Relationship between protein thermodynamic constraints and variation of evolutionary rates among sites

Physical Biology
Julian EchaveClaus O Wilke

Abstract

Evolutionary-rate variation among sites within proteins depends on functional and biophysical properties that constrain protein evolution. It is generally accepted that proteins must be able to fold stably in order to function. However, the relationship between stability constraints and among-sites rate variation is not well understood. Here, we present a biophysical model that links the thermodynamic stability changes due to mutations at sites in proteins ([Formula: see text]) to the rate at which mutations accumulate at those sites over evolutionary time. We find that such a 'stability model' generally performs well, displaying correlations between predicted and empirically observed rates of up to 0.75 for some proteins. We further find that our model has comparable predictive power as does an alternative, recently proposed 'stress model' that explains evolutionary-rate variation among sites in terms of the excess energy needed for mutants to adopt the correct active structure ([Formula: see text]). The two models make distinct predictions, though, and for some proteins the stability model outperforms the stress model and vice versa. We conclude that both stability and stress constrain site-specific sequence evolution in prot...Continue Reading

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Citations

Jan 20, 2016·Nature Reviews. Genetics·Julian EchaveClaus O Wilke
Dec 19, 2015·Journal of Theoretical Biology·Sanzo Miyazawa
Oct 9, 2015·Molecular Biology and Evolution·Matteo FigliuzziMartin Weigt
Mar 15, 2016·Protein Science : a Publication of the Protein Society·Eleisha L JacksonClaus O Wilke
May 4, 2016·PLoS Biology·Benjamin R JackClaus O Wilke
Mar 17, 2017·Annual Review of Biophysics·Julian Echave, Claus O Wilke
Oct 16, 2015·Journal of the Royal Society, Interface·Austin G Meyer, Claus O Wilke
Sep 9, 2020·Molecular Biology and Evolution·Noor YoussefJoseph P Bielawski
Nov 25, 2020·Journal of Molecular Evolution·Mackenzie M Johnson, Claus O Wilke
May 18, 2021·Frontiers in Molecular Biosciences·Benjamin Dubreuil, Emmanuel D Levy
Jul 9, 2021·Current Research in Structural Biology·María Laura Marcos, Julian Echave

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