Metabolic remodeling and de novo mutations transcend cryptic variation as drivers of adaptation in yeast.

This article focuses on how prolonged growth of yeast populations (Saccharomyces cerevisiae) in a predictable, nutrient-rich environment affects their fitness and adaptability to new stressful environments. Through laboratory evolution over 1,000 generations, yeast populations increased fitness in the original environment via metabolic remodeling, including enhanced respiratory activity and lipid accumulation, but generally showed reduced fitness and poor adaptability in novel stress conditions except for salt stress. Genome sequencing revealed distinct loss-of-function and nonsynonymous mutations accumulated during adaptation to the nutrient-rich medium, yet these mutations did not contribute significantly to adaptation in new environments, which was primarily driven by de novo mutations arising after exposure to stressors. The findings suggest that without exposure to environmental variability, populations may lose nonessential functions and their capacity to adapt, highlighting a limited role for cryptic genetic variation in facilitating adaptation under these conditions.