAA
CTACCTCAAATCCAAGAATGTGATCGCCAAAGATAAGTCTCTTGCTAACTACTTTAC GGTCGGA
GCCTACGATTACTTCTTATCTCAAAACGGTATTGACTTTTACAATAACATTATCGGG GGATTGCC
TGCCTTCGCCGGCCATGAGAAAATTCAGGGCTTAAACGAGTTCATAAATCAGGAATG TCAAAAG GACTCAGAGCTGAAATCAAAGCTTAAGAATCGACACGCATTTAAAATGGCGGTCTTGTTC AAAC
AGATCCTCAGCGATAGAGAGAAAAGCTTCGTTATTGATGAATTCGAGAGCGACGCAC AGGTGAT
TGATGCCGTGAAGAACTTCTATGCGGAACAGTGTAAAGACAATAATGTTATTTTCAA CCTATTA
AACTTGATTAAGAATATCGCGTTTTTAAGTGACGATGAACTCGACGGTATCTTTATA GAAGGCA
AGTACCTGTCCTCTGTCAGCCAAAAACTCTACTCAGATTGGTCCAAGCTAAGAAATG ACATCGA
GGACAGTGCTAACAGCAAACAGGGCAATAAAGAGCTGGCAAAGAAAATCAAGACTAA TAAAG
GGGATGTGGAGAAGGCGATATCTAAATATGAGTTCTCCCTCTCCGAACTGAACTCCA TCGTCCA
CGATAATACCAAGTTTAGTGATCTGTTGTCGTGTACACTGCACAAAGTGGCCAGTGA AAAACTC
GTCAAGGTGAACGAAGGCGATTGGCCCAAACACCTGAAAAATAATGAGGAGAAACAG AAGATC
AAAGAACCTTTGGATGCGTTGCTCGAAATATATAACACACTGTTGATCTTCAACTGT AAAAGCTT
CAACAAGAACGGGAACTTTTATGTAGACTACGATCGATGTATAAATGAACTGAGCAG CGTCGTT
TACCTGTACAACAAGACTCGCAATTATTGTACGAAAAAACCATATAACACCGATAAG TTCAAGC
TTAATTTCAACAGTCCCCAGCTGGGAGAAGGGTTCAGCAAATCAAAAGAAAACGATT GCCTGAC
ATTACTCTTTAAAAAGGATGATAATTATTATGTTGGGATTATTAGGAAAGGCGCTAA GATCAAC
TTTGACGACACACAGGCCATAGCTGACAACACTGATAACTGCATCTTTAAAATGAAT TACTTTCT
GTTGAAGGACGCCAAAAAATTCATTCCAAAATGCTCTATTCAGCTCAAGGAGGTTAA GGCCCAT
TTCAAGAAGTCTGAAGATGACTACATCCTCTCTGACAAGGAAAAATTCGCTAGTCCT CTGGTTAT
CAAAAAAAGTACCTTCTTGCTGGCTACAGCTCACGTGAAAGGCAAGAAAGGGAACAT TAAGAA
GTTCCAAAAGGAATACAGCAAAGAGAATCCAACCGAGTACAGAAATTCTCTGAACGA ATGGAT
CGCATTCTGTAAAGAATTTCTAAAGACGTACAAGGCCGCTACCATTTTCGATATTAC CACCTTGA
AAAAAGCCGAGGAGTACGCCGACATCGTCGAATTCTATAAAGACGTGGATAACCTGT GTTACAA
ATTGGAATTCTGCCCAATTAAGACCTCTTTCATTGAAAACCTCATCGACAATGGGGA CCTCTACT
TATTTAGAATTAACAATAAGGATTTTTCTTCGAAATCTACCGGAACTAAAAATCTGC ACACACTG
TATCTGCAAGCAATCTTCGATGAACGTAATCTCAACAACCCTACAATAATGCTGAAC GGCGGTG
CTGAACTGTTCTACCGTAAAGAGAGTATTGAACAGAAGAATCGAATCACACACAAAG CGGGCA
GTATTCTCGTCAATAAGGTGTGCAAAGACGGGACCAGCCTGGACGATAAGATCAGGA ATGAAA
TATATCAGTATGAGAACAAGTTTATCGACACCTTGTCGGATGAGGCAAAGAAGGTGC TACCTAA
CGTTATCAAGAAGGAAGCTACCCATGACATAACCAAGGATAAGCGGTTCACTTCTGA CAAGTTC
TTCTTCCACTGTCCTCTGACCATTAACTACAAGGAAGGAGACACTAAACAATTCAAT AATGAAG
TACTTAGCTTTTTGCGGGGTAATCCCGATATTAACATAATTGGTATCGACCGGGGAG AACGGAA
CCTGATATACGTGACAGTAATTAATCAGAAAGGAGAAATCCTGGATTCCGTATCCTT CAATACC
GTGACTAATAAATCTAGTAAAATCGAGCAGACGGTCGACTACGAGGAAAAGTTAGCA GTCAGA
GAGAAGGAGAGAATCGAGGCCAAACGTTCCTGGGATAGTATCAGCAAGATTGCTACT CTGAAA
GAAGGATATCTGTCCGCTATCGTCCATGAGATCTGTTTGTTGATGATCAAGCACAAT GCTATAGT
GGTTCTGGAGAACCTGAACGCAGGCTTCAAGCGAATTAGAGGGGGCCTGTCGGAAAA AAGCGT
TTACCAGAAGTTTGAAAAGATGCTAATCAATAAGTTAAATTACTTTGTAAGTAAAAA AGAAAGC
GATTGGAATAAGCCATCAGGACTTTTAAACGGGCTGCAACTGAGCGACCAGTTTGAG TCATTCG
AAAAACTGGGTATTCAGAGTGGTTTCATATTCTACGTACCTGCCGCTTACACTTCAA AGATCGAT
CCTACAACTGGTTTTGCGAATGTCCTGAATCTGTCTAAGGTGAGGAATGTGGACGCA ATCAAGT
CTTTCTTCAGCAACTTCAACGAGATATCTTACAGCAAGAAAGAGGCTCTGTTTAAAT TCAGTTTT
GATCTGGATAGCCTGAGCAAGAAAGGATTCTCTTCTTTCGTAAAGTTTTCTAAGTCC AAATGGA
ACGTCTACACGTTCGGAGAGAGAATCATTAAACCAAAGAACAAGCAGGGGTATCGGG AAGACA AAAGGATCAATCTGACTTTCGAAATGAAGAAACTATTGAATGAGTACAAAGTCTCATTCG ATTT
GGAGAACAATCTGATCCCCAATCTGACCAGCGCTAACCTCAAAGACACATTCTGGAA GGAGCTG
TTTTTCATCTTTAAGACCACCCTGCAGCTACGGAATAGTGTCACAAATGGGAAAGAG GATGTAC
TGATCTCACCTGTGAAAAACGCCAAGGGGGAGTTCTTTGTGTCCGGCACCCATAACA AAACCCT
GCCTCAGGACTGTGACGCGAACGGGGCCTACCACATCGCGCTAAAGGGGTTAATGAT TCTCGAA
CGTAATAATCTGGTGCGCGAAGAAAAAGACACAAAGAAAATTATGGCCATCAGCAAC GTTGAC
TGGTTTGAGTACGTGCAGAAGCGTCGAGGAGTTTTGTAA
SE ATGAACAACTATGACGAGTTCACTAAACTTTACCCCATTCAGAAAACCATCAGATTTGAA CTGA
Q AGCCTCAGGGTCGTACCATGGAACACTTGGAAACTTTCAACTTTTTCGAGGAGGACAGGG ATAG
no AGCTGAGAAATACAAGATCTTGAAAGAGGCCATCGACGAGTATCACAAAAAATTCATCGA TGA
N GCATCTCACCAACATGTCGCTGGATTGGAACAGTCTCAAGCAGATTTCCGAGAAGTACTA TAAA
O: TCTCGGGAGGAGAAAGATAAAAAGGTGTTTTTGAGCGAGCAAAAGCGAATGCGACAGGAG ATA 14 GTCTCTGAATTTAAGAAAGATGATCGGTTTAAAGACCTATTTTCCAAAAAGCTTTTTTCA GAGCT
9 GCTGAAGGAAGAGATCTATAAAAAAGGCAATCACCAAGAAATTGATGCCCTGAAATCATT CGA
CAAATTCAGTGGGTATTTCATAGGACTGCATGAGAACCGGAAGAATATGTATAGTGA TGGAGAC
GAGATCACAGCCATAAGCAATCGAATCGTTAACGAGAATTTCCCGAAGTTCCTGGAT AACCTGC
AGAAGTATCAAGAGGCTAGGAAAAAGTACCCTGAGTGGATCATCAAGGCTGAATCAG CTCTGG
TGGCTCACAATATCAAGATGGATGAAGTCTTTAGTCTTGAGTACTTTAATAAAGTCC TTAACCAG
GAGGGCATCCAGCGCTATAACCTGGCTCTCGGTGGCTACGTCACAAAAAGCGGAGAA AAGATG
ATGGGTCTCAACGATGCACTGAATTTGGCTCATCAGTCGGAGAAGTCATCTAAGGGA CGCATAC
ACATGACACCACTGTTTAAACAAATCCTGAGCGAAAAGGAATCATTTTCCTACATTC CCGACGT
ATTCACCGAGGACTCACAACTGCTGCCTAGTATAGGGGGGTTTTTCGCTCAGATAGA GAACGAC
AAAGATGGCAACATTTTTGACAGAGCCTTGGAGTTGATTTCATCTTACGCCGAGTAC GATACGG
AGCGCATTTATATTCGCCAGGCGGATATCAACAGGGTTTCCAATGTGATCTTTGGCG AGTGGGG
AACGCTGGGCGGGCTGATGCGGGAATACAAAGCCGACTCGATCAATGACATCAACCT GGAGAG
AACATGCAAGAAGGTCGATAAATGGTTGGATAGCAAAGAGTTCGCCCTGAGTGACGT CTTGGA
AGCTATCAAAAGAACCGGAAATAATGACGCGTTCAACGAGTATATCTCTAAAATGAG GACCGC
GAGAGAAAAAATTGATGCAGCAAGGAAGGAGATGAAGTTTATATCTGAGAAGATCTC AGGCGA
TGAAGAGTCCATCCATATTATTAAAACTCTTCTGGACTCAGTGCAGCAATTCCTGCA CTTTTTTA
ACCTCTTCAAGGCCAGGCAGGATATACCGTTAGACGGGGCTTTTTATGCCGAGTTTG ATGAAGT
TCATTCGAAACTTTTTGCTATAGTGCCTCTCTATAATAAAGTTCGCAATTACCTGAC AAAGAATA
ACTTAAACACAAAGAAAATCAAGCTCAACTTCAAAAACCCAACACTGGCAAACGGAT GGGATC
AGAACAAGGTATATGATTACGCCTCATTGATTTTCCTCCGGGACGGGAATTACTATC TGGGGAT
CATCAACCCTAAGCGCAAAAAGAACATTAAGTTCGAACAGGGATCTGGCAATGGTCC CTTCTAT
AGGAAAATGGTATACAAACAGATTCCTGGCCCCAACAAGAATCTCCCACGCGTCTTT CTGACGT
CCACTAAGGGAAAGAAGGAGTACAAGCCGTCTAAAGAAATTATCGAGGGCTATGAGG CAGACA
AGCATATTAGGGGTGACAAGTTTGACCTAGACTTTTGTCATAAGCTTATCGACTTTT TCAAGGAG
TCCATAGAGAAGCACAAAGATTGGTCAAAGTTTAATTTCTATTTTTCTCCAACAGAG TCCTACGG
GGATATCTCTGAGTTCTATCTGGATGTTGAAAAGCAGGGGTACAGAATGCACTTCGA AAATATC
TCAGCAGAAACTATCGATGAGTACGTAGAGAAAGGAGATCTGTTTCTTTTCCAAATC TACAATA
AGGATTTTGTGAAGGCCGCCACTGGGAAGAAGGACATGCACACTATTTACTGGAACG CTGCATT
TTCCCCTGAAAATCTGCAGGACGTAGTAGTGAAATTAAATGGTGAGGCAGAACTGTT TTACCGC GATAAATCAGACATCAAGGAAATAGTGCACCGGGAAGGCGAGATTCTTGTTAACCGAACA TAT
AATGGCAGGACACCTGTCCCTGATAAAATTCATAAGAAACTGACCGATTACCACAAC GGTCGAA
CCAAGGATCTGGGCGAGGCCAAGGAATACCTCGATAAGGTGAGGTACTTCAAAGCCC ATTATG
ACATCACCAAGGACCGAAGATACCTTAACGACAAAATCTACTTCCATGTCCCACTCA CCTTGAA
CTTCAAAGCTAACGGTAAGAAGAACCTCAATAAAATGGTGATTGAAAAATTTCTGTC CGATGAG
AAGGCCCATATCATCGGCATTGATCGCGGCGAGAGAAATCTCCTTTACTATTCTATC ATTGATCG
GTCGGGAAAGATTATCGACCAACAATCACTGAATGTCATCGACGGATTCGACTATAG AGAGAA
GCTGAACCAACGGGAAATCGAGATGAAGGACGCGCGCCAGTCCTGGAACGCTATCGG CAAAAT
TAAAGATTTGAAAGAAGGTTACCTCTCCAAAGCAGTGCACGAAATTACCAAAATGGC AATCCAG
TACAATGCTATTGTGGTAATGGAGGAGTTAAATTACGGATTTAAGCGCGGGAGGTTC AAGGTTG
AAAAGCAAATTTACCAAAAATTTGAGAACATGTTGATTGATAAGATGAACTACCTGG TGTTCAA
GGACGCACCTGACGAGTCGCCAGGCGGCGTGTTAAATGCATATCAGCTGACAAATCC ACTGGAG
AGCTTTGCCAAGCTAGGAAAGCAGACTGGCATTCTCTTTTACGTCCCTGCAGCGTAT ACATCCAA
AATTGACCCCACCACTGGCTTCGTCAATCTGTTTAACACCTCCTCCAAAACCAACGC ACAAGAA
CGGAAAGAATTTTTGCAAAAGTTTGAGTCCATTAGCTACTCTGCCAAAGACGGCGGG ATCTTTG
CTTTCGCATTCGACTACAGGAAATTCGGGACGAGTAAGACAGACCACAAGAACGTCT GGACCGC
GTACACTAATGGGGAACGCATGCGCTACATCAAAGAGAAAAAGAGGAATGAACTTTT TGACCC
TTCAAAGGAAATCAAGGAAGCTCTCACCTCAAGCGGTATCAAATACGATGGCGGGCA GAATATT
TTGCCAGATATCCTCAGATCGAACAATAATGGACTTATCTATACTATGTACTCCTCC TTCATTGC
AGCAATTCAAATGAGAGTGTACGATGGAAAGGAGGATTACATTATATCGCCAATTAA GAACTCC
AAAGGCGAATTCTTCCGCACGGATCCTAAGCGAAGAGAACTCCCAATCGACGCTGAT GCGAAC
GGCGCCTATAATATAGCCCTGCGGGGTGAATTAACAATGCGCGCTATTGCCGAGAAG TTCGACC
CCGATTCAGAAAAAATGGCTAAGCTTGAGCTGAAACACAAAGATTGGTTCGAATTCA TGCAGAC
AAGAGGCGACTAA
SE ATGACTAAGACCTTCGATTCCGAGTTCTTCAACCTTTATTCCCTGCAGAAAACTGTAAGG TTTGA
Q GCTGAAGCCGGTGGGCGAGACAGCCAGCTTCGTAGAGGATTTCAAGAATGAGGGTCTCAA ACG
no GGTAGTTAGTGAGGATGAGAGGAGAGCAGTGGACTATCAGAAGGTGAAAGAGATCATCGA TGA
N CTATCACCGGGATTTCATAGAGGAGTCGTTGAATTACTTCCCTGAGCAAGTATCCAAAGA CGCG
O: CTGGAACAGGCCTTTCATCTTTACCAGAAACTGAAGGCAGCGAAGGTTGAGGAGCGGGAA AAG 15 GCCTTGAAAGAGTGGGAAGCCCTGCAGAAAAAGCTCAGAGAAAAGGTTGTCAAATGCTTC AGC 0 GACAGCAACAAAGCCAGGTTCAGTAGGATCGATAAGAAAGAACTGATCAAAGAAGACTTG ATC
AATTGGCTGGTTGCACAGAACCGGGAAGATGATATTCCCACCGTAGAGACCTTCAAC AACTTCA
CAACTTACTTCACCGGCTTCCATGAGAATCGTAAAAACATCTACAGTAAAGATGATC ATGCAAC
CGCCATCTCCTTCCGGTTGATCCACGAGAATCTCCCCAAGTTCTTTGACAACGTGAT AAGTTTCA
ATAAGTTGAAAGAGGGATTTCCCGAACTCAAGTTCGATAAAGTGAAGGAGGATCTGG AAGTGG
ATTATGACCTTAAGCACGCTTTCGAGATAGAGTACTTCGTGAACTTTGTGACTCAGG CCGGCATC
GATCAGTATAACTACCTCCTCGGGGGTAAGACGCTCGAGGACGGTACTAAGAAGCAA GGAATG
AATGAGCAAATTAATCTATTTAAACAGCAGCAGACCAGGGATAAGGCTAGACAGATC CCCAAG
CTTATTCCTCTTTTTAAACAGATCCTAAGTGAAAGGACAGAAAGTCAAAGCTTCATA CCTAAGC
AATTTGAAAGTGATCAGGAGCTGTTTGACTCCCTGCAAAAGCTGCACAACAATTGCC AGGACAA
GTTTACCGTGCTGCAGCAGGCTATCCTCGGACTGGCTGAGGCGGATCTTAAGAAGGT ATTCATT
AAGACTAGCGACCTCAATGCCCTTAGTAACACCATCTTTGGAAATTACTCCGTTTTC AGCGATGC CCTCAATCTATACAAAGAGAGCTTGAAGACTAAAAAAGCTCAGGAAGCTTTTGAAAAATT ACCG
GCACATTCTATACACGACCTTATACAATACTTAGAGCAGTTCAACAGCAGCCTCGAC GCTGAGA
AACAGCAATCCACAGACACCGTCCTGAATTACTTCATCAAAACCGATGAACTGTACT CCCGATT
TATCAAGAGCACTTCAGAAGCCTTCACGCAAGTTCAGCCTCTGTTCGAGCTGGAGGC ACTGTCC
AGCAAGAGACGACCGCCAGAGTCTGAAGACGAGGGAGCCAAGGGTCAAGAGGGGTTT GAACA
GATAAAGCGAATTAAGGCTTACTTGGATACTCTCATGGAGGCGGTGCATTTCGCTAA GCCTTTGT
TGAAATGGCCTACCAGGAATTGGAATCCTTGATCATTCCAATCTATAATAAAGCCCG GAGTTAT
CTGAGCAGGAAGCCCTTCAAAGCCGACAAGTTCAAAATAAATTTTGACAATAATACG CTACTGT
CTGGTTGGGACGCTAACAAGGAAACAGCCAATGCTTCCATCCTGTTTAAGAAAGACG GCCTGTA
CTACCTGGGAATTATGCCAAAAGGCAAAACTTTTTTGTTCGATTACTTTGTGTCATC AGAGGATA
GCGAGAAGTTAAAGCAAAGACGGCAGAAGACCGCCGAAGAAGCCCTCGCACAAGACG GAGAA
TCATATTTCGAGAAAATTCGATATAAGCTCCTGCCTGGCGCATCAAAGATGTTGCCA AAAGTCTT
CTTTTCCAACAAAAACATCGGCTTTTATAACCCCAGCGATGATATCCTTCGCATCCG GAACACCG
CCTCACATACCAAAAATGGAACTCCACAGAAGGGCCACTCGAAGGTTGAATTCAACC TTAACGA
TTGTCACAAAATGATTGATTTTTTTAAGAGCTCCATTCAGAAACACCCCGAATGGGG GTCCTTTG
GCTTCACCTTTTCTGATACTTCAGACTTCGAGGACATGTCCGCCTTCTACAGGGAGG TGGAGAAC
CAGGGCTATGTCATCTCCTTCGACAAAATAAAAGAGACATACATTCAGAGCCAGGTC GAGCAGG
GAAATCTGTACCTGTTTCAGATCTATAACAAGGATTTCAGTCCCTATAGCAAGGGCA AGCCCAA
TTTACATACCCTGTACTGGAAGGCCCTGTTCGAAGAGGCAAACCTTAACAATGTAGT TGCTAAG
CTGAATGGGGAAGCAGAGATCTTCTTCCGAAGGCACAGCATCAAGGCAAGCGACAAA GTTGTA
CATCCTGCTAACCAGGCCATCGATAACAAGAACCCGCATACAGAAAAGACACAGTCA ACCTTTG
AATACGACCTCGTGAAGGACAAGAGGTACACACAAGATAAATTCTTCTTCCACGTGC CCATCAG
CTTGAATTTTAAAGCGCAGGGAGTGAGCAAATTTAACGACAAGGTCAACGGCTTCCT GAAGGGA
AACCCCGACGTGAATATCATCGGAATTGATCGCGGTGAAAGACATCTCCTCTACTTT ACTGTGGT
GAACCAGAAGGGTGAGATCCTAGTACAGGAGAGCCTGAACACCCTTATGAGTGATAA GGGCCA
TGTGAATGATTACCAGCAGAAGCTGGACAAGAAGGAACAGGAAAGGGACGCAGCGCG GAAGT
CCTGGACCACTGTTGAGAATATCAAAGAACTGAAGGAGGGATATCTTAGCCATGTGG TACACAA
ACTTGCACATCTGATTATCAAGTATAATGCCATAGTCTGCCTGGAAGACTTGAACTT CGGTTTCA
AGCGAGGAAGGTTTAAAGTGGAGAAGCAGGTGTACCAGAAGTTTGAGAAAGCCCTTA TTGATA
AGCTAAACTACCTTGTCTTTAAGGAAAAAGAACTCGGCGAAGTTGGCCACTATTTAA CCGCCTA
CCAACTAACCGCCCCTTTCGAGTCTTTTAAGAAACTGGGAAAGCAGAGCGGAATACT CTTCTAT
GTGCCTGCAGACTACACCTCTAAGATCGACCCCACTACCGGCTTTGTAAACTTTCTA GATCTCCG
CTATCAGTCAGTAGAAAAAGCCAAACAGCTCTTGTCAGATTTTAACGCCATCCGATT TAATTCCG
TCCAAAATTACTTCGAGTTCGAAATCGACTATAAAAAACTTACCCCCAAGAGAAAGG TTGGGAC
GCAGTCTAAGTGGGTAATCTGCACTTACGGTGACGTGAGATACCAGAACCGCCGAAA CCAGAA
AGGTCATTGGGAAACCGAGGAAGTGAATGTGACTGAGAAGCTCAAGGCCCTCTTCGC TAGCGA
CAGTAAAACAACAACAGTTATCGATTACGCCAATGACGATAATCTTATAGACGTGAT CTTGGAA
CAAGACAAAGCCTCTTTTTTTAAGGAATTGTTGTGGTTGCTGAAACTTACAATGACC CTTAGGCA
CAGCAAGATCAAATCAGAGGATGACTTCATCCTCAGCCCGGTGAAGAATGAACAGGG AGAGTT
CTACGATTCACGGAAGGCTGGAGAGGTGTGGCCCAAGGATGCCGACGCGAACGGGGC CTACCA
CATAGCTCTAAAAGGTCTGTGGAACCTGCAACAAATCAATCAATGGGAGAAAGGTAA GACACT GAACCTGGCCATCAAAAATCAAGATTGGTTCTCATTCATCCAGGAAAAGCCTTATCAAGA GTGA
SE ATGCATACGGGAGGCCTTTTATCAATGGACGCAAAAGAGTTCACCGGGCAGTATCCATTA TCTA
Q AGACACTCCGCTTCGAGCTGAGGCCCATTGGCAGGACCTGGGACAACCTGGAGGCGTCGG GCTA
no CCTGGCTGAGGACAGACATCGCGCAGAATGCTATCCGAGAGCTAAGGAGCTTTTGGACGA CAAT
N CATCGCGCGTTCCTTAACCGGGTGCTCCCACAGATCGATATGGACTGGCACCCGATCGCT GAGG
O: CTTTTTGCAAGGTCCATAAGAACCCTGGGAACAAAGAGCTCGCCCAGGACTACAACTTGC AGCT 15 GAGCAAGCGACGGAAAGAGATTTCTGCCTACCTTCAAGACGCCGATGGCTACAAAGGGCT CTTC 1 GCAAAGCCCGCATTGGATGAGGCCATGAAAATCGCCAAGGAGAACGGGAATGAAAGTGAC ATC
