title: Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures.
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.
authors.affiliation: The Broad Institute, Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02140, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stark
authors.forename: Michael F
authors.initials: MF
authors.lastname: Lin
authors.forename: Pouya
authors.initials: P
authors.lastname: Kheradpour
authors.forename: Jakob S
authors.initials: JS
authors.lastname: Pedersen
authors.forename: Leopold
authors.initials: L
authors.lastname: Parts
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Carlson
authors.forename: Madeline A
authors.initials: MA
authors.lastname: Crosby
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Rasmussen
authors.forename: Sushmita
authors.initials: S
authors.lastname: Roy
authors.forename: Ameya N
authors.initials: AN
authors.lastname: Deoras
authors.forename: J Graham
authors.initials: JG
authors.lastname: Ruby
authors.forename: Julius
authors.initials: J
authors.lastname: Brennecke
authors.forename: Emily
authors.initials: E
authors.lastname: Hodges
authors.forename: Angie S
authors.initials: AS
authors.lastname: Hinrichs
authors.forename: Anat
authors.initials: A
authors.lastname: Caspi
authors.forename: Benedict
authors.initials: B
authors.lastname: Paten
authors.forename: Seung-Won
authors.initials: SW
authors.lastname: Park
authors.forename: Mira V
authors.initials: MV
authors.lastname: Han
authors.forename: Morgan L
authors.initials: ML
authors.lastname: Maeder
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Polansky
authors.forename: Bryanne E
authors.initials: BE
authors.lastname: Robson
authors.forename: Stein
authors.initials: S
authors.lastname: Aerts
authors.forename: Jacques
authors.initials: J
authors.lastname: van Helden
authors.forename: Bassem
authors.initials: B
authors.lastname: Hassan
authors.forename: Donald G
authors.initials: DG
authors.lastname: Gilbert
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Eastman
authors.forename: Michael
authors.initials: M
authors.lastname: Rice
authors.forename: Michael
authors.initials: M
authors.lastname: Weir
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Hahn
authors.forename: Yongkyu
authors.initials: Y
authors.lastname: Park
authors.forename: Colin N
authors.initials: CN
authors.lastname: Dewey
authors.forename: Lior
authors.initials: L
authors.lastname: Pachter
authors.forename: W James
authors.initials: WJ
authors.lastname: Kent
authors.forename: David
authors.initials: D
authors.lastname: Haussler
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lai
authors.forename: David P
authors.initials: DP
authors.lastname: Bartel
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Kaufman
authors.forename: Michael B
authors.initials: MB
authors.lastname: Eisen
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Clark
authors.forename: Douglas
authors.initials: D
authors.lastname: Smith
authors.forename: Susan E
authors.initials: SE
authors.lastname: Celniker
authors.forename: William M
authors.initials: WM
authors.lastname: Gelbart
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D004330:Drosophila / Q000145:classification* / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D017344:Genes, Insect / Q000235:genetics; D049750:Genome, Insect / Q000235:genetics*; D023281:Genomics; D035683:MicroRNAs / Q000235:genetics; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010802:Phylogeny; D020506:Untranslated Regions / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D035683:MicroRNAs; D020506:Untranslated Regions