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Patterns of Positive Selection in Six Mammalian Genomes
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Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small numbers of available genomes. Here we present the most comprehensive examination of mammalian PSGs to date, using the six high-coverage genome assemblies now available for eutherian mammals. The increased phylogenetic depth of this dataset results in substantially improved statistical power, and permits several new lineage- and clade-specific tests to be applied. Of approximately 16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR<0.05), according to a standard likelihood ratio test. An additional 144 genes showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity and taste perception. Several pathways were strongly enriched for PSGs, suggesting possible co-evolution of interacting genes. A novel Bayesian analysis of the possible "selection histories" of each gene indicated that most PSGs have switched multiple times between positive selection and nonselection, suggesting that positive selection is often episodic. A detailed analysis of Affymetrix exon array data indicated that PSGs are expressed at significantly lower levels, and in a more tissue-specific manner, than non-PSGs. Genes that are specifically expressed in the spleen, testes, liver, and breast are significantly enriched for PSGs, but no evidence was found for an enrichment for PSGs among brain-specific genes. This study provides additional evidence for widespread positive selection in mammalian evolution and new genome-wide insights into the functional implications of positive selection.
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“Genomic comparisons between closely related species provide insights into the genetic basis of mammalian divergence and adaptation 8,9 .”
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Metadata
- Authors
- Kosiol, C., Vinař, T., da Fonseca, R. R., Hubisz, M. J., Bustamante, C. D., Nielsen, R., & Siepel, A.
- Affiliations
- Cornell University (US)
- University of Chicago (US)
- University of Copenhagen (DK)
- Corresponding author
- Siepel, Adam
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-08-01
- Volume
- 4
- Issue
- 8
- Pages
- e1000144
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC2483296
- OpenAlex
- W2154770881
- Cited by
- 576
- References
- 97
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 23 · 2023: 17 · 2022: 19 · 2021: 58 · 2020: 27 · 2019: 27 · 2018: 24 · 2017: 31 · 2016: 25 · 2015: 32 · 2014: 51 · 2013: 55 · 2012: 41
- FWCI
- 23.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Knowledge@UChicago (University of Chicago) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- University of Chicago (cc-by)
- Funders
- National Science Foundation (0644111, 0516310)
- Microsoft Research
- National Human Genome Research Institute (R01HG003229)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Keywords
- positive selection, mammalian evolution, placental mammals, orthologs, lineage-specific selection, immune-related genes, chemosensory perception, reproduction, taste perception, gene coevolution, episodic selection, gene expression, tissue-specific gene expression, spleen, testis, liver, breast
- MeSH terms
- Animals, Bayes Theorem, Pan troglodytes, Dogs, Humans, Macaca mulatta, Mammals, Phylogeny, Primates, Rodentia, Selection, Genetic, Gene Expression, Likelihood Functions, Sequence Alignment, Genome, Evolution, Molecular, Databases, Genetic, Mice, Rats
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