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

Nature
Authors
Keywords
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.

Year of Publication
2007
Journal
Nature
Volume
450
Issue
7167
Pages
219-32
Date Published
2007 Nov 08
ISSN
1476-4687
URL
DOI
10.1038/nature06340
PubMed ID
17994088
PubMed Central ID
PMC2474711
Links
Grant list
R01 GM067031-04 / GM / NIGMS NIH HHS / United States
R01 HG004037 / HG / NHGRI NIH HHS / United States
R01 HG002779-06 / HG / NHGRI NIH HHS / United States
R01 HG004037-01A1 / HG / NHGRI NIH HHS / United States
R01 GM067031 / GM / NIGMS NIH HHS / United States
R01 HG002779-05 / HG / NHGRI NIH HHS / United States
R01 GM083300 / GM / NIGMS NIH HHS / United States