GAAGTTCTCGAAGCGTTTAACGGATTTAGCGTGTACTTTACCGGCTATCATGAGTCA AGGGAGA
ATATTTATAGCGATGAGGACATGGTCTCTGTGGCCTACCGGATTACCGAGGATAATT TCCCGAG
GTTTGTTTCAAATGCACTAATATTCGACAAGTTAAATGAGAGCCACCCAGACATCAT CTCGGAG
GTCAGCGGCAACCTCGGAGTTGACGATATTGGCAAATACTTCGACGTGAGCAACTAT AACAACT
TCCTCTCACAGGCTGGCATCGACGACTATAATCATATTATAGGCGGCCACACTACTG AGGATGG
TCTCATTCAGGCATTCAATGTAGTCTTGAATCTTAGGCACCAGAAGGACCCTGGGTT TGAAAAG
ATACAGTTCAAGCAGCTGTATAAGCAGATATTATCCGTGCGAACATCTAAAAGTTAC ATCCCCA
AACAGTTTGATAACTCAAAGGAGATGGTGGATTGCATATGCGATTATGTGTCAAAAA TTGAAAA
GAGCGAGACTGTGGAGCGGGCTCTGAAGCTCGTCAGGAACATTAGCTCCTTTGACCT TAGAGGA
ATTTTCGTCAATAAAAAGAATCTGAGGATCCTGAGCAATAAGCTAATAGGAGATTGG GACGCCA
TAGAGACAGCATTGATGCATTCCAGCTCAAGCGAGAATGATAAGAAGTCTGTCTACG ATAGCGC
TGAAGCCTTCACGCTGGACGATATCTTCTCTTCCGTGAAAAAATTTAGTGATGCGTC CGCAGAA
GATATCGGGAATCGAGCCGAAGATATCTGCAGGGTAATTTCAGAGACCGCCCCTTTC ATCAATG
ACCTGCGCGCCGTGGACCTGGATAGCCTGAATGACGATGGTTACGAAGCTGCAGTTT CTAAGAT
CAGGGAGTCTCTGGAGCCATATATGGACTTGTTTCACGAACTTGAGATCTTTAGCGT GGGCGAC
GAGTTCCCGAAATGCGCAGCTTTCTATAGCGAGTTAGAGGAGGTCAGCGAGCAATTA ATCGAGA
TCATACCCCTGTTTAATAAGGCACGGAGCTTTTGTACTCGCAAGCGCTACAGCACCG ACAAGAT
TAAAGTTAATCTGAAATTTCCAACTCTCGCAGACGGGTGGGACCTAAACAAGGAACG CGATAAT
AAAGCCGCCATCCTTAGAAAGGACGGAAAGTACTATCTTGCCATCCTAGATATGAAA AAAGATC
TGAGTTCCATTCGTACTAGCGATGAAGACGAATCTTCTTTCGAAAAAATGGAGTATA AGCTGCT
CCCCTCGCCAGTCAAGATGCTACCCAAGATCTTTGTGAAGAGCAAAGCAGCCAAGGA AAAGTA
CGGGCTGACGGACAGGATGCTGGAGTGCTACGATAAGGGAATGCATAAATCAGGGTC AGCTTTT
GACTTGGGCTTTTGCCATGAGCTAATCGATTACTACAAGCGCTGTATCGCCGAGTAT CCAGGAT
GGGACGTTTTCGACTTTAAATTTCGGGAGACTTCTGATTATGGTTCAATGAAGGAGT TCAACGA
AGATGTCGCTGGTGCCGGTTACTACATGAGCCTTCGCAAGATTCCTTGTTCCGAAGT CTACCGGC
TACTGGACGAGAAATCTATATATTTGTTCCAGATATATAACAAGGACTACAGTGAGA ATGCACA
TGGGAATAAGAATATGCATACTATGTATTGGGAAGGTCTCTTTTCACCCCAAAATTT GGAGTCA
CCCGTGTTCAAACTTAGCGGTGGCGCAGAGCTGTTCTTTAGGAAATCCAGTATACCC AATGACG
CCAAGACAGTCCACCCAAAGGGTAGCGTCCTGGTGCCCAGAAACGATGTGAACGGCA GGAGAA
TCCCTGACAGCATTTACCGAGAACTTACCAGGTACTTCAACCGCGGCGACTGTAGAA TCTCTGA
TGAGGCAAAGTCTTATCTGGATAAGGTGAAGACTAAGAAGGCAGATCATGACATTGT GAAAGA
CCGCCGCTTTACTGTCGACAAAATGATGTTTCACGTGCCTATCGCAATGAATTTTAA GGCAATCT
CAAAACCGAATCTGAACAAGAAGGTGATAGATGGCATTATCGATGACCAGGACCTCA AGATCA
TCGGAATCGACAGAGGTGAGCGAAACCTGATATACGTCACAATGGTAGATCGGAAGG GTAATA TTCTGTACCAGGATTCACTAAACATCCTCAATGGATATGACTATCGAAAAGCTCTCGATG TCAG
GGAATACGACAACAAGGAGGCGCGACGGAATTGGACAAAGGTGGAAGGCATACGGAA GATGA
AGGAAGGCTATCTGTCACTAGCTGTCTCCAAATTGGCTGATATGATTATAGAGAACA ACGCCAT
TATCGTGATGGAAGATCTCAACCATGGATTCAAGGCAGGAAGAAGTAAAATTGAGAA GCAGGT
GTATCAGAAGTTCGAAAGCATGCTTATTAATAAGTTGGGTTATATGGTCTTAAAGGA CAAGTCT
ATCGATCAGAGCGGCGGCGCACTCCATGGGTATCAGCTGGCTAACCATGTCACCACA CTAGCAT
CCGTAGGCAAACAGTGTGGCGTGATTTTCTACATTCCTGCTGCGTTCACTTCTAAGA TCGATCCT
ACCACGGGATTCGCAGACCTGTTCGCACTGAGCAATGTTAAAAACGTGGCCTCCATG AGGGAGT
TCTTTAGCAAAATGAAAAGCGTGATTTATGACAAGGCCGAGGGCAAGTTCGCTTTCA CATTTGA
CTACCTGGACTACAATGTGAAATCAGAGTGCGGGAGAACCCTGTGGACCGTATACAC GGTAGG
GGAAAGATTCACTTACAGTCGAGTTAATCGGGAGTATGTCCGTAAAGTGCCAACTGA CATCATC
TACGATGCCCTTCAGAAGGCTGGCATAAGTGTTGAGGGGGATCTAAGGGACAGGATC GCTGAAT
CGGATGGCGATACTCTCAAATCAATCTTCTACGCCTTCAAGTATGCCCTCGACATGA GGGTAGA
GAACCGGGAGGAGGACTATATACAGTCTCCCGTGAAGAATGCGTCGGGAGAGTTCTT CTGCTCA
AAAAACGCCGGGAAATCTTTGCCGCAGGATTCTGATGCAAATGGGGCTTATAACATT GCTCTCA
AAGGCATCCTGCAGCTGCGCATGCTATCTGAACAATATGACCCAAACGCTGAAAGCA TTAGATT
GCCATTGATCACCAATAAGGCTTGGCTGACTTTCATGCAGAGCGGTATGAAGACATG GAAAAAC
TAA
SE ATGGATTCCCTTAAGGACTTCACAAATCTTTACCCCGTGAGTAAAACCCTGAGATTTGAA CTCAA
Q GCCCGTGGGAAAGACTCTCGAGAATATCGAGAAGGCCGGGATTTTGAAGGAAGACGAGCA TCG
no GGCGGAAAGTTACAGACGGGTGAAGAAGATTATAGATACTTATCACAAGGTCTTTATAGA CAGC
N TCTTTAGAGAACATGGCAAAGATGGGCATCGAGAACGAAATCAAGGCCATGCTGCAGTCC TTCT
O: GCGAGCTGTATAAAAAGGATCATCGGACCGAAGGCGAAGACAAGGCGCTGGATAAGATCA GGG 15 CAGTGCTGCGCGGCCTCATTGTGGGTGCCTTCACTGGGGTGTGCGGGCGGAGAGAGAACA CTGT 2 GCAGAATGAGAAATACGAGAGTTTGTTCAAAGAGAAACTCATCAAGGAAATCCTGCCCGA CTTC
GTCTTAAGCACAGAAGCCGAATCTCTCCCATTTTCTGTCGAGGAGGCCACGCGTTCC CTTAAAG
AGTTCGACAGTTTCACTTCATACTTTGCCGGATTTTATGAAAACCGTAAAAATATAT ACTCCACT
AAACCACAGTCAACTGCAATAGCTTACAGGTTAATCCACGAAAACCTGCCAAAATTC ATCGACA
ATATACTCGTCTTTCAAAAAATCAAGGAACCAATCGCGAAGGAACTTGAACACATCC GGGCTGA
CTTTAGTGCGGGAGGATACATCAAAAAAGACGAGCGCCTGGAGGATATATTTTCACT AAATTAT
TATATTCATGTACTGAGCCAGGCTGGCATAGAAAAGTACAACGCTCTAATTGGGAAA ATCGTGA
CAGAAGGTGACGGGGAAATGAAAGGGCTAAACGAACATATTAACTTATATAACCAAC AGCGGG
GTCGAGAAGATCGTCTGCCCCTGTTCAGACCTCTGTATAAGCAAATACTCTCCGACA GAGAGCA
GCTATCATATCTGCCCGAGTCCTTTGAGAAAGATGAAGAGCTGCTCCGGGCGCTCAA GGAGTTC
TATGATCATATAGCCGAGGACATTTTGGGCAGAACTCAGCAACTCATGACGTCTATT TCTGAAT
ATGATCTGTCTCGTATCTATGTCAGGAATGATAGCCAGCTGACCGATATATCCAAGA AGATGCT
GGGGGACTGGAACGCCATTTATATGGCGAGGGAGCGAGCATACGATCACGAGCAGGC ACCCAA
GAGAATCACAGCCAAATATGAGAGAGACCGCATTAAGGCGCTGAAGGGCGAAGAAAG TATCAG
TCTGGCCAATCTGAACTCCTGCATAGCTTTCCTTGATAACGTGAGGGATTGCAGAGT TGATACTT
ACCTGAGTACCCTGGGCCAGAAGGAAGGGCCTCACGGCCTCTCTAATCTAGTGGAGA ATGTATT
TGCCTCCTACCACGAAGCTGAGCAGCTGCTGTCATTTCCGTACCCAGAGGAAAATAA TTTAATA
CAGGATAAGGACAACGTAGTGCTTATCAAAAATCTACTGGATAACATTTCCGACCTC CAGCGCT TTCTCAAACCACTTTGGGGGATGGGCGACGAGCCTGATAAGGATGAGCGCTTTTACGGCG AGTA
CAACTACATCAGGGGCGCCTTGGACCAGGTGATTCCCCTCTATAATAAAGTCAGGAA TTACCTG
ACCCGAAAGCCATACAGTACAAGAAAGGTGAAATTAAATTTCGGCAATAGTCAGCTG CTGTCTG
GTTGGGACCGAAATAAGGAGAAAGACAACAGCTGCGTAATTCTCAGAAAAGGACAGA ACTTTT
ATTTGGCCATCATGAATAACAGACACAAGAGATCTTTCGAGAACAAAGTGCTCCCTG AGTATAA
GGAGGGGGAACCCTACTTCGAGAAGATGGACTATAAATTCCTTCCTGATCCAAATAA AATGCTG
CCTAAAGTATTTCTGTCAAAAAAAGGTATAGAAATCTACAAACCTTCACCTAAGCTA CTTGAAC
AGTATGGCCACGGCACCCATAAAAAAGGGGACACGTTCAGCATGGACGACCTACACG AACTGA
TTGACTTCTTTAAGCACAGCATAGAAGCTCATGAGGACTGGAAACAGTTCGGATTCA AATTCTC
AGATACCGCGACCTACGAAAACGTGTCTAGTTTTTACCGGGAAGTCGAGGACCAGGG CTACAAG
CTCAGCTTCAGAAAAGTTAGCGAATCTTACGTCTACTCCCTTATAGATCAAGGTAAG CTGTATCT
CTTTCAAATCTACAACAAGGACTTTTCCCCATGTAGCAAGGGCACCCCCAATCTGCA CACTCTCT
ACTGGCGGATGCTGTTCGACGAGCGTAACCTGGCAGACGTGATCTACAAATTAGATG GTAAAGC
TGAGATCTTCTTTCGTGAAAAGAGCCTAAAGAACGATCACCCCACTCACCCCGCCGG AAAGCCC
ATTAAGAAGAAAAGTAGGCAGAAGAAAGGAGAAGAATCGCTATTTGAGTACGACCTC GTCAAG
GATCGGCATTATACAATGGATAAGTTCCAGTTCCATGTGCCAATAACTATGAATTTC AAGTGCA
GTGCTGGCAGTAAGGTGAATGACATGGTAAACGCTCATATCCGGGAGGCAAAGGACA TGCATG
TTATTGGAATTGATAGGGGTGAGCGTAATCTCCTCTACATCTGTGTTATTGACTCCC GCGGCACA
ATCCTCGATCAGATTTCCTTGAATACAATTAATGATATAGACTACCATGACTTGCTT GAGTCTCG
CGACAAAGATAGACAGCAGGAGAGAAGAAATTGGCAGACCATCGAAGGCATCAAGGA ACTCA
AGCAAGGCTACCTTTCTCAGGCAGTGCATCGAATAGCCGAGCTGATGGTGGCTTATA AAGCCGT
CGTGGCACTAGAAGACCTAAATATGGGATTTAAACGAGGCAGGCAGAAGGTGGAATC ATCCGT
ATACCAGCAGTTCGAAAAACAGTTGATAGACAAACTCAATTACCTTGTAGACAAGAA GAAGCG
GCCTGAGGACATAGGGGGCCTGCTTAGAGCGTATCAATTTACAGCCCCATTCAAGTC TTTCAAA
GAAATGGGTAAACAGAACGGTTTTCTGTTTTACATCCCAGCGTGGAACACCAGCAAT ATAGATC
CAACCACTGGCTTCGTCAATCTGTTTCATGCTCAGTATGAAAATGTGGACAAGGCCA AATCCTTC
TTTCAGAAATTTGACAGCATCTCCTATAACCCAAAGAAAGACTGGTTTGAATTCGCC TTTGACTA
TAAGAATTTCACTAAGAAGGCCGAGGGATCAAGAAGCATGTGGATATTGTGCACGCA TGGCTCA
CGTATAAAGAACTTTAGAAACTCGCAAAAAAACGGGCAGTGGGACTCAGAAGAATTC GCACTC
ACCGAGGCTTTCAAATCCCTCTTCGTCCGGTATGAGATCGATTACACCGCCGATCTG AAGACGG
CAATCGTCGACGAGAAACAGAAAGACTTCTTTGTAGATCTACTTAAGCTCTTTAAGC TAACCGTT
CAGATGCGAAACAGTTGGAAAGAAAAGGATCTCGACTATCTCATTAGTCCAGTGGCT GGCGCGG
ATGGTAGATTTTTCGATACCCGGGAAGGTAACAAGTCCCTTCCCAAAGACGCCGACG CGAATGG
TGCCTACAATATTGCACTAAAGGGGCTCTGGGCGCTGCGGCAAATTAGACAGACATC TGAAGGG
GGCAAGCTTAAGCTGGCTATTTCTAATAAAGAGTGGTTGCAGTTTGTGCAGGAAAGG AGTTATG
AGAAGGACTAG
SE ATGAACAACGGCACCAACAACTTCCAGAACTTCATCGGCATATCGTCTCTGCAGAAAACA CTTA
Q GGAATGCCCTGATTCCAACTGAGACAACACAGCAGTTTATTGTGAAGAATGGGATCATCA AAGA
no GGACGAATTGCGCGGGGAGAATAGGCAGATCCTGAAGGACATCATGGACGATTACTACAG GGG
N TTTTATCTCCGAAACGCTGAGCTCGATTGACGATATTGACTGGACGTCCCTCTTTGAGAA GATGG
O: AAATCCAACTTAAAAATGGCGATAATAAAGATACCCTGATAAAGGAACAAACCGAATATA GAA 15 AGGCTATACACAAAAAATTCGCAAATGACGACCGCTTTAAGAACATGTTTTCTGCAAAAC TGAT TAGCGATATTCTGCCCGAGTTTGTGATTCACAATAATAACTATTCCGCTTCGGAGAAGGA GGAA AAGACTCAGGTGATTAAACTGTTTTCTCGGTTCGCCACTTCTTTCAAAGATTATTTCAAA AATCG CGCCAACTGTTTTTCCGCTGACGACATCTCCTCCTCTTCCTGCCACCGGATCGTAAACGA CAATG CCGAGATCTTTTTTAGTAACGCCCTTGTGTATCGGAGGATAGTGAAGAGCCTGTCCAATG ATGA CATAAACAAAATTTCTGGCGATATGAAGGATAGCCTCAAAGAGATGAGCCTTGAAGAAAT TTAC TCCTACGAGAAGTATGGGGAGTTCATCACCCAGGAGGGGATTTCCTTCTATAATGACATC TGTG GCAAGGTGAACAGCTTCATGAACCTGTACTGCCAGAAGAATAAGGAAAACAAAAATCTGT ACA AGCTTCAGAAGTTACATAAGCAGATCCTGTGTATCGCGGATACCTCATATGAGGTTCCTT ATAA GTTCGAGAGTGATGAAGAAGTGTACCAGTCTGTAAATGGATTCTTAGACAATATTTCGTC CAAA CATATAGTGGAGAGACTGAGAAAGATCGGGGACAATTACAATGGGTACAATCTCGACAAG ATT TATATCGTGTCGAAGTTTTACGAATCTGTGAGCCAGAAAACATACAGGGATTGGGAAACC ATTA ATACCGCGCTTGAAATTCACTACAATAATATTCTGCCTGGCAACGGAAAAAGCAAGGCCG ATAA GGTAAAAAAGGCAGTCAAAAATGACCTTCAGAAAAGTATCACCGAAATCAATGAGTTGGT GAG CAACTACAAATTGTGTTCAGACGATAATATTAAAGCGGAAACGTACATACATGAAATTAG CCAT ATTCTGAATAACTTTGAGGCGCAGGAACTTAAGTACAACCCTGAAATTCATCTCGTCGAA AGCG AATTGAAGGCCTCTGAATTGAAAAACGTTCTTGACGTGATAATGAACGCTTTCCATTGGT GCTCT GTGTTTATGACTGAAGAGCTGGTTGATAAGGACAACAACTTTTATGCTGAACTTGAGGAA ATCT ACGACGAGATCTACCCTGTGATTAGCTTGTATAACCTCGTCAGAAACTACGTTACCCAGA AGCC GTACAGCACGAAAAAAATAAAGCTGAACTTTGGTATTCCGACTCTCGCCGATGGATGGAG CAAG TCGAAGGAATATTCCAACAATGCCATCATTCTTATGCGAGACAATCTGTATTACCTCGGC ATCTT TAACGCCAAAAACAAGCCGGATAAGAAAATCATTGAAGGGAATACGAGCGAGAATAAGGG CG ACTATAAGAAAATGATCTACAACTTACTGCCAGGTCCCAATAAAATGATTCCTAAGGTGT TTCT GTCATCGAAAACAGGTGTAGAAACATATAAGCCCAGCGCATACATCCTGGAAGGCTACAA GCA AAACAAACACATCAAAAGCAGCAAGGACTTTGATATCACATTCTGCCACGATCTAATCGA CTAC TTCAAAAATTGCATCGCCATTCACCCTGAGTGGAAGAACTTCGGCTTTGACTTCTCCGAC ACCAG TACCTACGAAGACATTTCTGGATTCTACCGTGAGGTTGAGCTGCAGGGTTATAAAATTGA CTGG ACATACATCAGTGAAAAAGACATCGATCTACTGCAGGAGAAGGGGCAGCTCTATCTCTTC CAGA TTTATAATAAGGATTTCAGCAAGAAGTCCACTGGAAACGACAATCTGCATACAATGTATC TTAA GAACTTGTTTAGCGAAGAGAATTTGAAAGATATCGTTCTAAAGTTAAACGGGGAAGCCGA GATT TTCTTTCGAAAGTCTTCCATTAAGAATCCAATTATTCACAAGAAGGGCAGTATCCTGGTC AACAG AACCTATGAGGCCGAGGAAAAGGACCAGTTCGGTAATATACAAATTGTGCGCAAGAACAT CCC CGAGAACATTTACCAGGAGCTCTATAAATACTTCAACGACAAAAGCGATAAGGAGCTTTC CGAC GAGGCTGCCAAGCTGAAAAACGTGGTGGGACACCATGAAGCAGCCACCAACATCGTCAAA GAT TATCGTTATACATATGACAAATATTTTCTGCACATGCCTATTACAATAAACTTTAAGGCA AACAA GACCGGGTTCATCAATGACCGGATACTCCAGTACATCGCAAAAGAGAAGGACCTGCATGT GATC GGCATCGACCGCGGTGAAAGAAATCTCATTTACGTCAGCGTTATCGACACTTGTGGAAAC ATTG TGGAGCAGAAGTCCTTCAACATTGTTAACGGCTATGACTATCAGATCAAGCTCAAACAGC AGGA AGGTGCTCGTCAGATTGCGAGGAAAGAATGGAAAGAGATCGGCAAGATCAAGGAGATCAA AGA AGGGTATCTGAGCTTGGTCATTCACGAGATCTCCAAAATGGTCATCAAGTACAACGCTAT TATC GCGATGGAAGACCTCTCTTACGGCTTTAAGAAGGGGCGCTTTAAAGTGGAGCGCCAGGTC TATC AGAAGTTCGAGACTATGCTTATCAATAAGCTGAATTACTTGGTCTTTAAGGATATCAGTA TCACC GAGAACGGAGGACTGCTGAAAGGTTACCAGCTCACATATATTCCCGATAAGCTCAAGAAT GTGG GCCACCAATGCGGTTGTATTTTTTACGTTCCAGCTGCCTACACATCTAAGATCGATCCTA CCACC
GGATTCGTCAATATATTTAAATTTAAAGATCTAACCGTTGATGCCAAGCGTGAGTTT ATTAAGAA
ATTTGATTCAATCAGGTACGACAGCGAAAAGAACCTCTTCTGTTTCACTTTCGACTA CAACAACT
TCATCACACAAAATACTGTGATGAGCAAGTCATCATGGAGCGTTTATACTTATGGTG TAAGGAT
AAAAAGGCGCTTTGTTAATGGAAGGTTTTCCAATGAAAGCGATACAATAGACATCAC AAAAGA
CATGGAGAAGACACTGGAGATGACAGATATTAATTGGAGGGACGGGCATGACCTTAG ACAGGA
CATCATCGACTACGAAATCGTCCAACACATTTTTGAGATATTCAGACTCACTGTCCA GATGCGA
AACAGCCTGTCGGAACTCGAAGACCGGGACTACGATAGACTGATCTCCCCGGTGTTA AACGAAA
ATAATATTTTCTACGATTCTGCTAAGGCAGGAGACGCTCTTCCTAAAGATGCGGACG CCAATGG
CGCTTACTGTATAGCGTTGAAGGGATTGTATGAGATTAAACAGATCACTGAGAATTG GAAAGAA
GACGGTAAATTCTCCAGAGACAAGCTGAAAATCTCCAACAAAGACTGGTTTGATTTT ATTCAAA
ATAAGCGCTACCTGTAA
SE ATGACAAACAAATTTACTAATCAGTACAGCCTGTCAAAGACCCTCCGCTTCGAACTGATT CCAC
Q AAGGGAAGACCCTTGAATTCATCCAGGAAAAGGGTTTATTATCCCAGGATAAACAACGCG CAG
no AAAGCTATCAAGAGATGAAGAAGACGATCGATAAATTTCATAAGTATTTCATAGATTTAG CCCT
N GAGCAACGCTAAATTGACCCACCTGGAAACCTATTTGGAGCTGTACAACAAGTCAGCCGA GACA
