This Article Full Text (PDF) Drosophila 12 Genomes Supplemental Research Data All Versions of this Article: gr.6679507v1 17/12/1823    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lin, M. F. Articles by Kellis, M. Search for Related Content PubMed PubMed Citation Articles by Lin, M. F. Articles by Kellis, M. Social Bookmarking                   What's this?

12 Drosophila Genomes/Letter

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

¹ Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA; ² Berkeley Drosophila Genome Project, Department of Genome Biology, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA; ³ FlyBase, The Biological Laboratories, Harvard University, Cambridge, Massachusetts 02138, USA; ⁴ Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA; ⁵ MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, Massachusetts 02139, USA

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.

E-mail manoli{at}mit.edu; fax (617) 262-6121.

[Supplemental material is available online at www.genome.org. Additional supplemental materials are available online at http://compbio.mit.edu/fly/genes/. Full-length cDNA sequence data from this study have been submitted to GenBank under accession nos. BT029554–BT029635, BT029637–BT029727, BT029940–BT029957, BT030133– BT030144, BT030416–BT030421, and BT030448–BT030452. RT-PCR amplicon and primer sequence data have been submitted to GenBank under accession nos. ES439769–ES439782.]

Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.6679507

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Clamp, B. Fry, M. Kamal, X. Xie, J. Cuff, M. F. Lin, M. Kellis, K. Lindblad-Toh, and E. S. Lander From the Cover: Distinguishing protein-coding and noncoding genes in the human genome PNAS, December 4, 2007; 104(49): 19428 - 19433. [Abstract] [Full Text] [PDF]

				A. Stark, P. Kheradpour, L. Parts, J. Brennecke, E. Hodges, G. J. Hannon, and M. Kellis Systematic discovery and characterization of fly microRNAs using 12 Drosophila genomes Genome Res., December 1, 2007; 17(12): 1865 - 1879. [Abstract] [Full Text] [PDF]