Cryptic genetic variation is enriched for potential adaptations

Abstract

Cryptic genetic variation accumulates under weakened selection and has been proposed as a source of evolutionary innovations. Weakened selection may, however, also lead to the accumulation of strongly deleterious or lethal alleles, swamping the effect of any potentially adaptive alleles when they are revealed. Here I model variation that is partially shielded from selection, assuming that unconditionally deleterious variation is more strongly deleterious than variation that is potentially adaptive in a future environment. I find that cryptic genetic variation can be substantially enriched for potential adaptations under a broad range of realistic parameter values, including those applicable to alternative splices and readthrough products generated by the yeast prion [PSI+]. This enrichment is dramatically stronger when multiple simultaneous changes are required to generate a potentially adaptive phenotype. Cryptic genetic variation is likely to be an effective source of useful adaptations at a time of environmental change, relative to an equivalent source of variation that has not spent time in a hidden state.

Figure 1.

The normalized extent to which cryptic genetic variation is enriched for potential adaptations, as calculated by Equation 2. N is the population size, U is the frequency per replication of unconditionally deleterious mutations, θ is the probability of environmental change per generation, s₁ is the selection coefficient against potentially adaptive alleles in the ancestral environment, and s₂ is the penetrance of alleles in the hidden state, representing the extent to which variation is shielded. (A) Enrichment is greatest for an intermediate level of shielding s₂. Note that the curves for U = 10⁻² and θ = 10⁻⁵ are almost superimposable. (B) A similar curve is seen when j = 2 alleles are required in combination for an adaptation, but in this case the magnitude of enrichment is greater. (C) For enrichment to occur at all, we need either θ > U (environmental change occurs more often than deleterious mutation in one individual) or s₂N ≫ 1 (selection on strongly deleterious mutations is still appreciable in the hidden state). (D) The maximum extent of enrichment increases with s₁N (the effectiveness of selection against nonhidden potential adaptative alleles), subject to an upper bound determined by the deleterious mutation rate U. (E) When j = 2 alleles are required in combination, very high levels of enrichment, such as 1000-fold, are easily possible. (F) Enrichment is typically greater for low levels of deleterious mutation. Note that this plot is arranged as a set of four curves for j = 1 plus a set of four curves for j = 2, and the inset refers to both sets.