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Molecules 2019, 24(1), 198; https://doi.org/10.3390/molecules24010198

Effects of Population Dynamics on Establishment of a Restriction-Modification System in a Bacterial Host

1
Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia
2
Multidisciplinary PhD program in Biophysics, University of Belgrade, 11000 Belgrade, Serbia
3
Institute of Physics Belgrade, University of Belgrade, 11080 Belgrade, Serbia
4
Waksman Institute of Microbiology, Rutgers University, Piscataway, NJ 08854, USA
5
Center for Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo 143026, Russia
*
Author to whom correspondence should be addressed.
Academic Editor: Junji Iwahara
Received: 21 November 2018 / Revised: 28 December 2018 / Accepted: 3 January 2019 / Published: 7 January 2019
(This article belongs to the Special Issue Protein-DNA Interactions: From Biophysics to Genomics)
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Abstract

In vivo dynamics of protein levels in bacterial cells depend on both intracellular regulation and relevant population dynamics. Such population dynamics effects, e.g., interplay between cell and plasmid division rates, are, however, often neglected in modeling gene expression regulation. Including them in a model introduces additional parameters shared by the dynamical equations, which can significantly increase dimensionality of the parameter inference. We here analyse the importance of these effects, on a case of bacterial restriction-modification (R-M) system. We redevelop our earlier minimal model of this system gene expression regulation, based on a thermodynamic and dynamic system modeling framework, to include the population dynamics effects. To resolve the problem of effective coupling of the dynamical equations, we propose a “mean-field-like” procedure, which allows determining only part of the parameters at a time, by separately fitting them to expression dynamics data of individual molecular species. We show that including the interplay between kinetics of cell division and plasmid replication is necessary to explain the experimental measurements. Moreover, neglecting population dynamics effects can lead to falsely identifying non-existent regulatory mechanisms. Our results call for advanced methods to reverse-engineer intracellular regulation from dynamical data, which would also take into account the population dynamics effects. View Full-Text
Keywords: restriction-modification systems; bacterial population dynamics; gene expression control; statistical thermodynamics; transcription regulation restriction-modification systems; bacterial population dynamics; gene expression control; statistical thermodynamics; transcription regulation
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Graovac, S.; Rodic, A.; Djordjevic, M.; Severinov, K.; Djordjevic, M. Effects of Population Dynamics on Establishment of a Restriction-Modification System in a Bacterial Host. Molecules 2019, 24, 198.

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