Extrinsic Noise Driven Phenotype Switching in a Self-Regulating Gene

Phys Rev Lett. 2013 Aug 2;111(5):058102. doi: 10.1103/PhysRevLett.111.058102. Epub 2013 Jul 30.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Gene Expression Regulation*
  • Gene Regulatory Networks*
  • Models, Genetic*
  • Monte Carlo Method
  • Phenotype