Annotation of the Drosophila melanogastereuchromatic genome: a systematic review
Tóm tắt
The recent completion of the Drosophila melanogaster genomic sequence to high quality and the availability of a greatly expanded set of Drosophila cDNA sequences, aligning to 78% of the predicted euchromatic genes, afforded FlyBase the opportunity to significantly improve genomic annotations. We made the annotation process more rigorous by inspecting each gene visually, utilizing a comprehensive set of curation rules, requiring traceable evidence for each gene model, and comparing each predicted peptide to SWISS-PROT and TrEMBL sequences. Although the number of predicted protein-coding genes in Drosophila remains essentially unchanged, the revised annotation significantly improves gene models, resulting in structural changes to 85% of the transcripts and 45% of the predicted proteins. We annotated transposable elements and non-protein-coding RNAs as new features, and extended the annotation of untranslated (UTR) sequences and alternative transcripts to include more than 70% and 20% of genes, respectively. Finally, cDNA sequence provided evidence for dicistronic transcripts, neighboring genes with overlapping UTRs on the same DNA sequence strand, alternatively spliced genes that encode distinct, non-overlapping peptides, and numerous nested genes. Identification of so many unusual gene models not only suggests that some mechanisms for gene regulation are more prevalent than previously believed, but also underscores the complex challenges of eukaryotic gene prediction. At present, experimental data and human curation remain essential to generate high-quality genome annotations.
Tài liệu tham khảo
The FlyBase Consortium: The FlyBase database of the Drosophila genome projects and community literature. Nucleic Acids Res. 2002, 30: 106-108. 10.1093/nar/30.1.106.
FlyBase: a database of the Drosophila Genome. [http://www.flybase.org]
Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA, Galle RF, et al: The genome sequence of Drosophila melanogaster. Science. 2000, 287: 2185-2195. 10.1126/science.287.5461.2185.
Rubin GM, Yandell MD, Wortman JR, Gabor Miklos GL, Nelson CR, Hariharan IK, Fortini ME, Li PW, Apweiler R, Fleischmann W, et al: Comparative genomics of the eukaryotes. Science. 2000, 287: 2204-2215. 10.1126/science.287.5461.2204.
Rubin GM, Hong L, Brokstein P, Evans-Holm M, Frise E, Stapleton M, Harvey DA: A Drosophila complementary DNA resource. Science. 2000, 287: 2222-2224. 10.1126/science.287.5461.2222.
Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Rapp BA, Wheeler DL: GenBank. Nucleic Acids Res. 2002, 30: 17-20. 10.1093/nar/30.1.17.
GenBank via ftp. [http://www.ncbi.nlm.nih.gov/Genbank/GenBankFtp.html]
Stoesser G, Baker W, van den Broek A, Camon E, Garcia-Pastor M, Kanz C, Kulikova T, Leinonen R, Lin Q, Lombard V, et al: The EMBL nucleotide sequence database. Nucleic Acids Res. 2002, 30: 21-26. 10.1093/nar/30.1.21.
EMBL nucleotide sequence database. [http://www.ebi.ac.uk/embl]
Tateno Y, Imanishi T, Miyazaki S, Fukami-Kobayashi K, Saitou N, Sugawara H, Gojobori T: DNA Data Bank of Japan (DDBJ) for genome scale research in life science. Nucleic Acids Res. 2002, 30: 27-30. 10.1093/nar/30.1.27.
DDBJ DNA Databank of Japan. [http://www.ddbj.nig.ac.jp]
Mungall CJ, Misra S, Berman BP, Carlson J, Frise E, Harris N, Marshall B, Shu S, Kaminker JS, Prochnik SE, et al: An integrated computational pipeline and database to support whole-genome sequence annotation. Genome Biol. 2002, 3: research0081.1-0081.11. 10.1186/gb-2002-3-12-research0081.
Bairoch A, Apweiler R: The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000. Nucleic Acids Res. 2000, 28: 45-48. 10.1093/nar/28.1.45.
Karlin S, Bergman A, Gentles AJ: Genomics. Annotation of the Drosophila genome. Nature. 2001, 411: 259-260. 10.1038/35077152.
