Resource competition-driven bistability and stochastic switching amplify gene expressi noise

Abstract

Although the impact of resource competition on the deterministic behavior of synthetic gene circuits has been studied, its effects on gene expression noise remain obscure. In this work, we systematically analyze the role of resource competition in noise propagation within a genetic inhibition cascade circuit. We found that resource competition amplifies gene expression noise by introducing unexpected bistability and stochastic switching between the two stable states. This emergent bistability, driven by resource competition-mediated double negative feedback, allows one gene to dominate expression while suppressing the other in a “winner-takes-all” behavior. Our findings highlight the critical role of resource competition in shaping the noise dynamics and its propagation, underscoring the importance of considering these effects when designing and controlling synthetic circuits.