Carolin Kosiol, Tomas Vinar, Rute R. {da Fonseca}, Melissa J. Hubisz, Carlos D. Bustamante, Rasmus Nielsen, Adam Siepel. Patterns of positive selection in six Mammalian genomes. PLoS Genetics, 4(8):e1000144. 2008.

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Related www page: http://compgen.bscb.cornell.edu/projects/mammal-psg/

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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.



Last update: 08/06/2008