Extrinsic noise driven phenotype switching in a self-regulating gene

Michael Assaf, Elijah Roberts, Zaida Luthey-Schulten, Nigel Goldenfeld

Research output: Contribution to journalArticlepeer-review

Abstract

Analysis of complex gene regulation networks gives rise to a landscape of metastable phenotypic states for cells. Heterogeneity within a population arises due to infrequent noise-driven transitions of individual cells between nearby metastable states. While most previous works have focused on the role of intrinsic fluctuations in driving such transitions, in this Letter we investigate the role of extrinsic fluctuations. First, we develop an analytical framework to study the combined effect of intrinsic and extrinsic noise on a toy model of a Boolean regulated genetic switch. We then extend these ideas to a more biologically relevant model with a Hill-like regulatory function. Employing our theory and Monte Carlo simulations, we show that extrinsic noise can significantly alter the lifetimes of the phenotypic states and may fundamentally change the escape mechanism. Finally, our theory can be readily generalized to more complex decision making networks in biology.

Original languageEnglish (US)
Article number058102
Pages (from-to)58102
Number of pages1
JournalPhysical review letters
Volume111
Issue number5
DOIs
StatePublished - Aug 2 2013

ASJC Scopus subject areas

  • Physics and Astronomy(all)

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