Yeast adaptation and survival under acute exposure to lethal ethanol stress

The ability to respond to stress is universal in all domains of life. Failure to properly execute the stress response compromises the fitness of the organism. Several key stress pathways are conserved from unicellular organisms to higher eukaryotes, so knowledge of how these pathways operate in model organisms is crucial for understanding stress-related diseases and aging in humans. The mechanisms of stress tolerance have been well-studied in the budding yeast Saccharomyces cerevisiae. Yeast respond to diverse stresses by initiating both general and stress-specific responses that generally protect the cells during and after the stress exposure. While previous work has revealed mechanistic insights on adaptation and survival under mild and long-term exposure to stress, how they cope with acute exposure to lethal stress is not well understood. Here, we combined transcriptional profiling, fitness profiling, and laboratory evolution to investigate how S. cerevisiae survive acute exposure to lethal ethanol stress. By using high throughput methods such as RNA-seq and barcode sequencing of the pooled yeast deletion library, we were able to discover and characterize both existing and novel pathways that yeast utilize to adapt to and survive ethanol stress. We found both ethanol-specific and as well general stress response mechanisms. We were also able to evolve a strain of ethanol under lethal ethanol stress to exhibit a survival of at least an order of magnitude greater than the parental wild-type strain. Additionally, this evolved strain exhibited cross protection to other stresses without compromising bulk growth rate. We found that this strain adapted its global expression levels to a post-stress state, making it more robust to various stresses even under optimal growth conditions.