Hidden Complexity of Yeast Adaptation under Simple Evolutionary Conditions

Few studies have “quantitatively” probed how adaptive mutations result in increased fitness. Even in simple microbial evolution experiments, with full knowledge of the underlying mutations and specific growth conditions, it is challenging to determine where within a growth-saturation cycle those fitness gains occur. A common implicit assumption is that most benefits derive from an increased exponential growth rate. Here, we instead show that, in batch serial transfer experiments, adaptive mutants’ fitness gains can be dominated by benefits that are accrued in one growth cycle, but not realized until the next growth cycle. For thousands of evolved clones (most with only a single mutation), we systematically varied the lengths of fermentation, respiration, and stationary phases to assess how their fitness, as measured by barcode sequencing, depends on these phases of the growth-saturation-dilution cycles. These data revealed that, whereas all adaptive lineages gained similar and modest benefits from fermentation, most of the benefits for the highest fitness mutants came instead from the time spent in respiration. From monoculture and high-resolution pairwise fitness competition experiments for a dozen of these clones, we determined that the benefits “accrued” during respiration are only largely “realized” later as a shorter duration of lag phase in the following growth cycle. These results reveal hidden complexities of the adaptive process even under ostensibly simple evolutionary conditions, in which fitness gains can accrue during time spent in a growth phase with little cell division, and reveal that the memory of those gains can be realized in the subsequent growth cycle. •Fitness benefits from different phases of a growth dilution cycle were quantified•Benefits were “accrued” in respiration but largely “realized” as a shortened lag phase•Analysis of high-throughput data reveals different adaptive strategies•Trade-offs exist between accrued respiration benefits and stationary survival Quantitative details of how adaptive genotypes gain fitness have rarely been studied. By quantifying fitness benefits of thousands of yeast clones in different parts of the growth-saturation cycle, Li et al. identify distinct adaptive strategies, with some strategies showing clear trade-offs between growth and survival.