Gopal S, Schroeder M, Pieper U, Sczyrba A, Aytekin-Kurban G, Bekiranov S, Fajardo JE, Eswar N, Sanchez R, Sali A, et al: Homology-based annotation yields 1,042 new candidate genes in the Drosophila melanogaster genome. Nat Genet. 2001, 27: 337-340. 10.1038/85922.
Andrews J, Bouffard GG, Cheadle C, Lu J, Becker KG, Oliver B: Gene discovery using computational and microarray analysis of transcription in the Drosophila melanogaster testis. Genome Res. 2000, 10: 2030-2043. 10.1101/gr.10.12.2030.
Celniker SE, Wheeler DA, Kronmiller B, Carlson JW, Halpern A, Patel S, Adams M, Champe M, Dugan SP, Frise E, et al: Finishing a whole-genome shotgun: Release 3 of the Drosophila euchromatic genome sequence. Genome Biol. 2002, 3: research0079.1-0079.14. 10.1186/gb-2002-3-12-research0079.
Kaminker JS, Bergman CM, Kronmiller B, Carlson J, Svirskas R, Patel S, Frise E, Wheeler DA, Lewis SE, Rubin GM, et al: The transposable elements of the Drosophila melanogaster euchromatin - a genomics perspective. Genome Biol. 2002, 3: research0084.1-0084.20. 10.1186/gb-2002-3-12-research0084.
Lewis SE, Searle SMJ, Harris N, Gibson M, Iyer V, Richter J, Wiel C, Bayraktaroglu L, Birney E, Crosby L, et al: Apollo: a sequence annotation editor. Genome Biol. 2002, 3: research0082.1-0082.14. 10.1186/gb-2002-3-12-research0082.
Reese MG, Kulp D, Tammana H, Haussler D: Genie - gene finding in Drosophila melanogaster. Genome Res. 2000, 10: 529-538. 10.1101/gr.10.4.529.
Burge C, Karlin S: Prediction of complete gene structures in human genomic DNA. J Mol Biol. 1997, 268: 78-94. 10.1006/jmbi.1997.0951.
Wu-BLAST. [http://blast.wustl.edu]
Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ: Basic local alignment search tool. J Mol Biol. 1990, 215: 403-410. 10.1006/jmbi.1990.9999.
Florea L, Hartzell G, Zhang Z, Rubin GM, Miller W: A computer program for aligning a cDNA sequence with a genomic DNA sequence. Genome Res. 1998, 8: 967-974.
Hoskins RA, Smith CD, Carlson JW, Carvalho AB, Halpern A, Kaminker JS, Kennedy C, Mungall CJ, Sullivan BA, Sutton GG, et al: Heterochromatic sequences in a Drosophila whole-genome shotgun assembly. Genome Biol. 2002, 3: research0085.1-0085.16. 10.1186/gb-2002-3-12-research0085.
The C. elegans Sequencing Consortium: Genome sequence of the nematode C. elegans: a platform for investigating biology. Science. 1998, 282: 2012-2018. 10.1126/science.282.5396.2012.
Lin X, Kaul S, Rounsley S, Shea TP, Benito MI, Town CD, Fujii CY, Mason T, Bowman CL, Barnstead M, et al: Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana. Nature. 1999, 402: 761-768. 10.1038/45471.
Ensembl human genome browser. [http://www.ensembl.org/Homo_sapiens]
Stapleton M, Liao G, Brokstein P, Hong L, Carninci P, Shiraki T, Hayashizaki Y, Champe M, Pacleb J, Wan K, et al: The Drosophila gene collection: identification of putative full-length cDNAs for 70% of D. melanogaster genes. Genome Res. 2002, 12: 1294-1300. 10.1101/gr.269102.
Stapleton M, Carlson J, Brokstein J, Yu C, Champe M, George R, Guarin H, Kronmiller B, Pacleb J, Park S, et al: A Drosophila full-length cDNA resource. Genome Biol. 2002, 3: research0080.1-0080.8. 10.1186/gb-2002-3-12-research0080.
