Noise expands the response range of the Bacillus subtilis competence circuit

TL;DR

This paper demonstrates that intrinsic noise in the Bacillus subtilis competence circuit enhances its ability to respond to a wider range of stress levels and promotes phenotypic diversity, highlighting a functional role for noise in gene regulation.

Contribution

The study reveals how noise in a natural gene circuit expands response range and promotes heterogeneity, contrasting with synthetic analogs that reduce noise.

Findings

Noise increases the response range of the competence circuit.

Noise enables cells to exit terminal phenotypic states.

Phenotypic heterogeneity is driven by noise in the circuit.

Abstract

Gene regulatory circuits must contend with intrinsic noise that arises due to finite numbers of proteins. While some circuits act to reduce this noise, others appear to exploit it. A striking example is the competence circuit in Bacillus subtilis, which exhibits much larger noise in the duration of its competence events than a synthetically constructed analog that performs the same function. Here, using stochastic modeling and fluorescence microscopy, we show that this larger noise allows cells to exit terminal phenotypic states, which expands the range of stress levels to which cells are responsive and leads to phenotypic heterogeneity at the population level. This is an important example of how noise confers a functional benefit in a genetic decision-making circuit.