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Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures

Stark, Alexander and Pachter, Lior (2007) Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures. Nature, 450 (7167). pp. 219-232. ISSN 0028-0836. PMCID PMC2474711. doi:10.1038/nature06340.

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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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Pachter, Lior0000-0002-9164-6231
Additional Information:© 2007 Macmillan Publishers Limited. Received 21 July 2007; Accepted 4 October 2007. We thank the National Human Genome Research Institute (NHGRI) for continued support. A.S. was supported in part by the Schering AG/Ernst Schering Foundation and in part by the Human Frontier Science Program Organization (HFSPO). P.K. was supported in part by a National Science Foundation Graduate Research Fellowship. J.S.P. thanks B. Raney and R. Baertsch, and the Danish Medical Research Council and the National Cancer Institute for support. J.B. thanks the Schering AG/Ernst Schering Foundation for a postdoctoral fellowship. L.Parts thanks J. Vilo. S.R. was supported by a HHMI-NIH/NIBIB Interfaces Training Grant and thanks T. Lane and M. Werner-Washburne. D.H., D.P.B., G.J.H. and T.C.K. are Investigators of the Howard Hughes Medical Institute, and B.P., J.G.R., E.H. and J.B. are affiliated with these investigators. J.W.C. and S.E.C. were supported by the NHGRI. M.K. was supported by start-up funds from the MIT Electrical Engineering and Computer Science Laboratory, the Broad Institute of MIT and Harvard, and the MIT Computer Science and Artificial Intelligence Laboratory, and by the Distinguished Alumnus (1964) Career Development Professorship. Author Contributions -- Organizing committee: Manolis Kellis, William Gelbart, Doug Smith, Andrew G. Clark, Michael E. Eisen, Thomas C. Kaufman; protein-coding gene prediction: Michael F. Lin, Ameya N. Deoras, Mira V. Han, Matthew W. Hahn, Donald G. Gilbert, Michael Weir, Michael Rice, Manolis Kellis; manual curation of protein-coding genes: Madeline A. Crosby, Harvard FlyBase curators, William M. Gelbart; validation of protein-coding genes: Joseph W. Carlson, Berkeley Drosophila Genome Project, Susan E. Celniker; non-coding RNA gene prediction: Jakob S. Pedersen, David Haussler, Yongkyu Park, Seung-Won Park, Manolis Kellis; microRNA gene prediction: Alexander Stark, Pouya Kheradpour, Leopold Parts, Manolis Kellis; microRNA cloning and sequencing: Julius Brennecke, Emily Hodges, Gregory J. Hannon; microRNA target prediction: Alexander Stark, J. Graham Ruby, Manolis Kellis, Eric C. Lai, David P. Bartel; motif identification: Alexander Stark, Pouya Kheradpour, Manolis Kellis; motif instance prediction: Alexander Stark, Pouya Kheradpour, Sushmita Roy, Morgan L. Maeder, Benjamin J. Polansky, Bryanne E. Robson, Deborah A. Eastman, Stein Aerts, Bassem Hassan, Jacques van Helden, Manolis Kellis; genome alignments: Angie S. Hinrichs, W. James Kent, Anat Caspi, Lior Pachter, Colin N. Dewey, Benedict Paten; phylogeny and branch length estimation: Matthew D. Rasmussen, Manolis Kellis; final manuscript preparation: Alexander Stark, Michael F. Lin, Pouya Kheradpour, Jakob Pedersen, Manolis Kellis. The authors declare no competing financial interests.
Funding AgencyGrant Number
National Human Genome Research InstituteUNSPECIFIED
Ernst Schering FoundationUNSPECIFIED
Human Frontier Science ProgramUNSPECIFIED
NSF Graduate Research FellowshipUNSPECIFIED
Danish Medical Research CouncilUNSPECIFIED
National Cancer InstituteUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
National Institute of Biomedical Imaging and BioengineeringUNSPECIFIED
Massachusetts Institute of Technology (MIT)UNSPECIFIED
Broad Institute of MIT and HarvardUNSPECIFIED
Issue or Number:7167
PubMed Central ID:PMC2474711
Record Number:CaltechAUTHORS:20170307-112926954
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74849
Deposited By: George Porter
Deposited On:07 Mar 2017 20:35
Last Modified:11 Nov 2021 05:30

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