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Detecting Individual Sites Subject to Episodic Diversifying Selection

PLoS Genetics · 2012 · Vol. 8(7) · pp. e1002764–e1002764
Ben MurrellJoel O. WertheimSasha MoolaThomas WeighillKonrad SchefflerSergei L. Kosakovsky Pond

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.

Evolution and Genetic DynamicsRNA and protein synthesis mechanismsGenomics and Phylogenetic StudiesSelection (genetic algorithm)BiologyNatural selectionEpisodic memoryEvolutionary biologyNegative selectionComputational biologyGeneticsComputer scienceGene

MeSH terms

Amino AcidsAnimalsComputer SimulationModels, TheoreticalPhylogenyRhodopsinSelection, GeneticVertebratesOpen Reading FramesEvolution, MolecularComputational Biology

Funding

  • National Science Foundation
  • European Commission
  • National Research Foundation
  • National Institutes of Health
  • Center for AIDS Research, University of Washington
  • University of California, San Diego
  • National Institute of General Medical Sciences
  • National Institute of Allergy and Infectious Diseases
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