Detecting Individual Sites Subject to Episodic Diversifying Selection

By Ben Murrell, Joel O. Wertheim, Sasha Moola, Thomas Weighill, Konrad Scheffler, Sergei L. Kosakovsky Pond. PLoS Genetics, 2012

1,657 citations recorded by the source corpus.

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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/864040b90fa809a34cf45083b8bbbbe0b501de90

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Citations in the corpus

Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa (2020, neutral): “…in multiple epidemiologically unlinked lineages that have statistical support for non-neutral evolution (Mixed Effects Model of Evolution, MEME) 25 , (ii) sites where these polymorphisms have support for a greater than expected ratio of non-synonymous:synonymous nucleotide substitution rates…”
HyPhy 2.5 - a customizable platform for evolutionary hypothesis testing using phylogenies. (2019, methodology): “…this class include methods for characterizing the action of natural selection on genes (Murrell et al. 2015), specific sites (Pond and Frost 2005a; Murrell et al. 2012, 2013) in genes, and branches of phylogenetic trees (Smith et al. 2015), comparing selective regimes between sites and branches…”
RELAX: detecting relaxed selection in a phylogenetic framework. (2014, background): “2011) and mixed effects (Murrell et al. 2012) branch-site models allow detection of individual branches on which only a subset of sites are under positive selection or, conversely, individual sites which are under positive selection on only a subset of branches.”
Gene-wide identification of episodic selection. (2015, methodology): “= 1) used to evaluate the MEME method (Murrell, Wertheim, et al. 2012) (we refer the reader to the original manuscripts for details) as well as data simulated under BUSTED.”
Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil (2021, methodology): “Residues under selection are shown as spheres with associated mutations indicated and colored according to the respective type of selection as analyzed under MEME (91) and supported for at least one branch (red) or not supported (yellow).”
The 2019‐new coronavirus epidemic: Evidence for virus evolution (2020, methodology): “05.(14) Homology models have been built relying on the website SwissModel.”