Predicting the asymmetric response of a genetic switch to noise

TL;DR

This paper introduces an analytical method to predict how genetic switches respond asymmetrically to weak, rapid noise, demonstrated on the lac operon model, revealing noise-induced shifts in stationary states and their effects on bistability.

Contribution

The paper presents a simple analytical tool for predicting asymmetric responses of genetic switches to noise, validated on a lac operon model with excellent agreement to simulations.

Findings

Noise causes asymmetric shifts in stationary states.

Environmental fluctuations do not break bistability.

Noise stabilizes certain system behaviors against switching.

Abstract

We present a simple analytical tool which gives an approximate insight into the stationary behavior of nonlinear systems undergoing the influence of a weak and rapid noise from one dominating source, e.g. the kinetic equations describing a genetic switch with the concentration of one substrate fluctuating around a constant mean. The proposed method allows for predicting the asymmetric response of the genetic switch to noise, arising from the noise-induced shift of stationary states. The method has been tested on an example model of the lac operon regulatory network: a reduced Yildirim-Mackey model with fluctuating extracellular lactose concentration. We calculate analytically the shift of the system's stationary states in the presence of noise. The results of the analytical calculation are in excellent agreement with the results of numerical simulation of the noisy system. The simulation results suggest that the structure of the kinetics of the underlying biochemical reactions protects the bistability of the lactose utilization mechanism from environmental fluctuations. We also show that, in the consequence of the noise-induced shift of stationary states, the presence of fluctuations stabilizes the behavior of the system in a selective way: although the extrinsic noise facilitates, to some extent, switching off the lactose metabolism, the same noise prevents it from switching on.