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

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.

Pubmed ID: 17994088

Authors

  • Stark A
  • Lin MF
  • Kheradpour P
  • Pedersen JS
  • Parts L
  • Carlson JW
  • Crosby MA
  • Rasmussen MD
  • Roy S
  • Deoras AN
  • Ruby JG
  • Brennecke J
  • Harvard FlyBase curators
  • Berkeley Drosophila Genome Project
  • Hodges E
  • Hinrichs AS
  • Caspi A
  • Paten B
  • Park SW
  • Han MV
  • Maeder ML
  • Polansky BJ
  • Robson BE
  • Aerts S
  • van Helden J
  • Hassan B
  • Gilbert DG
  • Eastman DA
  • Rice M
  • Weir M
  • Hahn MW
  • Park Y
  • Dewey CN
  • Pachter L
  • Kent WJ
  • Haussler D
  • Lai EC
  • Bartel DP
  • Hannon GJ
  • Kaufman TC
  • Eisen MB
  • Clark AG
  • Smith D
  • Celniker SE
  • Gelbart WM
  • Kellis M

Journal

Nature

Publication Data

November 8, 2007

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM067031
  • Agency: NIGMS NIH HHS, Id: R01 GM067031-04
  • Agency: NHGRI NIH HHS, Id: R01 HG002779-05
  • Agency: NHGRI NIH HHS, Id: R01 HG002779-06
  • Agency: NHGRI NIH HHS, Id: R01 HG004037
  • Agency: NHGRI NIH HHS, Id: R01 HG004037-01A1

Mesh Terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Conserved Sequence
  • Drosophila
  • Drosophila Proteins
  • Evolution, Molecular
  • Exons
  • Gene Expression Regulation
  • Genes, Insect
  • Genome, Insect
  • Genomics
  • MicroRNAs
  • Molecular Sequence Data
  • Organ Specificity
  • Phylogeny
  • Untranslated Regions