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PMID: 17989253 Published · ppublish English Comparative Study Journal Article

Revisiting the protein-coding gene catalog of Drosophila melanogaster using 12 fly genomes.

Genome research ·Vol. 17 ·No. 12 ·2007-12-00 ·Pages 1823-36

Lin MF, Carlson JW, Crosby MA, Matthews BB, Yu C, Park S, Wan KH, Schroeder AJ, Gramates LS, St Pierre SE, Roark M, Wiley KL, Kulathinal RJ, Zhang P, Myrick KV, Antone JV, Celniker SE, Gelbart WM, Kellis M

Abstract

The availability of sequenced genomes from 12 Drosophila species has enabled the use of comparative genomics for the systematic discovery of functional elements conserved within this genus. We have developed quantitative metrics for the evolutionary signatures specific to protein-coding regions and applied them genome-wide, resulting in 1193 candidate new protein-coding exons in the D. melanogaster genome. We have reviewed these predictions by manual curation and validated a subset by directed cDNA screening and sequencing, revealing both new genes and new alternative splice forms of known genes. We also used these evolutionary signatures to evaluate existing gene annotations, resulting in the validation of 87% of genes lacking descriptive names and identifying 414 poorly conserved genes that are likely to be spurious predictions, noncoding, or species-specific genes. Furthermore, our methods suggest a variety of refinements to hundreds of existing gene models, such as modifications to translation start codons and exon splice boundaries. Finally, we performed directed genome-wide searches for unusual protein-coding structures, discovering 149 possible examples of stop codon readthrough, 125 new candidate ORFs of polycistronic mRNAs, and several candidate translational frameshifts. These results affect >10% of annotated fly genes and demonstrate the power of comparative genomics to enhance our understanding of genome organization, even in a model organism as intensively studied as Drosophila melanogaster.

