Author ORCID Identifier:
Date of Graduation
5-2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Cell & Molecular Biology (PhD)
Degree Level
Graduate
Department
Cell & Molecular Biology
Advisor/Mentor
Lewis, Jeffrey
Committee Member
Paré, Adam
Second Committee Member
Zhuang, Xuan
Third Committee Member
Kwon, Young
Keywords
Acquired stress resistance; BSA-seq; Cross-protection; QTL; Saccharomyces cerevisiae; Trehalose-6-Phosphate
Abstract
Stress is experienced across the tree of life. Survival in fluctuating environments depends on a robust genetic architecture. This dissertation examines the genetic and metabolic determinants underlying one such adaptive response: cross-protection. Leveraging natural variation in the stress responses of budding yeast, Saccharomyces cerevisiae, I examine the genetic variation contributing to ethanol-induced cross-protection against oxidative stress. Acquired stress resistance, in which mild pre-exposure improves survival to subsequent stresses, is prevalent across diverse organisms and can involve both same-stress and cross-protection. Using high-throughput bulk segregant analysis (BSA-seq) and advanced intercross mapping populations derived from natural yeast isolates, I identify quantitative trait loci (QTLs) associated with both basal and acquired stress resistance. While previous research identified the transcription factor HAP1 as a regulator, this work demonstrates that natural genetic variation extends beyond HAP1, revealing multiple novel loci influencing cross-protection and basal resistance, thereby uncovering candidate genes within strong QTL regions. These findings enhance the current understanding of the genetic basis and diversity of stress responses. Extending this analysis, I compare mapping strategies using F2 and F6 advanced intercross populations. While the advanced F6 population provides higher-resolution QTL mapping, thus uncovering novel loci not detected in the less advanced F2 population, I highlight a significant trade-off: some QTLs are lost due to selective sweeps and allele fixation during extended intercrossing. These findings underscore the importance of balancing mapping resolution and inadvertent allele sweeps in experimental design. Finally, I investigate the role of the conserved trehalose biosynthesis pathway in ethanol-induced cross-protection. Using a catalytically inactive enzyme, I show that the first enzyme in this pathway, Trehalose-6-Phosphate Synthase (Tps1p), does not moonlight as a regulator of ethanol-induced cross-protection. Thus, the findings support a novel role for the intermediary molecule: Trehalose-6-Phosphate in cross-protection, with both null and catalytic mutants displaying defective stress resistance across diverse yeast strains. Collectively, this work highlights the complexity of genetic regulation in stress responses, identifies new genetic determinants of ethanol-induced cross-protection, and demonstrates the power and limitations of BSA-seq and advanced intercross mapping in dissecting complex traits in yeast.
Citation
Lenaduwe, S. L. (2026). Dissecting the Complex Genomic Landscape Underlying Oxidative Stress Resistance Using Natural Variation in Yeast. Graduate Theses and Dissertations Retrieved from https://scholarworks.uark.edu/etd/6217
