Experimental Evolution of Yeast Reveals Trade-offs Between Early and Late Stationary Phase

Stationary phase begins when the limiting nutrient in the medium is exhausted and cell division ceases. Most cells subsequently enter quiescence and gradually lose viability. Performance in stationary phase is often considered a singular trait. However, whether performance in stationary phase is indeed a single trait is unknown. Here we perform experimental evolution varying the time spent in stationary phase and remeasure fitness in the same conditions to isolate and quantify performance during different intervals of stationary phase. We ask whether stationary phase performance is dependent on either the type of carbon-limiting environment or the time spent in stationary. We show that stationary phase performance is similar regardless of the type of carbon limitation. However, stationary phase can be broken down into early and late stationary phase, and performance in early stationary phase is negatively correlated with performance in late stationary phase, suggesting a trade-off between the two. We also show that increasing the time spent in stationary phase results in larger fitness effects, more rapid loss of diversity from evolving population, and distinct routes of adaptation that depend on how much time populations spent in stationary phase. SMF2 mutations dominate (~32.4% of sequenced clones) in populations that spend 4 days in stationary phase. These clones tend to have increased early stationary phase performance yet trade-off in late stationary phase performance. Additionally, within this cluster, we also see a strong negative correlation amongst the SMF2 mutants between late and early stationary phase. This negative relationship suggests that stationary phase performance is constrained such that increasing performance in early stationary phase comes at a proportional cost to late stationary phase, even within a single gene. Altogether, these results demonstrate that stationary phase consists of distinct fitness-related phenotypes and that the phenotypes that allow for high performance in the first few days of stationary phase are distinct from and trade-off with those that allow for high performance in later stationary phase.