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Hodges Lab

Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures.

AUTHORS

Stark AAlexander , Lin MF Michael F , Kheradpour P Pouya , Pedersen JS Jakob S , Parts L Leopold , Carlson JW Joseph W , Crosby MA Madeline A , Rasmussen MD Matthew D , Roy S Sushmita , Deoras AN Ameya N , Ruby JG J Graham , Brennecke J Julius , , , Hodges E Emily , Hinrichs AS Angie S , Caspi A Anat , Paten B Benedict , Park SW Seung-Won , Han MV Mira V , Maeder ML Morgan L , Polansky BJ Benjamin J , Robson BE Bryanne E , Aerts S Stein , van Helden J Jacques , Hassan B Bassem , Gilbert DG Donald G , Eastman DA Deborah A , Rice M Michael , Weir M Michael , Hahn MW Matthew W , Park Y Yongkyu , Dewey CN Colin N , Pachter L Lior , Kent WJ W James , Haussler D David , Lai EC Eric C , Bartel DP David P , Hannon GJ Gregory J , Kaufman TC Thomas C , Eisen MB Michael B , Clark AG Andrew G , Smith D Douglas , Celniker SE Susan E , Gelbart WM William M , Kellis M Manolis . Nature. 2007 11 8; 450(7167). 219-32

ABSTRACT

Sequencing of multiple related species followed by comparative genomics analysis constitutes a powerful approach for the systematic understanding of any genome. Here, we use the genomes of 12 Drosophila species for the de novo discovery of functional elements in the fly. Each type of functional element shows characteristic patterns of change, or ‘evolutionary signatures’, dictated by its precise selective constraints. Such signatures enable recognition of new protein-coding genes and exons, spurious and incorrect gene annotations, and numerous unusual gene structures, including abundant stop-codon readthrough. Similarly, we predict non-protein-coding RNA genes and structures, and new microRNA (miRNA) genes. We provide evidence of miRNA processing and functionality from both hairpin arms and both DNA strands. We identify several classes of pre- and post-transcriptional regulatory motifs, and predict individual motif instances with high confidence. We also study how discovery power scales with the divergence and number of species compared, and we provide general guidelines for comparative studies.