The role of epistasis in protein evolution

McCandlish, D. M., Rajon, E., Shah, P., Ding, Y., Plotkin, J. B. (May 2013) The role of epistasis in protein evolution. Nature, 497 (7451). E1-2; discussion E2. ISSN 1476-4687 (Electronic)0028-0836 (Linking)

DOI: 10.1038/nature12219


An important question in molecular evolution is whether an amino acid that occurs at a given site makes an independent contribution to fitness, or whether its contribution depends on the state of other sites in the organism’s genome, a phenomenon known as epistasis1, 2, 3, 4, 5. Breen and colleagues recently argued6 that epistasis must be “pervasive throughout protein evolution” because the observed ratio between the per-site rates of non-synonymous and synonymous substitutions (dN/dS)7 is much lower than would be expected in the absence of epistasis. However, when calculating the expected dN/dS ratio in the absence of epistasis, Breen et al.6 assumed that all amino acids observed at a given position in a protein alignment have equal fitness. Here, we relax this unrealistic assumption and show that any dN/dS value can in principle be achieved at a site, without epistasis; furthermore, for all nuclear and chloroplast genes in the Breen et al. data set, we show that the observed dN/dS values and the observed patterns of amino-acid diversity at each site are jointly consistent with a non-epistatic model of protein evolution.

Item Type: Paper
Uncontrolled Keywords: Animals Epistasis, Genetic/*genetics *Evolution, Molecular
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
CSHL Authors:
Communities: CSHL labs > McCandlish lab
Depositing User: Matt Covey
Date: 30 May 2013
Date Deposited: 18 Jan 2017 20:29
Last Modified: 18 Jan 2017 20:29
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