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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…

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…

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…

The fitness contribution of an allele at one genetic site may depend on alleles at other sites, a phenomenon known as epistasis. Epistasis can profoundly influence the process of evolution in populations under selection, and can shape the…

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…

Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing…

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 nature of epistasis has important consequences for the evolutionary significance of sex and recombination. Recent efforts to find negative epistasis as source of negative linkage disequilibrium and associated long-term sex advantage…

Population dynamics and evolutionary genetics underly the structure of ecosystems, changing on the same timescale for interacting species with rapid turnover, such as virus (e.g. HIV) and immune response. Thus, an important problem in…

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…

In epistatic fitness landscapes, the fitness effect of a mutation depends on the genetic background and may even switch between deleterious and beneficial depending on the presence of another mutation. Epistatic interactions may cause both…

Fitness landscapes provide a quantitative framework for understanding how natural selection shapes evolutionary trajectories. A central feature of these landscapes is their number of local optima, which determines whether fitness-increasing…

Identifying and quantifying the benefits of sex and recombination is a long standing problem in evolutionary theory. In particular, contradictory claims have been made about the existence of a benefit of recombination on high dimensional…

Despite the importance of a thermodynamically stable structure with a conserved fold for protein function, almost all evolutionary models neglect site-site correlations that arise from physical interactions between neighboring amino acid…

Biochemical and regulatory interactions central to biological networks are expected to cause extensive genetic interactions or epistasis affecting the heritability of complex traits and the distribution of genotypes in populations. However,…

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…

Living systems evolve one mutation at a time, but a single mutation can alter the effect of subsequent mutations. The underlying mechanistic determinants of such epistasis are unclear. Here, we demonstrate that the physical dynamics of a…

Understanding of the evolutionary origins of protein structures represents a key component of the understanding of molecular evolution as a whole. Here we seek to elucidate how the features of an underlying protein structural "space" might…

Epistasis describes the phenomenon that mutations at different loci do not have independent effects with regard to certain phenotypes. Understanding the global epistatic landscape is vital for many genetic and evolutionary theories. Current…