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

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.