Adaptive potential of epigenetic switching during adaptation to fluctuating environments.

Epigenetic regulation of gene expression allows for the emergence of distinct phenotypic states within the clonal population. Due to the instability of epigenetic inheritance, these phenotypes can inter-generationally switch between states in a stochastic manner. Theoretical studies of evolutionary dynamics predict that the phenotypic heterogeneity enabled by this rapid epigenetic switching between gene expression states would be favored under fluctuating environmental conditions, whereas genetic mutations, as a form of stable inheritance system, would be favored under a stable environment. To test this prediction, we engineered switcher and non-switcher yeast strains, in which the uracil biosynthesis gene URA3 is either continually expressed or switched on and off at two different rates (slow and fast switchers). Competitions between clones with an epigenetically controlled URA3 and clones without switching ability (SIR3 knock-out) show that the switchers are favored in fluctuating environments. This occurs in conditions where the environments fluctuate at similar rates to the rate of switching. However, in stable environments, but also in environments with fluctuation frequency higher than the rate of switching, we observed that genetic changes dominated. Remarkably, epigenetic clones with a high, but not with a low, rate of switching can co-exist with non-switchers even in a constant environment. Our study offers an experimental proof-of-concept that helps defining conditions of environmental fluctuation under which epigenetic switching provides an advantage.