MeSH Terms
Animals Base Sequence Codon/genetics Conserved Sequence Drosophila Proteins/chemistry,genetics Drosophila melanogaster/genetics Evolution, Molecular Genes, Insect Genome, Insect Molecular Sequence Data Reading Frames Sequence Alignment
Chemicals
Codon Drosophila Proteins
Authors & Affiliations
19 authors, click to expand affiliations / ORCID
Lin Michael F
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA.
Carlson Joseph W
Crosby Madeline A
Matthews Beverley B
Yu Charles
Park Soo
Wan Kenneth H
Schroeder Andrew J
Gramates L Sian
St Pierre Susan E
Roark Margaret
Wiley Kenneth L
Kulathinal Rob J
Zhang Peili
Myrick Kyl V
Antone Jerry V
Celniker Susan E
Gelbart William M
Kellis Manolis
References (45)
45 references, click to expand
  1. Amino acid substitution matrices from protein blocks.
    Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10915-9 PMID: 1438297
  2. Sequencing and comparison of yeast species to identify genes and regulatory elements.
    Nature. 2003 May 15;423(6937):241-54 PMID: 12748633
  3. Comparative analyses of multi-species sequences from targeted genomic regions.
    Nature. 2003 Aug 14;424(6950):788-93 PMID: 12917688
  4. High-throughput plasmid cDNA library screening.
    Nat Protoc. 2006;1(2):624-32 PMID: 17406289
  5. Gene prediction with a hidden Markov model and a new intron submodel.
    Bioinformatics. 2003 Oct;19 Suppl 2:ii215-25 PMID: 14534192
  6. The stoned locus of Drosophila melanogaster produces a dicistronic transcript and encodes two distinct polypeptides.
    Genetics. 1996 Aug;143(4):1699-711 PMID: 8844157
  7. GeneID in Drosophila.
    Genome Res. 2000 Apr;10(4):511-5 PMID: 10779490
  8. Finding functional features in Saccharomyces genomes by phylogenetic footprinting.
    Science. 2003 Jul 4;301(5629):71-6 PMID: 12775844
  9. Comparative genome sequencing of Drosophila pseudoobscura: chromosomal, gene, and cis-element evolution.
    Genome Res. 2005 Jan;15(1):1-18 PMID: 15632085
  10. The human genome browser at UCSC.
    Genome Res. 2002 Jun;12(6):996-1006 PMID: 12045153
  11. Systematic discovery and characterization of fly microRNAs using 12 Drosophila genomes.
    Genome Res. 2007 Dec;17(12):1865-79 PMID: 17989255
  12. The genome sequence of Drosophila melanogaster.
    Science. 2000 Mar 24;287(5461):2185-95 PMID: 10731132
  13. Structure, stability and function of RNA pseudoknots involved in stimulating ribosomal frameshifting.
    J Mol Biol. 2000 Apr 28;298(2):167-85 PMID: 10764589
  14. The Adh-related gene of Drosophila melanogaster is expressed as a functional dicistronic messenger RNA: multigenic transcription in higher organisms.
    EMBO J. 1997 Apr 15;16(8):2023-31 PMID: 9155028
  15. A Drosophila complementary DNA resource.
    Science. 2000 Mar 24;287(5461):2222-4 PMID: 10731138
  16. kelch encodes a component of intercellular bridges in Drosophila egg chambers.
    Cell. 1993 Mar 12;72(5):681-93 PMID: 8453663
  17. GENCODE: producing a reference annotation for ENCODE.
    Genome Biol. 2006;7 Suppl 1:S4.1-9 PMID: 16925838
  18. Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals.
    J Comput Biol. 2004;11(2-3):377-94 PMID: 15285897
  19. RNA editing by adenosine deaminases that act on RNA.
    Annu Rev Biochem. 2002;71:817-46 PMID: 12045112
  20. MAVID: constrained ancestral alignment of multiple sequences.
    Genome Res. 2004 Apr;14(4):693-9 PMID: 15060012
  21. Finishing a whole-genome shotgun: release 3 of the Drosophila melanogaster euchromatic genome sequence.
    Genome Biol. 2002;3(12):RESEARCH0079 PMID: 12537568
  22. New mammalian selenocysteine-containing proteins identified with an algorithm that searches for selenocysteine insertion sequence elements.
    J Biol Chem. 1999 Nov 26;274(48):33888-97 PMID: 10567350
  23. Hepatitis D virus RNA editing: specific modification of adenosine in the antigenomic RNA.
    J Virol. 1995 Dec;69(12):7593-600 PMID: 7494266
  24. Methods in comparative genomics: genome correspondence, gene identification and regulatory motif discovery.
    J Comput Biol. 2004;11(2-3):319-55 PMID: 15285895
  25. In silico identification of novel selenoproteins in the Drosophila melanogaster genome.
    EMBO Rep. 2001 Aug;2(8):697-702 PMID: 11493597
  26. The Drosophila gene collection: identification of putative full-length cDNAs for 70% of D. melanogaster genes.
    Genome Res. 2002 Aug;12(8):1294-300 PMID: 12176937
  27. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes.
    Genome Res. 2005 Aug;15(8):1034-50 PMID: 16024819
  28. Genome annotation past, present, and future: how to define an ORF at each locus.
    Genome Res. 2005 Dec;15(12):1777-86 PMID: 16339376
  29. Aligning multiple genomic sequences with the threaded blockset aligner.
    Genome Res. 2004 Apr;14(4):708-15 PMID: 15060014
  30. Selenium metabolism in Drosophila: selenoproteins, selenoprotein mRNA expression, fertility, and mortality.
    J Biol Chem. 2001 Aug 10;276(32):29798-804 PMID: 11389138
  31. Rapid and efficient cDNA library screening by self-ligation of inverse PCR products (SLIP).
    Nucleic Acids Res. 2005 Dec 02;33(21):e185 PMID: 16326860
  32. Translational readthrough in the hdc mRNA generates a novel branching inhibitor in the drosophila trachea.
    Genes Dev. 1998 Apr 1;12(7):956-67 PMID: 9531534
  33. Genie--gene finding in Drosophila melanogaster.
    Genome Res. 2000 Apr;10(4):529-38 PMID: 10779493
  34. Programmed translational frameshifting.
    Microbiol Rev. 1996 Mar;60(1):103-34 PMID: 8852897
  35. Regulatory autonomy and molecular characterization of the Drosophila out at first gene.
    Genetics. 1995 Mar;139(3):1331-46 PMID: 7768442
  36. Assessing the impact of comparative genomic sequence data on the functional annotation of the Drosophila genome.
    Genome Biol. 2002;3(12):RESEARCH0086 PMID: 12537575
  37. A computational and experimental approach to validating annotations and gene predictions in the Drosophila melanogaster genome.
    Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1566-71 PMID: 15668397
  38. Global discriminative learning for higher-accuracy computational gene prediction.
    PLoS Comput Biol. 2007 Mar 16;3(3):e54 PMID: 17367206
  39. Prediction of complete gene structures in human genomic DNA.
    J Mol Biol. 1997 Apr 25;268(1):78-94 PMID: 9149143
  40. Statistical methods for detecting molecular adaptation.
    Trends Ecol Evol. 2000 Dec 1;15(12):496-503 PMID: 11114436
  41. A specific base transition occurs on replicating hepatitis delta virus RNA.
    J Virol. 1990 Mar;64(3):1021-7 PMID: 2304136
  42. The Drosophila gene for antizyme requires ribosomal frameshifting for expression and contains an intronic gene for snRNP Sm D3 on the opposite strand.
    Mol Cell Biol. 1998 Mar;18(3):1553-61 PMID: 9488472
  43. The K(A)/K(S) ratio test for assessing the protein-coding potential of genomic regions: an empirical and simulation study.
    Genome Res. 2002 Jan;12(1):198-202 PMID: 11779845
  44. Gene finding in novel genomes.
    BMC Bioinformatics. 2004 May 14;5:59 PMID: 15144565
  45. Biological function of unannotated transcription during the early development of Drosophila melanogaster.
    Nat Genet. 2006 Oct;38(10):1151-8 PMID: 16951679
Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
Published
2007-12-00
Epub
2007-00-07
Pages
1823-36
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC2099591
Subset
IM
Databases
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