Abstract
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.
Links and resources
Tags
- 3'
- Data,Saccharomyces,Saccharomyces:
- Intergenic,Evolution,
- Molecular,Genome,Humans,Insects,Insects:
- Pairing,Base
- Pairing:
- Regions,Animals,Base
- Sequence
- Sequence,Caenorhabditis
- Sequence,DNA,
- Untranslated
- elegans,Caenorhabditis
- elegans:
- genetics
- genetics,Base
- genetics,Conserved
- genetics,Molecular
- genetics,Vertebrates,Vertebrates:
- genetics,Yeasts,Yeasts:
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