Patterns of positive selection in six Mammalian genomes

Kosiol, C., Vinar, T., da Fonseca, R. R., Hubisz, M. J., Bustamante, C. D., Nielsen, R., Siepel, A. (2008) Patterns of positive selection in six Mammalian genomes. Plos Genetics, 4 (8). e1000144. ISSN 1553-7390

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DOI: 10.1371/journal.pgen.1000144


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.

Item Type: Paper
Uncontrolled Keywords: Animals Bayes Theorem Databases, Genetic Dogs *Evolution, Molecular Gene Expression *Genome Humans Likelihood Functions Macaca mulatta Mammals/classification/*genetics Mice Pan troglodytes Phylogeny Primates Rats Rodentia *Selection, Genetic Sequence Alignment
Subjects: bioinformatics
bioinformatics > genomics and proteomics > alignment > sequence alignment
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
Investigative techniques and equipment > assays > whole genome sequencing
CSHL Authors:
Communities: CSHL labs > Siepel lab
Depositing User: Matt Covey
Date: 2008
Date Deposited: 14 Jan 2015 20:38
Last Modified: 14 Jan 2015 20:38
PMCID: PMC2483296
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