Measuring cellular memory and heterogeneity at the single-cell level*

Microbial populations live in a wide range of ecological settings. In changing environments, survival is improved by heterogeneity. In contrast, in stable environments the population is best off when cells adopt the single optimal phenotype. In a clonal population, heterogeneity occurs at the phenotypic (protein) level; as cellular protein levels vary over time, phenotypes can change dynamically, with the timescale given by “cellular memory”. However, the population-level distribution of phenotypes remains stable, optimised by evolution to its ecological setting. An interesting situation occurs when a population moves from one setting to another. In this case, one can encounter a bimodal population in a constant environment for which it is not adapted. How does evolution shape this population? We examine this in yeast containing a synthetic gene circuit that gives a phenotypically bimodal population. We expose cells to a stable environment and observe changes in heterogeneity. Using a microfluidic platform, we measure the cellular memory of many single cells. Thus, we investigate the relationship between fitness, cellular memory and phenotype distribution during evolution in a constant environment.