DISSERTATION RESEARCH: Alcohol dehydrogenase in Drosophila: Functional characterization of adaptive genetic variation

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How organisms adapt to environments is a fundamental question in biology, and exploring this process can enrich our understanding of factors that shape the evolution of forms, functions, and species. A precise way to study adaptive traits is by experimentally characterizing the mechanisms through which genes drive evolution. This approach can reveal general principles about how changes at the DNA level affect function over time. Here, this framework is used to rigorously characterize alcohol tolerance in fruit flies, a classic model of adaptive evolution. The researchers will investigate a long-standing hypothesis about adaptation to ethanol and the relationship of variation at genetic, biochemical, and physiological levels. This work will demonstrate how biochemical methods can be deployed in evolutionary contexts to yield novel insights. Broader impacts of this project include training of a graduate student in the emerging discipline of evolutionary biochemistry as well as collaboration with local high school teachers to design, present, and publicly distribute an educational module emphasizing the interface of biochemistry and evolutionary genetics. The evolution of alcohol dehydrogenase (ADH) in Drosophila melanogaster is an iconic example of adaptation: inter- and intraspecific variations in ADH harbor signatures of positive and balancing selection, respectively, and past works have hypothesized the responsible selective forces. The signature of positive selection on ADH is thought to reflect protein evolution in response to expansion and adaptation to ethanol-rich environments by D. melanogaster. This research utilizes ancestral sequence reconstruction of proteins, biochemical characterization, and physiological assays of transgenic organisms to test if functional changes occurred in ADH as predicted. The signature of balancing selection - supported by recurrent and dynamic allele frequency clines across continents - is thought to be due to allele-by-temperature interactions. This project investigates the role of temperature interactions as a mechanism. It will test a hypothesis about how temperature might shape patterns of genetic variance by characterizing the propensity of natural alleles to misfold at environmentally realistic temperatures. These experiments will have broad significance as methodological exemplars of utilizing detailed, mechanistic studies in evolutionary contexts to elucidate general insights pertaining to the functional determinants of adaptation.