Literature DB >> 17994088

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

Alexander Stark1, Michael F Lin, Pouya Kheradpour, Jakob S Pedersen, Leopold Parts, Joseph W Carlson, Madeline A Crosby, Matthew D Rasmussen, Sushmita Roy, Ameya N Deoras, J Graham Ruby, Julius Brennecke, Emily Hodges, Angie S Hinrichs, Anat Caspi, Benedict Paten, Seung-Won Park, Mira V Han, Morgan L Maeder, Benjamin J Polansky, Bryanne E Robson, Stein Aerts, Jacques van Helden, Bassem Hassan, Donald G Gilbert, Deborah A Eastman, Michael Rice, Michael Weir, Matthew W Hahn, Yongkyu Park, Colin N Dewey, Lior Pachter, W James Kent, David Haussler, Eric C Lai, David P Bartel, Gregory J Hannon, Thomas C Kaufman, Michael B Eisen, Andrew G Clark, Douglas Smith, Susan E Celniker, William M Gelbart, Manolis Kellis.   

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.

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Year:  2007        PMID: 17994088      PMCID: PMC2474711          DOI: 10.1038/nature06340

Source DB:  PubMed          Journal:  Nature        ISSN: 0028-0836            Impact factor:   49.962


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