Genotypic and phenotypic variation during adaptation in fungal microbes

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The appearance of beneficial variation in a population is required for an organism to adapt. The long-term goal of my research program is to understand how different factors influence the appearance and spread of beneficial variation. We apply evolutionary principles to understand the predictability of adaptation in fungal microbes. Fungi are critically understudied relative to other taxa, and our experiments will clarify the specific patterns that underlie adaptation in fungal microbes, and more generally provide insight into the genotypic and phenotypic basis of adaptation. We primarily use the model eukaryote Saccharomyces cerevisiae to take advantage of the unparalleled genetic resources available for this species. In the short-term we have two major goals: I: Precisely quantify karyotypic mutations during adaptation Many fungal microbes are able to reproduce asexually, and compared to species that habitually undergo sexual reproduction, karyotypic mutations (changes in ploidy, the base number of chromosome sets), and aneuploidy (copy number change in one or several chromosomes) are prevalent. We will develop a new statistical analysis program to quantify karyotypic variation in populations that contain individuals of mixed ploidy. This program will be the first available method to comprehensively analyze these populations and will enable new avenues of research on the prevalence and influence of karyotypic variation and subpopulations during adaptation. Students in my lab will then use the program we develop in tandem with whole genome sequencing techniques to precisely quantify karyotypic variation throughout a long term evolution experiment. II: Characterize evolutionary responses to inhibitory environmental stresses We will investigate the evolutionary implications of inhibitory (static) environments compared to lethal (cidal) environments. We will conduct the first quantification of diverse environmental challenges (e.g., high and low pH, heavy metals, nitrosative and oxidative stress) to determine the conditions that are cidal versus static to fungal microbes. We will then use two complementary experimental approaches, genome wide association studies (GWAS) and short-term experimental evolution, to pinpoint specific genotypes that are beneficial in fungistatic environments. We will characterize the diversity and nature of mutations that improve growth under static environments, and evaluate how the predictability of evolution is influenced by this important and fundamental feature of environmental stress. I expect to train 4 graduate and at least 6 undergraduate students in the next five years. As I am cross-appointed between the Microbiology and Statistics departments, these students will gain a mix of empirical and analytical experience from both fields. This will enable students to acquire a diverse and marketable skillset that will serve them well regardless of their career goals.