Phenotypic robustness can increase phenotypic variability after non-genetic perturbations in gene regulatory circuits

Non-genetic perturbations, such as environmental change or developmental noise, can induce novel phenotypes. If an induced phenotype confers a fitness advantage, selection may promote its genetic stabilization. Non-genetic perturbations can thus initiate evolutionary innovation. Genetic variation that is not usually phenotypically visible may play an important role in this process. Populations under stabilizing selection on a phenotype that is robust to mutations can accumulate such variation. After non-genetic perturbations, this variation can become a source of new phenotypes. We here study the relationship between a phenotype's robustness to mutations and a population's potential to generate novel phenotypic variation. To this end, we use a well-studied model of transcriptional regulation circuits. Such circuits are important in many evolutionary innovations. We find that phenotypic robustness promotes phenotypic variability in response to non-genetic perturbations, but not in response to mutation. Our work suggests that non-genetic perturbations may initiate innovation more frequently in mutationally robust gene expression traits.