Related papers: Historical contingency and entrenchment in protein…
The interconnected processes of protein folding, mutations, epistasis, and evolution have all been the subject of extensive analysis throughout the years due to their significance for structural and evolutionary biology. The origin…
The contribution to an organism's phenotype from one genetic locus may depend upon the status of other loci. Such epistatic interactions among loci are now recognized as fundamental to shaping the process of adaptation in evolving…
Epistatic interactions between residues determine a protein's adaptability and shape its evolutionary trajectory. When a protein experiences a changed environment, it is under strong selection to find a peak in the new fitness landscape. It…
We introduce a data-driven epistatic model of protein evolution, capable of generating evolutionary trajectories spanning very different time scales reaching from individual mutations to diverged homologs. Our in silico evolution…
Understanding the relationship between protein sequence, function, and stability is a fundamental problem in biology. While high-throughput methods have produced large numbers of sequence-function pairs, functional assays do not distinguish…
Genetic interactions can strongly influence the fitness effects of individual mutations, yet the impact of these epistatic interactions on evolutionary dynamics remains poorly understood. Here we investigate the evolutionary role of…
Proteins have evolved through mutations, amino acid substitutions, since life appeared on Earth, some 109 years ago. The study of these phenomena has been of particular significance because of their impact on protein stability, function,…
Epistasis occurs when the effect of a mutation depends on its carrier's genetic background. Despite increasing evidence that epistasis for fitness is common, its role during evolution is contentious. Fitness landscapes, mappings of genotype…
Epistasis refers to the phenomenon in which phenotypic consequences caused by mutation of one gene depend on one or more mutations at another gene. Epistasis is critical for understanding many genetic and evolutionary processes, including…
This piece serves two purposes. Firstly, it aims at elucidating the role of epistasis in shaping, at a molecular level, the evolutionary paths of proteins, as well as the extent to which these epistatic effects are the outcome of an…
The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…
Protein evolution involves mutations occurring across a wide range of time scales. In analogy with disordered systems in statistical physics, this dynamical heterogeneity suggests strong correlations between mutations happening at distinct…
We investigate the fitness advantage associated with the robustness of a phenotype against deleterious mutations using deterministic mutation-selection models of quasispecies type equipped with a mesa shaped fitness landscape. We obtain…
An important question in molecular evolution is whether an amino acid that occurs at a given position makes an independent contribution to fitness, or whether its effect depends on the state of other loci in the organism's genome, a…
The common understanding of protein evolution has been that neutral or slightly deleterious mutations are fixed by random drift, and evolutionary rate is determined primarily by the proportion of neutral mutations. However, recent studies…
Epistatic interactions between mutations add substantial complexity to adaptive landscapes, and are often thought of as detrimental to our ability to predict evolution. Yet, patterns of global epistasis, in which the fitness effect of a…
Since protein mutations are the main driving force of evolution at the molecular level, a proper analysis of them (and the factors controlling them) will enable us to find a response to several crucial queries in evolutionary biology. Among…
The primary aim of this work is to explore how proteins point mutations impact their marginal stability and, hence, their evolvability. With this purpose, we show that the use of four classic notions, namely, those from Leibniz & Kant…
Modern biomedicine is challenged to predict the effects of genetic variation. Systematic functional assays of point mutants of proteins have provided valuable empirical information, but vast regions of sequence space remain unexplored.…
The ability to absorb mutations while retaining structure and function, or mutational robustness, is a remarkable property of natural proteins. In this Letter, we use a computational model of organismic evolution [Zeldovich et al, PLOS Comp…