RELAX: detecting relaxed selection in a phylogenetic framework.
By Joel O. Wertheim, Ben Murrell, Martin D. Smith, Sergei L. Kosakovsky Pond, Konrad Scheffler. Molecular biology and evolution, 2014
672 citations recorded by the source corpus.
Relaxation of selective strength, manifested as a reduction in the efficiency or intensity of natural selection, can drive evolutionary innovation and presage lineage extinction or loss of function. Mechanisms through which selection can be relaxed range from the removal of an existing selective constraint to a reduction in effective population size. Standard methods for estimating the strength and extent of purifying or positive selection from molecular sequence data are not suitable for detecting relaxed selection, because they lack power and can mistake an increase in the intensity of positive selection for relaxation of both purifying and positive selection. Here, we present a general hypothesis testing framework (RELAX) for detecting relaxed selection in a codon-based phylogenetic framework. Given two subsets of branches in a phylogeny, RELAX can determine whether selective strength was relaxed or intensified in one of these subsets relative to the other. We establish the validity of our test via simulations and show that it can distinguish between increased positive selection and a relaxation of selective strength. We also demonstrate the power of RELAX in a variety of biological scenarios where relaxation of selection has been hypothesized or demonstrated previously. We find that obligate and facultative γ-proteobacteria endosymbionts of insects are under relaxed selection compared with their free-living relatives and obligate endosymbionts are under relaxed selection compared with facultative endosymbionts. Selective strength is also relaxed in asexual Daphnia pulex lineages, compared with sexual lineages. Endogenous, nonfunctional, bornavirus-like elements are found to be under relaxed selection compared with exogenous Borna viruses. Finally, selection on the short-wavelength sensitive, SWS1, opsin genes in echolocating and nonecholocating bats is relaxed only in lineages in which this gene underwent pseudogenization; however, selection on the functional medium/long-wavelength sensitive opsin, M/LWS1, is found to be relaxed in all echolocating bats compared with nonecholocating bats.
Subfields: Ecology, Evolution, Behavior and Systematics, Genetics, Infectious Diseases
View Paper: https://www.semanticscholar.org/paper/41e3398050c16a449afa8a1ab727ac4793ab6b3f
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In Genetics
- Sergei L. Kosakovsky Pond
- Simon D. W. Frost
- Ben Murrell
- Art F. Y. Poon
- Scott Weaver
- Diego Forni
- Mario Clerici
- Anton Nekrutenko
In Infectious Diseases
Citations in the corpus
- HyPhy 2.5 - a customizable platform for evolutionary hypothesis testing using phylogenies. (2019, methodology): “Key analyses in 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…”
- Molecular Evolution of Human Coronavirus Genomes (2016, positive): “Instead, we obtained evidence that relaxation of natural selection [18] in ORF8 accompanied the shift from bats to civets/humans (Figure 2A).”