Stable maintenance of a hidden switch as a way to increase the gene expression stability

In response to severe stress, wild-type organisms can release alternative phenotypes that are hidden under normal conditions and are associated with underlying genetic variations. A number of such stress-induced phenotypic switchings have been reported to be based on reactivation of hidden thresholds; under the normal condition, a high barrier separating alternative phenotypes ensures the expression of single discrete phenotype, but a severe perturbation can lower the barrier to a level at which to expose cryptic alternatives. While the importance of such threshold-based switches as the mechanism to generate adaptive novelties under variable environments has been appreciated, it still remains elusive how naturally selected organisms can maintain the phenotypic switching capability when such switching has been disused for a long period of time. Here, through the use of computer simulation, we analyzed adaptive evolution of gene circuits under stabilizing selection. We found that different strategies evolved to acquire reduced levels of gene expression noise around the optimum expression level. To incrementally improve the gene expression stability from a founding population with bistable individuals, the evolution consistently took the direction to raise the height of the potential barrier of bistable systems. Our results demonstrate that hidden phenotypic switches can be stably maintained during environmental stasis, facilitating the release of potentially adaptive phenotypic alternatives in the event of substantial perturbations.