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Comparison of deterministic and stochastic models of the lac operon genetic network

Stamatakis, M; Mantzaris, NV; (2009) Comparison of deterministic and stochastic models of the lac operon genetic network. Biophysical Journal , 96 (3) 887 - 906. 10.1016/j.bpj.2008.10.028. Green open access

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Abstract

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. © 2009 by the Biophysical Society.

Type: Article
Title: Comparison of deterministic and stochastic models of the lac operon genetic network
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bpj.2008.10.028
Publisher version: http://dx.doi.org/10.1016/j.bpj.2008.10.028
Language: English
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Chemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/1356187
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