From noisy cell size control to population growth: when variability can be beneficial

TL;DR

This paper develops a model linking single-cell variability in growth and size control to population growth rate, revealing that certain fluctuations can enhance overall fitness across different cell types.

Contribution

It introduces a comprehensive model connecting single-cell stochasticity with population growth, including effects of size control mechanisms and growth laws, extending beyond exponential growth.

Findings

Fluctuations in growth rates can benefit population growth.

Cell size control mechanisms influence how variability affects fitness.

The model applies to various growth laws beyond exponential.

Abstract

Single-cell experiments revealed substantial variability in generation times, growth rates but also in birth and division sizes between genetically identical cells. Understanding how these fluctuations determine the fitness of the population, i.e. its growth rate, is necessary in any quantitative theory of evolution. Here, we develop a biologically-relevant model which accounts for the stochasticity in single-cell growth rates, birth sizes and division sizes. We derive expressions for the population growth rate and for the mean birth size in the population in terms of the single-cell fluctuations. Allowing division sizes to fluctuate reveals how the mechanism of cell size control (timer, sizer, adder) influences population growth. Surprisingly, we find that fluctuations in single-cell growth rates can be beneficial for population growth when slow-growing cells tend to divide at smaller sizes than fast-growing cells. Our framework is not limited to exponentially-growing cells like $\textit{Escherichia coli}$, and we derive similar expressions for cells with linear and bi-linear growth laws, such as $\textit{Mycobacterium tuberculosis}$ and fission yeast $\textit{Schizosaccharomyces pombe}$, respectively.