Phenotypic plasticity can facilitate adaptive evolution in gene regulatory circuits

We here analyze a well-studied model of gene regulatory circuits. A circuit's genotype encodes the regulatory interactions among circuit genes, and its phenotype corresponds to a stable gene activity pattern the circuit forms. For this model, we study how genotypes are arranged in genotype space, where the distance between two genotypes reflects the number of regulatory mutations that set those genotypes apart. Specifically, we address whether this arrangement favors adaptive evolution mediated by plasticity. We find that plasticity facilitates the origin of genotypes that produce a new phenotype in response to non-genetic perturbations. We also find that selection can then stabilize the new phenotype genetically, allowing it to become a circuit's dominant gene expression phenotype. These are generic properties of the circuits we study here.Taken together, our observations suggest that phenotypic plasticity frequently facilitates the evolution of novel beneficial gene activity patterns in gene regulatory circuits.Novel adaptive phenotypes endow organisms with new means to survive and reproduce. Such new phenotypes arise through a process that involves natural selection and random genotypic change caused by mutation. Life's ability to adapt through random change is remarkable, as many man-made systems do not have this ability [1,2]. It is a result of how genotypic change translates into phenotypic change [1,3].Different classes of biological systems, ranging from protein and RNA molecules [4-6] to regulatory circuits [7] and genome-scale metabolic networks [8], share some similarities in how they translate genotypic change into phenotypic change. First, any genotype G produces some phenotype P in the absence of environmental and other perturbations. We will refer to such a 'default' phenotype as G's native phenotype (analogous to the native conformation of a protein). Second, in all these systems genotypes exist in vast genotype spaces. In a genotype space, the dista