On the Implications of Controller Resource Consumption for the Long-Term Performance of Synthetic Gene Circuits

Loss-of-function due to mutation presents a fundamental roadblock to the widespread application of engineered biological systems. The onset of mutations in synthetic gene regulatory networks creates parametric uncertainty while the resulting growth competition between mutant populations creates perturbations to the uptake of nutrients. Negative feedback is therefore an attractive strategy to extend the performance of gene circuits over evolutionary time. Here, we develop a mathematical model to evaluate the performance of a simple gene circuit within an evolving population. We show that negative feedback can improve evolutionary longevity. However, when we account for additional host resource consumption by the controller, this benefit can be reversed.