O: AAGAAAGAGCAGAAGTTTAAGGACGACCTGAAAAAAGTACAGGACAATTTGCGAAAAGAG ATC 15 GTCAAGTCTTTTTCCGACGGAGACGCCAAGTCAATATTTGCCATCCTGGACAAAAAGGAA CTCA 4 TCACTGTGGAGTTGGAGAAGTGGTTTGAGAATAATGAGCAGAAGGACATCTATTTTGACG AAAA
GTTCAAGACATTTACTACTTACTTCACCGGATTTCACCAAAACCGGAAGAACATGTA CTCTGTTG
AGCCGAACTCAACCGCCATCGCCTACCGCCTTATTCACGAAAATCTGCCAAAGTTTC TCGAGAA
TGCTAAAGCCTTTGAGAAAATTAAGCAGGTCGAGTCGCTCCAGGTGAACTTTCGAGA GCTGATG
GGTGAATTCGGGGACGAGGGCCTGATTTTCGTGAATGAACTCGAAGAGATGTTTCAG ATCAACT
ACTATAATGATGTACTCTCACAGAACGGGATCACTATCTACAACAGCATTATCTCTG GATTCACT
AAGAACGATATCAAGTATAAAGGGCTGAATGAATACATCAACAATTATAATCAGACT AAGGAC
AAAAAGGACAGGCTGCCTAAATTGAAACAGCTGTATAAGCAGATCCTCAGTGATAGA ATTAGCT
TGTCATTTCTCCCAGATGCCTTCACTGACGGAAAGCAGGTGCTTAAGGCGATATTCG ATTTCTAT
AAGATCAACCTCCTCTCTTATACAATCGAGGGCCAGGAGGAGTCACAGAACCTCCTG CTCCTGA
TTCGACAAACTATTGAAAATCTGTCCTCTTTCGATACGCAGAAGATATACCTGAAAA ATGACAC
CCATCTCACTACAATATCCCAACAGGTATTCGGAGATTTCTCCGTCTTCAGTACAGC CCTGAATT
ACTGGTACGAGACAAAGGTGAACCCTAAGTTCGAAACAGAGTACAGCAAGGCGAACG AAAAGA
AGAGGGAGATCCTGGACAAAGCCAAAGCCGTTTTCACCAAGCAAGATTACTTTAGCA TCGCATT
TCTGCAGGAAGTCCTGTCTGAGTACATACTGACACTCGATCACACAAGCGACATAGT TAAGAAG
CACTCTTCCAATTGTATCGCGGACTACTTCAAAAATCATTTTGTCGCGAAAAAGGAG AACGAGA
CAGATAAGACCTTCGATTTTATCGCGAATATTACCGCAAAGTATCAATGCATTCAGG GTATCTTG
GAGAACGCCGACCAGTACGAAGACGAGCTTAAACAGGATCAGAAGCTCATCGACAAC CTAAAG
TTCTTTTTGGACGCTATACTGGAACTCCTTCATTTTATTAAGCCACTACATCTGAAG AGTGAGTC
TAACCCCTCTGTATAACATGGTGAGAAACTATGTGACACAGAAACCTTATAGTACCG AGAAGAT TAAGTTGAACTTCGAGAACGCACAATTGCTGAATGGGTGGGATGCAAACAAAGAGGGTGA TTA CCTCACAACAATCCTCAAGAAAGATGGCAATTACTTCCTGGCCATTATGGATAAAAAACA TAAC AAGGCATTTCAGAAATTTCCCGAGGGGAAGGAAAATTATGAAAAGATGGTATACAAGTTG CTG CCCGGGGTGAACAAAATGCTCCCGAAGGTGTTTTTCTCGAATAAGAATATCGCGTACTTT AACC
CGTCCAAGGAACTGTTGGAAAATTATAAAAAGGAAACACACAAGAAGGGGGACACTT TTAATT
TGGAGCACTGCCACACACTCATTGACTTCTTTAAAGATAGTCTCAACAAACATGAGG ATTGGAA
ATATTTTGACTTTCAGTTTAGCGAGACCAAGTCTTATCAGGATCTGTCGGGATTTTA TAGGGAAG
TTGAGCACCAGGGTTACAAGATAAATTTCAAGAACATCGATAGCGAGTACATTGACG GACTGGT
GAACGAAGGGAAGCTGTTCCTGTTTCAGATTTACAGCAAAGATTTCTCTCCTTTCTC AAAAGGCA
AGCCGAACATGCATACCCTGTATTGGAAGGCCCTGTTCGAGGAGCAAAACCTTCAGA ATGTGAT
TTACAAGCTGAACGGTCAGGCCGAGATTTTTTTTAGGAAGGCCTCTATCAAGCCCAA AAACATC
ATTCTGCACAAGAAAAAGATAAAGATCGCCAAAAAACACTTCATTGATAAAAAGACA AAGACT
TCTGAGATCGTACCTGTTCAGACAATCAAGAATCTCAACATGTATTATCAGGGGAAG ATTAGCG
AGAAAGAGCTGACACAGGACGATTTGAGGTACATCGACAACTTCTCTATCTTTAACG AGAAGAA
CAAGACAATCGATATCATCAAGGACAAGCGGTTTACCGTCGATAAATTCCAGTTCCA TGTGCCT
ATCACGATGAATTTCAAGGCCACCGGTGGGAGTTATATCAACCAGACTGTGCTGGAG TATCTGC
AGAACAACCCCGAAGTAAAAATTATTGGCCTGGACAGAGGAGAGCGGCATCTGGTGT ACTTGA
CCCTCATCGATCAGCAGGGAAATATCCTGAAACAAGAATCTCTGAATACTATTACGG ACTCCAA
AATCAGCACACCTTACCACAAGCTGCTTGATAATAAAGAGAATGAGAGGGACTTGGC CCGCAA
AAATTGGGGCACCGTCGAGAATATTAAGGAATTGAAAGAAGGATACATCTCACAGGT GGTTCA
CAAAATCGCAACCCTGATGTTAGAAGAGAACGCTATTGTGGTGATGGAGGACTTAAA CTTCGGA
TTTAAAAGAGGAAGATTTAAAGTCGAGAAACAGATTTATCAGAAACTGGAAAAAATG CTCATT
GACAAATTAAATTACCTGGTGCTGAAAGATAAACAGCCACAGGAGCTGGGTGGCCTG TATAATG
CTCTGCAGCTGACCAACAAGTTCGAGTCGTTTCAGAAAATGGGCAAGCAGTCAGGCT TCCTTTTT
TACGTGCCCGCTTGGAACACCTCAAAAATCGACCCTACAACAGGCTTTGTGAATTAT TTCTATAC
CAAGTATGAAAACGTGGACAAGGCAAAGGCCTTTTTCGAGAAGTTTGAAGCAATCAG GTTCAAT
GCCGAGAAAAAATACTTTGAGTTCGAGGTCAAAAAATATAGCGACTTCAACCCTAAG GCCGAA
GGCACGCAACAAGCCTGGACAATATGCACGTATGGGGAGAGAATTGAGACTAAGCGG CAGAAG
GATCAGAATAACAAATTCGTGAGCACACCGATTAACCTGACAGAGAAGATAGAGGAC TTCCTC
GGCAAGAATCAGATCGTGTACGGCGACGGCAATTGCATCAAGTCACAAATTGCATCT AAAGATG
ACAAAGCATTCTTCGAAACACTGCTGTATTGGTTCAAGATGACACTCCAGATGCGAA ATAGCGA
AACAAGAACAGATATTGACTACCTCATCAGCCCTGTGATGAATGATAACGGCACGTT TTACAAT
TCCCGGGACTATGAAAAATTAGAGAACCCGACACTGCCAAAAGACGCCGACGCAAAT GGTGCA
TATCACATCGCAAAGAAAGGTTTGATGCTGTTGAACAAAATTGATCAGGCTGATCTG ACAAAAA
AGGTCGATCTGAGTATCAGTAACCGCGACTGGTTGCAGTTTGTCCAGAAGAACAAAT AA
SE ATGGAACAAGAGTACTATCTGGGCCTGGACATGGGCACCGGGAGTGTCGGATGGGCAGTC ACC
Q GACTCAGAGTACCACGTCCTCAGAAAGCACGGTAAGGCACTTTGGGGAGTGCGACTCTTC GAGT
no CCGCTAGTACTGCTGAAGAGAGGAGGATGTTTCGAACTTCCAGGCGCAGGCTGGATCGGC GAA
N ACTGGAGAATAGAGATTCTCCAGGAGATATTTGCTGAAGAGATTTCAAAGAAGGATCCTG GTTT
O: TTTCCTGCGCATGAAAGAATCTAAGTATTACCCCGAAGATAAACGCGACATCAACGGCAA TTGT 15 CCTGAACTGCCCTATGCTCTGTTTGTCGACGACGATTTCACCGACAAAGATTACCACAAG AAATT 5 CCCCACCATATACCACCTGAGAAAGATGTTGATGAACACCGAGGAGACACCCGACATACG TCTG
GTTTACCTGGCTATCCATCATATGATGAAGCACCGCGGGCATTTCCTGCTGTCTGGA GACATCAA
TGAGATAAAGGAATTTGGTACTACGTTCTCCAAGTTGTTAGAAAACATTAAGAATGA AGAGTTG
GACTGGAATCTTGAACTGGGAAAGGAAGAGTATGCAGTTGTAGAGTCGATTTTGAAA GATAAC ATGTTAAACCGGTCAACTAAGAAAACCAGGTTAATTAAGGCACTAAAGGCCAAATCGATA TGC
GAGAAGGCTGTGCTAAATCTGCTGGCTGGAGGCACCGTGAAACTGTCTGATATTTTC GGCCTGG
AAGAGCTCAATGAAACCGAGCGGCCTAAAATTTCTTTCGCCGATAACGGATACGATG ACTATAT
TGGGGAGGTGGAAAACGAGCTCGGAGAACAATTCTACATTATTGAAACCGCTAAGGC AGTCTAT
GACTGGGCCGTGCTCGTCGAGATTTTAGGCAAGTACACCAGCATTAGCGAAGCAAAG GTGGCTA
CCTATGAAAAGCACAAATCTGACCTCCAGTTTCTGAAAAAGATTGTGCGCAAATACT TAACAAA
AGAAGAGTACAAGGACATCTTTGTGAGCACATCAGATAAGCTCAAGAATTACTCAGC ATACATT
GGAATGACAAAGATTAACGGGAAGAAGGTGGATCTCCAAAGCAAACGTTGTTCAAAG GAGGAG
TTTTACGATTTCATAAAGAAGAACGTGCTGAAGAAACTGGAGGGACAACCGGAGTAC GAGTATT
TAAAGGAGGAGCTCGAGCGAGAAACTTTCCTGCCCAAGCAAGTGAACAGAGACAATG GTGTCA
TTCCTTACCAGATTCACTTATATGAGCTGAAGAAAATCCTGGGGAACTTGAGAGACA AGATAGA
CCTCATCAAGGAAAATGAAGATAAGTTGGTCCAGTTGTTCGAATTCAGAATCCCATA TTACGTC
GGCCCGCTCAATAAGATCGACGACGGCAAGGAAGGCAAATTCACTTGGGCGGTGCGA AAAAGC
AACGAAAAAATATACCCATGGAACTTTGAGAACGTCGTTGACATCGAGGCCAGCGCC GAGAAA
TTTATAAGACGCATGACTAATAAGTGTACTTACCTCATGGGCGAGGATGTTCTGCCC AAGGACA
GCCTGCTGTATTCCAAGTACATGGTGCTTAACGAGCTGAATAATGTAAAGTTAGATG GTGAGAA
GCTCAGCGTGGAGCTTAAACAGAGGCTGTACACTGATGTGTTTTGCAAGTATCGGAA AGTTACC
GTTAAGAAGATAAAGAATTACCTGAAATGCGAAGGGATCATTTCCGGCAACGTGGAA ATTACC
GGAATCGACGGCGATTTTAAGGCGTCGTTGACCGCTTATCATGATTTCAAGGAGATT TTAACCG
GCACGGAGCTCGCGAAGAAAGACAAGGAGAACATAATCACGAATATAGTTCTGTTTG GGGACG
ATAAAAAACTTCTTAAAAAACGACTCAATCGACTGTATCCGCAGATTACCCCCAACC AGCTGAA
GAAGATTTGCGCTCTGAGCTATACCGGGTGGGGCCGGTTCTCTAAGAAATTCCTCGA GGAGATC
ACAGCACCAGACCCAGAGACTGGTGAGGTGTGGAATATTATTACAGCTCTGTGGGAA TCCAATA
ATAACCTTATGCAATTGTTGAGCAATGAATATAGGTTCATGGAGGAAGTGGAAACCT ACAATAT
GGGCAAGCAGACAAAGACCCTATCTTACGAGACCGTTGAGAATATGTATGTCTCCCC TTCAGTG
AAACGGCAAATCTGGCAAACTTTGAAGATCGTGAAGGAGCTCGAAAAGGTGATGAAA GAGAGC
CCGAAGAGGGTTTTTATTGAAATGGCCAGAGAGAAACAGGAGAGCAAGAGAACAGAG TCTAGG
AAGAAGCAGCTAATCGATTTGTATAAAGCCTGCAAGAACGAGGAAAAAGACTGGGTC AAGGAG
CTAGGCGATCAGGAAGAACAGAAGTTGCGCTCTGATAAGCTGTACTTATATTATACC CAGAAAG
GACGGTGCATGTACTCAGGTGAGGTCATTGAGCTGAAAGATCTGTGGGACAATACTA AGTATGA
TATTGATCACATCTACCCTCAGTCAAAAACTATGGACGACTCCCTCAACAACAGGGT GTTGGTT
AAGAAGAAATACAATGCTACAAAGTCCGATAAATACCCTCTTAACGAAAACATCCGG CACGAA
AGAAAGGGCTTCTGGAAGTCCCTGCTGGATGGGGGTTTTATCAGTAAAGAAAAGTAT GAGAGG
CTGATCCGAAATACCGAGCTCTCCCCCGAGGAACTGGCTGGCTTTATCGAAAGGCAG ATCGTAG
AGACTAGGCAATCTACAAAGGCAGTCGCTGAGATCCTGAAGCAAGTGTTTCCTGAGT CAGAAAT
CGTGTACGTCAAAGCTGGCACAGTGTCACGGTTCCGAAAGGACTTTGAGTTGTTAAA AGTTCGG
GAGGTGAATGACCTGCACCACGCTAAAGACGCCTATCTGAATATCGTTGTGGGGAAC TCCTATT
ATGTTAAGTTTACTAAGAATGCGTCCTGGTTTATTAAGGAGAACCCGGGGCGCACCT ATAACCT
GAAGAAGATGTTCACCTCCGGCTGGAACATAGAACGGAACGGAGAAGTCGCGTGGGA GGTGGG
TAAGAAAGGGACCATTGTGACCGTCAAACAGATTATGAACAAAAACAACATATTGGT AACTCG
CCAGGTGCATGAGGCCAAAGGGGGCCTCTTTGATCAGCAGATTATGAAAAAGGGCAA AGGACA
GATCGCAATCAAGGAAACCGACGAGCGCCTGGCATCCATTGAGAAGTACGGAGGCTA CAACAA GGCGGCAGGTGCGTACTTCATGCTCGTCGAGTCCAAAGATAAGAAAGGCAAAACTATTAG AAC
AATCGAGTTCATCCCTCTATATTTGAAAAATAAGATCGAAAGTGACGAAAGCATCGC CCTTAAC
TTCTTGGAGAAGGGCCGGGGCTTAAAGGAACCAAAGATTCTGCTCAAGAAGATCAAG ATCGAC
ACACTCTTCGATGTGGATGGTTTTAAGATGTGGCTGTCAGGCAGGACAGGGGATCGC TTGCTGT
TCAAATGCGCAAATCAGTTGATTCTGGACGAAAAGATCATTGTGACGATGAAGAAGA TCGTTAA
ATTCATTCAGCGGAGACAGGAAAACAGAGAACTGAAACTCTCCGATAAGGATGGAAT TGACAA
TGAAGTCCTCATGGAGATTTACAATACCTTTGTGGACAAGCTTGAGAACACAGTCTA TCGGATC
CGACTGTCCGAACAGGCAAAGACTCTGATCGACAAACAGAAAGAATTCGAAAGACTA AGCTTA
GAGGACAAAAGTTCAACTCTCTTTGAAATTCTCCACATCTTCCAATGTCAAAGTAGT GCAGCCA
ACTTGAAGATGATCGGGGGTCCCGGCAAGGCTGGAATCTTAGTCATGAACAACAACA TCTCCAA
ATGTAACAAAATCTCCATCATAAACCAGTCTCCCACCGGCATTTTCGAGAACGAAAT TGATTTA
CTCAAG
SE ATGAAATCTTTCGATTCTTTCACCAACCTCTACTCCCTTAGCAAAACCCTTAAGTTTGAA ATGAG
Q GCCGGTGGGGAATACACAGAAGATGCTTGACAATGCTGGCGTCTTTGAAAAGGACAAATT AATC
no CAGAAGAAGTATGGTAAAACAAAGCCATATTTTGACCGATTGCATCGGGAATTCATTGAA GAGG
N CTCTTACAGGAGTAGAATTGATCGGACTGGACGAGAACTTCCGTACCTTAGTAGACTGGC AGAA
O: GGACAAGAAGAACAACGTGGCAATGAAGGCCTATGAGAACTCACTCCAGCGCCTTAGAAC CGA 15 GATCGGAAAGATCTTTAATCTTAAGGCGGAAGATTGGGTAAAAAATAAGTACCCGATCCT GGGA
6 CTGAAAAACAAAAACACAGACATCCTGTTTGAAGAAGCCGTCTTTGGTATCTTGAAGGCC AGGT
ATGGAGAGGAGAAAGACACGTTTATAGAGGTAGAGGAGATTGATAAAACAGGCAAGA GTAAG
ATTAATCAGATCAGTATCTTTGATTCTTGGAAGGGGTTCACAGGCTACTTTAAGAAG TTTTTCGA
AACCAGGAAAAATTTCTATAAGAACGATGGCACCTCCACAGCTATCGCGACACGCAT CATAGAT
CAGAATCTGAAACGGTTCATTGATAATCTGAGCATTGTTGAATCCGTGCGCCAGAAG GTCGACC
TAGCTGAGACTGAGAAGTCTTTCTCTATATCACTCTCCCAGTTCTTCTCAATAGATT TTTATAATA
AGTGCCTTCTGCAAGATGGCATAGACTACTATAACAAGATCATCGGCGGCGAAACTC TCAAAAA
CGGTGAAAAGCTCATTGGCCTGAATGAGCTCATCAACCAATATAGACAAAATAACAA GGATCA
GAAAATCCCATTCTTTAAGCTGCTAGATAAACAGATCCTATCAGAAAAAATCCTGTT CCTCGAC
GAAATCAAAAACGACACCGAACTCATCGAGGCTCTCTCGCAGTTTGCCAAGACGGCT GAGGAG
AAGACGAAGATTGTGAAAAAGCTGTTTGCAGACTTTGTGGAGAACAACTCTAAATAC GATTTGG
CTCAGATTTATATCTCCCAGGAAGCATTTAACACAATCTCCAATAAGTGGACTAGCG AGACTGA
AACCTTCGCCAAATACCTGTTCGAGGCCATGAAAAGCGGCAAGCTCGCCAAATACGA GAAGAA
GGACAATTCCTATAAGTTTCCCGATTTCATCGCATTATCTCAGATGAAGTCCGCGCT ACTTAGCA
TTAGCCTGGAAGGCCATTTTTGGAAGGAGAAATACTATAAGATTTCCAAATTCCAAG AAAAGAC
CAATTGGGAGCAGTTCTTGGCTATTTTTCTATACGAGTTCAACTCTTTGTTCAGTGA CAAGATCA
ACACTAAGGACGGTGAGACCAAACAAGTGGGGTACTACCTCTTCGCCAAAGATCTTC ATAACCT
GATACTGTCCGAACAGATCGACATACCCAAGGATTCAAAGGTGACCATCAAGGATTT TGCGGAT
TCGGTATTGACGATCTATCAGATGGCGAAGTATTTCGCTGTCGAGAAAAAGCGGGCA TGGCTGG
CCGAATACGAGTTGGACTCCTTCTATACTCAACCCGATACAGGGTACCTGCAGTTTT ACGATAAT
GCATACGAGGATATAGTCCAGGTGTACAATAAACTCAGGAACTACCTCACTAAGAAA CCATACT
CCGAAGAAAAATGGAAACTTAATTTTGAGAATAGTACACTGGCCAATGGATGGGACA AGAACA
AGGAATCAGACAACTCCGCTGTAATTCTCCAGAAGGGTGGCAAGTATTATCTGGGAC TGATAAC
AAAGGGCCATAACAAGATTTTCGATGACCGTTTTCAGGAGAAGTTTATAGTGGGCAT AGAGGGT GGCAAGTATGAAAAAATAGTCTACAAGTTCTTTCCCGATCAGGCGAAGATGTTCCCCAAA GTAT
GCTTCAGTGCTAAAGGCCTCGAGTTTTTCCGGCCATCTGAAGAGATACTCCGCATCT ATAATAAC
GCAGAGTTTAAAAAGGGAGAGACGTACTCAATCGACTCGATGCAGAAACTCATTGAC TTCTACA
AAGATTGTCTCACAAAATACGAGGGCTGGGCTTGCTACACGTTTCGGCACTTGAAGC CAACCGA
GGAATATCAAAACAACATCGGGGAGTTCTTCCGTGACGTCGCCGAAGACGGCTATAG AATTGAC
TTTCAGGGCATAAGTGATCAGTATATTCACGAGAAGAATGAGAAAGGTGAGTTGCAT CTTTTCG
AAATCCACAATAAAGACTGGAATCTTGACAAGGCTCGCGATGGAAAATCAAAGACTA CCCAGA
AGAATCTTCATACACTTTACTTCGAGTCCCTCTTTTCCAACGACAACGTCGTACAGA ATTTCCCA
ATAAAACTGAACGGCCAGGCCGAAATTTTTTACAGGCCCAAAACCGAAAAAGATAAA CTGGAA
TCCAAGAAAGACAAGAAGGGAAATAAGGTGATAGATCACAAAAGGTATTCCGAGAAC AAGATT
TTTTTCCACGTACCTCTTACCCTGAACAGAACGAAGAACGACTCTTATAGATTCAAT GCCCAGAT
AAACAACTTTCTCGCAAACAACAAAGATATCAATATTATCGGCGTCGATAGAGGTGA GAAGCAC
TTGGTATATTATTCTGTGATCACGCAAGCATCCGATATCTTGGAGTCCGGTTCTTTG AACGAACT
GAATGGTGTCAACTACGCCGAGAAACTCGGTAAGAAAGCTGAGAATCGGGAGCAGGC TAGAAG
GGACTGGCAGGACGTTCAGGGTATCAAGGACCTGAAGAAGGGCTACATTTCTCAGGT GGTTCGA
AAACTGGCTGATTTGGCCATTAAGCACAATGCAATCATCATTTTAGAAGATTTGAAC ATGCGGT
TTAAACAAGTCAGGGGGGGGATAGAGAAATCAATTTACCAACAGCTGGAAAAAGCTC TGATTG
AGCCTATCAACTGAGCGCACCTTTCGAGACATTCCAGAAGATGGGAAAGCAAACCGG CATCATT
TTCTATACCCAGGCTTCCTATACATCCAAGTCTGATCCAGTGACTGGGTGGAGACCC CATCTCTA
CCTCAAGTACTTTTCTGCCAAAAAAGCTAAGGACGACATTGCTAAGTTCACAAAAAT CGAGTTC
GTGAACGACAGGTTCGAGCTGACTTATGACATAAAAGATTTCCAGCAGGCCAAGGAG TACCCA
AACAAGACAGTTTGGAAAGTGTGTTCCAATGTGGAGAGGTTTCGGTGGGACAAGAAT CTGAATC
AGAATAAAGGGGGATATACTCACTACACCAACATTACCGAGAACATCCAAGAGTTGT TCACCAA
ATACGGCATCGACATTACTAAAGATCTGCTGACACAGATCTCCACCATCGATGAGAA GCAGAAC
ACATCTTTCTTCCGGGATTTCATCTTTTATTTTAACTTGATCTGTCAGATTAGAAAT ACCGACGAC
AGTGAGATAGCTAAAAAAAACGGGAAAGACGATTTCATTCTCTCTCCCGTGGAGCCG TTTTTTG
ACTCCCGCAAAGACAATGGCAATAAGCTTCCGGAAAACGGGGACGATAACGGCGCCT ACAACA
TCGCTCGTAAGGGAATCGTTATCCTCAATAAAATAAGCCAGTATTCCGAGAAGAACG AGAATTG
