Environment Determines Epistatic Patterns for a ssDNA Virus

Abstract

Despite the accumulation of substantial quantities of information about epistatic interactions among both deleterious and beneficial mutations in a wide array of experimental systems, neither consistent patterns nor causal explanations for these interactions have yet emerged. Furthermore, the effects of mutations depend on the environment in which they are characterized, implying that the environment may also influence epistatic interactions. Recent work with beneficial mutations for the single-stranded DNA bacteriophage ID11 demonstrated that interactions between pairs of mutations could be understood by means of a simple model that assumes that mutations have additive phenotypic effects and that epistasis arises through a nonlinear phenotype-fitness map with a single intermediate optimum.To determine whether such a model could also explain changes in epistatic patterns associated with changes in environment, we measured epistatic interactions for these same mutations under conditions for which we expected to find the wild-type ID11 at different distances from its phenotypic optimum by assaying fitnesses at three different temperatures: 33°, 37°, and 41°. Epistasis was present and negative under all conditions, but became more pronounced as temperature increased. We found that the additive-phenotypes model explained these patterns as changes in the parameters of the phenotype-fitness map, but that a model that additionally allows the phenotypes to vary across temperatures performed significantly better. Our results show that ostensibly complex patterns of fitness effects and epistasis across environments can be explained by assuming a simple structure for the genotype-phenotype relationship.

Evaluating the within-host fitness effects of mutations fixed during virus adaptation to different ecotypes of a new host

“…This dependence of virus landscape topology on the environmental conditions has been previously reported for TEV [60] and ssDNA bacteriophage ID11 [61]. Therefore, rather than thinking in a fix fitness surface, we should better consider a highly dynamic and flexible adaptive surface: the seascape [62].…”

Evolutionary inevitability of sexual antagonism

“…Fisher's model also makes simplifying assumptions about the mutational architecture of traits, yet its original assumptions can be relaxed without greatly altering the model's basic predictions [21][22][23] and these predictions are adept at explaining a variety of interesting empirical patterns that emerge from the study of real organisms (e.g. [24][25][26][27][28]). In extending Fisher's model to a two-sex system, we characterize the evolution of n traits that are each expressed, but not necessarily equally, in males and females (see the electronic supplementary material).…”

What can we learn from fitness landscapes?

“…Negative pairwise epistasis for fitness arises because the mapping from biochemical and physiological traits to fitness is nearly always concave [12,14,16,24,32,33]. This pattern is observed experimentally and also one expected on theoretical grounds [29,34••,35].…”

“…Little data of this sort exist among the combinatorially complete datasets, and even limited data exist outside combinatorial completeness that would allow the key issue to be addressed. One relevant example concerns beneficial mutations in a single-stranded DNA bacteriophage, in which negative pairwise epistasis maintained the same pattern across temperature but intensified as temperature increased [33]. Another concerns the manner in which driver antibiotic molecules favor evolutionary divergence of extended-spectrum beta-lactamases [47].…”