Non-equilibrium dynamics of stochastic gene regulation.

Abstract

The process of gene regulation is comprised of intrinsically random events resulting in large cell-to-cell variability in mRNA and protein numbers. With gene expression being the central dogma of molecular biology, it is essential to understand the origin and role of these fluctuations. An intriguing observation is that the number of mRNA present in a cell are not only random and small but also that they are produced in bursts. The gene switches between an active and an inactive state, and the active gene transcribes mRNA in bursts. Transcriptional noise being bursty, so are the number of proteins and the subsequent gene expression levels. It is natural to ask the question: what is the reason for the bursty mRNA dynamics? And can the bursty dynamics be shown to be entropically favorable by studying the reaction kinetics underlying the gene regulation mechanism? The dynamics being an out-of-equilibrium process, the fluctuation theorem for entropy production in the reversible reaction channel is discussed. We compute the entropy production rate for varying degrees of burstiness. We find that the reaction parameters that maximize the burstiness simultaneously maximize the entropy production rate.