Cryptic genetic variation is enriched for potential adaptations.

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.