Deterministic and stochastic descriptions of gene expression dynamics

TL;DR

This paper systematically compares deterministic and stochastic models of gene expression, analyzing errors from common approximations and the impact of different noise sources on protein content variability.

Contribution

It provides a detailed comparison of mathematical descriptions of gene expression, highlighting the effects of growth, division, and noise sources on model accuracy and variability.

Findings

Models with implicit cell growth have small errors.

Burstiness dominates intrinsic noise when protein synthesis is highly bursty.

Growth rate fluctuations significantly impact protein content variability.

Abstract

A key goal of systems biology is the predictive mathematical description of gene regulatory circuits. Different approaches are used such as deterministic and stochastic models, models that describe cell growth and division explicitly or implicitly etc. Here we consider simple systems of unregulated (constitutive) gene expression and compare different mathematical descriptions systematically to obtain insight into the errors that are introduced by various common approximations such as describing cell growth and division by an effective protein degradation term. In particular, we show that the population average of protein content of a cell exhibits a subtle dependence on the dynamics of growth and division, the specific model for volume growth and the age structure of the population. Nevertheless, the error made by models with implicit cell growth and division is quite small. Furthermore, we compare various models that are partially stochastic to investigate the impact of different sources of (intrinsic) noise. This comparison indicates that different sources of noise (protein synthesis, partitioning in cell division) contribute comparable amounts of noise if protein synthesis is not or only weakly bursty. If protein synthesis is very bursty, the burstiness is the dominant noise source, independent of other details of the model. Finally, we discuss two sources of extrinsic noise: cell-to-cell variations in protein content due to cells being at different stages in the division cycles, which we show to be small (for the protein concentration and, surprisingly, also for the protein copy number per cell) and fluctuations in the growth rate, which can have a significant impact.