Comparative functional genomics of Saccharomyces cerevisiae reveals genetic determinants of stress tolerance and...

Saccharomyces cerevisiae strains from diverse origins exhibit distinct phenotypic traits, providing valuable diversity and adaptability for industrial applications. Here, we conducted a comparative analysis of phenotypic and genomic features across 41 S. cerevisiae strains with clear industrial niche associations, aiming to identify genetic determinants underlying stress resistance and ethanol fermentation efficiency. These strains displayed niche-specific growth advantages under fermentation-related stress conditions, yet none showed broad tolerance. During ethanol fermentation using wheat and sorghum substrates, ethanol yields varied from 0.42 to 0.48 g ethanol/g glucose, with strains exhibiting superior maltose utilization achieving higher ethanol titers. Substantial variation was also observed in glycerol and acetic acid production, and a strong negative correlation was detected between their yields. Whole-genome sequencing revealed that chromosomal aberrations, DNA recombination-mediated chromosomal rearrangements, loss of heterozygosity, and gene gain or loss were major genetic factors contributing to phenotypic diversity. Furthermore, identification of novel genes acquired through horizontal gene transfer expanded the genetic repertoire of Saccharomyces strains. An additional SOD2 gene obtained from Torulaspora microellipsoides contributed to oxidative stress tolerance. Furthermore, our results demonstrate that whole-genome duplication in S. cerevisiae enhances maltose utilization and ethanol production in starchy substrate fermentation. Together, these findings offer novel mechanistic insights into the genomic evolution of yeast in industrial/ecological niches.IMPORTANCEThis study systematically analyzed phenotypic diversity and genomic variations across 41 diverse Saccharomyces cerevisiae strains. Key findings include strain-specific stress resistance linked to ecological niches, a strong glycerol-acetic acid negative correlation in starchy substrate fermentation, horizontal transfer-acquired SOD2 enhancing oxidative tolerance, and genome duplication boosting maltose utilization and ethanol yield. These results uncover niche-specific genetic mechanisms driving S. cerevisiae adaptive evolution and provide references for screening of strains with improved industrial traits.