Dimerization induces bimodality in protein number distributions

Abstract

We examined gene expression with DNA switching between two states, active and inactive. Subpopulations emerge from mechanisms that do not arise from trivial transcriptional heterogeneity. Although the RNA demonstrates a unimodal distribution, dimerization intriguingly causes protein bimodality. No control loop or deterministic bistability are present. In such a situation, increasing the degradation rate of the protein does not lead to bimodality. The bimodality is achieved through the interplay between the protein monomer and the formation of protein dimer. We applied Stochastic Simulation Algorithm (SSA) and found that cells spontaneously change states at the protein level. While sweeping parameters, decreasing the rate constant of dimerization severely impairs the bimodality. We also examined the influence of DNA switching. To have bimodality, the system requires a proper ratio of DNA in the active state to the inactive state. In addition to bimodality of the monomer, tetramerization also causes the bimodality of the dimer.

Keywords: Bistable toggle switches; Mathematic model; Transition probability.