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Divergence in the physiological and transcriptional response to phosphate starvation between related yeast species
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Divergence in the physiological and transcriptional response to phosphate starvation between related yeast species

Emily O'Brien
University of Iowa
Master of Science (MS), University of Iowa
Spring 2026
DOI: 10.25820/etd.008434
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Abstract

For any organism, proper response to the environment is vital and must be adapted to the unique stressors it faces. In this thesis, I investigate how a group of genetically related, yet ecologically diverse yeast species differ in their response to the limitation of phosphate (Pi), an essential micronutrient whose availability differs between ecological niches. Although the transcriptional response to Pi starvation has been well studied and intriguing differences have been revealed between the model yeast S. cerevisiae and its relatives, their physiological responses to Pi limitation are still poorly characterized. In Chapter 2, I investigate the divergent physiological response among four related yeast species: S. cerevisiae, K. lactis, C. glabrata, and C. albicans - two of which independently evolved to be human opportunistic pathogens. I identify two major differences. First, these species exhibit distinct patterns of growth dynamics in response to Pi limitation: they either slow their growth but reach a higher final density, or they show rapid initial growth but plateau early at a lower final density. Second, these species store varied amounts of polyphosphate. S. cerevisiae stores significantly higher amounts than the other three, which it then mobilizes in the first 2h of Pi starvation. This mobilization coincides with changes in the induction of several environmental stress response genes and is associated with a quickened recovery. Chapter 3 investigates the divergence of Pho4: the main transcription factor (TF) regulating the Phosphate Starvation (PHO) response. Our lab previously identified two “Activation Enhancing Domains” (AEDs) in C. glabrata Pho4. My results clarify how these two domains and the corresponding regions in S. cerevisiae Pho4 depend on the co-TF Pho2, providing necessary information for unravelling the molecular basis of this new class of TF functional domains. I also established a Protein Complementation Assay based on the split Dihydrofolate Reductase (DHFR), to identify the regions mediating Pho4-Pho2 interaction. This technique will enable a detailed genetic dissection of the evolution of TF-TF interactions over millions of years. In summary, my thesis research explores the evolution of related yeast species and areas of divergence related to phosphate starvation response, with the goal of gaining insight into species specific genetic and physiological evolution in response to environmental changes.
Genetics

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