TGAAAAAATGAAGTGGGGGGACCTTTACGTCAGCAACATCGATTGGGATAACTTTGT GACACAA
GCCAATGCGAGACACTAG
SE ATGGAAAACTTCAAAAACCTCTACCCCATCAACAAGACCTTGAGGTTTGAGCTCCGGCCA TATG
Q GGAAGACACTGGAGAACTTCAAAAAGTCCGGTCTGCTGGAAAAGGATGCTTTTAAGGCTA ACTC
no TAGGAGGTCTATGCAGGCCATTATCGATGAGAAATTCAAGGAGACCATAGAGGAGCGTCT GAA
N ATATACTGAGTTTTCCGAGTGTGACCTAGGAAATATGACCAGTAAGGACAAAAAGATCAC CGAC
O: AAGGCAGCGACAAACCTGAAGAAACAGGTGATTTTAAGCTTTGATGATGAGATTTTCAAT AACT 15 ACTTGAAGCCGGACAAAAACATCGACGCTCTGTTCAAGAATGATCCAAGCAACCCGGTCA TCTC
7 TACTTTCAAGGGCTTCACCACATACTTTGTAAATTTCTTCGAAATACGGAAACACATCTT CAAGG
GAGAGTCTTCCGGTAGCATGGCTTACAGAATAATCGATGAGAACCTAACTACATATC TAAACAA
TATCGAGAAGATCAAGAAATTGCCTGAAGAACTGAAATCTCAGCTTGAGGGAATCGA TCAAATT
GACAAACTGAACAACTATAACGAGTTCATCACCCAGTCCGGCATTACTCATTATAAC GAAATTA
TTGGAGGGATTTCGAAGTCTGAAAATGTCAAAATTCAAGGCATTAACGAAGGGATTA ATCTTTA CTGTCAAAAGAATAAAGTGAAGCTACCACGCTTAACTCCTCTGTATAAGATGATTCTCTC TGATC
GGGTCTCTAATTCCTTTGTGCTGGATACCATTGAAAATGATACCGAGTTAATTGAAA TGATCTCT
GATCTGATAAATAAGACAGAGATAAGTCAGGATGTTATTATGTCCGACATCCAAAAT ATTTTCA
TCAAATATAAACAACTCGGCAACTTGCCGGGGATTAGCTACTCATCTATAGTGAATG CTATCTGT
TCGGATTACGACAATAACTTTGGTGACGGCAAACGTAAAAAAAGCTATGAGAATGAT CGCAAA
AAACACCTCGAGACTAACGTGTATAGCATTAACTATATCTCAGAGTTACTGACAGAC ACCGACG
TCTCCAGCAACATAAAGATGCGGTACAAAGAGCTGGAGCAGAATTATCAGGTATGCA AGGAAA
ATTTCAACGCCACTAACTGGATGAACATCAAAAACATTAAGCAGTCTGAGAAAACCA ATCTGAT
CAAGGACCTTCTTGACATCCTCAAGAGCATCCAGCGGTTTTATGATTTGTTTGACAT CGTGGATG
AAGACAAAAATCCTAGTGCTGAGTTCTATACCTGGCTGTCTAAAAACGCGGAGAAAC TGGACTT
CGAGTTTAATTCAGTGTACAACAAGAGCAGGAACTACCTCACGAGAAAGCAGTACTC CGATAA
AAAGATTAAGTTGAACTTCGATAGTCCTACTCTCGCCAAGGGGTGGGATGCGAACAA AGAAATT
GATAATAGCACAATTATCATGAGGAAGTTCAACAACGACCGGGGCGATTACGATTAC TTCTTGG
GGATCTGGAATAAGAGCACACCTGCCAACGAAAAGATCATCCCATTAGAGGATAATG GACTGTT
TGAAAAAATGCAATATAAGCTGTATCCCGATCCTAGTAAAATGCTGCCAAAGCAATT CCTTTCT
AAGATCTGGAAAGCTAAACATCCAACTACACCCGAGTTTGATAAGAAGTACAAAGAA GGTCGG
CACAAGAAGGGGCCTGATTTTGAGAAAGAGTTTCTGCACGAGTTGATCGATTGCTTT AAGCATG
GATTGGTAAACCACGACGAAAAATATCAGGATGTGTTCGGGTTCAATCTGCGCAACA CGGAAG
ACTACAACTCTTATACAGAGTTTCTGGAGGACGTCGAAAGGTGCAACTATAATCTTA GTTTCAAT
AAAATCGCTGACACGTCTAACTTGATAAATGATGGGAAACTCTATGTTTTTCAGATC TGGAGCA
AGGATTTCAGCATAGATAGCAAGGGAACAAAAAACTTGAACACAATATACTTTGAAT CCCTCTT
CTCGGAGGAAAATATGATCGAGAAGATGTTCAAGCTCTCAGGGGAAGCCGAAATATT CTATCGT
CCAGCAAGTTTGAATTATTGTGAAGATATTATCAAGAAGGGACACCACCACGCCGAA CTGAAGG
ACAAATTCGACTATCCCATCATCAAGGACAAGCGATATAGCCAGGACAAATTTTTTT TTCATGTC
CCCATGGTTATCAACTACAAAAGCGAGAAGTTAAACTCCAAATCACTTAACAATAGG ACGAACG
AAAATTTAGGCCAATTCACGCACATCATCGGTATCGACCGCGGAGAGCGACATCTCA TCTACCT
GACCGTGGTGGATGTGTCCACCGGTGAGATCGTTGAGCAAAAGCACCTGGATGAAAT TATAAAT
ACAGATACAAAAGGCGTCGAGCATAAAACTCATTATCTCAATAAATTAGAAGAGAAG TCCAAG
ACGCGGGATAATGAAAGAAAGTCCTGGGAAGCAATCGAGACGATTAAGGAGCTGAAA GAAGG
CTATATTAGCCACGTGATCAATGAAATCCAGAAATTGCAGGAAAAGTATAACGCACT GATAGTG
ATGGAGAACCTCAATTATGGGTTTAAGAACTCGCGTATCAAAGTGGAAAAGCAGGTC TACCAGA
AATTCGAGACCGCCCTGATTAAAAAGTTTAATTACATCATTGACAAGAAAGATCCTG AAACCTA
CATTCATGGATACCAACTGACGAATCCAATCACTACACTCGATAAAATTGGTAACCA GAGCGGT
ATTGTGTTGTACATTCCGGCTTGGAATACAAGCAAGATTGATCCAGTCACTGGTTTC GTTAACCT
CCTGTATGCAGACGATTTGAAATACAAGAACCAGGAGCAGGCTAAAAGCTTTATCCA GAAAATC
GATAATATCTACTTCGAAAATGGTGAGTTTAAATTTGATATAGATTTCAGCAAATGG AACAACC
GCTACTCAATTAGCAAGACGAAATGGACACTGACAAGCTACGGAACCCGGATACAGA CGTTCC
GAAACCCCCAGAAAAATAACAAGTGGGACAGCGCCGAGTATGACCTGACCGAAGAGT TTAAAT
TAATCCTGAACATCGATGGTACTCTGAAATCTCAGGATGTGGAAACCTATAAGAAAT TCATGTC
TTTATTCAAGCTGATGTTGCAGCTGCGAAACTCCGTTACTGGAACAGACATTGACTA CATGATTA
GCCCTGTGACAGATAAAACTGGAACCCACTTTGATTCACGGGAGAATATCAAGAACC TGCCCGC
CGATGCTGATGCGAACGGAGCTTACAACATTGCTAGGAAGGGCATCATGGCAATCGA GAATATT ATGAACGGCATTAGCGACCCTCTGAAGATCAGTAATGAGGACTACCTGAAGTACATTCAG AACC AACAAGAGTAA
SE ATGACCCAGTTTGAGGGTTTCACCAATCTTTATCAGGTGTCAAAAACACTCAGATTTGAG CTCAT
Q CCCACAGGGTAAAACTTTAAAGCATATTCAAGAGCAGGGCTTTATAGAGGAAGACAAAGC CAG
no AAACGACCATTATAAGGAACTAAAACCGATCATTGACCGCATCTACAAAACCTATGCCGA CCAA
N TGCCTTCAGCTCGTCCAACTCGATTGGGAGAATCTGAGCGCCGCTATTGACAGCTACAGG AAGG
O: AGAAGACCGAGGAGACTAGAAACGCCCTGATCGAGGAGCAGGCGACCTATAGAAACGCTA TTC 15 ACGATTATTTTATCGGCCGCACCGACAATTTGACAGATGCCATCAACAAGCGGCACGCCG AAAT 8 TTATAAGGGGTTATTTAAGGCCGAGCTGTTCAATGGAAAAGTACTGAAACAGCTGGGCAC CGTA
ACAACCACCGAACACGAGAATGCTCTGTTGAGGTCCTTCGACAAGTTTACTACCTAC TTTAGCG
GCTTCTACGAAAACCGTAAAAACGTGTTTTCCGCGGAGGATATTTCAACAGCCATTC CTCATAG
GATCGTGCAGGATAATTTCCCCAAGTTTAAGGAGAACTGCCATATCTTTACCAGACT TATCACTG
CTGTGCCAAGTTTACGAGAACACTTCGAGAATGTTAAGAAGGCTATAGGCATATTCG TTTCCAC
CTCCATCGAAGAAGTATTCAGTTTTCCATTCTACAATCAGTTACTCACGCAGACCCA GATAGATC
TCTACAATCAGCTGCTCGGAGGCATTTCTAGAGAAGCAGGCACGGAAAAGATCAAGG GCTTAA
ATGAAGTACTCAATCTTGCAATTCAGAAGAACGATGAGACAGCACACATTATTGCAT CTCTCCC
TCACAGATTCATTCCCCTGTTCAAACAGATCCTGTCCGATCGCAACACACTAAGCTT TATACTTG
AGGAGTTTAAGTCAGATGAGGAAGTGATCCAGAGCTTCTGTAAGTATAAGACTTTGC TCCGTAA
TGAAAACGTGCTTGAGACAGCAGAGGCTCTCTTTAACGAGTTGAATTCCATCGACCT GACACAC
ATTTTTATCAGCCATAAAAAGCTGGAAACGATTAGCTCTGCCTTGTGCGACCACTGG GACACCC
TGCGTAACGCCCTCTATGAAAGGCGCATTTCCGAGCTCACCGGGAAGATCACAAAAA GTGCCAA
GGAAAAAGTCCAGAGGTCCCTTAAACATGAAGACATCAACCTACAAGAGATCATCTC TGCGGCT
GGGAAAGAGCTGTCAGAAGCATTTAAACAGAAGACTTCCGAGATCCTGAGCCACGCA CACGCC
GCATTAGACCAGCCCCTGCCTACAACTCTTAAAAAACAGGAGGAGAAGGAGATTTTA AAGAGC
CAGCTGGACTCATTACTCGGCCTGTATCATCTCCTGGACTGGTTCGCCGTGGACGAA TCCAACGA
GGTGGACCCAGAATTTAGCGCCAGGCTGACAGGAATTAAACTGGAAATGGAGCCAAG TTTGAG
CTTTTACAACAAGGCTCGGAACTATGCCACTAAAAAGCCCTACAGCGTGGAAAAGTT CAAGCTG
AATTTTCAGATGCCGACCCTGGCTTCCGGGTGGGATGTTAATAAGGAAAAGAATAAT GGGGCTA
TACTGTTCGTCAAAAATGGTCTCTACTACCTGGGAATCATGCCCAAACAGAAGGGCA GGTACAA
AGCCCTTTCGTTTGAGCCGACCGAAAAAACCAGCGAAGGCTTTGATAAGATGTATTA CGACTAT
TTCCCAGATGCAGCCAAGATGATCCCAAAATGTAGCACTCAGTTGAAGGCGGTAACC GCTCACT
TTCAGACACACACCACTCCTATCTTGCTCTCCAACAACTTTATTGAGCCGCTGGAGA TCACGAAG
GAAATCTACGACCTTAACAACCCAGAGAAGGAACCCAAGAAATTCCAAACAGCTTAT GCTAAG
AAGACTGGGGATCAAAAGGGCTATCGAGAGGCTTTGTGTAAGTGGATTGACTTTACA CGGGATT
TCCTGAGTAAGTATACCAAGACCACATCTATTGACCTGTCCTCACTGAGACCTTCCT CACAATAT
AAGGATCTCGGAGAGTATTATGCCGAACTCAACCCTCTACTCTATCACATCTCTTTC CAGAGGAT
CGCCGAAAAGGAAATTATGGACGCCGTCGAGACAGGCAAGCTGTACCTCTTCCAGAT TTACAAC
AAGGATTTCGCAAAGGGCCACCACGGAAAACCCAATTTGCACACTTTGTACTGGACA GGGCTCT
TCTCTCCCGAAAATTTGGCCAAAACTTCAATAAAACTGAACGGGCAAGCCGAGCTGT TCTATCG
GCCCAAGTCACGTATGAAGCGGATGGCCCACCGGCTGGGCGAGAAGATGCTCAACAA GAAACT
GAAGGATCAGAAGACGCCCATACCAGACACTCTTTACCAAGAGCTGTATGACTACGT GAATCAC
AGACTGAGTCACGACCTGTCTGATGAAGCCCGGGCTCTTCTTCCAAATGTGATTACC AAAGAAG TTTCCCACGAAATTATCAAGGACCGGCGCTTCACCTCTGACAAATTCTTTTTCCACGTCC CAATC
ACCCTCAACTACCAGGCAGCCAATTCCCCTTCAAAGTTTAACCAGCGTGTGAATGCC TACCTGA
AAGAGCATCCGGAGACCCCCATCATAGGGATAGACAGAGGAGAGCGGAATCTTATCT ACATTA
CTGTGATTGACAGCACAGGTAAGATCTTGGAGCAGAGATCTTTAAATACAATCCAGC AGTTTGA
CTACCAGAAGAAACTGGATAACCGAGAGAAGGAAAGGGTTGCTGCAAGACAGGCCTG GTCAGT
GGTCGGCACCATCAAAGACCTGAAGCAGGGCTACTTATCCCAAGTAATTCACGAAAT TGTCGAT
CTTATGATTCATTATCAAGCCGTTGTTGTGCTGGAGAACCTGAATTTTGGCTTCAAA AGCAAACG
AACAGGTATCGCCGAGAAAGCCGTGTATCAGCAGTTCGAAAAGATGCTCATAGACAA GCTGAA
CTGCTTAGTGCTGAAGGATTATCCTGCTGAGAAGGTCGGCGGCGTACTTAACCCATA CCAGCTG
ACCGATCAGTTCACTAGTTTCGCCAAGATGGGAACGCAAAGTGGCTTCCTTTTCTAC GTGCCCGC
TCCCTACACGAGTAAGATCGACCCTCTGACCGGCTTCGTCGACCCATTCGTCTGGAA GACCATC
AAGAATCACGAATCACGGAAACACTTCTTAGAGGGGTTTGACTTCCTGCACTACGAC GTGAAGA
CAGGGGACTTCATCTTACACTTTAAGATGAATCGAAACCTCTCCTTCCAGCGGGGCC TGCCTGGT
TTCATGCCCGCATGGGACATCGTGTTTGAGAAAAACGAGACACAGTTTGACGCTAAG GGAACCC
CCTTTATTGCGGGGAAGCGGATTGTCCCAGTCATCGAAAACCATCGGTTCACCGGGC GATACCG
GGATCTGTACCCGGCCAACGAGCTCATCGCGCTGCTGGAGGAGAAGGGTATTGTGTT TAGGGAT
GGATCCAACATTCTGCCTAAGTTGCTGGAAAATGATGATTCGCACGCCATTGATACC ATGGTTG
CACTGATTAGATCCGTACTGCAGATGAGGAATAGCAATGCTGCAACCGGGGAGGATT ATATTAA
TTCCCCAGTGCGAGATCTGAATGGTGTCTGTTTTGACTCGCGCTTTCAGAATCCAGA ATGGCCAA
TGGATGCAGACGCTAACGGGGCGTACCACATTGCTCTGAAAGGCCAGCTACTCCTGA ACCACCT
CAAGGAGAGCAAAGATCTGAAGCTGCAGAACGGCATTTCCAACCAAGACTGGCTCGC CTACAT
ACAAGAACTGCGCAATTAA
SE ATGGCTGTCAAATCCATCAAGGTTAAATTACGGCTTGATGACATGCCCGAGATCCGCGCC GGGC
Q TCTGGAAACTCCATAAAGAAGTGAATGCTGGCGTTAGATACTACACAGAATGGCTCTCCC TGCT
no GCGCCAGGAAAATTTGTACCGCCGGTCACCTAATGGAGATGGAGAGCAGGAATGCGATAA AAC
N AGCAGAAGAGTGCAAAGCCGAATTGCTGGAGCGACTGCGGGCACGGCAGGTTGAGAATGG ACA
O: CCGAGGTCCGGCGGGATCGGACGACGAGCTGCTCCAGCTCGCCAGACAATTATATGAACT GCTG 15 GTGCCTCAGGCTATTGGGGCAAAGGGTGACGCACAGCAGATTGCTAGAAAATTTCTGTCT CCCC
9 TCGCCGACAAAGACGCTGTCGGCGGCCTTGGGATAGCCAAAGCCGGCAACAAACCCCGAT GGG
TGCGCATGAGGGAGGCTGGTGAGCCTGGCTGGGAGGAAGAAAAGGAAAAGGCCGAAA CCAGA
AAGTCCGCCGACAGGACCGCGGACGTACTCCGAGCATTGGCCGATTTTGGGCTGAAG CCCTTAA
TGCGAGTCTACACCGATAGTGAAATGTCTAGCGTGGAGTGGAAGCCATTACGCAAAG GGCAGG
CAGTGCGGACGTGGGACCGTGACATGTTCCAGCAAGCCATCGAGCGAATGATGAGCT GGGAGA
GCTGGAACCAGAGAGTGGGGCAGGAGTATGCCAAGCTGGTCGAGCAGAAAAACCGGT TTGAGC
AAAAAAATTTTGTAGGTCAGGAACACCTGGTGCATCTCGTTAACCAGCTCCAGCAAG ATATGAA
GGAAGCTTCGCCTGGATTAGAGAGCAAAGAGCAGACTGCACACTATGTAACCGGAAG AGCACT
GAGGGGCAGTGACAAAGTGTTCGAAAAATGGGGAAAACTGGCTCCCGATGCCCCCTT TGACCTG
TACGACGCAGAAATAAAAAACGTGCAGCGGCGAAACACCAGGCGATTTGGTAGCCAT GATCTG
TTCGCCAAATTGGCAGAGCCGGAATATCAGGCTCTTTGGCGAGAAGACGCATCATTT CTCACTA
GGTACGCGGTCTATAACTCCATTTTGAGGAAATTGAACCACGCAAAAATGTTTGCCA CCTTCAC
GTTGCCTGACGCCACCGCTCATCCCATTTGGACACGGTTTGATAAGCTGGGCGGCAA TCTGCATC
AGTATACATTCCTGTTTAACGAGTTTGGAGAGCGAAGACATGCGATACGATTCCACA AGCTACT GAAGGTCGAAAATGGCGTGGCACGTGAGGTGGACGATGTCACCGTGCCCATCAGCATGAG CGA
ACAGCTGGATAATTTGTTGCCGCGGGACCCAAATGAACCTATAGCCCTTTATTTTAG GGACTAC
GGGGCGGAGCAACATTTCACTGGGGAGTTTGGCGGCGCAAAAATTCAGTGCCGACGC GACCAG
CTCGCCCACATGCATAGAAGACGCGGGGCCCGGGACGTATACCTTAACGTCTCTGTG AGGGTGC
AGTCCCAGTCAGAGGCAAGAGGGGAACGCAGACCACCTTACGCAGCAGTATTCAGGC TGGTAG
GCGATAACCACCGGGCGTTTGTACACTTTGATAAACTTTCTGACTACCTGGCCGAAC ACCCGGA
TGACGGCAAATTAGGATCGGAGGGGCTGCTTAGCGGCCTGCGTGTGATGAGCGTCGA TCTGGGG
CTACGGACCTCTGCTTCCATCTCTGTGTTCCGTGTGGCCCGAAAGGACGAGTTGAAA CCTAATTC
GAAGGGCCGTGTACCATTCTTTTTCCCTATTAAGGGAAATGATAATCTCGTCGCGGT GCACGAG
CGTTCCCAACTGCTGAAACTGCCTGGCGAGACCGAGTCCAAAGATCTCAGAGCAATC CGGGAGG
AGCGACAACGTACACTTAGGCAACTCCGCACCCAGCTGGCCTATCTGCGCTTGCTGG TGCGGTG
CGGCTCCGAGGATGTAGGGAGAAGAGAGCGAAGCTGGGCAAAGCTGATAGAGCAACC AGTTGA
CGCCGCGAATCACATGACCCCCGACTGGCGCGAAGCGTTTGAAAATGAGCTGCAGAA GTTGAA
ATCTCTGCATGGGATTTGCTCAGATAAGGAGTGGATGGACGCCGTATACGAGTCTGT TCGCCGG
GTATGGCGGCACATGGGGAAGCAGGTGAGAGATTGGAGAAAGGACGTTCGCTCTGGG GAACGG
CCGAAAATTCGGGGATACGCAAAGGATGTCGTGGGCGGCAATAGCATTGAGCAGATC GAGTAC
CTGGAAAGGCAATACAAATTTCTGAAATCTTGGTCTTTCTTTGGGAAGGTAAGCGGA CAAGTTA
TCAGAGCCGAAAAGGGATCTCGCTTTGCTATCACATTGAGGGAACACATTGATCACG CCAAAGA
AGACAGGTTGAAAAAGTTGGCTGATCGCATTATCATGGAAGCACTCGGTTACGTCTA CGCCCTT
GATGAGCGCGGTAAAGGGAAGTGGGTAGCCAAGTATCCCCCATGTCAGCTGATCCTG CTCGAGG
AACTTTCTGAGTATCAGTTCAATAACGACCGTCCTCCCTCCGAAAATAATCAGCTCA TGCAATGG
TCCCACCGGGGTGTGTTCCAAGAACTGATCAATCAGGCTCAGGTGCACGACCTCCTC GTAGGCA
CTATGTATGCAGCCTTTAGCTCCCGTTTTGACGCGCGCACAGGCGCCCCTGGAATAC GATGTAG
GCGAGTTCCCGCACGGTGCACTCAAGAACATAACCCGGAGCCTTTCCCATGGTGGCT CAATAAG
TTTGTTGTGGAGCATACCCTCGACGCTTGCCCATTGAGGGCGGATGACTTGATTCCC ACAGGCG
AGGGGGAGATCTTCGTGAGCCCATTTTCTGCCGAAGAAGGGGATTTCCACCAAATAC ATGCCGA
CTTGAATGCTGCCCAAAATCTGCAGCAAAGGCTGTGGTCAGACTTCGACATCTCGCA AATCAGA
CTGCGGTGTGACTGGGGCGAAGTAGACGGCGAGCTGGTGCTGATACCTAGACTGACG GGTAAG
CGTACCGCCGATAGCTATAGTAATAAGGTTTTTTATACGAATACGGGGGTGACATAT TACGAGC
GTGAGAGAGGCAAGAAGCGTCGGAAGGTGTTCGCGCAGGAGAAGCTGAGCGAAGAGG AGGCG
GAGCTACTGGTAGAGGCAGATGAGGCAAGAGAAAAGTCCGTCGTCCTGATGCGGGAT CCTAGC
GGGATTATTAACAGAGGTAATTGGACACGGCAGAAAGAATTCTGGAGCATGGTGAAT CAAAGA
ATCGAGGGTTACCTGGTGAAGCAAATTCGAAGCCGGGTGCCCCTTCAAGACAGCGCA TGTGAAA
ACACTGGGGACATCTAG
SE ATGGCTACTCGGTCCTTCATCCTGAAAATCGAGCCAAATGAAGAGGTGAAAAAGGGCCTG TGGA
Q AGACCCATGAGGTACTTAACCACGGCATAGCATACTATATGAATATCCTAAAACTTATAC GGCA
no GGAGGCTATCTACGAGCATCACGAGCAAGATCCTAAAAATCCAAAGAAGGTTAGTAAGGC TGA
N AATCCAGGCTGAATTGTGGGACTTCGTGCTGAAGATGCAGAAATGCAACAGTTTCACGCA TGAA
