Comparison of deterministic and stochastic models of the lac operon genetic network.
The lac operon has been a paradigm for genetic regulation with positive feedback, and several modeling studies have described its dynamics at various levels of detail. However, it has not yet been analyzed how stochasticity can enrich the system's behavior, creating effects that are not observed in the deterministic case. To address this problem we use a comparative approach. We develop a reaction network for the dynamics of the lac operon genetic switch and derive corresponding deterministic and stochastic models that incorporate biological details. We then analyze the effects of key biomolecular mechanisms, such as promoter strength and binding affinities, on the behavior of the models. No assumptions or approximations are made when building the models other than those utilized in the reaction network. Thus, we are able to carry out a meaningful comparison between the predictions of the two models to demonstrate genuine effects of stochasticity. Such a comparison reveals that in the presence of stochasticity, certain biomolecular mechanisms can profoundly influence the region where the system exhibits bistability, a key characteristic of the lac operon dynamics. For these cases, the temporal asymptotic behavior of the deterministic model remains unchanged, indicating a role of stochasticity in modulating the behavior of the system.
Stamatakis
Michail
M
Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas 77005, USA. mstam@rice.edu
Mantzaris
Nikos V
NV
D005110:Extracellular Space / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D007763:Lac Operon / Q000235:genetics*; D008957:Models, Genetic; D012680:Sensitivity and Specificity; D013269:Stochastic Processes; D013862:Thiogalactosides / Q000378:metabolism; D013997:Time Factors
D013862:Thiogalactosides