Metabolic diversification as a buffer against environmental instability in budding yeast

Abstract

To grow and divide, cells rely on the resources present in dynamic and unpredictable environments. Organisms weather this instability by utilizing any of multiple metabolic pathways that offer distinct advantages in distinct contexts; in budding yeast, ATP can be produced from carbon sugars by mechanisms that prioritize either speed or frugality. The growth of a yeast population stalls for hours as a culture transitions to respiratory activity, the higher- maintenance, higher-yield strategy, implying that this flexibility is not optimized in practice. We find that in the absence of predictive cues, cells vary in their intrinsic ability to switch metabolic strategies. We observe subpopulations of yeast cells which are variously fast-adapting or which enter a state of shock characterized by the loss of structural integrity in many structures, including mitochondrial networks. Adaptation capacity is a bimodal, inheritable state associated with preparation for respiration or cellular memory of respiratory activity but not with obvious sources of yeast heterogeneity such as age or cell cycle state. We demonstrate that respiratory preparedness confers a fitness advantage during an environmental shift but is costly in a constant environment, and we accordingly observe natural variation in the frequency of prepared cells across wild yeasts. These experiments collectively offer the best evidence to date for the evolution of bet-hedging in budding yeast.