O: GTTGATAAGGACGTCGTGTTTAATATACTCCGGGAGCTGTACGAAGAACTGGTACCAAGC TCTG 16 TGGAAAAGAAAGGAGAGGCCAACCAGCTAAGTAATAAGTTCCTCTATCCTCTCGTGGACC CCAA 0 TTCACAGAGCGGCAAAGGTACCGCATCTTCTGGGAGGAAACCACGCTGGTACAACTTGAA GATC
GCTGGCGATCCCAGCTGGGAGGAGGAAAAGAAGAAATGGGAAGAGGATAAAAAGAAA GACCC CCTGGCCAAAATCTTAGGCAAGCTCGCCGAGTACGGTCTGATTCCACTTTTCATCCCGTT CACAG
ATAGCAATGAGCCGATCGTCAAGGAGATTAAGTGGATGGAAAAGAGCCGCAATCAGA GTGTGC
GGAGGCTGGACAAAGACATGTTTATTCAGGCCCTGGAACGCTTCCTTAGCTGGGAAA GCTGGAA
CCTGAAGGTTAAGGAAGAGTACGAAAAAGTCGAGAAGGAGCATAAGACTTTGGAGGA GCGCAT
CAAAGAAGACATCCAGGCCTTTAAGTCTCTAGAACAGTATGAGAAAGAACGGCAGGA ACAGCT
GCTGCGTGATACACTGAACACAAACGAATATCGCCTGAGCAAGAGGGGACTCAGAGG CTGGAG
AGAAATCATTCAAAAGTGGCTCAAAATGGATGAAAATGAGCCGTCTGAAAAATACCT TGAAGTT
TTCAAGGACTACCAGCGGAAGCACCCTAGAGAAGCCGGCGACTATAGTGTTTACGAA TTCTTGA
GCAAGAAGGAGAATCATTTTATATGGAGGAATCACCCGGAGTACCCATATCTGTACG CAACCTT
CTGCGAAATCGACAAGAAAAAAAAAGACGCCAAGCAACAGGCTACATTTACTCTGGC CGACCC
TATCAATCACCCTCTATGGGTCCGGTTTGAGGAGCGCTCCGGAAGCAATCTGAATAA ATATCGT
ATTCTGACTGAACAGTTACACACAGAGAAGCTCAAGAAGAAACTTACGGTGCAGCTG GACCGC
CTGATATACCCAACAGAGTCCGGAGGATGGGAAGAGAAAGGAAAGGTTGACATCGTA CTGCTT
CCATCTCGTCAGTTTTACAACCAGATATTCCTGGACATCGAGGAGAAGGGGAAACAC GCCTTCA
CATACAAGGACGAGTCCATAAAGTTCCCACTGAAGGGTACTTTAGGCGGTGCTAGGG TGCAGTT
CGACCGCGATCACCTGAGACGGTACCCCCACAAGGTGGAGAGCGGGAACGTGGGACG AATCTA
CTTTAATATGACAGTGAACATTGAACCCACAGAGAGTCCAGTTAGTAAATCCCTGAA AATTCAC
CGTGACGACTTTCCGAAATTTGTGAATTTCAAGCCAAAGGAGCTTACGGAGTGGATC AAGGATT
CAAAGGGAAAGAAGCTGAAATCTGGTATCGAATCTCTCGAGATCGGTCTCCGTGTCA TGAGCAT
CGATCTGGGACAGCGCCAGGCAGCTGCCGCCAGTATATTCGAGGTGGTAGACCAAAA GCCTGA
CATCGAGGGAAAGCTCTTCTTCCCAATCAAAGGCACAGAGCTGTATGCGGTGCACCG GGCGTCC
TTTAATATAAAGCTGCCCGGTGAAACCCTGGTGAAGTCACGGGAGGTGCTTAGAAAA GCGCGA
GAGGATAACCTCAAACTGATGAACCAAAAACTGAACTTTCTGAGGAACGTCCTGCAC TTTCAGC
AGTTCGAAGATATTACCGAACGCGAAAAGAGAGTAACCAAGTGGATATCTCGTCAAG AGAACA
GCGACGTCCCGTTAGTCTATCAGGACGAACTCATCCAAATACGGGAGTTGATGTATA AGCCCTA
CAAGGATTGGGTCGCCTTTCTTAAGCAGCTTCACAAACGCCTAGAGGTCGAAATAGG TAAAGAG
GTGAAACATTGGCGGAAGTCGCTCAGCGACGGGAGGAAGGGACTTTATGGCATCTCT TTGAAGA
ACATTGACGAAATCGATAGAACCAGAAAATTTTTGTTGAGATGGTCCCTCCGACCCA CCGAGCC
TGGAGAGGTGAGGCGGTTAGAACCAGGACAGAGGTTCGCTATCGATCAGCTGAATCA CCTCAAT
GCTCTGAAGGAGGACCGCCTCAAGAAAATGGCCAATACAATCATAATGCACGCCCTT GGCTACT
GCTACGACGTCCGAAAGAAGAAGTGGCAGGCCAAGAATCCCGCCTGTCAAATTATCC TTTTTGA
GGATCTTAGCAATTACAACCCCTATGAAGAGCGGTCCAGATTCGAAAATAGTAAGCT CATGAAG
TGGAGCCGCAGGGAGATCCCGCGCCAAGTGGCCCTTCAGGGGGAAATTTATGGGCTG CAGGTA
GGCGAGGTCGGGGCCCAATTCTCCTCGCGCTTTCATGCGAAAACTGGAAGTCCTGGA ATCCGGT
GCTCAGTGGTGACAAAGGAGAAGTTGCAAGACAATCGGTTTTTTAAAAACTTACAGC GGGAGG
GAAGGCTGACCCTGGATAAGATAGCCGTACTTAAGGAAGGAGATCTGTACCCTGACA AAGGCG
GTGAAAAGTTCATTAGCTTGAGCAAGGACCGAAAACTTGTGACCACCCACGCTGACA TCAATGC
GGCACAGAACCTGCAGAAGAGATTTTGGACTCGCACCCACGGATTCTACAAAGTTTA CTGCAAA
GCATATCAAGTAGACGGACAGACCGTATACATCCCCGAGTCCAAAGATCAGAAGCAG AAAATT
ATTGAAGAGTTTGGGGAAGGGTACTTTATCCTGAAGGATGGTGTCTACGAATGGGGC AACGCTG
GTAAACTTAAAATTAAGAAGGGCAGCTCTAAACAGTCCTCCAGCGAGTTAGTTGATT CTGATAT
TCTGAAAGACAGTTTCGACCTGGCCAGCGAACTTAAAGGGGAAAAATTAATGCTGTA CCGGGAC CCCAGCGGAAACGTCTTTCCATCCGATAAGTGGATGGCCGCTGGAGTGTTCTTTGGCAAG TTAG AGAGGATTCTCATAAGTAAGCTGACCAACCAATACTCAATCTCCACAATCGAGGATGACT CATC CAAGCAGTCTATGTGA
SE ATGCCTACACGCACTATCAACCTGAAACTGGTTCTTGGCAAGAATCCAGAGAATGCTACC CTTC
Q GTCGGGCACTATTTTCAACGCATAGACTGGTGAATCAGGCTACCAAACGGATTGAAGAGT TCCT
no CTTGCTTTGTCGGGGGGAAGCATATAGGACGGTGGATAATGAGGGGAAAGAGGCTGAAAT TCC
N GAGACACGCCGTGCAGGAGGAAGCTCTTGCGTTTGCAAAGGCCGCTCAACGGCACAATGG TTGC
O: ATCTCTACTTATGAAGACCAGGAAATCCTGGATGTGCTCCGGCAACTGTATGAAAGGCTG GTGC 16 CTTCTGTGAATGAAAATAATGAAGCAGGGGACGCTCAAGCCGCAAACGCGTGGGTGTCGC CACT 1 GATGTCCGCCGAGTCCGAGGGAGGGCTCAGCGTTTACGACAAGGTGCTGGACCCACCCCC AGTG
TGGATGAAACTCAAAGAGGAAAAAGCTCCGGGCTGGGAGGCTGCTTCCCAGATCTGG ATCCAG
TCCGACGAAGGGCAGTCCCTTCTTAACAAGCCTGGTTCGCCCCCGCGGTGGATTAGG AAACTGA
GGTCAGGCCAGCCTTGGCAGGACGATTTTGTTAGCGACCAGAAAAAGAAGCAGGACG AGCTGA
CAAAGGGGAATGCGCCACTGATCAAACAATTAAAGGAAATGGGCTTATTGCCTCTTG TGAATCC
CTTTTTTAGACATCTGCTTGACCCGGAGGGGAAGGGGGTGTCACCTTGGGACAGACT CGCTGTT
AGGGCCGCTGTCGCTCATTTCATATCATGGGAATCATGGAACCACCGGACACGCGCC GAATACA
ATAGTTTGAAGCTGCGGAGGGATGAGTTCGAAGCAGCTTCCGACGAATTCAAGGACG ACTTCAC
GCTGCTTCGGCAGTACGAGGCTAAGAGGCACTCCACACTGAAGAGTATAGCTTTAGC CGATGAT
TCAAACCCTTATAGGATCGGCGTACGCTCCCTCCGCGCTTGGAACCGCGTCCGCGAG GAGTGGA
TCGACAAGGGAGCGACCGAGGAGCAGCGGGTCACCATTCTCAGCAAGTTGCAGACCC AACTAA
GGGGCAAATTTGGAGATCCTGACTTGTTCAACTGGCTGGCGCAGGACCGGCACGTGC ACCTCTG
GAGCCCTAGAGATAGTGTTACCCCACTGGTTAGGATCAACGCTGTTGACAAAGTATT GCGACGG
AGAAAACCGTACGCCTTGATGACTTTTGCCCACCCAAGATTCCACCCTCGGTGGATA CTTTACGA
AGCCCCAGGGGGCAGCAATCTCCGCCAGTATGCACTGGATTGTACCGAAAATGCTCT GCACATT
ACACTGCCTCTGCTGGTTGACGATGCACATGGCACATGGATTGAGAAAAAAATTAGG GTTCCTC
TTGCCCCCAGCGGCCAGATTCAGGACCTGACACTAGAAAAGCTCGAGAAGAAGAAAA ATCGTC
TCTACTACCGTTCTGGGTTCCAGCAGTTTGCCGGCCTGGCCGGAGGTGCCGAGGTGC TTTTCCAT
CGACCATACATGGAGCACGATGAGAGGAGCGAGGAGAGCTTATTAGAACGCCCTGGT GCTGTTT
GGTTCAAACTCACCTTGGACGTGGCAACCCAGGCCCCTCCAAACTGGTTGGACGGAA AGGGCCG
CGTCCGAACGCCCCCCGAGGTTCACCACTTCAAGACAGCCCTCAGTAACAAGTCTAA GCACACA
CGGACCCTCCAGCCCGGACTCAGAGTGTTATCCGTGGATCTGGGAATGCGCACCTTC GCCTCTTG
CTCCGTATTTGAGCTGATCGAGGGCAAACCAGAGACTGGCAGAGCGTTCCCTGTGGC CGACGAA
CGTTCCATGGATTCACCAAACAAGCTGTGGGCCAAGCACGAAAGATCCTTTAAACTC ACGCTCC
CCGGCGAAACCCCCAGTCGGAAAGAAGAGGAGGAACGGAGCATTGCAAGAGCCGAAA TCTATG
CGTTGAAAAGAGATATTCAGAGATTAAAAAGTCTTCTGCGCCTGGGGGAAGAGGATA ACGATA
ATAGACGCGATGCACTTCTTGAGCAATTTTTCAAGGGCTGGGGCGAGGAAGACGTGG TTCCAGG
TCAGGCCTTTCCCCGGAGTCTGTTCCAGGGGCTGGGGGCCGCCCCATTCAGATCCAC CCCTGAGT
TGTGGAGACAACACTGTCAAACCTATTATGATAAAGCAGAGGCGTGCCTGGCTAAAC ACATCAG
CGATTGGCGCAAGAGAACCAGGCCTAGGCCTACCTCACGTGAGATGTGGTACAAGAC ACGCTCT
TATCACGGCGGAAAGTCAATCTGGATGCTGGAATACCTCGACGCTGTGAGGAAACTG CTCTTAT
CCTGGAGCCTCAGAGGCCGGACCTACGGGGCTATCAACAGACAGGACACAGCAAGGT TCGGGA
GCTTAGCCAGCCGGCTCCTTCACCACATTAACTCACTCAAAGAGGATCGAATAAAGA CCGGAGC CGACTCGATCGTGCAGGCAGCCCGAGGGTACATCCCCCTGCCTCATGGGAAGGGCTGGGA GCA
GCGATATGAACCCTGCCAGCTGATCTTGTTTGAGGACCTTGCCCGTTATAGATTTCG CGTTGATA
GACCTCGCCGTGAGAATTCTCAGCTGATGCAGTGGAACCACAGAGCGATCGTGGCTG AGACCAC
TATGCAGGCCGAGCTGTATGGACAGATCGTGGAGAACACCGCCGCAGGGTTCAGTTC TCGGTTT
CATGCTGCCACCGGAGCTCCCGGCGTCCGGTGCCGCTTCCTCTTAGAGCGTGATTTT GACAATGA
CCTCCCAAAGCCCTATCTGCTGAGGGAACTGAGCTGGATGCTGGGGAACACAAAAGT AGAATC
GGAGGAGGAGAAGCTACGGCTCCTCTCCGAAAAGATACGTCCAGGCTCTCTGGTACC ATGGGAC
GGAGGAGAGCAGTTCGCGACACTGCATCCTAAGAGACAGACGTTATGTGTGATTCAC GCCGATA
TGAACGCCGCTCAGAATCTGCAGCGAAGATTCTTTGGCCGCTGCGGCGAAGCCTTCA GGCTGGT
ATGTCAGCCCCACGGGGATGATGTGCTGCGGCTGGCCTCAACCCCTGGGGCTAGACT CTTGGGG
GCACTCCAGCAGCTGGAAAATGGCCAAGGGGCTTTCGAACTCGTTCGGGACATGGGC AGCACA
AGCCAGATGAACAGATTCGTCATGAAGAGCCTGGGAAAGAAAAAGATCAAACCCTTA CAGGAC
AATAATGGCGACGACGAACTGGAGGACGTGTTGTCCGTGCTGCCAGAGGAAGACGAC ACAGGC
CGCATCACTGTCTTCCGCGACTCAAGTGGGATATTCTTTCCTTGCAACGTGTGGATT CCGGCCAA
ACAGTTCTGGCCTGCCGTCAGAGCCATGATTTGGAAAGTGATGGCTAGTCATTCATT GGGATGA
SE ATGACAAAGCTGAGGCACAGACAAAAGAAGCTTACACACGACTGGGCAGGGAGCAAGAAA CG
Q TGAGGTCCTTGGGTCAAATGGAAAACTGCAGAACCCCTTGCTCATGCCTGTAAAGAAGGG GCAG
no GTAACAGAATTTAGAAAAGCATTCTCCGCGTACGCTCGGGCAACTAAGGGGGAAATGACC GAT
N GGACGGAAGAACATGTTCACCCATTCTTTCGAGCCATTCAAAACAAAGCCGTCATTGCAC CAAT
O: GCGAGCTGGCCGATAAGGCTTACCAGTCTTTGCATAGTTACCTCCCCGGTTCCCTGGCCC ATTTC 16 TTGCTTTCCGCACACGCACTGGGCTTTCGTATTTTCTCTAAATCTGGGGAGGCAACTGCC TTCCA 2 GGCCAGCTCAAAAATCGAGGCCTATGAGTCCAAGCTCGCTTCGGAGCTAGCCTGTGTCGA TTTG
AGTATCCAGAATTTGACGATTAGTACTCTTTTCAACGCTCTCACAACTTCAGTTCGG GGCAAGGG
GGAGGAAACTTCAGCAGATCCCCTTATCGCACGGTTCTACACTCTCCTGACGGGCAA GCCCCTG
AGCCGAGACACACAGGGCCCAGAACGGGACTTGGCAGAGGTCATCTCCAGAAAGATC GCCTCG
TCCTTCGGCACATGGAAGGAAATGACTGCCAACCCTCTGCAGAGCCTCCAGTTCTTC GAAGAAG
AGCTTCATGCACTAGATGCCAACGTGTCTTTATCTCCAGCTTTTGATGTGTTAATCA AGATGAAT
GATCTCCAAGGTGATCTGAAGAACCGTACTATAGTGTTCGACCCAGATGCACCCGTG TTCGAGT
ACAACGCTGAGGATCCAGCCGATATCATCATAAAGCTGACAGCTCGGTATGCGAAGG AGGCCG
TCATCAAGAATCAGAACGTGGGCAATTATGTGAAAAACGCCATTACCACCACTAATG CCAATGG
GCTGGGGTGGCTCCTCAATAAAGGGCTTTCACTACTGCCAGTTTCTACTGACGATGA GCTGCTCG
AATTCATTGGGGTGGAGAGAAGCCATCCCAGCTGTCACGCGCTGATAGAGCTGATTG CCCAGCT
AGAGGCGCCGGAACTGTTTGAGAAGAATGTGTTTAGTGACACCCGTTCCGAGGTTCA GGGTATG
ATCGACAGTGCAGTGTCGAACCACATTGCTCGGCTGTCCAGCAGCCGAAACTCCCTG AGCATGG
ACAGCGAGGAATTGGAACGCTTGATTAAATCTTTCCAGATTCATACTCCCCATTGTT CTCTGTTC
ATAGGCGCTCAGTCCTTATCTCAGCAGCTGGAGAGCTTACCTGAGGCGCTGCAGTCC GGAGTGA
ACAGCGCTGATATCTTATTAGGCAGCACACAGTATATGCTGACCAACTCTCTCGTTG AAGAGTC
AATTGCAACATATCAAAGGACATTAAATAGGATCAATTACCTGAGTGGGGTGGCTGG GCAGATT
AACGGTGCTATCAAAAGAAAGGCAATCGACGGCGAAAAAATACACCTGCCTGCCGCC TGGAGT
GAGCTCATCTCCTTACCTTTCATTGGACAGCCGGTGATTGATGTGGAGAGCGACCTG GCACACTT
AAAAAACCAGTACCAGACCCTGTCCAATGAATTTGACACCCTCATTTCGGCCCTGCA GAAGAAC
TTCGATTTGAATTTCAACAAAGCACTCCTTAACCGCACGCAGCATTTCGAGGCAATG TGCCGGA GCACAAAAAAAAATGCTTTATCTAAGCCCGAGATCGTGTCCTACAGAGATCTGCTGGCGC GGCT
GACCAGTTGCCTTTATCGAGGCTCGCTGGTTCTCAGAAGGGCGGGAATCGAAGTTCT GAAAAAG
CACAAAATCTTTGAGTCGAATAGTGAGCTGAGAGAACACGTCCACGAGCGAAAGCAC TTCGTGT
TCGTTAGTCCATTGGACAGAAAGGCAAAAAAACTGTTGCGCCTGACCGATTCCCGCC CTGACTT
GCTCCATGTGATCGATGAGATCCTGCAACATGACAATCTGGAGAATAAGGACAGAGA GTCCCTT
TGGCTGGTCCGGTCTGGGTACCTCCTTGCTGGTCTGCCGGACCAGCTGAGTTCTTCG TTTATCAA
TCTCCCCATAATCACGCAAAAGGGCGATCGCCGGCTGATTGACCTGATTCAGTATGA CCAGATC
AATCGCGATGCTTTCGTAATGTTGGTGACAAGTGCTTTCAAAAGCAATCTCTCTGGG TTGCAGTA
CCGCGCTAACAAGCAGTCTTTCGTGGTCACCCGCACCCTGTCTCCTTACCTGGGTAG TAAGCTCG
TATACGTCCCTAAAGACAAAGATTGGCTGGTCCCATCCCAGATGTTTGAGGGAAGAT TCGCCGA
TATTCTGCAGAGTGACTACATGGTCTGGAAGGATGCCGGACGCCTGTGCGTGATCGA CACTGCC
AAACATCTCTCTAACATTAAAAAAAGCGTGTTTAGTAGCGAAGAAGTCCTTGCTTTT CTTCGAGA
GCTGCCTCACCGGACCTTCATCCAGACCGAGGTACGGGGGTTAGGAGTGAACGTCGA TGGAATC
GCATTTAATAACGGGGATATCCCGAGCTTGAAGACATTCTCGAATTGTGTGCAGGTG AAGGTGA
GTAGGACTAATACTAGTCTCGTGCAGACTCTAAACAGGTGGTTCGAGGGTGGCAAAG TGTCACC
TCCCTCTATTCAGTTCGAAAGAGCTTACTACAAAAAAGACGATCAGATTCACGAGGA CGCAGCC
AAGAGAAAGATACGCTTCCAGATGCCAGCAACGGAATTAGTGCACGCCAGCGATGAC GCTGGT
TGGACCCCCAGCTACCTGCTGGGCATCGACCCCGGTGAGTACGGAATGGGTCTCAGT TTGGTGT
CCATCAACAATGGAGAGGTCCTGGATTCTGGATTCATCCACATTAATTCCCTGATCA ATTTCGCG
TCCAAAAAAAGCAATCACCAGACCAAAGTAGTCCCCCGCCAGCAGTACAAGTCCCCC TACGCG
AATTATCTCGAGCAGTCAAAGGATTCAGCAGCAGGGGATATAGCTCACATTCTGGAT CGGCTAA
TCTACAAATTGAACGCCTTGCCTGTGTTCGAGGCGCTGTCTGGCAACAGTCAGAGTG CTGCTGAT
CAGGTATGGACCAAAGTTCTATCCTTCTATACATGGGGAGACAACGACGCACAGAAC AGTATAC
GGAAGCAGCACTGGTTCGGTGCCTCACACTGGGATATTAAGGGGATGCTGCGCCAAC CCCCAAC
CGAAAAAAAACCCAAACCATATATAGCCTTTCCCGGGAGTCAAGTGTCATCCTATGG AAATAGT
CAAAGGTGTAGTTGTTGCGGCCGCAATCCCATTGAGCAGTTGCGTGAGATGGCAAAG GACACGA
GTATCAAGGAGCTGAAAATCCGAAATAGTGAGATCCAACTATTCGATGGTACAATCA AGCTGTT
TAACCCCGACCCTTCCACCGTCATCGAGAGGCGGCGGCATAACCTAGGACCCTCACG CATTCCT
GTGGCAGACCGAACTTTCAAGAATATTAGCCCTTCTTCGTTAGAGTTCAAGGAGCTC ATTACTAT
CGTTTCTCGAAGCATCCGCCATAGCCCCGAATTTATTGCTAAGAAACGGGGTATCGG GTCTGAG
TACTTTTGTGCTTATTCTGACTGCAACTCCTCACTGAACTCAGAGGCCAATGCCGCG GCCAATGT
GGCACAGAAGTTTCAGAAGCAACTCTTTTTCGAACTCTGA
SE ATGAAACGTATTCTGAACTCTCTGAAAGTCGCCGCACTGAGGCTGCTGTTTCGAGGAAAG GGCT
Q CAGAGCTGGTGAAGACCGTCAAGTACCCTCTGGTTTCGCCCGTCCAGGGTGCTGTGGAAG AACT
no CGCCGAAGCAATACGCCACGACAACCTACATTTATTTGGGCAGAAGGAAATCGTAGATCT GATG
N GAGAAGGACGAGGGCACCCAGGTCTACTCGGTGGTGGACTTTTGGCTCGACACACTCCGT CTAG
O: GGATGTTCTTCAGTCCAAGTGCTAATGCCCTTAAGATCACTCTGGGGAAGTTTAACAGCG ACCA 16 AGTTTCCCCTTTCAGGAAGGTTCTGGAGCAGTCCCCTTTCTTTCTCGCGGGTAGACTCAA AGTGG
3 AGCCCGCTGAACGTATCCTCAGCGTGGAGATCCGCAAGATCGGTAAGAGGGAGAATAGAG TGG
AGAACTACGCCGCAGATGTAGAGACTTGTTTTATCGGTCAGCTGTCTAGTGATGAAA AGCAGTC
TATCCAGAAGCTCGCTAACGATATCTGGGACTCTAAGGATCACGAAGAGCAAAGGAT GCTTAAG
GCGGATTTCTTTGCCATTCCCCTCATCAAAGACCCAAAGGCAGTGACCGAGGAAGAT CCCGAGA ATGAAACCGCAGGCAAACAGAAGCCTCTCGAATTATGTGTGTGCTTAGTGCCCGAGTTGT ACAC
CCGCGGGTTCGGTTCAATAGCGGACTTCCTGGTCCAGCGTCTGACACTATTAAGAGA CAAAATG
AGCACAGACACAGCAGAAGACTGCCTTGAGTATGTCGGCATAGAGGAGGAGAAGGGT AATGGG
ATGAACTCGCTGCTGGGGACGTTCCTCAAGAACCTGCAGGGAGACGGGTTCGAACAG ATCTTCC
AATTTATGCTCGGCAGTTACGTGGGATGGCAAGGTAAGGAAGACGTCCTACGCGAAC GGCTTGA
TTTGCTAGCGGAGAAGGTTAAAAGACTGCCGAAACCTAAGTTTGCCGGCGAGTGGTC CGGCCAT
