Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes.

Adam Siepel; Gill Bejerano; Jakob Skou Pedersen; Angie S Hinrichs; Minmei Hou; Kate Rosenbloom; Hiram Clawson; John Spieth; Ladeana W Hillier; Stephen Richards; George M Weinstock; Richard K Wilson; Richard A Gibbs; W James Kent; Webb Miller; David Haussler

doi:10.1101/gr.3715005

Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes.

Adam Siepel, Gill Bejerano, Jakob Skou Pedersen, Angie S Hinrichs, Minmei Hou, Kate Rosenbloom, Hiram Clawson, John Spieth, Ladeana W Hillier, Stephen Richards, George M Weinstock, Richard K Wilson, Richard A Gibbs, W James Kent, Webb Miller, David Haussler

Functional Genomics

2303 Citations (Scopus)

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.

Original language	English
Journal	Genome Research
Volume	15
Issue number	8
Pages (from-to)	1034-50
Number of pages	16
ISSN	1088-9051
DOIs	https://doi.org/10.1101/gr.3715005
Publication status	Published - 2005

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Siepel, A., Bejerano, G., Pedersen, J. S., Hinrichs, A. S., Hou, M., Rosenbloom, K., Clawson, H., Spieth, J., Hillier, L. W., Richards, S., Weinstock, G. M., Wilson, R. K., Gibbs, R. A., Kent, W. J., Miller, W., & Haussler, D. (2005). Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Research, 15(8), 1034-50. https://doi.org/10.1101/gr.3715005

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title = "Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes.",

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.",

author = "Adam Siepel and Gill Bejerano and Pedersen, {Jakob Skou} and Hinrichs, {Angie S} and Minmei Hou and Kate Rosenbloom and Hiram Clawson and John Spieth and Hillier, {Ladeana W} and Stephen Richards and Weinstock, {George M} and Wilson, {Richard K} and Gibbs, {Richard A} and Kent, {W James} and Webb Miller and David Haussler",

note = "Keywords: 3' Untranslated Regions; Animals; Base Pairing; Base Sequence; Caenorhabditis elegans; Conserved Sequence; DNA, Intergenic; Evolution, Molecular; Genome; Humans; Insects; Molecular Sequence Data; Saccharomyces; Vertebrates; Yeasts",

year = "2005",

doi = "10.1101/gr.3715005",

language = "English",

volume = "15",

pages = "1034--50",

journal = "Genome Research",

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T1 - Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes.

AU - Siepel, Adam

AU - Bejerano, Gill

AU - Pedersen, Jakob Skou

AU - Hinrichs, Angie S

AU - Hou, Minmei

AU - Rosenbloom, Kate

AU - Clawson, Hiram

AU - Spieth, John

AU - Hillier, Ladeana W

AU - Richards, Stephen

AU - Weinstock, George M

AU - Wilson, Richard K

AU - Gibbs, Richard A

AU - Kent, W James

AU - Miller, Webb

AU - Haussler, David

N1 - Keywords: 3' Untranslated Regions; Animals; Base Pairing; Base Sequence; Caenorhabditis elegans; Conserved Sequence; DNA, Intergenic; Evolution, Molecular; Genome; Humans; Insects; Molecular Sequence Data; Saccharomyces; Vertebrates; Yeasts

PY - 2005

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N2 - 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.

AB - 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.

U2 - 10.1101/gr.3715005

DO - 10.1101/gr.3715005

M3 - Journal article

C2 - 16024819

SN - 1088-9051

VL - 15

SP - 1034

EP - 1050

JO - Genome Research

JF - Genome Research

IS - 8

ER -

Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes.

Abstract

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