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Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures

2007; Nature Portfolio; Volume: 450; Issue: 7167 Linguagem: Inglês

10.1038/nature06340

1476-4687

Alexander Stark, Michael F. Lin, Pouya Kheradpour, Jakob Skou Pedersen, Leopold Parts, Joseph W. Carlson, Madeline A. Crosby, Matthew D. Rasmussen, Sushmita Roy, Ameya N. Deoras, J. Graham Ruby, Julius Brennecke, Madeline A. Crosby, Beverley B Matthews, Andrew J. Schroeder, L. Sian Gramates, Susan E. St. Pierre, Margaret Roark, Kenneth L. Wiley, Rob J. Kulathinal, Peili Zhang, Kyl V. Myrick, Jerry V. Antone, William M Gelbart, Joseph W. Carlson, Charles Yu, Soo Park, Kenneth H. Wan, Susan E. Celniker, 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 A. Hassan, Donald G. Gilbert, Deborah Eastman, Michael Rice, Michael P. 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,

Genetic diversity and population structure

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. This issue includes a landmark collection of papers on the stalwart of the genetics lab, the Drosophila fruit fly. The centrepiece is the publication by the Drosophila 12 Genomes Consortium of the genomic sequence for ten Drosophila species. The paper compares the newly sequenced genomes (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi species), with the two previously known sequences for D. melanogaster and D. pseudoobscura. The resulting database of genetic variation will be invaluable for the study of the forces of evolutionary change. A second major collaboration has mined the dozen Drosophila genome sequences for conserved elements, and reports the relationship between conservation and function for many specific sequence motifs. A detailed regulatory network emerges, identifying protein-coding genes and exons, RNA genes, microRNAs and their targets. These papers are discussed in News and Views. Two further research papers use the new genomic data to study gene expression, first for genes with male-biased expression and those unique to each species and second, to track the evolution of gene dosage compensation on Drosophila sex chromosomes. Four new reviews focus on how the latest work on Drosophila is taking this genetically pliant lab model into exciting new fields. Pierre Leopold and Norbert Perrimon review advances in the study of endocrinology and homeostasis that are establishing Drosophila as a model for mammalian physiology. Drosophila has proved a powerful system in which to study the pathways controlling cell shape in growing tissue, as reported by Thomas Lecuit and Loïc Le Goff. Leslie Vosshall reviews the remarkable work linking neural circuits and behaviour and John Lis reviews work on Drosophila that has rewritten the textbook view of gene transcription. The cover shows anaesthetized individuals of all twelve Drosophila species. The genomic sequences of 12 Drosophila species for conserved elements and describe the relationship between conservation and function for many specific sequence motifs.