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Detecting individual sites subject to episodic diversifying selection.

ABSTRACT: The imprint of natural selection on protein coding genes is often difficult to identify because selection is frequently transient or episodic, i.e. it affects only a subset of lineages. Existing computational techniques, which are designed to identify sites subject to pervasive selection, may fail to recognize sites where selection is episodic: a large proportion of positively selected sites. We present a mixed effects model of evolution (MEME) that is capable of identifying instances of both episodic and pervasive positive selection at the level of an individual site. Using empirical and simulated data, we demonstrate the superior performance of MEME over older models under a broad range of scenarios. We find that episodic selection is widespread and conclude that the number of sites experiencing positive selection may have been vastly underestimated.

SUBMITTER: Murrell B

PROVIDER: S-EPMC3395634 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Detecting individual sites subject to episodic diversifying selection.

Murrell Ben B Wertheim Joel O JO Moola Sasha S Weighill Thomas T Scheffler Konrad K Kosakovsky Pond Sergei L SL

PLoS genetics 20120712 7

The imprint of natural selection on protein coding genes is often difficult to identify because selection is frequently transient or episodic, i.e. it affects only a subset of lineages. Existing computational techniques, which are designed to identify sites subject to pervasive selection, may fail to recognize sites where selection is episodic: a large proportion of positively selected sites. We present a mixed effects model of evolution (MEME) that is capable of identifying instances of both ep ...[more]

PMID: 22807683

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Project description:UnlabelledGibbon ape leukemia viruses (GALVs) are part of a larger group of pathogenic gammaretroviruses present across phylogenetically diverse host species of Australasian mammals. Despite the biomedical utility of GALVs as viral vectors and in cancer gene therapy, full genome sequences have not been determined for all of the five identified GALV strains, nor has a comprehensive evolutionary analysis been performed. We therefore generated complete genomic sequences for each GALV strain using hybridization capture and high-throughput sequencing. The four strains of GALV isolated from gibbons formed a monophyletic clade that was closely related to the woolly monkey virus (WMV), which is a GALV strain that likely originated in a gibbon host. The GALV-WMV clade in turn formed a sister group to the koala retroviruses (KoRVs). Genomic signatures of episodic diversifying selection were detected among the gammaretroviruses with concentration in the env gene across the GALV strains that were particularly oncogenic and KoRV strains that were potentially exogenous, likely reflecting their adaptation to the host immune system. In vitro studies involving vectors chimeric between GALV and KoRV-B established that variable regions A and B of the surface unit of the envelope determine which receptor is used by a viral strain to enter host cells.ImportanceThe gibbon ape leukemia viruses (GALVs) are among the most medically relevant retroviruses due to their use as viral vectors for gene transfer and in cancer gene therapy. Despite their importance, full genome sequences have not been determined for the majority of primate isolates, nor has comprehensive evolutionary analysis been performed, despite evidence that the viruses are facing complex selective pressures associated with cross-species transmission. Using hybridization capture and high-throughput sequencing, we report here the full genome sequences of all the GALV strains and demonstrate that diversifying selection is acting on them, particularly in the envelope gene in functionally important domains, suggesting that host immune pressure is shaping GALV evolution.

Project description:BackgroundThe pentatricopeptide repeat (PPR) is a degenerate 35 amino acid motif that occurs in multiple tandem copies in members of a recently recognized eukaryotic gene family. Most analyzed eukaryotic genomes contain only a small number of PPR genes, but in plants the family is greatly expanded. The factors that underlie the expansion of this gene family in plants are not as yet understood.ResultsWe show that the location of PPR genes is highly variable in comparisons between orthologous, closely related, and otherwise co-linear chromosomal regions of the Brassica rapa or radish and Arabidopsis thaliana. This observation also pertains to paralogous duplicated segments of the genomes of Arabidopsis thaliana and Brassica rapa. In addition, we show that PPR genes that seem closely linearly aligned in these comparisons are not generally found to be closely related to one another at the nucleotide and amino acid sequence level. We observe a relatively high level of non-synonomous vs synonomous changes among a group tandemly repeated radish PPR genes, suggesting that these, and possibly other PPR genes, are subject to diversifying selection. We also show that a duplicated region of the Arabidopsis genome possesses a relatively high density of PPR genes showing high similarity to restorers of fertility of cytoplasmic male sterile (CMS) systems of petunia, radish and rice. The PPR genes in these regions, together with the restorer genes, are more highly similar to one another, in sequence as well as in structure, than to other PPR genes, even within the same sub-family.ConclusionOur results suggest are consistent with a model in which at least some PPR genes undergo a "birth and death" process that involves transposition to unrelated chromosomal sites. PPR genes hold certain features in common with disease resistance genes (R genes), and their "nomadic" character suggests that their evolutionary expansion in plants may have involved novel molecular processes and selective pressures.

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Detecting individual sites subject to episodic diversifying selection.

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Detecting individual sites subject to episodic diversifying selection.

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