CGGATGTTCCTGCATGGTCAATTGAAGAGCTGGTCCTCTAACTTTTTCCGCCTGTTT AACGAGAC
TAGGGAGCTCCTCGAAAGCATAAAATCCGACATCCAACACGCGACCATGTTAATCAG CTACGTC
GAAGAGAAAGGGGGATACCACCCACAACTCTTGTCACAGTACAGGAAACTAATGGAG CAGCTG
CCAGCTCTCAGAACAAAGGTGTTAGATCCAGAGATAGAAATGACTCACATGAGCGAG GCGGTA
AGGTCGTACATTATGATCCACAAGTCGGTAGCAGGATTTCTGCCTGACTTACTCGAG TCCCTCGA
TAGGGACAAGGACAGGGAATTCCTGCTGAGTATATTTCCAAGGATCCCCAAAATTGA CAAAAA
AACTAAGGAAATCGTGGCCTGGGAGCTCCCAGGCGAGCCCGAAGAAGGATACCTGTT CACTGC
CAATAATCTTTTTCGCAACTTTCTGGAGAATCCTAAACATGTTCCACGTTTCATGGC AGAAAGGA
TCCCGGAAGATTGGACGCGCCTGCGGTCCGCTCCCGTATGGTTTGACGGCATGGTGA AACAATG
GCAGAAAGTGGTAAACCAGCTGGTGGAGTCACCTGGAGCATTGTATCAGTTCAATGA AAGCTTT
CTCCGACAACGTTTACAGGCAATGCTGACAGTGTATAAGAGAGACCTGCAGACAGAG AAATTCC
TTAAGTTGTTGGCTGATGTCTGCAGGCCTCTGGTGGACTTCTTTGGGCTGGGGGGAA ACGATATC
ATCTTCAAAAGCTGCCAGGACCCGAGGAAACAATGGCAAACTGTCATTCCCTTGAGT GTCCCCG
CTGATGTGTACACCGCGTGTGAGGGGCTGGCAATCCGGCTTCGTGAGACATTGGGAT TTGAGTG
GAAGAACCTTAAGGGCCATGAAAGGGAGGACTTTCTAAGACTGCACCAGCTTTTAGG GAATCTG
CTTTTCTGGATTCGAGATGCCAAACTGGTGGTGAAATTGGAAGATTGGATGAATAAT CCCTGTG
TTCAGGAGTACGTTGAGGCTCGTAAGGCCATTGATCTCCCACTGGAGATCTTCGGCT TTGAGGTC
CCCATCTTCCTGAACGGATATCTGTTTAGTGAACTGAGGCAGTTAGAACTGCTGCTC CGCCGTAA
GTCGGTTATGACCAGCTATTCGGTTAAGACAACTGGCAGTCCAAACAGGCTTTTCCA GTTAGTCT
ACCTGCCATTAAATCCTTCCGACCCTGAGAAAAAAAATTCTAATAACTTTCAGGAAC GCCTGGA
CACCCCCACTGGCTTATCACGTCGCTTCCTGGACCTTACTCTGGACGCCTTCGCCGG CAAGTTGC
TGACAGACCCCGTGACTCAAGAGCTTAAAACTATGGCTGGGTTCTACGATCACCTGT TTGGTTTC
AAGCTCCCATGTAAGCTGGCAGCCATGTCTAACCACCCTGGCTCTAGCAGCAAGATG GTCGTGT
TGGCCAAACCTAAAAAAGGGGTTGCATCTAATATAGGATTCGAACCAATCCCTGATC CCGCGCA
CCCCGTATTCCGGGTGAGATCATCATGGCCAGAGCTGAAGTATCTGGAGGGGTTACT GTATCTT
CCAGAAGACACTCCACTGACAATAGAGCTCGCAGAGACAAGTGTTAGTTGTCAGAGC GTCAGTA
GCGTGGCATTCGATCTGAAAAATCTGACTACTATCCTTGGACGCGTGGGTGAGTTCC GTGTGAC
CGCAGACCAGCCTTTTAAGTTGACCCCCATCATCCCTGAGAAGGAGGAGTCCTTCAT AGGAAAA
ACATATCTAGGCCTTGATGCCGGGGAACGCTCAGGCGTAGGGTTCGCTATCGTCACA GTCGACG
GGGATGGGTACGAGGTACAGCGCCTGGGGGTGCATGAAGATACACAGCTGATGGCCC TACAGC
AGGTGGCCTCTAAAAGCTTGAAGGAGCCGGTGTTCCAGCCGCTCAGAAAGGGTACTT TTCGGCA
GCAGGAACGTATTAGAAAATCTCTCAGAGGATGTTATTGGAACTTCTATCACGCTCT GATGATT
AAGTACCGCGCCAAGGTAGTGCACGAAGAGAGCGTGGGCAGTTCCGGCCTGGTTGGG CAGTGG
TTACGAGCATTCCAGAAGGACCTCAAGAAAGCCGATGTGTTGCCAAAAAAGGGAGGC AAAAAC
GGAGTCGATAAGAAAAAGAGAGAGTCTTCTGCACAAGACACATTGTGGGGAGGGGCT TTTAGC
AAGAAGGAAGAACAGCAGATAGCTTTCGAAGTCCAAGCTGCTGGTTCTAGCCAGTTC TGCCTGA AGTGCGGATGGTGGTTCCAACTCGGAATGCGTGAGGTTAATCGCGTGCAGGAATCCGGCG TCGT GCTGGATTGGAATCGGAGTATTGTCACATTCCTGATTGAGAGCTCTGGCGAGAAAGTGTA TGGG TTCTCCCCTCAGCAACTCGAAAAGGGGTTCAGACCAGACATTGAAACCTTCAAGAAGATG GTTC GGGATTTCATGCGCCCGCCTATGTTTGACCGGAAGGGTCGCCCAGCAGCTGCCTACGAAA GGTT TGTCTTGGGACGCCGGCATCGGCGGTATAGATTCGACAAGGTTTTTGAAGAACGATTCGG ACGA TCCGCGCTATTCATTTGCCCGAGGGTTGGCTGTGGCAACTTTGACCACAGCAGCGAGCAG TCAG CCGTAGTGCTGGCTCTAATCGGATATATTGCCGACAAAGAGGGGATGAGCGGAAAAAAGC TAG TCTACGTGCGTCTGGCAGAACTAATGGCGGAATGGAAATTGAAGAAACTGGAGAGGAGTA GAG TTGAGGAGCAAAGCTCCGCTCAGTGA
SE ATGGCGGAGTCGAAGCAAATGCAGTGCAGGAAGTGTGGAGCCTCTATGAAGTACGAAGTG ATC
Q GGCCTCGGGAAGAAAAGCTGCAGATATATGTGTCCCGACTGCGGGAATCACACATCTGCA AGA
no AAGATTCAGAATAAGAAGAAAAGGGACAAGAAGTATGGATCTGCCAGTAAAGCACAAAGC CA
N ACGAATCGCAGTTGCAGGGGCCTTATACCCGGATAAAAAGGTTCAGACCATCAAGACTTA TAAG
O: TATCCAGCCGACCTGAATGGTGAGGTCCATGACTCAGGGGTGGCCGAAAAAATAGCCCAA GCA 16 ATCCAGGAGGATGAAATAGGGCTCCTCGGCCCCTCTTCCGAGTACGCCTGTTGGATCGCT AGCC 4 AGAAACAGAGCGAGCCCTACAGTGTTGTAGACTTTTGGTTTGACGCTGTGTGCGCCGGAG GCGT
GTTCGCCTATTCTGGGGCTAGATTGCTGTCTACCGTCCTGCAGCTATCTGGGGAGGA GAGCGTCC
TACGCGCAGCCCTGGCATCCTCCCCTTTTGTCGACGATATCAATCTGGCACAGGCCG AAAAATTT
CTGGCGGTGTCCAGGCGAACCGGCCAAGATAAGCTGGGGAAGCGCATTGGAGAGTGC TTCGCA
GAGGGCCGACTTGAGGCCCTAGGCATCAAGGACCGGATGCGTGAATTTGTCCAGGCT ATCGATG
TCGCTCAGACCGCTGGGCAGCGTTTTGCCGCGAAACTGAAAATCTTTGGGATTTCTC AGATGCCC
GAGGCAAAGCAGTGGAACAATGACAGCGGACTCACCGTGTGCATCCTGCCCGACTAT TACGTCC
CAGAAGAAAATCGCGCAGATCAGTTGGTCGTCCTGCTAAGACGACTGAGAGAGATAG CATACT
GTATGGGGATCGAAGATGAGGCCGGTTTTGAACATCTTGGAATTGATCCTGGCGCAC TATCAAA
TTTTTCCAATGGCAATCCTAAACGCGGATTTTTGGGCCGCCTGCTGAACAATGATAT TATTGCCT
TAGCGAACAACATGTCCGCCATGACGCCTTACTGGGAGGGCAGGAAGGGAGAACTGA TTGAAA
GATTGGCTTGGCTGAAGCACCGTGCAGAGGGGCTTTATCTGAAGGAACCGCATTTTG GAAATAG
TTGGGCCGACCATAGGTCTAGAATTTTTTCCAGAATAGCCGGGTGGCTTTCTGGGTG CGCTGGG
AAGCTAAAGATCGCCAAAGACCAGATCAGCGGAGTGCGTACTGATCTGTTCCTTCTG AAGAGAC
TGCTGGATGCGGTCCCGCAGTCCGCCCCTTCTCCCGACTTCATAGCCTCTATCTCTG CCTTGGAT
CGCTTCCTGGAGGCCGCAGAATCTAGTCAGGATCCTGCCGAACAGGTGAGGGCCCTA TACGCCT
TTCATCTGAACGCACCCGCGGTGCGAAGCATCGCCAACAAGGCAGTCCAGCGATCCG ACAGCCA
AGAATGGCTTATAAAGGAACTGGACGCTGTGGACCACCTGGAGTTTAACAAGGCCTT TCCCTTC
TTCTCTGATACGGGAAAGAAGAAAAAGAAAGGGGCTAACTCGAATGGCGCTCCGTCC GAGGAG
GAGTACACCGAGACTGAGAGCATCCAGCAGCCCGAGGACGCTGAGCAAGAGGTTAAT GGTCAG
GAAGGCAACGGGGCCTCGAAGAACCAGAAGAAGTTTCAGAGAATCCCCCGATTCTTC GGCGAG
GGGAGTCGCAGCGAGTATCGCATCCTCACTGAAGCCCCGCAGTACTTCGACATGTTC TGTAACA
ACATGCGGGCCATCTTTATGCAATTAGAATCCCAACCGCGTAAAGCTCCCAGGGATT TTAAGTG
TTTCCTGCAGAATCGGCTGCAGAAATTGTATAAGCAGACATTCCTGAACGCTCGATC CAACAAG
TGCCGGGCATTACTAGAGTCCGTATTGATTAGTTGGGGAGAGTTTTACACCTACGGG GCTAACG
AGAAAAAATTTCGACTGCGTCATGAAGCTTCTGAGCGCTCCTCGGACCCAGATTACG TGGTGCA
ACAGGCGCTGGAGATCGCTCGGAGGCTGTTTCTCTTCGGCTTTGAGTGGAGGGACTG TAGCGCA GGTGAAAGAGTGGATCTGGTCGAAATACATAAGAAAGCCATATCTTTCCTGTTGGCCATC ACTC
AGGCTGAGGTGTCTGTGGGCAGCTATAACTGGCTGGGCAATTCTACCGTGAGTCGGT ACCTGTC
CGTGGCAGGGACTGATACCCTTTACGGCACCCAGCTGGAAGAATTCTTAAATGCAAC CGTGTTA
TCTCAGATGCGGGGGCTGGCTATCAGGTTATCATCTCAGGAACTGAAGGATGGATTT GACGTAC
AGCTGGAGTCTAGTTGCCAGGATAATCTGCAACACTTGCTCGTGTACAGGGCTTCAC GAGACCT
TGCCGCCTGCAAGCGCGCTACTTGTCCAGCTGAGTTGGATCCTAAGATTCTGGTACT GCCCGTGG
GGGCCTTTATCGCTAGCGTGATGAAAATGATTGAAAGAGGGGATGAGCCTTTAGCTG GAGCTTA
TCTGAGACACAGACCCCATAGTTTCGGGTGGCAGATCCGCGTTCGAGGTGTGGCAGA GGTGGGA
ATGGACCAAGGGACCGCCCTGGCGTTCCAGAAACCGACCGAGAGCGAACCCTTCAAG ATAAAG
CCGTTTTCCGCTCAATACGGCCCCGTTCTATGGCTGAACAGCTCCAGTTATAGCCAG AGCCAGTA
CCTGGACGGGTTCCTATCACAGCCCAAGAACTGGAGTATGCGGGTGCTGCCACAGGC CGGCTCA
GTGCGGGTAGAACAGCGCGTCGCCTTGATTTGGAATCTCCAGGCCGGAAAGATGAGG CTGGAA
CGGAGCGGAGCGCGGGCTTTCTTCATGCCCGTCCCATTCAGTTTCCGCCCCAGTGGC AGCGGCG
ACGAGGCAGTCCTGGCTCCAAATAGGTACCTGGGACTCTTTCCACACAGCGGCGGCA TAGAGTA
CGCTGTGGTCGATGTTCTTGACTCTGCCGGCTTCAAAATACTCGAGAGAGGAACAAT AGCCGTC
AATGGCTTCTCCCAGAAACGAGGAGAAAGACAAGAGGAAGCCCATCGCGAAAAACAA AGACG
CGGTATCTCCGATATTGGGCGCAAGAAGCCAGTCCAGGCCGAAGTCGATGCGGCCAA CGAGCTC
CATCGAAAATACACCGATGTTGCTACTCGGCTGGGGTGTCGAATTGTCGTTCAATGG GCACCCC
AACCCAAACCAGGCACTGCGCCGACCGCTCAGACTGTGTACGCTAGGGCCGTGAGGA CTGAAG
CACCAAGATCCGGCAATCAGGAAGATCACGCCAGGATGAAATCTTCCTGGGGATACA CATGGG
GTACGTATTGGGAAAAAAGGAAGCCCGAGGACATCCTCGGCATTAGTACCCAGGTGT ATTGGAC
AGGCGGGATCGGCGAGTCCTGCCCGGCTGTCGCCGTCGCGCTATTGGGACACATCAG GGCCACC
TCAACCCAGACTGAATGGGAGAAAGAGGAAGTCGTGTTTGGGCGATTGAAAAAGTTC TTCCCAT
CCTGA
SE ATGGAGAAGCGCATCAATAAAATTCGCAAGAAGCTGTCTGCCGATAACGCCACAAAACCA GTT
Q AGTCGAAGCGGCCCAATGAAGACCCTGCTAGTTCGAGTGATGACTGATGATCTGAAGAAA AGG
no CTCGAAAAGCGACGCAAGAAGCCTGAGGTAATGCCTCAGGTTATAAGTAACAATGCAGCA AAC
N AATCTGCGGATGCTGCTTGACGATTACACAAAGATGAAGGAAGCCATTCTCCAGGTGTAT TGGC
O: AGGAGTTCAAGGATGATCACGTAGGCCTGATGTGTAAATTCGCGCAACCTGCAAGCAAGA AGA 16 TCGACCAAAACAAGCTGAAACCCGAGATGGATGAAAAAGGCAATTTAACAACCGCCGGAT TCG 5 CTTGTTCCCAGTGTGGGCAGCCACTGTTCGTGTACAAGTTAGAACAGGTGTCGGAAAAAG GAAA
GGCATACACTAACTACTTTGGACGGTGCAATGTTGCAGAACACGAAAAGCTGATACT GCTTGCC
CAGCTTAAGCCCGAAAAAGACAGCGACGAAGCGGTGACCTACAGCCTGGGAAAATTC GGGCAG
CGGGCACTGGACTTCTATTCTATCCACGTTACCAAGGAGAGCACCCACCCAGTGAAG CCGTTGG
CCCAAATCGCTGGAAACCGGTACGCCAGCGGACCAGTCGGCAAGGCCCTGTCCGATG CCTGTAT
GGGCACAATTGCTTCTTTCCTGTCCAAGTACCAGGACATCATAATCGAGCACCAAAA AGTTGTG
AAAGGGAATCAGAAACGCCTGGAATCCCTTCGAGAACTGGCCGGCAAGGAGAACCTT GAGTAC
CCGTCCGTGACCCTGCCTCCACAGCCACATACCAAAGAGGGCGTAGACGCGTATAAT GAGGTCA
TTGCCCGCGTTCGCATGTGGGTTAATTTAAACCTGTGGCAGAAATTAAAACTAAGCC GAGATGA
TGCTAAACCGTTACTGAGATTGAAGGGATTCCCTAGCTTTCCTGTGGTGGAGAGAAG GGAAAAC
GAGGTTGATTGGTGGAATACTATTAATGAGGTGAAAAAGCTTATTGACGCCAAGAGG GATATGG
GCAGGGTGTTCTGGAGCGGGGTGACTGCCGAAAAGAGAAATACCATCCTCGAGGGAT ACAATT ACCTCCCCAACGAGAATGATCATAAGAAAAGAGAGGGGAGCTTAGAGAATCCAAAGAAAC CTG
CAAAGAGGCAATTCGGTGATCTCCTGCTCTACCTCGAGAAGAAATACGCGGGGGACT GGGGAA
AAGTTTTTGACGAAGCCTGGGAGCGCATTGACAAGAAGATCGCCGGGCTGACGTCTC ACATTGA
ACGGGAAGAGGCACGGAATGCAGAGGACGCCCAGTCTAAGGCCGTGCTGACTGACTG GCTGCG
CGCAAAGGCCTCCTTCGTGCTCGAACGTCTGAAGGAAATGGATGAGAAAGAGTTTTA CGCGTGT
GAAATACAGCTGCAGAAGTGGTACGGCGATCTAAGGGGAAATCCCTTCGCAGTGGAA GCCGAG
AATAGGGTAGTTGACATCAGTGGGTTCTCCATCGGCAGTGATGGACATTCTATCCAG TATAGAA
ACCTGCTCGCCTGGAAGTACTTAGAGAACGGCAAGAGAGAGTTCTATCTGCTGATGA ACTACGG
GAAAAAAGGTAGAATTCGCTTTACAGATGGCACCGACATAAAGAAGTCCGGAAAGTG GCAAGG
CCTCTTATACGGAGGCGGCAAAGCAAAGGTGATAGACTTGACTTTTGACCCTGACGA CGAACAG
CTGATAATCTTGCCGCTGGCCTTTGGCACAAGACAAGGTAGGGAATTTATCTGGAAT GATCTTCT
TTCTCTCGAGACCGGACTCATCAAGCTCGCAAACGGAAGGGTCATCGAGAAGACAAT CTACAAT
AAAAAGATAGGCCGAGACGAGCCAGCCCTGTTTGTGGCTTTGACATTTGAGCGGAGA GAGGTC
GTAGATCCCAGCAACATCAAACCCGTGAACCTGATCGGTGTTGACAGGGGCGAGAAC ATCCCG
GCGGTTATCGCACTGACGGATCCAGAAGGATGTCCTCTGCCCGAGTTCAAAGATTCA TCGGGAG
GGCCAACCGACATTTTGAGGATAGGGGAGGGGTACAAGGAGAAGCAGCGAGCTATCC AGGCGG
CCAAAGAAGTGGAGCAACGAAGAGCTGGTGGTTATTCTCGCAAGTTCGCTTCCAAAA GTCGTAA
CCTGGCTGACGATATGGTGCGCAATTCTGCCCGTGACCTTTTCTACCACGCCGTTAC ACACGACG
CCGTGTTAGTGTTTGAAAATCTTAGTCGAGGCTTCGGGCGACAGGGGAAGCGGACCT TTATGAC
CGAGAGACAGTATACAAAAATGGAGGATTGGCTGACCGCCAAACTGGCGTATGAAGG ACTCAC
ATCCAAGACCTATCTCTCAAAAACTTTGGCCCAGTATACATCTAAGACGTGCAGTAA CTGTGGC
TTCACCATTACCACAGCTGACTACGATGGCATGCTGGTCCGCTTAAAAAAGACATCT GACGGCT
GGGCTACTACCCTCAACAATAAAGAGCTCAAAGCCGAAGGACAAATTACCTATTATA ACAGGTA
TAAAAGACAGACTGTCGAGAAGGAGTTGAGCGCGGAGCTGGACCGCCTATCAGAGGA GTCAGG
GAACAACGATATCTCTAAGTGGACTAAGGGACGCCGAGACGAGGCGTTGTTCTTGCT GAAAAA
GCGGTTCTCTCATCGACCCGTGCAGGAGCAGTTCGTGTGTCTGGACTGCGGCCACGA GGTTCAT
GCTGATGAGCAAGCTGCTCTAAATATTGCCCGTAGTTGGTTGTTCCTGAACAGCAAT TCAACAG
AGTTCAAGTCATACAAGAGCGGAAAGCAGCCGTTTGTGGGCGCATGGCAGGCATTTT ACAAAA
GACGCCTGAAGGAAGTGTGGAAGCCAAACGCC
SE ATGAAAAGGATTAACAAAATCCGAAGGCGGCTTGTAAAGGATTCTAACACCAAAAAGGCT GGC
Q AAGACGGGGCCCATGAAAACATTACTCGTTAGAGTTATGACCCCCGACCTCAGAGAGCGA CTGG
no AAAATTTACGCAAGAAGCCAGAGAACATACCTCAGCCAATTAGTAATACCTCTCGGGCAA ACCT
N AAACAAGTTGCTTACTGATTACACGGAGATGAAAAAGGCCATACTGCATGTGTACTGGGA GGA
O: GTTTCAAAAGGACCCTGTCGGGCTAATGAGCAGGGTGGCTCAGCCTGCACCTAAAAACAT CGAC 16 CAGCGGAAACTCATCCCAGTTAAGGACGGAAATGAGAGATTGACAAGTTCAGGTTTCGCC TGCT
6 CACAGTGCTGTCAACCGCTGTACGTTTATAAGTTAGAACAAGTGAATGACAAAGGAAAGC CTCA
CACAAATTATTTTGGCCGGTGTAATGTCTCTGAGCATGAGCGTCTGATTCTGTTGTC CCCGCATA
AACCGGAAGCTAATGACGAGCTCGTAACCTACAGCTTGGGGAAGTTTGGCCAAAGAG CATTGG
ACTTCTATTCAATCCATGTGACCCGCGAATCCAATCATCCCGTCAAGCCCTTGGAGC AGATAGG
GGGCAATAGTTGCGCTTCTGGCCCTGTGGGCAAAGCCCTGTCCGACGCCTGTATGGG AGCCGTG
GCTTCATTCCTGACCAAATATCAGGATATCATCTTGGAGCACCAGAAAGTGATCAAG AAAAATG
AAAAAAGGTTAGCAAACCTCAAGGATATTGCAAGCGCTAACGGCTTGGCTTTTCCTA AAATCAC ACTTCCACCTCAGCCTCACACAAAGGAAGGCATCGAGGCATACAACAATGTGGTGGCCCA GATC
GTCATCTGGGTTAACTTAAACCTGTGGCAGAAACTTAAAATTGGCAGGGATGAGGCA AAACCCT
TACAGCGCCTGAAAGGATTCCCCAGCTTTCCACTGGTGGAGCGCCAGGCTAACGAAG TGGACTG
GTGGGATATGGTGTGTAACGTCAAGAAGCTCATCAATGAAAAGAAAGAGGACGGTAA AGTCTT
CTGGCAGAACCTCGCCGGTTACAAACGGCAGGAGGCGCTGTTACCTTATCTGTCGAG TGAAGAG
GACCGGAAAAAAGGCAAGAAATTTGCTCGTTATCAGTTTGGTGATTTGCTCCTACAT TTGGAGA
AGAAGCACGGCGAGGACTGGGGAAAAGTATACGATGAGGCCTGGGAGAGGATTGACA AAAAG
GTGGAGGGACTGTCAAAGCACATCAAGCTCGAAGAAGAGCGCAGAAGCGAGGACGCC CAATCC
AAAGCAGCGCTGACTGACTGGCTGCGGGCGAAGGCCAGTTTTGTAATCGAAGGCCTT AAAGAA
GCCGACAAGGATGAATTCTGCAGATGCGAATTAAAACTCCAGAAGTGGTACGGCGAT CTCCGA
GGTAAGCCTTTCGCAATCGAGGCCGAGAATTCCATACTGGACATTAGTGGATTCAGT AAACAGT
ATAATTGTGCCTTTATATGGCAGAAGGATGGTGTCAAGAAACTCAACCTGTACCTTA TTATTAAT
TATTTCAAAGGCGGGAAACTGAGATTTAAGAAGATAAAGCCTGAAGCCTTTGAGGCG AACCGA
TTCTACACAGTTATTAACAAGAAATCTGGTGAAATTGTACCCATGGAGGTAAACTTC AACTTCG
ATGATCCCAATCTGATTATATTGCCACTAGCTTTTGGCAAGCGGCAGGGTAGGGAAT TCATTTGG
AACGATTTGCTTTCACTGGAAACAGGGTCCCTTAAGCTGGCAAACGGGAGAGTGATT GAAAAGA
