Detecting Individual Sites Subject to Episodic Diversifying Selection
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Open Access
- 12 July 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Genetics
- Vol. 8 (7), e1002764
- https://doi.org/10.1371/journal.pgen.1002764
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. Identifying regions of protein coding genes that have undergone adaptive evolution is important to answering many questions in evolutionary biology and genetics. In order to tease out genetic evidence for natural selection, genes from a diverse array of taxa must be analyzed, only a subset of which may have undergone adaptive evolution; the same gene region may be under stabilizing or relaxed selection in lineages leading to other taxa. Most current computational methods designed to detect the imprint of natural selection at a site in a protein coding gene assume the strength and direction of natural selection is constant across all lineages. Here, we present a method to detect adaptive evolution, even when the selective forces are not constant across taxa. Using a variety of well-characterized genes, we find evidence suggesting that natural selection is generally episodic and that modeling it as such reveals that many more sites are subject to episodic positive selection than previously appreciated.Keywords
This publication has 40 references indexed in Scilit:
- A Random Effects Branch-Site Model for Detecting Episodic Diversifying SelectionMolecular Biology and Evolution, 2011
- Evolutionary Fingerprinting of GenesMolecular Biology and Evolution, 2009
- Reliabilities of identifying positive selection by the branch-site and the site-prediction methodsProceedings of the National Academy of Sciences of the United States of America, 2009
- Models of coding sequence evolutionBriefings in Bioinformatics, 2008
- Elucidation of phenotypic adaptations: Molecular analyses of dim-light vision proteins in vertebratesProceedings of the National Academy of Sciences of the United States of America, 2008
- A Maximum Likelihood Method for Detecting Directional Evolution in Protein Sequences and Its Application to Influenza A VirusMolecular Biology and Evolution, 2008
- A single positively selected West Nile viral mutation confers increased virogenesis in American crowsNature Genetics, 2007
- Adaptive protein evolution at the Adh locus in DrosophilaNature, 1991
- Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selectionNature, 1988
- Evolutionary trees from DNA sequences: A maximum likelihood approachJournal of Molecular Evolution, 1981