title: Asymmetric stochastic switching driven by intrinsic molecular noise.
abstract: Low-copy-number molecules are involved in many functions in cells. The intrinsic fluctuations of these numbers can enable stochastic switching between multiple steady states, inducing phenotypic variability. Herein we present a theoretical and computational study based on Master Equations and Fokker-Planck and Langevin descriptions of stochastic switching for a genetic circuit of autoactivation. We show that in this circuit the intrinsic fluctuations arising from low-copy numbers, which are inherently state-dependent, drive asymmetric switching. These theoretical results are consistent with experimental data that have been reported for the bistable system of the gallactose signaling network in yeast. Our study unravels that intrinsic fluctuations, while not required to describe bistability, are fundamental to understand stochastic switching and the dynamical relative stability of multiple states.
authors.affiliation: Department of Estructura i Constituents de la Matèria, Facultat de Fsica, Universitat de Barcelona, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Frigola
authors.forename: Laura
authors.initials: L
authors.lastname: Casanellas
authors.forename: José M
authors.initials: JM
authors.lastname: Sancho
authors.forename: Marta
authors.initials: M
authors.lastname: Ibañes
mesh_terms: D007700:Kinetics; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D015398:Signal Transduction; D013269:Stochastic Processes