Wilkin MB, Becker MN, Mulvey D, Phan I, Chao A, Cooper K, Chung HJ, Campbell ID, MacIntyre M, Macintyre R: Drosophila dumpy is a gigantic extracellular protein required to maintain tension at epidermalcuticle attachment sites. Curr Biol. 2000, 10: 559-567. 10.1016/S0960-9822(00)00482-6.
Lowe TM, Eddy SR: tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res. 1997, 25: 955-964. 10.1093/nar/25.5.955.
Wooley JC, Cone RD, Tartof D, Chung SY: Small nuclear ribonucleoprotein complexes of Drosophila melanogaster. Proc Natl Acad Sci USA. 1982, 79: 6762-6766. 10.1073/pnas.79.22.6762.
Tycowski KT, Steitz JA: Non-coding snoRNA host genes in Drosophila: expression strategies for modification guide snoRNAs. Eur J Cell Biol. 2001, 80: 119-125. 10.1078/0171-9335-00150.
Lowe TM, Eddy SR: A computational screen for methylation guide snoRNAs in yeast. Science. 1999, 283: 1168-1171. 10.1126/science.283.5405.1168.
Shendure J, Church GM: Computational discovery of sense-antisense transcription in the human and mouse genomes. Genome Biol. 2002, 3: research0044.1-0044.14. 10.1186/gb-2002-3-9-research0044.
Echols N, Harrison P, Balasubramanian S, Luscombe NM, Bertone P, Zhang Z, Gerstein M: Comprehensive analysis of amino acid and nucleotide composition in eukaryotic genomes, comparing genes and pseudogenes. Nucleic Acids Res. 2002, 30: 2515-2523. 10.1093/nar/30.11.2515.
Mounsey A, Bauer P, Hope IA: Evidence suggesting that a fifth of annotated Caenorhabditis elegans genes may be pseudogenes. Genome Res. 2002, 12: 770-775. 10.1101/gr208802. Article published online before print in April 2002.
Stein L, Sternberg P, Durbin R, Thierry-Mieg J, Spieth J: WormBase: network access to the genome and biology of Caenorhabditis elegans. Nucleic Acids Res. 2001, 29: 82-86. 10.1093/nar/29.1.82.
WormBase, The Genome and Biology of C. elegans, Release WS88. [http://www.wormbase.org]
Gu Z, Cavalcanti A, Chen FC, Bouman P, Li WH: Extent of gene duplication in the genomes of Drosophila, nematode, and yeast. Mol Biol Evol. 2002, 19: 256-262.
De Gregorio E, Spellman PT, Rubin GM, Lemaitre B: Genome-wide analysis of the Drosophila immune response by using oligonucleotide microarrays. Proc Natl Acad Sci USA. 2001, 98: 12590-12595. 10.1073/pnas.221458698.
Krauss V, Reuter G: Two genes become one: the genes encoding heterochromatin protein Su(var)3-9 and translation initiation factor subunit eIF-2gamma are joined to a dicistronic unit in holometabolic insects. Genetics. 2000, 156: 1157-1167.
Ashburner M, Misra S, Roote J, Lewis SE, Blazej R, Davis T, Doyle C, Galle R, George R, Harris N, et al: An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region. Genetics. 1999, 153: 179-219.
Spencer CA, Gietz RD, Hodgetts RB: Overlapping transcription units in the dopa decarboxylase region of Drosophila . Nature. 1986, 322: 279-281. 10.1038/322279a0.
Kumar M, Carmichael GG: Antisense RNA: function and fate of duplex RNA in cells of higher eukaryotes. Microbiol Mol Biol Rev. 1998, 62: 1415-1434.
Vanhee-Brossollet C, Vaquero C: Do natural antisense transcripts make sense in eukaryotes?. Gene. 1998, 211: 1-9. 10.1016/S0378-1119(98)00093-6.
Labrador M, Mongelard F, Plata-Rengifo P, Baxter EM, Corces VG, Gerasimova TI: Protein encoding by both DNA strands. Nature. 2001, 409: 1000-10.1038/35059000.