CATTGTACAATCGGAGGACACGTCAGGATGAACCTGCCCTTTTCGTGGCTCTGACAT TCGAGCG
CAGGGAGGTTCTGGACTCTAGCAATATCAAGCCAATGAACCTGATCGGCATAGACCG AGGAGA
GAATATTCCGGCTGTGATCGCACTCACCGATCCCGAAGGATGTCCCCTTTCTCGGTT CAAGGACT
CCTTAGGCAATCCAACTCATATCCTGAGAATCGGCGAGTCATACAAGGAGAAGCAGC GAACAA
TTCAGGCCGCCAAGGAAGTCGAGCAGAGGCGAGCTGGCGGCTACAGCCGTAAATACG CTAGTA
AAGCTAAGAACCTGGCCGACGATATGGTGCGCAATACTGCTAGAGACCTGCTGTACT ATGCAGT
GACGCAGGACGCAATGCTGATATTCGAGAATCTGTCCAGAGGATTCGGAAGGCAGGG CAAGCG
GACGTTCATGGCCGAGCGCCAGTATACAAGGATGGAGGATTGGTTAACGGCCAAGCT TGCCTAT
GAGGGGCTACCTAGTAAGACCTATCTGTCTAAGACGCTGGCTCAATACACCAGTAAG ACCTGCT
CAAACTGTGGCTTTACAATCACTTCTGCTGATTATGATAGAGTGCTCGAGAAGCTAA AAAAAAC
TGCCACCGGCTGGATGACTACTATTAATGGGAAGGAACTGAAAGTGGAAGGACAGAT TACCTAT
TATAATCGCTACAAGCGTCAAAACGTCGTCAAGGACCTGTCGGTGGAATTGGACAGA CTCAGTG
AAGAGTCCGTGAACAATGATATCAGCTCCTGGACAAAAGGGCGCAGTGGGGAGGCAC TCAGCT
TGCTTAAAAAGAGGTTTTCACATCGGCCGGTCCAGGAGAAATTTGTCTGCCTGAACT GCGGATT
CGAGACACACGCCGACGAGCAGGCAGCACTGAACATTGCCAGATCCTGGCTGTTCCT TAGGTCC
CAGGAATATAAGAAGTACCAGACTAACAAAACCACGGGAAACACAGATAAAAGGGCC TTTGTC
GAAACTTGGCAATCCTTTTACCGGAAGAAGTTAAAGGAAGTGTGGAAGCCC
SE ATGGATAAGAAATACTCAATAGGCTTAGCAATCGGCACAAATAGCGTCGGATGGGCGGTG ATC
Q ACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCAC AGTA
no TCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTC GTCT
N CAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGA GATT
O: TTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTT TTGGT 16 GGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGC TTAT
7 CATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAA GCGG
ATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTT TGATTGAGG
GAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAA CCTACAA TCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTC TGCA
CGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAG AAAAATG
GCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAA ATTTTGATT
TGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATA ATTTATT
GGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGA TGCTATTT
TACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTT CAATGATT
AAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAA CAACTTCC
AGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATAT TGATGGG
GGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGAT GGTACTG
AGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTG ACAACGG
CTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGA AGACTTTT
ATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTC CTTATTAT
GTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAA GAAACAA
TTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTA TTGAACGC
ATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTG CTTTATG
AGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGC GAAAACC
AGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAA TCGAAAA
GTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGT GTTGAAA
TTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAA AAATTATT
AAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTT TTAACAT
TGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACC TCTTTGA
TGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTC TCGAAAA
TTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAA TCAGATG
GTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAG AAGACATT
CAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTA GCTGGTA
GCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCA AAGTAAT
GGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAAC TCAAAA
GGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATT AGGAAG
TCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTA TCTCTATT
ATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAA GTGATTA
TGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAA GGTCTTAA
CGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCA AAAAGAT
GAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGA TAATTTA
ACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGC CAATTGG
TTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATA CTAAATA
CGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATT AGTTTCT
GACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCAT GCCCATG
ATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTG AATCGGA
GTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGA GCAAGAAA
TAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAA CAGAAATT
ACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACT GGAGAA
ATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCC CAAGTCA ATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAA AAA
GAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTG GTTTTGA
TAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATC GAAGAAG
TTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAA AAAAATC
CGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTA AACTACC
TAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGG AGAATTA
CAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCT AGTCATT
ATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGC AGCATA
AGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTT TAGCAGAT
GCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGT GAACAAG
CAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTA AATATTTTG
ATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTC TTATCCA
TCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGA CTGA
SE ATGGATAAGAAGTATTCAATTGGACTTGCGATTGGCACTAACAGTGTGGGCTGGGCGGTG ATTA
Q CAGACGAGTATAAGGTGCCGTCAAAAAAGTTTAAAGTTCTGGGCAACACTGATCGCCATT CCAT
no CAAGAAAAACCTAATCGGGGCCCTTCTTTTTGATAGTGGCGAAACGGCCGAGGCGACGCG TCTA
N AAACGTACCGCGCGGCGTCGCTACACCCGACGAAAAAACCGTATTTGTTACCTTCAGGAG ATCT
O: TCAGTAACGAAATGGCTAAGGTGGACGATTCATTCTTCCACCGTCTGGAGGAGTCCTTTT TAGTT 16 GAAGAAGACAAGAAGCATGAGCGACACCCAATTTTTGGTAACATTGTCGACGAAGTCGCC TATC 8 ACGAAAAATATCCGACCATTTATCACCTGCGCAAAAAACTGGTCGATAGCACGGATAAAG CGG
ATCTGCGGCTTATTTACCTGGCGCTTGCCCACATGATCAAGTTCCGCGGCCACTTCC TGATAGAA
GGAGACCTGAACCCGGATAATAGCGATGTAGACAAACTGTTTATTCAGCTGGTCCAG ACCTACA
ACCAGCTGTTTGAAGAAAATCCGATTAATGCGTCAGGCGTGGATGCGAAAGCGATAC TGAGTGC
CCGCCTGTCGAAATCTCGCCGTCTCGAAAATCTGATTGCACAGCTGCCCGGCGAAAA AAAAAAC
CCTGGCAGAGGATGCGAAGCTTCAACTGTCGAAGGACACCTATGACGATGATCTGGA TAATCTT
CTGGCACAAATCGGTGATCAGTATGCGGATTTATTCCTTGCAGCGAAAAACCTATCT GACGCAA
TTCTGTTGAGCGATATCCTCCGCGTCAACACCGAAATCACTAAAGCCCCCCTGTCAG CGTCGATG
ATTAAACGTTATGATGAGCACCATCAGGATCTGACCTTGCTAAAGGCGCTGGTGCGA CAGCAGC
TTCCCGAAAAATATAAAGAGATCTTTTTTGATCAATCGAAGAATGGTTATGCCGGAT ACATTGA
TGGCGGAGCCAGTCAGGAAGAATTTTACAAATTCATCAAACCGATCCTGGAAAAAAT GGATGG
CACAGAAGAACTGCTTGTGAAATTGAACCGGGAAGATTTACTGCGCAAACAGCGTAC GTTCGAC
AACGGCTCCATACCCCATCAGATTCACTTAGGTGAGCTGCATGCAATACTCCGTCGC CAGGAAG
ATTTTTATCCATTTTTAAAAGACAACCGTGAGAAGATTGAAAAAATTTTAACTTTTC GTATTCCA
TATTACGTCGGGCCTTTGGCCCGAGGTAACTCTCGATTCGCCTGGATGACGAGAAAA AGCGAGG
AGACCATCACTCCGTGGAATTTTGAAGAGGTTGTTGATAAAGGCGCGAGCGCCCAGT CGTTTAT
CGAACGTATGACCAACTTTGATAAAAATCTGCCGAATGAAAAAGTGCTTCCGAAGCA TTCTCTG
TTGTATGAATATTTCACTGTGTACAATGAGTTAACGAAAGTGAAATATGTGACCGAA GGCATGC
GGAAACCTGCTTTTCTGTCCGGAGAACAGAAAAAAGCAATTGTGGACCTGCTGTTCA AAACGAA
CCGGAAAGTAACTGTGAAGCAGCTGAAAGAGGACTACTTCAAAAAAATCGAATGCTT CGACTC
AGTAGAGATCTCTGGTGTTGAAGATCGCTTCAACGCGAGTCTGGGAACGTACCATGA TTTGTTG
AAAATCATCAAAGATAAAGACTTTCTGGATAACGAAGAGAATGAGGACATTCTTGAA GATATTG TTTTGACACTGACTCTGTTTGAGGATCGCGAAATGATTGAAGAGCGCCTGAAAACGTATG CCCA
TTTATTCGATGACAAAGTCATGAAGCAGCTGAAACGTCGCCGCTATACTGGGTGGGG CAGACTT
TCACGTAAATTGATCAATGGTATAAGAGACAAACAGAGCGGCAAAACTATCTTAGAT TTCCTGA
AGAGTGATGGATTTGCCAACCGGAATTTTATGCAGCTTATACATGATGACTCGCTAA CGTTTAA
AGAAGACATTCAGAAGGCGCAGGTCAGCGGCCAGGGTGATTCGCTGCATGAACACAT TGCAAA
TCTTGCCGGATCGCCAGCGATCAAAAAAGGCATCCTTCAGACAGTAAAAGTTGTGGA TGAACTG
GTGAAAGTAATGGGTCGTCACAAGCCAGAAAATATTGTGATCGAAATGGCCCGGGAA AATCAG
ACTACTCAAAAAGGTCAGAAAAATTCTCGCGAGCGTATGAAACGTATTGAAGAAGGC ATCAAA
GAGCTAGGCAGCCAGATATTAAAGGAACATCCGGTTGAGAACACTCAGCTGCAGAAT GAAAAA
CTGTATCTGTATTATCTTCAGAACGGCCGTGACATGTATGTTGATCAAGAACTGGAT ATCAATCG
CTTGTCCGATTATGACGTGGATCATATTGTTCCGCAAAGCTTTCTGAAAGACGATTC TATTGACA
ATAAAGTACTGACACGTTCGGACAAAAACCGTGGTAAAAGCGATAACGTACCGTCGG AAGAAG
TTGTTAAGAAAATGAAAAATTATTGGCGCCAACTCCTGAATGCTAAATTGATTACCC AGCGGAA
ATTTGATAACTTAACCAAAGCCGAGCGGGGTGGCTTAAGTGAACTGGATAAAGCGGG TTTTATT
AAACGCCAACTGGTAGAAACCCGCCAGATAACGAAACATGTAGCTCAAATCCTCGAT AGTCGC
ATGAATACGAAATATGACGAAAATGATAAATTGATCCGTGAAGTAAAAGTGATTACT CTTAAAA
GCAAATTGGTATCTGATTTTCGGAAAGATTTCCAATTCTATAAGGTGAGAGAAATTA ACAATTA
CCATCATGCACATGATGCGTATTTAAATGCAGTTGTTGGCACCGCCTTAATCAAAAA ATATCCG
AAATTAGAATCTGAGTTCGTGTATGGTGATTATAAAGTTTATGATGTTCGAAAAATG ATTGCTAA
GTCTGAACAGGAAATCGGCAAAGCGACCGCAAAGTATTTTTTTTATAGCAATATTAT GAATTTTT
TTAAAACTGAGATTACCCTGGCGAATGGCGAAATTCGCAAACGTCCTCTGATTGAAA CCAATGG
CGAAACCGGCGAGATAGTATGGGACAAGGGCCGTGATTTTGCGACCGTCCGGAAAGT CCTGTCA
ATGCCGCAGGTGAATATTGTCAAGAAAACAGAAGTTCAGACAGGCGGTTTTAGTAAA GAGTCTA
TTCTGCCCAAACGTAATTCGGATAAATTGATTGCCCGCAAGAAAGATTGGGATCCGA AGAAATA
TGGTGGATTCGATTCTCCGACGGTCGCCTATAGCGTTCTAGTCGTCGCCAAGGTCGA AAAAGGT
AAATCCAAAAAACTGAAATCTGTGAAAGAACTGTTAGGCATTACAATCATGGAACGT AGTAGTT
TTGAAAAGAACCCGATCGACTTCCTCGAGGCGAAAGGCTACAAAGAAGTCAAGAAGG ATTTGA
TTATTAAACTCCCAAAATATTCATTATTTGAGTTAGAAAACGGTAGGAAGCGTATGC TGGCGAG
TGCTGGGGAATTACAGAAAGGGAATGAGTTAGCACTGCCGTCAAAATATGTGAACTT TCTGTAT
CTGGCCTCCCATTACGAGAAACTGAAAGGTAGCCCGGAAGATAATGAACAGAAACAA CTATTT
GTCGAGCAACACAAACATTATCTGGATGAAATTATTGAACAGATTAGTGAATTCTCT AAACGTG
TTATTTTAGCGGATGCCAACCTTGACAAGGTGCTGAGCGCATATAATAAACACCGTG ATAAACC
CATTCGTGAACAGGCTGAAAATATCATACATCTGTTCACGTTAACCAACTTGGGAGC TCCTGCC
GCTTTTAAATATTTCGATACCACAATTGACCGCAAACGTTATACGTCTACAAAAGAG GTGCTCG
ATGCGACCCTGATCCACCAGTCTATTACAGGCCTGTATGAAACTCGTATCGACCTGT CACAACTG
GGCGGCGACTGA
SE ATGGACAAGAAATATTCAATCGGTTTAGCAATAGGAACTAACTCAGTAGGTTGGGCTGTA ATTA
Q CAGACGAATACAAGGTACCGTCCAAAAAGTTTAAGGTGTTGGGGAACACAGATAGACACT CTA
no TAAAAAAAAATTTAATAGGCGCTTTACTTTTCGATTCAGGCGAAACTGCAGAAGCGACAC GTCT
N GAAGAGAACCGCTAGACGTAGATACACGAGGAGAAAGAACAGAATATGTTACCTACAAGA AAT
O: TTTTTCTAATGAGATGGCTAAGGTGGATGATTCGTTTTTTCATAGACTCGAAGAATCTTT CTTAG 16 TTGAAGAAGATAAAAAACACGAAAGGCATCCTATCTTTGGAAACATAGTTGATGAGGTGG CTTA CCATGAAAAATATCCCACTATATATCACCTTAGAAAAAAGTTGGTTGATTCAACCGACAA AGCG
GATCTAAGGTTAATTTACCTCGCGTTGGCTCACATGATAAAATTTAGAGGACATTTC TTGATCGA
AGGTGATTTAAATCCCGATAACTCTGATGTAGATAAACTGTTCATCCAGTTGGTTCA AACATATA
ATCAGTTGTTCGAAGAGAACCCCATTAACGCATCAGGTGTTGATGCTAAAGCAATCT TATCAGC
AAGGTTGAGCAAGAGCAGACGTCTGGAAAACTTGATTGCCCAATTGCCAGGTGAAAA GAAGAA
CGGTCTTTTTGGAAATTTAATTGCACTTTCACTTGGGTTGACACCGAATTTTAAAAG CAATTTCG
ACCTCGCTGAGGATGCTAAACTCCAGTTATCTAAGGATACATATGACGATGATTTGG ATAATCT
ATTGGCCCAGATAGGTGATCAGTATGCAGATTTGTTTTTGGCAGCTAAGAATTTATC AGATGCA
ATTCTACTGAGCGATATTTTAAGGGTGAATACAGAAATAACTAAAGCACCTTTGTCT GCATCTAT
GATAAAAAGATACGATGAACACCATCAAGATCTCACACTATTAAAAGCTTTAGTTAG ACAACAA
TTACCAGAAAAATATAAAGAAATCTTTTTCGATCAGTCCAAGAACGGATACGCCGGC TATATAG
ATGGCGGTGCCTCCCAAGAAGAATTTTACAAATTTATCAAACCCATTTTGGAAAAGA TGGATGG
TACTGAAGAATTATTGGTCAAATTAAACAGGGAAGATTTATTAAGAAAACAAAGGAC CTTTGAT
AATGGTTCTATTCCACACCAAATCCATCTAGGGGAATTACATGCGATTCTTAGAAGA CAAGAAG
ATTTTTATCCATTCTTGAAAGATAACAGGGAAAAGATAGAGAAAATCTTAACTTTTA GAATTCC
CTACTACGTCGGGCCCTTAGCTAGGGGGAATTCTAGATTCGCCTGGATGACACGCAA ATCAGAA
GAAACAATTACGCCTTGGAATTTTGAAGAAGTTGTTGATAAAGGAGCCTCTGCTCAA TCTTTTAT
TGAACGAATGACCAATTTTGATAAGAATTTACCCAATGAAAAGGTCTTACCCAAACA TTCACTC
CTATACGAGTACTTTACTGTTTACAATGAGTTGACAAAAGTGAAGTATGTTACCGAG GGTATGC
GAAAACCTGCTTTCTTGAGTGGTGAACAAAAGAAGGCCATTGTTGACTTGTTATTCA AAACTAA
CAGAAAGGTCACTGTGAAGCAGCTTAAAGAAGATTATTTCAAAAAGATCGAATGTTT CGACTCG
GTAGAAATTAGTGGTGTGGAAGATAGATTTAATGCTTCTCTTGGAACATATCATGAT CTACTAA
AGATCATCAAAGATAAAGATTTCTTGGACAATGAAGAAAATGAAGATATTCTTGAAG ACATCGT
GTTGACACTTACATTGTTTGAGGACAGAGAAATGATTGAAGAAAGGCTGAAGACCTA CGCCCAT
TTGTTTGATGATAAAGTCATGAAACAGTTAAAGAGGAGAAGGTATACCGGATGGGGT AGGCTGT
CTCGCAAATTGATTAATGGTATTCGTGATAAACAATCGGGTAAAACAATCCTAGATT TCCTGAA
