Functional characteristics of additional positive feedback in genetic circuits

Abstract

Multiple-positive feedback circuits are ubiquitous regulatory motifs in complex bio-molecular networks. A popular topic is why multiple-positive feedback mechanisms have been evolved and selected by organisms. To this end, a two-component dual-positive feedback genetic circuit is investigated, which consists of an auto-activation loop and a double negative feedback circuit. The auto-activation loop acts as an additional positive feedback loop (APFL), and our aim is to explore the functional characteristics of the APFL. Investigations reveal that the APFL can regulate the size of bistable region and the robust attractiveness of stable steady states. It is also found that the APFL can regulate global relative input–output sensitivities of the system. Furthermore, the APFL can tune the response speed, noise resistance and stochastic switch behavior of the system, which makes it easy to realize functional tunability and robust decision-making. Therefore, rationalizing why multiple-positive feedback circuits so frequently appear in real-world biological systems. Potential applications of the associated investigations include the design of artificial genetic circuits, the modeling and model reduction for large-scale bio-molecular networks.