The Population Genetic Theory of Hidden Variation and Genetic Robustness

Abstract

One of the most solid generalizations of transmission genetics is that the phenotypic variance of populations carrying a major mutation is increased relative to the wild type. At least some part of this higher variance is genetic and due to release of previously hidden variation. Similarly, stressful environments also lead to the expression of hidden variation. These two observations have been considered as evidence that the wild type has evolved robustness against genetic variation, i.e., genetic canalization. In this article we present a general model for the interaction of a major mutation or a novel environment with the additive genetic basis of a quantitative character under stabilizing selection. We introduce an approximation to the genetic variance in mutation-selection-drift balance that includes the previously used stochastic Gaussian and house-of-cards approximations as limiting cases. We then show that the release of hidden genetic variation is a generic property of models with epistasis or genotype-environment interaction, regardless of whether the wild-type genotype is canalized or not. As a consequence, the additive genetic variance increases upon a change in the environment or the genetic background even if the mutant character state is as robust as the wild-type character. Estimates show that this predicted increase can be considerable, in particular in large populations and if there are conditionally neutral alleles at the loci underlying the trait. A brief review of the relevant literature suggests that the assumptions of this model are likely to be generic for polygenic traits. We conclude that the release of hidden genetic variance due to a major mutation or environmental stress does not demonstrate canalization of the wild-type genotype.

Evolution under canalization and the dual roles of microRNAs—A hypothesis

“…Given that HSP90 is a chaperon protein that helps the folding of many other proteins, it can conceivably influence the phenotypic consequences of those gene products. The hsp90 gene was suggested to be a canalizing gene (but see Bergman and Siegal [2003] and Hermisson and Wagner [2004] for discussions on the connection between canalization and cryptic genetic variation).…”

Mutations Leading to Loss of Sporulation Ability in Bacillus subtilis Are Sufficiently Frequent to Favor Genetic Canalization

“…Reinterpreting the results of Hermisson and Wagner (2004) in the context of neutral network theory, variation can be revealed when a set of genotypes occupy a range of locations on the neutral network, as shown in Figure 1, A and B. This is a distinct concept from adaptive canalization, which refers to the shift of the set of genotypes toward their optimal distribution shown in Figure 1A.…”

“…Hermisson and Wagner (2004) have described a flaw in this logic. According to their metaphor, standing genetic variation is ''dust'' and canalization is a ''rug.''…”

“…A major mutation shifts the rug, revealing dust (variation) underneath. Modeling certain forms of epistasis using a quantitative genetic approach, Hermisson and Wagner (2004) showed that revealing variation (shifting the rug) can occur without a change in canalization (size of the rug). Mutants can be more variable than wild-type individuals simply because of a shift in the rug, and so this observation does not prove that the system was canalized.…”

The Effects of Stabilizing and Directional Selection on Phenotypic and Genotypic Variation in a Population of RNA Enzymes

“…However, this is not necessarily the case. Whether it does depends on several factors, including the shape -convex or concave -of the fitness function (Layzer 1978), the distribution of trait values (Bürger 1991;Hansen 1992), whether a trait optimum fluctuates with time, the presence and kind of genotype-by-environment interactions (Hermisson and Wagner 2004), the existence of epistatic interactions among loci (Hansen 2006), and the extent of phenotypic canalization before the onset of directional selection (de Visser et al 2003;Hermisson and Wagner 2004). The change in phenotypic variance caused by periods of stabilizing selection is no easier to predict.…”