Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes.
We have conducted a comprehensive search for conserved elements in vertebrate genomes, using genome-wide multiple alignments of five vertebrate species (human, mouse, rat, chicken, and Fugu rubripes). Parallel searches have been performed with multiple alignments of four insect species (three species of Drosophila and Anopheles gambiae), two species of Caenorhabditis, and seven species of Saccharomyces. Conserved elements were identified with a computer program called phastCons, which is based on a two-state phylogenetic hidden Markov model (phylo-HMM). PhastCons works by fitting a phylo-HMM to the data by maximum likelihood, subject to constraints designed to calibrate the model across species groups, and then predicting conserved elements based on this model. The predicted elements cover roughly 3%-8% of the human genome (depending on the details of the calibration procedure) and substantially higher fractions of the more compact Drosophila melanogaster (37%-53%), Caenorhabditis elegans (18%-37%), and Saccharaomyces cerevisiae (47%-68%) genomes. From yeasts to vertebrates, in order of increasing genome size and general biological complexity, increasing fractions of conserved bases are found to lie outside of the exons of known protein-coding genes. In all groups, the most highly conserved elements (HCEs), by log-odds score, are hundreds or thousands of bases long. These elements share certain properties with ultraconserved elements, but they tend to be longer and less perfectly conserved, and they overlap genes of somewhat different functional categories. In vertebrates, HCEs are associated with the 3' UTRs of regulatory genes, stable gene deserts, and megabase-sized regions rich in moderately conserved noncoding sequences. Noncoding HCEs also show strong statistical evidence of an enrichment for RNA secondary structure.
Siepel
Adam
A
Center for Biomolecular Science and Engineering, University of California, Santa Cruz, Santa Cruz, California 95064, USA. acs@soe.ucsc.edu
Bejerano
Gill
G
Pedersen
Jakob S
JS
Hinrichs
Angie S
AS
Hou
Minmei
M
Rosenbloom
Kate
K
Clawson
Hiram
H
Spieth
John
J
Hillier
Ladeana W
LW
Richards
Stephen
S
Weinstock
George M
GM
Wilson
Richard K
RK
Gibbs
Richard A
RA
Kent
W James
WJ
Miller
Webb
W
Haussler
David
D
D020413:3' Untranslated Regions; D000818:Animals; D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics; D017124:Conserved Sequence; D021901:DNA, Intergenic; D019143:Evolution, Molecular; D016678:Genome; D006801:Humans; D007313:Insecta / Q000235:genetics*; D008969:Molecular Sequence Data; D012440:Saccharomyces / Q000235:genetics; D014714:Vertebrates / Q000235:genetics*; D015003:Yeasts / Q000235:genetics*
D020413:3' Untranslated Regions; D021901:DNA, Intergenic