Optimizing periodicity and polymodality in noise-induced genetic oscillators

Abstract

Many cellular functions are based on the rhythmic organization of biological processes into self-repeating cascades of events. Some of these periodic processes, such as the cell cycles of several species, exhibit conspicuous irregularities in the form of period skippings, which lead to polymodal distributions of cycle lengths. A recently proposed mechanism that accounts for this quantized behavior is the stabilization of a Hopf-unstable state by molecular noise. Here we investigate the effect of varying noise in a model system, namely an excitable activator-repressor genetic circuit, that displays this noise-induced stabilization effect. Our results show that an optimal noise level enhances the regularity (coherence) of the cycles, in a form of coherence resonance. Similar noise levels also optimize the multimodal nature of the cycle lengths. Together, these results illustrate how molecular noise within a minimal gene regulatory motif confers robust generation of polymodal patterns of periodicity.