Dorn R, Reuter G, Loewendorf A: Transgene analysis proves mRNA trans-splicing at the complex mod(mdg4) locus in Drosophila. Proc Natl Acad Sci USA. 2001, 98: 9724-9729. 10.1073/pnas.151268698.
Giniger E, Tietje K, Jan LY, Jan YN: lola encodes a putative transcription factor required for axon growth and guidance in Drosophila. Development. 1994, 120: 1385-1398.
Read D, Butte MJ, Dernburg AF, Frasch M, Kornberg TB: Functional studies of the BTB domain in the Drosophila GAGA and Mod(mdg4) proteins. Nucleic Acids Res. 2000, 28: 3864-3870. 10.1093/nar/28.20.3864.
Bell AC, West AG, Felsenfeld G: Insulators and boundaries: versatile regulatory elements in the eukaryotic genome. Science. 2001, 291: 447-450. 10.1126/science.291.5503.447.
Harvey AJ, Bidwai AP, Miller LK: Doom, a product of the Drosophila mod(mdg4) gene, induces apoptosis and binds to baculovirus inhibitor-of-apoptosis proteins. Mol Cell Biol. 1997, 17: 2835-2843.
Pauli D, Tonka CH, Ayme-Southgate A: An unusual split Drosophila heat shock gene expressed during embryogenesis, pupation and in testis. J Mol Biol. 1988, 200: 47-53. 10.1016/0022-2836(88)90332-4.
Schulz RA, Miksch JL, Xie XL, Cornish JA, Galewsky S: Expression of the Drosophila gonadal gene: alternative promoters control the germ-line expression of monocistronic and bicistronic gene transcripts. Development. 1990, 108: 613-622.
Andrews J, Smith M, Merakovsky J, Coulson M, Hannan F, Kelly LE: The stoned locus of Drosophila melanogaster produces a dicistronic transcript and encodes two distinct polypeptides. Genetics. 1996, 143: 1699-1711.
Brogna S, Ashburner M: The Adh-related gene of Drosophila melanogaster is expressed as a functional dicistronic messenger RNA: multigenic transcription in higher organisms. EMBO J. 1997, 16: 2023-2031. 10.1093/emboj/16.8.2023.
Niimi T, Yokoyama H, Goto A, Beck K, Kitagawa Y: A Drosophila gene encoding multiple splice variants of Kazal-type serine protease inhibitor-like proteins with potential destinations of mitochondria, cytosol and the secretory pathway. Eur J Biochem. 1999, 266: 282-292. 10.1046/j.1432-1327.1999.00873.x.
Gray TA, Nicholls RD: Diverse splicing mechanisms fuse the evolutionarily conserved bicistronic MOCS1A and MOCS1B open reading frames. RNA. 2000, 6: 928-936. 10.1017/S1355838200000182.
Liu H, Jang JK, Graham J, Nycz K, McKim KS: Two genes required for meiotic recombination in Drosophila are expressed from a dicistronic message. Genetics. 2000, 154: 1735-1746.
Walker DL, Wang D, Jin Y, Rath U, Wang Y, Johansen J, Johansen KM: Skeletor, a novel chromosomal protein that redistributes during mitosis provides evidence for the formation of a spindle matrix. J Cell Biol. 2000, 151: 1401-1412. 10.1083/jcb.151.7.1401.
Levine F, Yee JK, Friedmann T: Efficient gene expression in mammalian cells from a dicistronic transcriptional unit in an improved retroviral vector. Gene. 1991, 108: 167-174. 10.1016/0378-1119(91)90431-A.
Peabody DS, Berg P: Termination-reinitiation occurs in the translation of mammalian cell mRNAs. Mol Cell Biol. 1986, 6: 2695-2703.
Oh SK, Scott MP, Sarnow P: Homeotic gene Antennapedia mRNA contains 5'-noncoding sequences that confer translational initiation by internal ribosome binding. Genes Dev. 1992, 6: 1643-1653. 10.1101/gad.6.9.1643.
