Contribution of Selection for Protein Folding Stability in Shaping the Patterns of Polymorphisms in Coding Regions

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Contribution of Selection for Protein Folding Stability in Shaping the Patterns of Polymorphisms in Coding Regions

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Title: Contribution of Selection for Protein Folding Stability in Shaping the Patterns of Polymorphisms in Coding Regions
Author: Serohijos, Adrian W.R.; Shakhnovich, Eugene I.

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Citation: Serohijos, Adrian W.R., and Eugene I. Shakhnovich. 2013. “Contribution of Selection for Protein Folding Stability in Shaping the Patterns of Polymorphisms in Coding Regions.” Molecular Biology and Evolution 31 (1): 165-176. doi:10.1093/molbev/mst189. http://dx.doi.org/10.1093/molbev/mst189.
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Abstract: The patterns of polymorphisms in genomes are imprints of the evolutionary forces at play in nature. In particular, polymorphisms have been extensively used to infer the fitness effects of mutations and their dynamics of fixation. However, the role and contribution of molecular biophysics to these observations remain unclear. Here, we couple robust findings from protein biophysics, enzymatic flux theory, the selection against the cytotoxic effects of protein misfolding, and explicit population dynamics simulations in the polyclonal regime. First, we recapitulate results on the dynamics of clonal interference and on the shape of the DFE, thus providing them with a molecular and mechanistic foundation. Second, we predict that if evolution is indeed under the dynamic equilibrium of mutation–selection balance, the fraction of stabilizing and destabilizing mutations is almost equal among single-nucleotide polymorphisms segregating at high allele frequencies. This prediction is proven true for polymorphisms in the human coding region. Overall, our results show how selection for protein folding stability predominantly shapes the patterns of polymorphisms in coding regions.
Published Version: doi:10.1093/molbev/mst189
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879451/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879545
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