Characterization of Evolutionary Rates and Constraints in Three Mammalian Genomes
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We present an analysis of rates and patterns of microevolutionary phenomena that have shaped the human, mouse, and rat genomes since their last common ancestor. We find evidence for a shift in the mutational spectrum between the mouse and rat lineages, with the net effect being a relative increase in GC content in the rat genome. Our estimate for the neutral point substitution rate separating the two rodents is 0.196 substitutions per site, and 0.65 substitutions per site for the tree relating all three mammals. Small insertions and deletions of 1–10 bp in length (“microindels”) occur at ∼5% of the point substitution rate. Inferred regional correlations in evolutionary rates between lineages and between types of sites support the idea that rates of evolution are influenced by local genomic or cell biological context. No substantial correlations between rates of point substitutions and rates of microindels are found, however, implying that the influences that affect these processes are distinct. Finally, we have identified those regions in the human genome that are evolving slowly, which are likely to include functional elements important to human biology. At least 5% of the human genome is under substantial constraint, most of which is noncoding.
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About 5% or more of bases in mammalian genomes are under purifying selection.
“Analyses of human and rodent genomes (Mouse Genome Sequencing Consortium 2002;Chiaromonte et al. 2003;Roskin et al. 2003;Cooper et al. 2004;Rat Genome Sequencing Project Consortium 2004) indicate that about 5% or more of bases in mammalian genomes are under purifying selection”
From Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes (2005) · cites this paper as Cooper et al. 2004
The Global Identification of Constrained Elements section estimates that 5.2% of the human genome evolves at 40% or less of the neutral rate and explains that slowly evolving functional sequences tend to be under purifying selection. The analysis compares human, mouse, and rat genomes, but the quantified estimate is for the human genome, not mammalian genomes generally. Page numbers are unavailable in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe vertebrate coverage is similar to recent estimates of 5%-8% for the share of the human genome under purifying selection.
“Note that the vertebrate coverage is similar to recent estimates of 5%-8% for the share of the human genome that is under purifying selection”
From Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes (2005) · cites this paper as Cooper et al. 2004
The estimated nonconserved branch lengths for vertebrates were fairly consistent with recent results based on apparently neutrally evolving DNA in mammals.
“The estimated “nonconserved” branch lengths for vertebrates were fairly consistent with recent results based on (apparently) neutrally evolving DNA in mammals (Cooper et al. 2004), but were not accurate representations of the neutral substitution process in all respects.”
From Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes (2005) · cites this paper as Cooper et al. 2004
The composition of vertebrate conserved elements agrees with bulk statistical estimates of the share of the human genome under selection and with an analysis of conserved elements in the CFTR region.
“These numbers are in good agreement both with bulk statistical estimates, based on genome-wide human/mouse and human/ mouse/rat alignments, of the share of the human genome that is under selection (Chiaromonte et al. 2003;Roskin et al. 2003;Cooper et al. 2004), and with an analysis of conserved elements in the region of the CFTR gene (Margulies et al. 2003;Thomas et al. 2003).”
From Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes (2005) · cites this paper as Cooper et al. 2004
Margulies et al. found that 72% of bases in predicted conserved elements in the CFTR region were not in exons, and Cooper et al. reported similar results based on whole-genome human/mouse/rat alignments.
“Margulies et al. (2003), using two different methods, found that 72% of bases in predicted conserved elements in the CFTR region were not in exons.Cooper et al. (2004) reported similar results based on wholegenome human/mouse/rat alignments.”
From Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes (2005) · cites this paper as Cooper et al. 2004
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Cites
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The ENCODE Project Consortium (2007) · Nature · doi:10.1038/nature05874 · Cited by 5,223 · see citing works
Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes
Siepel, A., Bejerano, G., Pedersen, J. S., Hinrichs, A. S., Hou, M., Rosenbloom, K., Clawson, H., Spieth, J., Hillier, L. W., Richards, S., et al. (2005) · Genome Research · doi:10.1101/gr.3715005 · Cited by 4,408 · see citing works
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Ultraconserved Elements in the Human Genome
Bejerano, G., Pheasant, M., Makunin, I., Stephen, S., Kent, W. J., Mattick, J. S., & Haussler, D. (2004) · Science · doi:10.1126/science.1098119 · Cited by 1,732 · see citing works
Distribution and intensity of constraint in mammalian genomic sequence
Cooper, G. M., Stone, E. A., Asimenos, G., Green, E. D., Batzoglou, S., & Sidow, A. (2005) · Genome Research · doi:10.1101/gr.3577405 · Cited by 1,359 · see citing works
Self-citation
- Authors
- Cooper, G. M., Brudno, M., Stone, E. A., Dubchak, I., Batzoglou, S., & Sidow, A.
- Affiliations
- Stanford University (US)
- Lawrence Berkeley National Laboratory (US)
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-04
- Volume
- 14
- Issue
- 4
- Pages
- 539-548
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC383297
- OpenAlex
- W7100675991
- Cited by
- 134
- References
- 3
- Citations by year
- 2026: 1 · 2024: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 7 · 2014: 2 · 2013: 3 · 2012: 2
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- University of North Texas Digital Library (University of North Texas) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute
- National Institute of General Medical Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- microevolution, mutation spectrum, GC content, indels, human genome, mouse genome, rat genome, non-coding regions, functional elements, mammalian evolution
- MeSH terms
- Animals, Chromosome Deletion, Humans, Species Specificity, Genetic Variation, Genome, Human, Mutagenesis, Insertional, Genome, Point Mutation, Evolution, Molecular, Computational Biology, Mice, Rats
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