Bergman CM, Pfeiffer BD, Rincón-Limas DE, Hoskins RA, Gnirke A, Mungall CJ, Wang AM, Kronmiller B, Pacleb J, Park S, et al: Assessing the impact of comparative genomic sequence data on the functional annotation of the Drosophila genome. Genome Biol. 2002, 3: research0086.1-0086.20. 10.1186/gb-2002-3-12-research0086.
Reese MG, Hartzell G, Harris NL, Ohler U, Abril JF, Lewis SE: Genome annotation assessment in Drosophila melanogaster . Genome Res. 2000, 10: 483-501. 10.1101/gr.10.4.483.
Haas BJ, Volfovsky N, Town CD, Troukhan M, Alexandrov N, Feldmann KA, Flavell RB, White O, Salzberg SL: Full-length messenger RNA sequences greatly improve genome annotation. Genome Biol. 2002, 3: research0029.1-0029.12. 10.1186/gb-2002-3-6-research0029.
Gaasterland T, Oprea M: Whole-genome analysis: annotations and updates. Curr Opin Struct Biol. 2001, 11: 377-381. 10.1016/S0959-440X(00)00213-X.
Expressed Sequence Tags Database (dbEST). [http://www.ncbi.nlm.nih.gov/dbEST]
Kans JA, Ouellette BF: Submitting DNA sequences to the databases. Methods Biochem Anal. 2001, 43: 65-81. 10.1002/0471223921.ch4.
Sequin - a DNA sequence submission and update tool. [http://www.ncbi.nlm.nih.gov/Sequin]
Apweiler R, Attwood TK, Bairoch A, Bateman A, Birney E, Biswas M, Bucher P, Cerutti L, Corpet F, Croning MD, et al: InterPro - an integrated documentation resource for protein families, domains and functional sites. Bioinformatics. 2000, 16: 1145-1150. 10.1093/bioinformatics/16.12.1145.
Spradling AC, Stern D, Beaton A, Rhem EJ, Laverty T, Mozden N, Misra S, Rubin GM: The Berkeley Drosophila Genome Project gene disruption project: single P-element insertions mutating 25% of vital Drosophila genes. Genetics. 1999, 153: 135-177.
Apollo gene annotation tool: developer page. [http://www.fruitfly.org/annot/apollo]
BDGP: download BDGP sequence and annotation databases. [http://www.fruitfly.org/sequence/download.html]
FlyBase update form. [http://www.fruitfly.org/cgi-bin/annot/FBupdate]
Ohler U, Liao G-C, Niemann H, Rubin GM: Computational analysis of core promoters in the Drosophila genome. Genome Biol. 2002, 3: research0087.1-0087.12. 10.1186/gb-2002-3-12-research0087.
Gene Ontology Consortium. [http://www.geneontology.org]
Mi H, Vandergriff J, Campbell MJ, Marechania A, Majoros W, Lewis S, Thomas PD, Ashburner M: Assessment of genome-wide protein function classification for Drosophila melanogaster.Genome Res.
SWISS-PROT. [http://www.ebi.ac.uk/swissprot]
TrEMBL. [http://www.ebi.ac.uk/trembl/index.html]
BDGP re-annotation guidelines. [http://www.fruitfly.org/annot/reannot-guidelines.html]
SP-TrEMBL (SWALL, SWISS-PROT/TrEMBL/TrEMBLNEW) database. [http://www.ebi.ac.uk/trembl]
UniGene Mus musculus. [http://www.ncbi.nlm.nih.gov/UniGene/query.cgi?ORG=Mm]
TrEMBL Protein Database Statistics. [http://www2.ebi.ac.uk/swissprot/sptr_stats]
Zdobnov EM, Von Mering C, Letunic I, Torrents D, Suyama M, Copley RR, Christophides GK, Thomasova D, Holt RA, Subramanian GM, et al: Comparative genome and proteome analysis of Anopheles gambiae and Drosophila melanogaster. Science. 2002, 298: 149-159. 10.1126/science.1077061.
GFF format: an exchange format for feature description. [http://www.sanger.ac.uk/Software/formats/GFF]