Single-cell heterogeneity and the growth laws

Abstract

Previous work has suggested that the number of ribosomes in a cell is optimized to maximize cell growth given nutrient availability. The resulting correlation between ribosome number and growth rate, called a 'growth law', appears to be independent of which nutrient limits growth rate and is apparent in many organisms. Growth laws have had a powerful impact on many biological disciplines, having fueled predictions about how organisms evolve to maximize their growth and models about how cells regulate their growth. Problematically, the growth law is rarely studied at the single-cell level. While populations of fast-growing cells tend to have more ribosomes than populations of slow-growing cells, it is unclear whether individual cells tightly regulate their ribosome content to match their environment. Here we use recent ground-breaking single-cell RNA sequencing techniques to study the growth law at the single cell level in two different microbes, S. cerevisiae (a single-celled yeast and eukaryote) and B. subtilis (a bacterium and prokaryote). In both species, we find enormous variation in the ribosomal content of single cells that is not predictive of growth rate. Fast-growing populations of cells include cells showing transcriptional signatures of slow growth and stress, as do some cells with the highest ribosome content we survey. These results demonstrate that single-cell ribosome levels are not finely tuned to match population growth rates or nutrient availability and encourage expansion of models that predict how growth rates evolve or are regulated to consider single-cell heterogeneity.