The causes of epistasis

Abstract

Since Bateson's discovery that genes can suppress the phenotypic effects of other genes, gene interactions-called epistasis-have been the topic of a vast research effort. Systems and developmental biologists study epistasis to understand the genotype -phenotype map, whereas evolutionary biologists recognize the fundamental importance of epistasis for evolution. Depending on its form, epistasis may lead to divergence and speciation, provide evolutionary benefits to sex and affect the robustness and evolvability of organisms. That epistasis can itself be shaped by evolution has only recently been realized. Here, we review the empirical pattern of epistasis, and some of the factors that may affect the form and extent of epistasis. Based on their divergent consequences, we distinguish between interactions with or without mean effect, and those affecting the magnitude of fitness effects or their sign. Empirical work has begun to quantify epistasis in multiple dimensions in the context of metabolic and fitness landscape models. We discuss possible proximate causes (such as protein function and metabolic networks) and ultimate factors (including mutation, recombination, and the importance of natural selection and genetic drift). We conclude that, in general, pleiotropy is an important prerequisite for epistasis, and that epistasis may evolve as an adaptive or intrinsic consequence of changes in genetic robustness and evolvability.

Effect of Host Species on Topography of the Fitness Landscape for a Plant RNA Virus

“…Pleiotropy and epistasis have strong parallelisms because the effect of an allele depends on the context in both cases, i.e., the host species for pleiotropy and the viral genetic background for epistasis. Indeed, it has been postulated that pleiotropy is a prerequisite for epistasis (3,40). This dependence is obvious for the case of sign pleiotropy, where mutations with a positive effect in the new host have a negative effect in the primary one (13).…”

“…For such simple landscapes, predicting the result of evolution is an easy task. In contrast, epistatic interactions create curvature in the landscape, and if they are of the sign or reciprocal sign type, they create multiple peaks separated by low-fitness valleys (1)(2)(3). The reproducibility of evolution in such complex landscapes, and therefore our ability to predict its outcome, diminishes as the number of possible peaks, that is, the ruggedness of the landscape, increases.…”

Benefit of transferred mutations is better predicted by the fitness of recipients than by their ecological or genetic relatedness

“…epistasis | mutation-by-genetic background interactions | beneficial mutations | horizontal gene transfer M utations can interact with one another and with their broader genetic background to affect fitness, a phenomenon known as epistasis (1). Epistasis plays a key role in many aspects of biology, including theories of speciation (2,3), the evolution and maintenance of sex (4,5), adaptation (6)(7)(8), and evolutionary contingency (9,10).…”

The Origin of Population Diversity: Stochastic Interactions between a Modifier Variant and the Individual Genetic Background

“…Therefore, one extreme tail may include the non-fittest who cannot leave offspring and the other tail or the border flanking to the non-fittest tail may provide the founder or pioneer who is the key person for human terrestrial migration and local adaptation. In spite of the stochastic manner of the stochastic epistasis, the repeated purge of the same non-fittest extremes may be another process of evolutionary trends in which the phenotypic mean value can be passively changed [67]. In a liability-probability model, the non-fittest extreme tail possesses extremely low fecundity and the fecundity is continuously and sharply recovered at the majority of the bell-shaped population [73].…”

“…This diversification strategy is, no doubt, the only way to win the chance at survival [64] [65]. Interactions between polymorphic loci can make the organisms insensitive to the impact of novel mutations or environmental perturbation [59] [66] [67], and stochastic epistatic modules may have critical roles in this buffer system. A variant which was buffered and harbored in the stochastic genetic network is one of the modifiers of the module and can participate in an active evolutionary phenotypic change through a nonlinear alteration of the mean value or the position of the distribution in multi-dimensions of trait vectors [63] [68].…”