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Patterns of positive selection in six Mammalian genomes.

Kosiol C, Vinar T, da Fonseca RR, Hubisz MJ, Bustamante CD, Nielsen R, Siepel A - PLoS Genet. (2008)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, United States of America.

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.

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Patterns of positive selection on the mammalian phylogeny.(A) Probabilities that each gene gains (green) or loses (red) positive selection on each branch, under the Bayesian switching model. Switching events are allowed to occur early (near ancestor) or late (near descendant) on internal branches, and early on external branches. The prior probability of selection at the root of the tree is shown in parentheses. (The primate-rodent ancestor is treated as the root for this analysis; see Text S1.) The values shown are posterior means. The full posterior distributions are summarized in Figure S2. (B) Expected numbers of genes under positive selection on each branch (blue) and under positive selection only on each branch (red), out of the 544 PSGs examined, with 95% credible intervals in parentheses. Branch thicknesses are proportional to numbers in blue. Similar estimates are also shown for genes under positive selection on all branches of the primate and rodent clades (blue), on only the branches of these clades (red), and on all branches of the tree (blue). All estimates are based on 10,000 iterations of the Gibbs sampler, excluding a 100 iteration burn-in period. On each iteration, all switching parameters and the selection histories for all genes were sampled (see Text S1).
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pgen-1000144-g004: Patterns of positive selection on the mammalian phylogeny.(A) Probabilities that each gene gains (green) or loses (red) positive selection on each branch, under the Bayesian switching model. Switching events are allowed to occur early (near ancestor) or late (near descendant) on internal branches, and early on external branches. The prior probability of selection at the root of the tree is shown in parentheses. (The primate-rodent ancestor is treated as the root for this analysis; see Text S1.) The values shown are posterior means. The full posterior distributions are summarized in Figure S2. (B) Expected numbers of genes under positive selection on each branch (blue) and under positive selection only on each branch (red), out of the 544 PSGs examined, with 95% credible intervals in parentheses. Branch thicknesses are proportional to numbers in blue. Similar estimates are also shown for genes under positive selection on all branches of the primate and rodent clades (blue), on only the branches of these clades (red), and on all branches of the tree (blue). All estimates are based on 10,000 iterations of the Gibbs sampler, excluding a 100 iteration burn-in period. On each iteration, all switching parameters and the selection histories for all genes were sampled (see Text S1).

Mentions: Briefly, the model is defined in terms of a simple switching process along the branches of the phylogeny. It has separate parameters for the rates of gain and loss of positive selection at several switch points on the tree, with two switch points per internal branch and one per external branch (see Figure 4A and Methods). The joint posterior distribution of these parameters and of all selection histories is inferred from the data by a Gibbs sampling algorithm (see Methods and Text S1). The inference procedure is computationally intensive, so it was applied only to the 544 genes identified by one or more LRTs as showing significant evidence of positive selection. Because in these cases the model of no positive selection had already been rejected by a conservative test, the history without selection on any branch was excluded, leaving 29−1 = 511 possible histories for the nine-branch (unrooted) phylogeny. To reduce computational cost, the inference of selection histories was conditioned on the maximum likelihood estimates of the parameters of the codon models (see Methods).


Patterns of positive selection in six Mammalian genomes.

Kosiol C, Vinar T, da Fonseca RR, Hubisz MJ, Bustamante CD, Nielsen R, Siepel A - PLoS Genet. (2008)

Patterns of positive selection on the mammalian phylogeny.(A) Probabilities that each gene gains (green) or loses (red) positive selection on each branch, under the Bayesian switching model. Switching events are allowed to occur early (near ancestor) or late (near descendant) on internal branches, and early on external branches. The prior probability of selection at the root of the tree is shown in parentheses. (The primate-rodent ancestor is treated as the root for this analysis; see Text S1.) The values shown are posterior means. The full posterior distributions are summarized in Figure S2. (B) Expected numbers of genes under positive selection on each branch (blue) and under positive selection only on each branch (red), out of the 544 PSGs examined, with 95% credible intervals in parentheses. Branch thicknesses are proportional to numbers in blue. Similar estimates are also shown for genes under positive selection on all branches of the primate and rodent clades (blue), on only the branches of these clades (red), and on all branches of the tree (blue). All estimates are based on 10,000 iterations of the Gibbs sampler, excluding a 100 iteration burn-in period. On each iteration, all switching parameters and the selection histories for all genes were sampled (see Text S1).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2483296&req=5

pgen-1000144-g004: Patterns of positive selection on the mammalian phylogeny.(A) Probabilities that each gene gains (green) or loses (red) positive selection on each branch, under the Bayesian switching model. Switching events are allowed to occur early (near ancestor) or late (near descendant) on internal branches, and early on external branches. The prior probability of selection at the root of the tree is shown in parentheses. (The primate-rodent ancestor is treated as the root for this analysis; see Text S1.) The values shown are posterior means. The full posterior distributions are summarized in Figure S2. (B) Expected numbers of genes under positive selection on each branch (blue) and under positive selection only on each branch (red), out of the 544 PSGs examined, with 95% credible intervals in parentheses. Branch thicknesses are proportional to numbers in blue. Similar estimates are also shown for genes under positive selection on all branches of the primate and rodent clades (blue), on only the branches of these clades (red), and on all branches of the tree (blue). All estimates are based on 10,000 iterations of the Gibbs sampler, excluding a 100 iteration burn-in period. On each iteration, all switching parameters and the selection histories for all genes were sampled (see Text S1).
Mentions: Briefly, the model is defined in terms of a simple switching process along the branches of the phylogeny. It has separate parameters for the rates of gain and loss of positive selection at several switch points on the tree, with two switch points per internal branch and one per external branch (see Figure 4A and Methods). The joint posterior distribution of these parameters and of all selection histories is inferred from the data by a Gibbs sampling algorithm (see Methods and Text S1). The inference procedure is computationally intensive, so it was applied only to the 544 genes identified by one or more LRTs as showing significant evidence of positive selection. Because in these cases the model of no positive selection had already been rejected by a conservative test, the history without selection on any branch was excluded, leaving 29−1 = 511 possible histories for the nine-branch (unrooted) phylogeny. To reduce computational cost, the inference of selection histories was conditioned on the maximum likelihood estimates of the parameters of the codon models (see Methods).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, United States of America.

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.

Show MeSH
Related in: MedlinePlus