Noise and Epigenetic Inheritance of Single-Cell Division Times Influence Population Fitness

Abstract

The fitness effect of biological noise remains unclear. For example, even within clonal microbial populations, individual cells grow at different speeds. Although it is known that the individuals' mean growth speed can affect population-level fitness, it is unclear how or whether growth speed heterogeneity itself is subject to natural selection. Here, we show that noisy single-cell division times can significantly affect population-level growth rate. Using time-lapse microscopy to measure the division times of thousands of individual S. cerevisiae cells across different genetic and environmental backgrounds, we find that the length of individual cells' division times can vary substantially between clonal individuals and that sublineages often show epigenetic inheritance of division times. By combining these experimental measurements with mathematical modeling, we find that, for a given mean division time, increasing heterogeneity and epigenetic inheritance of division times increases the population growth rate. Furthermore, we demonstrate that the heterogeneity and epigenetic inheritance of single-cell division times can be linked with variation in the expression of catabolic genes. Taken together, our results reveal how a change in noisy single-cell behaviors can directly influence fitness through dynamics that operate independently of effects caused by changes to the mean. These results not only allow a better understanding of microbial fitness but also help to more accurately predict fitness in other clonal populations, such as tumors.

Aneuploidy Causes Non-genetic Individuality

“…Phenotypic differences in genetically identical populations have been observed in a variety of experimental settings (Cerulus et al, 2016; reviewed in Raj and van Oudenaarden, 2008; Raser and O’Shea, 2005). Variability can arise from stochastic synthesis and degradation of molecules (Elowitz et al, 2002; Paulsson, 2004) as well as binomial partitioning at cell division (Huh and Paulsson, 2011).…”

“…Increased variance has the potential to enhance population fitness in euploid populations (Cerulus et al, 2016); therefore, aneuploidy may occur in evolution as a mechanism to further increase population variance, and thus fitness.…”

To grow is not enough: impact of noise on cell environmental response and fitness

“…We focus on the case where the CV is roughly constant and without the consideration of epigenetic inheritance; but for cases where the CCDD are poorly mean scaled, epigenetics make a big impact, or the mean cycle duration is limited while τ * is effectively zero, we want to make it clear to the reader that the results of this paper are incomplete and wish to direct them to the work referenced above. 19,20 …”

The quick and the dead: microbial demography at the yeast thermal limit

“…) especially for microorganisms for which this influence remains largely unexplored (although see Cerulus et al . for a recent example). Similarly, TrackScar can be used to estimate fitness variation which is a fundamental parameter in models of adaptation (e.g.…”

“…The power of model organisms like S. cerevisiae coupled with the TrackScar method offers to evolutionary biologists and ecologists the tools to deeply test whether and how individuals behaviour can effect changes in the mean phenotype of a population independent of natural selection (e.g. Ozgul et al 2009) especially for microorganisms for which this influence remains largely unexplored (although see Cerulus et al 2016 for a recent example). Similarly, TrackScar can be used to estimate fitness variation which is a fundamental parameter in models of adaptation (e.g.…”