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.
Stark
Alexander
A
The Broad Institute, Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02140, USA.
Lin
Michael F
MF
Kheradpour
Pouya
P
Pedersen
Jakob S
JS
Parts
Leopold
L
Carlson
Joseph W
JW
Crosby
Madeline A
MA
Rasmussen
Matthew D
MD
Roy
Sushmita
S
Deoras
Ameya N
AN
Ruby
J Graham
JG
Brennecke
Julius
J
Hodges
Emily
E
Hinrichs
Angie S
AS
Caspi
Anat
A
Paten
Benedict
B
Park
Seung-Won
SW
Han
Mira V
MV
Maeder
Morgan L
ML
Polansky
Benjamin J
BJ
Robson
Bryanne E
BE
Aerts
Stein
S
van Helden
Jacques
J
Hassan
Bassem
B
Gilbert
Donald G
DG
Eastman
Deborah A
DA
Rice
Michael
M
Weir
Michael
M
Hahn
Matthew W
MW
Park
Yongkyu
Y
Dewey
Colin N
CN
Pachter
Lior
L
Kent
W James
WJ
Haussler
David
D
Lai
Eric C
EC
Bartel
David P
DP
Hannon
Gregory J
GJ
Kaufman
Thomas C
TC
Eisen
Michael B
MB
Clark
Andrew G
AG
Smith
Douglas
D
Celniker
Susan E
SE
Gelbart
William M
WM
Kellis
Manolis
M
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
D029721:Drosophila Proteins; D035683:MicroRNAs; D020506:Untranslated Regions