Laboratory adaptive evolution of thermotolerance is linked to the evolution of a robust proteostasis in S. cerevisiae

Thermophilic organisms have evolved a proteome that resists thermal denaturation. While the evolution of their complete proteome would require multiple generations, early on, organisms would need to develop strategies to survive at high temperatures despite their thermolabile proteome. We hypothesized that the organisms would do this by reinforcing their proteostasis capacity. We tested this hypothesis using adaptive laboratory evolution of thermotolerance in Saccharomyces cerevisiae and found that the cells reproducibly evolved better proteostasis capacity in short-term evolution experiments. However, rather than improving the global proteostasis capacity, most of the evolved strains demonstrated enhanced capacity to tackle misfolding in the Endoplasmic Reticulum (ER), specifically by increasing their capacity for ER-associated degradation (ERAD). Given the strong selective advantage of these strains, we posit that protein folding in the ER may be exquisitely sensitive to chronic thermal stress and may act as an early indicator for adaptation to higher temperatures.