Related papers: Strong Selection Significantly Increases Epistatic…
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…
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…
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…
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…
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…
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…
Evolutionary adaptation is often likened to climbing a hill or peak. While this process is simple for fitness landscapes where mutations are independent, the interaction between mutations (epistasis) as well as mutations at loci that affect…
The evolutionary reason for the increase in gene length from archaea to prokaryotes to eukaryotes observed in large scale genome sequencing efforts has been unclear. We propose here that the increasing complexity of protein-protein…
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…
Viral capsids are structurally constrained by interactions amongst the amino acids of the constituting proteins. Therefore, epistasis is expected to evolve amongst sites engaged in physical interactions, and to influence their substitution…
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…
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 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…
Protein electrostatics have been demonstrated to play a vital role in protein functionality, with many functionally important amino acid residues exhibiting an electrostatic state that is altered from that of a normal amino acid residue.…
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…
The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the…
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 evolution of drug resistance in HIV occurs by the fixation of specific, well-known, drug-resistance mutations, but the underlying population genetic processes are not well understood. By analyzing within-patient longitudinal sequence…