Extrinsic noise driven phenotype switching in a self-regulating gene

Abstract

Due to inherent noise in intracellular networks cellular decisions can be random, so genetically identical cells can display different phenotypic behavior even in identical environments. Most previous work in understanding the decision-making process has focused on the role of intrinsic noise in these systems. Yet, especially in the high copy-number regime, extrinsic noise has been shown to be much more significant. Here, using a prototypical example of a bistable self-regulating gene model, we develop a theoretical framework describing the combined effect of intrinsic and extrinsic noise on the dynamics of stochastic genetic switches. Employing our theory and Monte Carlo simulations, we show that extrinsic noise not only significantly alters the lifetimes of the phenotypic states, but can induce bistability in unexpected regions of parameter space, and may fundamentally change the escape mechanism. These results have implications for interpreting experimentally observed heterogeneity in cellular populations and for stochastic modeling of cellular decision processes.

5 pages, 4 figures

References in corpus (7)

• Diamondoid Molecules
• Colored extrinsic fluctuations and stochastic gene expression
• Spectral theory of metastability and extinction in birth-death systems
• Eliminating fast reactions in stochastic simulations of biochemical networks: a bistable genetic switch
• Slow protein fluctuations explain the emergence of growth phenotypes and persistence in clonal bacterial populations
• Multiprotein DNA looping
• Impact of Colored Environmental Noise on the Extinction of a Long-Lived Stochastic Population: Role of the Allee Effect

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