ArticleNature ecology & evolution2017
Sequence entropy of folding and the absolute rate of amino acid substitutions.
Article in Nature ecology & evolution, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Site-Specific Structure and Stability Constrained Substitution Models Improve Phylogenetic Inference.Systematic biology · 2026Article
- Exploring Evolution to Uncover Insights Into Protein Mutational Stability.Molecular biology and evolution · 2025Article
- Estimating the proportion of beneficial mutations that are not adaptive in mammals.PLoS genetics · 2024Article
- Selection among site-dependent structurally constrained substitution models of protein evolution by approximate Bayesian computation.Bioinformatics (Oxford, England) · 2024Article
- Main Factors Shaping Amino Acid Usage Across Evolution.Journal of molecular evolution · 2023Review
- Genes and sites under adaptation at the phylogenetic scale also exhibit adaptation at the population-genetic scale.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Using machine learning to predict the effects and consequences of mutations in proteins.Current opinion in structural biology · 2023Review
- Arrow of Time, Entropy, and Protein Folding: Holistic View on Biochirality.International journal of molecular sciences · 2022Review
- Evolution of Amino Acid Propensities under Stability-Mediated Epistasis.Molecular biology and evolution · 2022Article
- Evolutionary coupling range varies widely among enzymes depending on selection pressure.Biophysical journal · 2021Article
- Shifts in amino acid preferences as proteins evolve: A synthesis of experimental and theoretical work.Protein science : a publication of the Protein Society · 2021Review
- Inferring Long-Term Effective Population Size with Mutation-Selection Models.Molecular biology and evolution · 2021Article
- Inferring the number and position of changes in selective regime in a non-equilibrium mutation-selection framework.BMC ecology and evolution · 2021Article
- Senescence and entrenchment in evolution of amino acid sites.Nature communications · 2020Article
- The Marginal Stability of Proteins: How the Jiggling and Wiggling of Atoms is Connected to Neutral Evolution.Journal of molecular evolution · 2020Article
- Epistatic contributions promote the unification of incompatible models of neutral molecular evolution.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The variation among sites of protein structure divergence is shaped by mutation and scaled by selection.Current research in structural biology · 2020Article
- Biophysics and population size constrains speciation in an evolutionary model of developmental system drift.PLoS computational biology · 2019Article
- Evolution of protein interfaces in multimers and fibrils.The Journal of chemical physics · 2019Article
- mtProtEvol: the resource presenting molecular evolution analysis of proteins involved in the function of Vertebrate mitochondria.BMC evolutionary biology · 2019Article
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2 authors.
Funding
Abstract
Adequate representations of protein evolution should consider how the acceptance of mutations depends on the sequence context in which they arise. However, epistatic interactions among sites in a protein result in hererogeneities in the substitution rate, both temporal and spatial, that are beyond the capabilities of current models. Here we use parallels between amino acid substitutions and chemical reaction kinetics to develop an improved theory of protein evolution. We constructed a mechanistic framework for modelling amino acid substitution rates that uses the formalisms of statistical mechanics, with principles of population genetics underlying the analysis. Theoretical analyses and computer simulations of proteins under purifying selection for thermodynamic stability show that substitution rates and the stabilization of resident amino acids (the 'evolutionary Stokes shift') can be predicted from biophysics and the effect of sequence entropy alone. Furthermore, we demonstrate that substitutions predominantly occur when epistatic interactions result in near neutrality; substitution rates are determined by how often epistasis results in such nearly neutral conditions. This theory provides a general framework for modelling protein sequence change under purifying selection, potentially explains patterns of convergence and mutation rates in real proteins that are incompatible with previous models, and provides a better null model for the detection of adaptive changes.
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