Convergent Cellular Adaptation to Freeze-Thaw Stress via a Quiescence-like State in Yeast

Extreme stress, such as freeze-thaw, poses a severe challenge to many organisms, but the mechanisms underlying their adaptation to survive such stress remain elusive. Here, we show that Saccharomyces cerevisiae can rapidly evolve freeze-thaw tolerance through a physiological state transition, with survival increasing nearly two orders of magnitude from ≈2% to ≈70% in about 25 cycles of stress exposure. Evolved yeast cells exhibit a quiescence-like state, characterized by altered cellular physiology: increased intracellular trehalose accumulation, reduced membrane damage, cytoplasmic stiffening and an exit from a proliferative cycle. This mechano-chemically reinforced survival strategy emerges across independent evolutionary lines despite distinct genetic backgrounds, suggesting a convergent mechanism of adaptation. By integrating experimental evolution, biophysical measurements, genomic analysis, and a quantitative model that captures the adaptation dynamics, we reveal that stress tolerance can arise via a potentially generalizable, physiologically mediated adaptation strategy. These findings provide new insights into microbial survival under extreme conditions and suggest broader implications for cellular stress responses beyond yeast.