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Molecular evolution is often conceptualised as adaptive walks on rugged fitness landscapes, driven by mutations and constrained by incremental fitness selection. It is well known that epistasis shapes the ruggedness of the landscape's…
Evolutionary adaptation is the process that increases the fit of a population to the fitness landscape it inhabits. As a consequence, evolutionary dynamics is shaped, constrained, and channeled, by that fitness landscape. Much work has been…
A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the…
On rugged fitness landscapes where sign epistasis is common, adaptation can often involve either individually beneficial "uphill" mutations or more complex mutational trajectories involving fitness valleys or plateaus. The dynamics of the…
Biological evolution can be conceptualized as a search process in the space of gene sequences guided by the fitness landscape, a mapping that assigns a measure of reproductive value to each genotype. Here we discuss probabilistic models of…
The structure and function of a protein are determined by its amino acid sequence. While random mutations change a protein's sequence, evolutionary forces shape its structural fold and biological activity. Studies have shown that neutral…
We consider a population evolving due to mutation, selection and recombination, where selection includes single-locus terms (additive fitness) and two-loci terms (pairwise epistatic fitness). We further consider the problem of inferring…
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…
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…
Defining the extent of epistasis - the non-independence of the effects of mutations - is essential for understanding the relationship of genotype, phenotype, and fitness in biological systems. The applications cover many areas of biological…
Growing efforts to measure fitness landscapes in molecular and microbial systems are premised on a tight relationship between landscape topography and evolutionary trajectories. This relationship, however, is far from being straightforward:…
Epistasis, or the context-dependence of the effects of mutations, limits our ability to predict the functional impact of combinations of mutations, and ultimately our ability to predict evolutionary trajectories. Information about the…
Genotype-to-phenotype maps and the related fitness landscapes that include epistatic interactions are difficult to measure because of their high dimensional structure. Here we construct such a map using the recently collected corpora of…
Although many phenotypic traits are determined by a large number of genetic variants, the behavior of allele frequencies in a polygenic trait is not completely understood. The problem is especially challenging when the quantitative trait of…
Evolution depends on the fitness of organisms, the expected rate of reproducing. Directly getting offspring is the most basic form of fitness, but fitness can also be increased indirectly by helping genetically related individuals (such as…
The energy landscapes of proteins have evolved to be different from most random heteropolymers. Many studies have concluded that evolutionary selection for rapid and reliable folding to a given structure that is stable at biological…
We show that higher order epistasis has a substantial impact on evolutionary dynamics by analyzing peaks in the fitness landscapes. There are 193,270,310 fitness graphs, or cube orientations, for 4-locus systems, distributed on 511, 863…
In a living system composed of interacting components such as molecules, cells, and tissues, each component often adaptively changes its internal states in response to interactions with its surrounding components. For example, individual…
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…
In this work, we integrate theoretical modeling, molecular simulation, and empirical analysis to identify and characterize evolutionary hysteresis. We first show how epistatic interactions create bistable fitness landscapes and structural…