RUI: Understanding how de novo evolved genes evolve protein interactions and regulatory mechanisms in Drosophila reproduction

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Newly evolved genes, which are non-essential at first, can acquire essential roles over time, but how they do so is currently unclear. This project will use the tractable fruit fly model system to investigate how three young genes, which have gained essential functions in male fertility, evolved novel capabilities, including physical binding partners and complex expression patterns. Ultimately, these findings will shed light on the kinds of genetic changes a new gene requires to gain functionality. This project will also enhance the research capacity of an exclusively undergraduate institution, thus providing opportunities for students to conduct original research. The PI’s lab will participate in an immersive, paid summer research program for second- and third-year students and a cohort-based mentoring program for first-year students designed to bolster the persistence of first-year students from backgrounds historically underrepresented in STEM fields. The host department’s bioinformatic curriculum will be expanded through the development of a lab-based genomics course that will provide a course-based research experience to undergraduates who may not otherwise participate in original research.This project will explore how newly evolved genes that likely arose from non-protein-coding DNA sequences acquire essential functions. It will use as case studies of three genes shown previously to be essential for spermatogenesis in Drosophila melanogaster. First, an evolutionary approach will be used to estimate when each gene became essential for reproduction and to identify key amino acids stretches important for the function of the encoded protein. Specifically, the ability of both extant orthologous protein sequences and inferred ancestral sequences to rescue D. melanogaster flies lacking an endogenous copy of the gene will be measured. These experiments will generate testable hypotheses about which sequence features are required for these proteins’ essential functions in extant D. melanogaster flies. Second, to investigate how newly evolved proteins evolve functions in existing cellular networks and gain interactions with other molecules, a combination of biochemical and genetic approaches will be used to identify interacting partners of each focal protein. Third, this project will investigate how newly evolved genes gain post-transcriptional mechanisms of gene regulation and thus evolve spatiotemporal patterns of expression. These experiments will compare transcript and protein localization patterns and investigate genetically the role of different upstream and downstream regulatory regions on new gene expression.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.