Dynamics and bistability in a reduced model of the lac operon.
It is known that the lac operon regulatory pathway is capable of showing bistable behavior. This is an important complex feature, arising from the nonlinearity of the involved mechanisms, which is essential to understand the dynamic behavior of this molecular regulatory system. To find which of the mechanisms involved in the regulation of the lac operon is the origin of bistability, we take a previously published model which accounts for the dynamics of mRNA, lactose, allolactose, permease and beta-galactosidase involvement and simplify it by ignoring permease dynamics (assuming a constant permease concentration). To test the behavior of the reduced model, three existing sets of data on beta-galactosidase levels as a function of time are simulated and we obtain a reasonable agreement between the data and the model predictions. The steady states of the reduced model were numerically and analytically analyzed and it was shown that it may indeed display bistability, depending on the extracellular lactose concentration and growth rate.
Yildirim
Necmettin
N
Centre for Nonlinear Dynamics, McGill University, Montreal, Quebec H3G 1Y6, Canada.
Santillan
Moises
M
Horike
Daisuke
D
Mackey
Michael C
MC
D003198:Computer Simulation; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development; D005246:Feedback / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D007763:Lac Operon / Q000502:physiology*; D007785:Lactose / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D008957:Models, Genetic; D017711:Nonlinear Dynamics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D001616:beta-Galactosidase; D007785:Lactose