,Time-scale separation and stochasticity conspire to impact phenotypic dynamics in the canonical and

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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.
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