GTCCGATGGTTTCGCCAACAGGAATTTTATGCAATTGATTCATGACGATTCTTTGAC TTTTAAAG
AGGATATTCAGAAAGCACAGGTCTCAGGACAGGGCGATTCACTCCATGAACATATAG CTAACCT
GGCTGGCTCCCCTGCTATTAAGAAAGGTATCTTGCAAACCGTCAAAGTAGTAGACGA ACTTGTT
AAAGTTATGGGAAGACACAAACCTGAAAATATCGTTATTGAAATGGCTCGCGAAAAC CAGACA
ACACAAAAGGGTCAAAAGAATTCGAGAGAGAGAATGAAGCGTATCGAAGAAGGTATT AAAGA
ACTTGGGTCCCAAATACTTAAAGAACATCCAGTAGAAAACACTCAGCTTCAAAATGA AAAATTA
TACTTATATTATCTTCAGAATGGCCGCGATATGTATGTTGACCAAGAGTTAGATATA AATAGGTT
GTCTGATTACGACGTGGATCATATTGTACCTCAATCTTTTCTAAAAGATGATTCAAT TGATAATA
AGGTATTAACGAGAAGTGATAAAAATAGAGGTAAATCTGACAACGTGCCAAGCGAAG AGGTGG
TGAAGAAAATGAAAAATTATTGGCGTCAACTGTTGAACGCCAAGTTAATTACGCAGA GAAAGTT
TGATAATCTAACAAAAGCTGAAAGAGGAGGCCTATCTGAGTTAGATAAGGCCGGTTT TATCAAA
CGTCAGTTAGTTGAAACCAGGCAAATCACGAAGCACGTTGCCCAAATTCTAGATTCA AGGATGA
ATACCAAATACGATGAAAACGATAAACTGATTCGGGAAGTCAAGGTTATAACTCTAA AAAGCA
AACTAGTTTCAGATTTTCGCAAAGATTTTCAATTTTACAAAGTTCGAGAAATCAATA ATTATCAT
CATGCTCACGACGCGTACTTGAACGCGGTCGTTGGTACAGCTTTAATAAAGAAATAT CCTAAAC
TGGAATCGGAATTTGTATATGGGGATTACAAAGTATACGACGTGAGAAAGATGATCG CTAAATC TGAACAAGAAATTGGGAAAGCAACTGCCAAATATTTTTTTTACAGCAACATAATGAATTT TTTTA
AAACGGAAATTACATTGGCAAATGGCGAAATTAGAAAGCGCCCATTGATAGAGACCA ATGGAG
AGACTGGGGAAATCGTGTGGGATAAAGGACGTGATTTTGCCACAGTGAGGAAAGTGT TAAGTA
TGCCACAAGTTAATATTGTAAAAAAGACCGAGGTCCAAACGGGTGGATTTAGCAAAG AATCAA
TTTTACCTAAGAGAAATTCAGATAAATTAATTGCCCGCAAAAAGGATTGGGATCCTA AAAAATA
TGGTGGTTTTGATTCCCCAACAGTTGCTTACTCCGTCCTAGTTGTTGCTAAGGTTGA AAAAGGAA
AGTCTAAGAAACTTAAATCCGTAAAAGAGTTACTGGGAATTACAATAATGGAAAGAT CCTCTTT
CGAAAAGAACCCTATTGACTTCTTGGAGGCGAAAGGTTATAAAGAAGTCAAAAAAGA TTTGATC
ATAAAACTACCAAAGTATTCTCTATTTGAATTGGAAAACGGCAGAAAAAGGATGTTG GCAAGCG
CTGGTGAACTACAAAAGGGTAACGAATTGGCATTGCCGAGTAAATACGTGAATTTTC TATATTT
GGCATCACATTACGAAAAGTTAAAGGGATCACCCGAGGATAACGAGCAGAAACAACT GTTTGT
TGAACAACACAAACATTATCTTGATGAAATTATAGAACAAATTAGTGAGTTCAGTAA GAGAGTT
ATTTTAGCCGATGCAAATTTAGACAAAGTTTTATCTGCTTATAACAAACATAGAGAT AAGCCTAT
AAGGGAACAAGCCGAAAATATTATTCATTTGTTTACGTTAACAAATTTAGGGGCACC AGCAGCA
TTCAAGTACTTCGATACGACTATCGATCGTAAGCGTTACACATCTACCAAAGAAGTT CTTGATGC
AACTTTGATTCATCAATCTATAACAGGCTTATATGAAACTAGAATCGATCTGTCACA ACTTGGTG
GTGACTAA
SE ATGGACAAGAAGTACTCAATTGGGCTTGCTATCGGCACTAACAGCGTTGGCTGGGCGGTC ATCA
Q CAGACGAATATAAGGTCCCATCAAAGAAATTCAAAGTCCTTGGCAATACGGACCGACATT CAAT
no CAAGAAGAACCTGATTGGAGCTCTGCTGTTTGATTCCGGTGAAACCGCCGAGGCAACACG ATTG
N AAACGTACCGCTCGTAGGAGGTATACGCGGCGGAAAAATAGGATCTGCTATCTGCAGGAA ATA
O: TTTAGCAACGAAATGGCCAAGGTAGACGACAGCTTCTTCCACCGGCTCGAGGAATCTTTC CTCG 17 TGGAAGAAGACAAAAAGCACGAGCGCCACCCCATTTTCGGCAATATCGTGGACGAGGTAG CTT 0 ACCATGAAAAGTATCCAACTATTTACCACTTACGTAAGAAGTTAGTGGACAGCACCGATA AAGC
CGACCTTCGCCTGATTTACCTAGCACTTGCACACATGATTAAGTTCCGAGGCCACTT CTTGATAG
AGGGAGACCTGAATCCTGACAATTCCGATGTGGATAAATTGTTCATCCAGCTGGTAC AGACATA
CAATCAGTTGTTTGAGGAAAATCCGATTAATGCCAGTGGCGTGGACGCCAAGGCTAT CCTGTCT
GCTCGGCTTAGTAAGAGTAGACGCCTGGAAAATCTAATCGCACAGCTGCCCGGCGAA AAGAAA
AATGGACTGTTCGGTAATTTGATCGCCCTGAGCCTGGGCCTCACCCCTAACTTTAAG TCTAACTT
CGACCTGGCCGAAGATGCTAAGCTCCAGCTGTCCAAAGATACTTACGATGACGATCT CGATAAT
CTACTGGCTCAGATCGGGGACCAGTACGCTGACCTGTTTCTAGCTGCCAAGAACCTC AGTGACG
CCATTCTCCTGTCCGATATTCTGAGGGTTAACACTGAAATTACAAAGGCCCCGCTGA GCGCGAG
CATGATCAAAAGGTACGACGAGCATCACCAGGACCTCACGCTGCTGAAGGCCTTAGT CAGACA
GCAACTGCCCGAAAAGTACAAAGAAATCTTTTTCGACCAATCCAAGAACGGGTACGC CGGCTAC
ATTGATGGCGGGGCTTCACAAGAGGAGTTTTACAAGTTTATCAAGCCCATCCTGGAG AAAATGG
ACGGCACTGAAGAACTGCTTGTGAAACTCAATAGGGAAGACTTACTGAGGAAACAGC GCACAT
TCGATAATGGCTCCATACCCCACCAAATCCATCTGGGAGAGTTGCATGCCATCTTGC GAAGGCA
GGAGGACTTCTACCCCTTTCTTAAGGACAACAGGGAGAAAATCGAGAAAATTCTGAC TTTCCGT
ATCCCCTACTACGTGGGCCCACTTGCTCGCGGAAACTCACGATTCGCATGGATGACC AGAAAGT
CCGAGGAAACAATTACACCCTGGAATTTTGAGGAGGTAGTAGACAAGGGAGCCAGCG CTCAAT
CTTTCATTGAGAGGATGACGAATTTCGACAAGAACCTTCCAAACGAGAAAGTGCTTC CTAAGCA
CAGCCTGCTGTATGAGTATTTCACGGTGTACAACGAACTTACGAAGGTCAAGTATGT GACAGAG GGTATGCGGAAACCTGCTTTTCTGTCTGGTGAACAGAAGAAAGCTATCGTCGATCTCCTG TTTAA
AACCAACCGAAAGGTGACGGTGAAACAGTTGAAGGAGGATTACTTCAAGAAGATCGA GTGTTT
TGATTCTGTTGAAATTTCTGGGGTCGAGGATAGATTCAACGCCAGCCTGGGCACCTA CCATGATT
TGCTGAAGATTATCAAGGATAAGGATTTTCTGGATAATGAGGAGAATGAAGACATTT TGGAGGA
TATAGTGCTGACCCTCACCCTGTTCGAGGACCGGGAGATGATCGAGGAGAGACTGAA AACATAC
GCTCACCTGTTTGACGACAAGGTCATGAAGCAGCTTAAGAGACGCCGTTACACAGGC TGGGGAA
GATTATCCCGCAAATTAATCAACGGGATACGCGATAAACAAAGTGGCAAGACCATAC TCGACTT
CCTAAAGAGCGATGGATTCGCAAATCGCAATTTCATGCAGTTGATCCACGACGATAG CCTGACC
TTCAAAGAGGACATTCAGAAAGCGCAGGTGAGTGGTCAAGGGGATTCCCTGCACGAA CACATT
GCTAACTTGGCTGGATCACCAGCCATTAAGAAAGGCATACTGCAGACCGTTAAAGTG GTAGATG
AGCTTGTGAAAGTCATGGGAAGACATAAGCCAGAGAACATAGTGATCGAAATGGCCA GGGAAA
ATCAGACCACGCAAAAGGGGCAGAAGAACTCAAGAGAGCGTATGAAGAGGATCGAGG AGGGC
ATCAAGGAGCTGGGTAGCCAGATCCTTAAAGAGCACCCAGTTGAGAATACCCAGCTG CAGAAT
GAGAAACTTTATCTCTATTATCTCCAGAACGGAAGGGATATGTATGTCGACCAGGAA CTGGACA
TCAATCGGCTGAGTGATTATGACGTCGACCACATTGTGCCTCAAAGCTTTCTGAAGG ATGATTCC
ATCGACAATAAAGTTCTGACCCGGTCTGATAAAAATAGAGGCAAATCCGACAACGTA CCTAGCG
AAGAAGTCGTCAAAAAAATGAAGAACTATTGGAGGCAGTTGCTGAATGCCAAGCTGA TTACAC
AACGCAAGTTTGACAATCTCACCAAGGCAGAAAGGGGGGGCCTGTCAGAACTCGACA AAGCAG
GTTTCATTAAAAGGCAGCTAGTTGAAACTAGGCAGATTACTAAGCACGTGGCCCAGA TCCTCGA
CTCACGGATGAATACAAAGTATGATGAGAATGATAAGCTAATCCGGGAGGTGAAGGT GATTAC
TCTGAAATCTAAGCTGGTGTCAGATTTCAGAAAAGACTTCCAGTTCTACAAAGTCAG AGAGATC
AACAATTATCACCATGCCCACGATGCATATCTTAATGCAGTAGTGGGGACAGCTCTG ATCAAAA
AATATCCTAAACTGGAGTCTGAATTCGTTTATGGTGACTATAAAGTCTATGACGTCA GAAAAAT
GATCGCAAAGAGCGAGCAGGAGATAGGGAAGGCCACAGCAAAGTACTTCTTTTACAG TAATAT
GAGACTAACGGAGAGACAGGGGAGATTGTTTGGGATAAGGGCCGTGACTTCGCCACC GTTAGG
AAAGTGCTGTCCATGCCCCAGGTGAACATTGTGAAGAAGACAGAAGTGCAGACGGGT GGGTTC
TCAAAAGAGTCTATTCTGCCTAAGCGGAATAGTGACAAACTGATCGCACGTAAAAAG GACTGG
GATCCAAAAAAGTACGGCGGATTCGACAGTCCTACCGTTGCATATTCCGTGCTTGTG GTCGCTA
AGGTGGAGAAGGGAAAAAGCAAGAAACTGAAGTCAGTCAAAGAACTACTGGGCATAA CGATC
ATGGAGCGCTCCAGTTTCGAAAAAAACCCAATCGATTTTCTTGAAGCCAAGGGATAC AAGGAGG
TAAAGAAAGACCTTATCATTAAGCTGCCTAAGTACAGTCTGTTCGAACTGGAGAATG GGAGGAA
GCGCATGCTGGCATCAGCTGGAGAACTCCAAAAAGGGAACGAGTTGGCCCTCCCCTC AAAGTAT
GTCAATTTTCTCTACCTGGCTTCTCACTACGAGAAGTTAAAGGGGTCTCCAGAGGAT AATGAGC
AGAAACAGCTGTTTGTGGAACAGCACAAGCACTATTTGGACGAAATCATCGAACAAA TTTCCGA
GTTCAGTAAGAGGGTGATTCTGGCCGACGCAAACCTTGACAAAGTTCTGTCCGCATA CAATAAG
CACAGAGACAAACCAATCCGCGAGCAAGCCGAGAATATAATTCACCTTTTCACTCTG ACTAATC
TGGGGGCCCCCGCAGCATTTAAATATTTCGATACAACAATCGACCGGAAGCGGTATA CATCTAC
TAAGGAAGTCCTCGATGCGACACTGATCCACCAGTCAATTACAGGTTTATATGAAAC AAGAATC
GACCTGTCCCAGCTGGGCGGCGACTAG
SE AAAATTCcatGCAAAATGCTCCGGTTTCATGTCATCAAAATGATGACGTAATTAAGCATT GATAAT
Q TGAGATCCCTCTCCCTGACAGGATGATTACATAAATAATAGTGACAAAAATAAATTATTT ATTTA E ) TCCAGAAAATGAATTGGAAAATCAGGAGAGCGTTTTCAATCCTACCTCTGGCGCAGTTGA TATG N TcaaaCAGGTtgccgtcactgcgtcttttactggctcttctcgctaaccaaaccggtaac cccgcttattaaaagcattctgtaacaaagcgggaccaaagc O: catgacaaaaacgcgtaacaaaagtgtctataatcacggcagaaaagtccacattgatta tttgcacggcgtcacactttgctatgccatagcatttttatccataa 17 gattagcggatcctacctgacgctttttatcgcaactctctactgtttctccatacccgt ttttttgggctagcaccgcctatctcgtgtgagataggcggagatacga 1 actttaagAAGGAGatataccATGGAACAGGAATATTATCTGGGCTTGGACATGGGCACC GGTTCCGTCG GCTGGGCTGTTACTGACAGTGAATATCACGTTCTAAGAAAGCATGGTAAGGCATTGTGGG GTGT AAGACTTTTCGAATCTGCTTCCACTGCTGAAGAGCGTAGAATGTTTAGAACGAGTCGACG TAGG CTAGACAGGCGCAATTGGAGAATCGAAATTTTACAAGAAATTTTTGCGGAAGAGATATCT AAGA AAGACCCAGGCTTTTTCCTGAGAATGAAGGAATCTAAGTATTACCCTGAGGATAAAAGAG ATAT AAATGGTAACTGTCCCGAATTGCCTTACGCATTATTTGTGGACGATGATTTTACCGATAA GGATT ACCATAAAAAGTTCCCAACTATCTACCATTTACGCAAAATGTTAATGAATACAGAGGAAA CCCC AGACATAAGACTAGTTTATCTGGCAATACACCATATGATGAAACATAGAGGCCATTTCTT ACTTT CCGGGGATATCAACGAAATCAAAGAGTTTGGTACCACATTTAGTAAGTTACTGGAAAACA TAAA GAATGAAGAATTGGATTGGAACTTAGAACTCGGAAAAGAAGAATACGCGGTTGTCGAATC TAT CCTGAAGGATAATATGCTGAATAGGTCGACCAAAAAAACTAGGCTGATCAAAGCACTGAA AGC CAAATCTATCTGCGAAAAAGCTGTTTTAAATTTACTTGCTGGTGGCACTGTTAAGTTATC AGACA TTTTTGGTTTGGAAGAATTGAACGAAACCGAGCGTCCAAAAATTAGTTTCGCTGATAATG GCTA CGATGATTACATTGGTGAGGTGGAAAACGAGTTGGGCGAACAATTTTATATTATAGAGAC AGCT AAGGCAGTCTATGACTGGGCTGTTTTAGTAGAAATCCTTGGTAAATACACATCTATCTCC GAAG CGAAAGTTGCTACTTACGAAAAGCACAAGTCCGATCTCCAGTTTTTGAAGAAAATTGTCA GGAA ATATCTGACTAAGGAAGAATATAAAGATATTTTCGTTAGTACCTCTGACAAACTGAAAAA TTAC TCCGCTTACATCGGGATGACCAAGATTAATGGCAAAAAAGTTGATCTGCAAAGCAAAAGG TGTT CGAAGGAAGAATTTTATGATTTCATTAAAAAGAATGTCTTAAAAAAATTAGAAGGTCAGC CAGA ATACGAATATTTGAAAGAAGAACTGGAAAGAGAGACATTCTTACCAAAACAAGTCAACAG AGA TAATGGGGTAATTCCATATCAAATTCACCTCTACGAATTAAAAAAAATTTTAGGCAATTT ACGC GATAAAATTGACCTTATCAAAGAAAATGAGGATAAGCTGGTTCAACTCTTTGAATTCAGA ATAC CCTATTATGTGGGCCCACTGAACAAGATTGATGACGGCAAAGAAGGTAAATTCACATGGG CCGT CCGCAAATCCAATGAAAAAATTTACCCATGGAACTTTGAAAATGTAGTAGATATTGAAGC GTCT GCGGAGAAATTTATTCGAAGAATGACTAATAAATGCACTTACTTGATGGGAGAGGATGTT CTGC CTAAAGACAGCTTATTATACAGCAAGTACATGGTTCTAAACGAACTTAACAACGTTAAGT TGGA CGGTGAGAAATTAAGTGTAGAATTGAAACAAAGATTGTATACTGACGTCTTCTGCAAGTA CAGA AAAGTGACAGTTAAAAAAATTAAGAATTACTTGAAGTGCGAAGGTATAATTTCTGGAAAC GTAG AGATTACTGGTATTGATGGTGATTTCAAAGCATCCCTAACAGCTTACCACGATTTCAAGG AAAT CCTGACAGGAACTGAACTCGCAAAAAAAGATAAAGAAAACATTATTACTAATATTGTTCT TTTC GGTGATGACAAGAAATTGTTGAAGAAAAGACTGAATAGACTTTACCCCCAGATTACTCCC AATC AACTTAAGAAAATTTGTGCTTTGTCTTACACAGGATGGGGTCGTTTTTCAAAAAAGTTCT TAGAA GAGATTACCGCACCTGATCCAGAAACAGGCGAAGTATGGAATATAATTACCGCCTTATGG GAAT CGAACAATAATCTTATGCAACTTCTGAGCAATGAATATCGTTTCATGGAAGAAGTTGAGA CTTA CAACATGGGCAAACAGACGAAGACTTTATCCTATGAAACTGTGGAAAATATGTATGTATC ACCT TCTGTCAAGAGACAAATTTGGCAAACCTTAAAAATTGTCAAAGAATTAGAAAAGGTAATG AAG GAGTCTCCTAAACGTGTGTTTATTGAAATGGCTAGAGAAAAACAAGAGTCAAAAAGAACC GAG TCAAGAAAGAAGCAGTTAATCGATTTATATAAGGCTTGTAAAAACGAAGAGAAAGATTGG GTT AAAGAATTGGGGGACCAAGAGGAACAAAAACTACGGTCGGATAAGTTGTATTTATACTAT ACG
CAAAAGGGACGATGTATGTATTCCGGCGAGGTAATAGAATTGAAGGATTTATGGGAC AATACA
AAATATGACATAGACCATATATATCCCCAATCAAAAACGATGGACGATAGCTTGAAC AATAGA
GTACTCGTGAAAAAAAAATATAATGCGACCAAATCTGATAAGTATCCTCTGAATGAA AATATCA
GACATGAAAGAAAGGGGTTCTGGAAGTCCTTGTTAGATGGTGGGTTTATAAGCAAAG AAAAGT
ACGAGCGTCTAATAAGAAACACGGAGTTATCGCCAGAAGAACTCGCTGGTTTTATTG AGAGGCA
AATCGTGGAAACGAGACAATCTACCAAAGCCGTTGCTGAGATCCTAAAGCAAGTTTT CCCAGAG
TCGGAGATTGTCTATGTCAAAGCTGGCACAGTGAGCAGGTTTAGGAAAGACTTCGAA CTATTAA
AGGTAAGAGAAGTGAACGATTTACATCACGCAAAGGACGCTTACCTAAATATCGTTG TAGGTAA
CTCATATTATGTTAAATTTACCAAGAACGCCTCTTGGTTTATAAAGGAGAACCCAGG TAGAACA
TATAACCTGAAAAAGATGTTCACCTCTGGTTGGAATATTGAGAGAAACGGAGAAGTC GCATGGG
AAGTTGGTAAGAAAGGGACTATAGTGACAGTAAAGCAAATTATGAACAAAAATAATA TCCTCG
TTACAAGGCAGGTTCATGAAGCAAAGGGCGGCCTTTTTGACCAACAAATTATGAAGA AAGGGA
AAGGTCAAATTGCAATAAAAGAAACCGATGAGAGACTAGCGTCAATAGAAAAGTATG GTGGCT
ATAATAAAGCTGCGGGTGCATACTTTATGCTTGTTGAATCAAAAGACAAGAAAGGTA AGACTAT
TAGAACTATAGAATTTATACCCCTGTACCTTAAAAACAAAATTGAATCGGATGAGTC AATCGCG
TTAAATTTTCTAGAGAAAGGAAGGGGTTTAAAAGAACCAAAGATCCTGTTAAAAAAG ATTAAG
ATTGACACCTTGTTCGATGTAGATGGATTTAAAATGTGGTTATCTGGCAGAACAGGC GATAGAC
TTTTGTTTAAGTGCGCTAATCAATTAATTTTGGATGAGAAAATCATTGTCACAATGA AAAAAATA
GTTAAGTTTATTCAGAGAAGACAAGAAAACAGGGAGTTGAAATTATCTGATAAAGAT GGTATCG
ACAATGAAGTTTTAATGGAAATCTACAATACATTCGTTGATAAACTTGAAAATACCG TATATCG
AATCAGGTTAAGTGAACAAGCCAAAACATTAATTGATAAACAAAAAGAATTTGAAAG GCTATC
ACTGGAAGACAAATCCTCCACCCTATTTGAAATTTTGCATATATTCCAGTGCCAATC TTCAGCAG
CTAATTTAAAAATGATTGGCGGACCTGGGAAAGCCGGCATCCTAGTGATGAACAATA ATATCTC
CAAGTGTAACAAAATATCAATTATTAACCAATCTCCGACAGGTATTTTTGAAAATGA AATAGAC
TTGCTTAAGATATAAGAAATCATCCTTAGCGAAAGCTAAGGATTTTTTTTATCTGAA ATTTATTA
TATCGCGTTGATTATTGATGCTGTTTTTAGTTTTAACGGCAATTAATATATGTGTTA TTAATTGAA
TGAATTTTATCATTCATAATAAGTATGTGTAGGATCAAGCTCAGGTTAAATATTCAC TCAGGAAG
TTATTACTCAGGAAGCAAAGAGGATTACAGAATTATCTCATAACAAGTGTTAAGGGA TGTTATT
TCC
SE AATTCAAAGGATAATCAAAC
Q
no
N
O:
17
2
SE AATCTCTACTCTTTGTAGAT
Q
no
N
O: 17
3
SE AATTTCTACTGTTGTAGAT
Q
no
N
0:
17
4
SE AATTTCTACTAGTGTAGAT
Q
ID
N
0:
17
5
SE AATTTCTACTATTGT
Q
ID
N
0:
17
6
SE AATTTCTACTGTTGTAGA
Q
ID
N
0:
17
7
SE AATTTCTACTATTGTA
Q
ID
N
0:
17
8
SE AATTTCTACTTTTGTAGAT
Q
ID
N
0: 17
9
SE AATTTCTACTGTTGTAGAT
Q
no
N
0:
18
0
SE AATTTCTACTCTTGTAGAT
Q
ID
N
0:
18
1