Time-scale separation and stochasticity conspire to impact phenotypic dynamics in the canonical and inverted Bacillus subtilis core genetic regulation circuits

Abstract

Background: In this work, we study two seemingly unrelated aspects of core genetic nonlinear dynamical control of the competence phenotype in Bacillus subtilis, a common Gram-positive bacterium living in the soil.

Methods: We focus on hitherto unchartered aspects of the dynamics by exploring the effect of time-scale separation between transcription and translation and, as well, the effect of intrinsic molecular stochasticity. We consider these aspects of regulatory control as two possible evolutionary handles.

Results: Hence, using theory and computations, we study how the onset of oscillations breaks the excitability-based competence phenotype in two topologically close evolutionary-competing circuits: the canonical “wild-type” regulation circuit selected by Evolution and the corresponding indirect-feedback inverted circuit that failed to be selected by Evolution, as was shown elsewhere, due to dynamical reasons.

Conclusions: Relying on in-silico perturbation of the living state, we show that the canonical core genetic regulation of excitability-based competence is more robust against switching to phenotype-breaking oscillations than the inverted feedback organism. We show how this is due to time-scale separation and stochasticity.

Graphical abstract

Keywords

Bacillus subtilis / competence / gene regulation / deterministic dynamics / stochastic dynamics

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ACKNOWLEDGEMENTS

Marc Turcotte would like to thank Chen Ling and Weigang Sun for their hospitality during a stay at Hangzhou Dianzi University in Hangzhou and Jinzhi Lei for his hospitality during a stay at Tsinghua University in Beijing, where some aspects of this research were developed. Special thanks to an anonymous reviewer who provided valuable insight and useful suggestions.

COMPLIANCE WITH ETHICS GUIDELINES

The authors Lijie Hao, Zhuoqin Yang and Marc Turcotte declare that they have no conflict of interests.

This article does not contain any studies with human or animal subjects performed by any of the authors.

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