Asymmetric stochastic switching driven by intrinsic molecular noise

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...

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Detalles Bibliográficos
Autores: Frigola, David, Casanellas Vilageliu, Laura, Sancho, José M., Ibañes Miguez, Marta
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/52849
Acceso en línea:https://hdl.handle.net/2445/52849
Access Level:acceso abierto
Palabra clave:Fenotip
ADN
Equació de Fokker-Planck
Dinàmica molecular
Processos estocàstics
Diferenciació cel·lular
Phenotype
DNA
Fokker-Planck equation
Molecular dynamics
Stochastic processes
Cell diferentiation
Descripción
Sumario: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.