On the dephasing of genetic oscillations

TL;DR

This paper develops a theoretical framework to understand how stochastic gene expression causes dephasing in genetic oscillations, reconciling single-cell and population experiment observations.

Contribution

It introduces a combined approach of stochastic limit cycle dynamics and Markov models to analyze genetic oscillation dephasing.

Findings

Simulations demonstrate dephasing effects in NFκB/IκB network

Framework explains discrepancies between single-cell and population data

Highlights importance of stochasticity in genetic oscillations

Abstract

The digital nature of genes combined with the associated low copy numbers of proteins regulating them is a significant source of stochasticity, which affects the phase of biochemical oscillations. We provide a theoretical framework for understanding the dephasing evolution of genetic oscillations by combining the phenomenological stochastic limit cycle dynamics and the discrete Markov state models that describe the genetic oscillations. Through simulations of the realistic model of the NF\kappa B/I\kappa B network we illustrate the dephasing phenomena which are important for reconciling single cell and population based experiments on this system.