Single-cell bacterial sequencing of invertible loci reveals promoter inversion rates as a strong determinant of population heterogeneity

Single-cell heterogeneity can promote population-level fitness in response to unpredictable environmental conditions. In the human gut symbiont Bacteroides sp., the combinatorial phase variation of capsular polysaccharides (CPS) by promoter inversions generates diverse phenotypes across a population. By combining single-cell sequencing and stochastic modeling, we provide insights into fundamental questions about the regulation of heterogeneity in this health-relevant system. We show that B. fragilis populations can access diverse CPS promoter states and that promoter inversion rates are a major mechanism driving population composition. Exploiting control over the diversification mechanism, we show that populations with different initial compositions converge to a similar steady-state population-level compositions over time. More broadly, this approach could elucidate the population dynamics underlying stochastic genomic variation in a wide range of biological systems. ### Competing Interest Statement The authors have declared no competing interest.