ArticleGenome biology and evolution2013
Population size dependence of fitness effect distribution and substitution rate probed by biophysical model of protein thermostability.
Article in Genome biology and evolution, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- The distribution of fitness effects of nonsynonymous mutations varies phylogenetically across animals.PLoS biology · 2026Article
- Empirical Validation of the Nearly Neutral Theory at Divergence and Population-Genomic Scales Using 144 Placental Mammal Genomes.Genome biology and evolution · 2026Article
- EMPIRICAL VALIDATION OF THE NEARLY NEUTRAL THEORY AT DIVERGENCE AND POPULATION GENOMIC SCALE USING 144 PLACENTAL MAMMALS GENOMES.bioRxiv : the preprint server for biology · 2026Article
- Article
- Evolutionary consequences of domestication on the selective effects of new amino acid changing mutations in canids.bioRxiv : the preprint server for biology · 2024Article
- Selection among site-dependent structurally constrained substitution models of protein evolution by approximate Bayesian computation.Bioinformatics (Oxford, England) · 2024Article
- Substitution Models of Protein Evolution with Selection on Enzymatic Activity.Molecular biology and evolution · 2024Article
- Half a Century of Controversy: The Neutralist/Selectionist Debate in Molecular Evolution.Genome biology and evolution · 2024Article
- Inferring the distributions of fitness effects and proportions of strongly deleterious mutations.G3 (Bethesda, Md.) · 2023Article
- Highly Abundant Proteins Are Highly Thermostable.Genome biology and evolution · 2023Article
- A review of visualisations of protein fold networks and their relationship with sequence and function.Biological reviews of the Cambridge Philosophical Society · 2023Review
- Evolution of Amino Acid Propensities under Stability-Mediated Epistasis.Molecular biology and evolution · 2022Article
- 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
- The Marginal Stability of Proteins: How the Jiggling and Wiggling of Atoms is Connected to Neutral Evolution.Journal of molecular evolution · 2020Article
- Evolutionary Processes and Biophysical Mechanisms: Revisiting Why Evolved Proteins Are Marginally Stable.Journal of molecular evolution · 2020Article
- Protein evolution depends on multiple distinct population size parameters.BMC evolutionary biology · 2018Review
- Sequence entropy of folding and the absolute rate of amino acid substitutions.Nature ecology & evolution · 2017Article
- Characterizing the roles of changing population size and selection on the evolution of flux control in metabolic pathways.BMC evolutionary biology · 2017Article
- Inference of the Distribution of Selection Coefficients for New Nonsynonymous Mutations Using Large Samples.Genetics · 2017Article
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Abstract
The predicted effect of effective population size on the distribution of fitness effects and substitution rate is critically dependent on the relationship between sequence and fitness. This highlights the importance of using models that are informed by the molecular biology, biochemistry, and biophysics of the evolving systems. We describe a computational model based on fundamental aspects of biophysics, the requirement for (most) proteins to be thermodynamically stable. Using this model, we find that differences in population size have minimal impact on the distribution of population-scaled fitness effects, as well as on the rate of molecular evolution. This is because larger populations result in selection for more stable proteins that are less affected by mutations. This reduction in the magnitude of the fitness effects almost exactly cancels the greater selective pressure resulting from the larger population size. Conversely, changes in the population size in either direction cause transient increases in the substitution rate. As differences in population size often correspond to changes in population size, this makes comparisons of substitution rates in different lineages difficult to interpret.
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