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PMID: 18670650 Published · epublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Patterns of positive selection in six Mammalian genomes.

PLoS genetics ·Vol. 4 ·No. 8 ·2008-08-01 ·Pages e1000144

Kosiol C, Vinar T, da Fonseca RR, Hubisz MJ, Bustamante CD, Nielsen R, Siepel A

Abstract

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.

MeSH Terms
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
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kosiol Carolin
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, United States of America.
Vinar Tomás
da Fonseca Rute R
Hubisz Melissa J
Bustamante Carlos D
Nielsen Rasmus
Siepel Adam
Conflict of Interest

The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1000144
Published
2008-08-01
Epub
2008-00-01
Pages
e1000144
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2483296
Subset
IM
Grants
NHGRI NIH HHS · R01 HG003229 · United States
NHGRI NIH HHS · R01 HG003229-03 · United States
External Links
PubMed source DOI: 10.1371/journal.pgen.1000144 PMC Full Text View journal details
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