Regulation of gene regulation - smooth binding with dynamic affinity affects evolvability

Understanding the evolvability of simple differentiating multicellular systems is a fundamental problem in the biology of genetic regulatory networks and in computational applications inspired by the metaphor of growing and developing networks of cells. We compare the evolvability of a static network model to a more realistic regulatory model with dynamic structure. In the former model, each regulatory protein-binding site is always influenced by exactly one gene product. In the latter model, binding is only more likely to occur the better the match between site and gene product is (smooth binding) and, in addition, affinity dynamically changes under the action of specificity factors during a cellpsilas lifetime. On evolutionary timescales, this means that often the strength of influences between nodes is perturbed instead of direct changes being made to network connectivity. A main result is that for evolutionary search spaces of increasing sizes evolved performance drops much more strongly in the classical network model as compared to the smooth binding model. This effect was even greater in the case of using smooth binding together with specificity factors.