A biophysical protein folding model accounts for most mutational fitness effects in viruses.

ABSTRACT: Fitness effects of mutations fall on a continuum ranging from lethal to deleterious to beneficial. The distribution of fitness effects (DFE) among random mutations is an essential component of every evolutionary model and a mathematical portrait of robustness. Recent experiments on five viral species all revealed a characteristic bimodal-shaped DFE featuring peaks at neutrality and lethality. However, the phenotypic causes underlying observed fitness effects are still unknown and presumably, are thought to vary unpredictably from one mutation to another. By combining population genetics simulations with a simple biophysical protein folding model, we show that protein thermodynamic stability accounts for a large fraction of observed mutational effects. We assume that moderately destabilizin

SUBMITTER: Wylie CS 

PROVIDER: S-EPMC3116435 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature