Genetic Basis and Evolution of the Transcriptional Response to Oxidative Stress in Diverse Yeasts

Organisms must respond to changing environmental conditions to survive, such as when cells are exposed to toxic chemicals or sudden changes in temperature. Central to this response is through genetic networks that control how genes are turned on or off in response to stress. Although a lot is known about how a few well-studied organisms respond to stresses, the rules for how these systems diverge between species as they are adapted to novel environments remain largely a major knowledge gap. This project will investigate the evolution of oxidative stress resistance and response in a diverse group of yeast species with multiple, independently derived human pathogens. Understanding how resistance to common reactive oxygen species, such as hydrogen peroxide, diverge across them in relation to their pathogenic potential is likely to elucidate a key mechanism in the adaptation to the host. In addition to advancing scientific knowledge, the project will provide research training for both undergraduate and graduate students and will offer a summer coding workshop that teaches programming skills to students in biology. These activities will help broaden participation in science and prepare a new generation of biologists to work at the interface of data science and biology. Gene regulatory evolution is a key driver of morphological novelty and adaptation. Stress response is crucial for survival and must be adapted to the particular environment a species lives in. Therefore, the stress response gene regulatory networks are expected to be targets of natural selection and hence diverge between related species living in distinct habitats. This research will examine how oxidative stress resistance varies across a diverse group of yeast species and the relationship with the repeated emergence of opportunistic human pathogens. Subsequent molecular studies will reveal how the transcriptional response to oxidative stress diverged by combining unbiased transcriptome profiling to identify broad stress response program with focused dissection of a core transcriptional network regulated by two transcription factors with conserved roles across species. The comparative studies will provide a detailed molecular picture of how stress response gene regulatory networks diverge. It will also offer a broader framework for understanding gene network evolution beyond the traditional focus on development and will shed light on how organisms can evolve new responses to environmental challenges. This project is co-funded with the Evolutionary Processes program in the Division of Environmental Biology, and with the Division of Molecular and Cellular Biosciences. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.