Cryptic genetic variation accelerates evolution by opening access to diverse adaptive peaks.

Cryptic genetic variation can facilitate adaptation in evolving populations. To elucidate the underlying genetic mechanisms, we used directed evolution in Escherichia coli to accumulate variation in populations of yellow fluorescent proteins and then evolved these proteins toward the new phenotype of green fluorescence. Populations with cryptic variation evolved adaptive genotypes with greater diversity and higher fitness than populations without cryptic variation, which converged on similar genotypes. Populations with cryptic variation accumulated neutral or deleterious mutations that break the constraints on the order in which adaptive mutations arise. In doing so, cryptic variation opens paths to adaptive genotypes, creates historical contingency, and reduces the predictability of evolution by allowing different replicate populations to climb different adaptive peaks and explore otherwise-inaccessible regions of an adaptive landscape.