CAREER: Investigation Of How Proto-Gene Expression Impacts Growth In Budding Yeast

University Of Pittsburgh, Pittsburgh PA

Investigators

Abstract

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117- 2). This project investigates how species evolve unique characteristics at the molecular level. Genomes consist of genes and non-genic sequences. Gene sequences encode the information necessary to build proteins, which are the workhorses of our cells. Genes tend to be highly conserved across species because mutations that change their sequences can cause disease or other adverse outcomes. In contrast, non-genic sequences do not encode proteins and are very different across species. Surprisingly, the PI and others discovered that thousands of rapidly evolving sequences previously thought to be non-genic instead do seem to encode small proteins. These sequences, which are neither genes (because they are not conserved across species) nor non-genes (because they encode proteins), have been named “proto-genes.” This research aims to understand how proto-genes contribute to species-specific biology using budding yeast as a model organism. The research will be performed with undergraduate students at primarily undergraduate institutions who will “adopt a proto-gene” and characterize it in their home institutions. A collaborative educational initiative will develop novel teaching modules, virtual workshops and networking tools for educators. This project will grow the STEM workforce by providing undergraduates with cutting-edge computational skills for sequence analyses, with paid summer research opportunities in the PI’s laboratory, and with the empowering experience of having made the very first discovery about a novel proto-gene. The findings from the synergistic research and education activities will improve our understanding of the genome and shed light on what makes a species unique and how entirely novel genes arise in evolution. The central hypothesis of this project is that evolutionarily novel proto-genes can mediate beneficial phenotypes by modulating established cellular processes in a species-specific manner. The project combines gain- and loss-of-function approaches with integrative systems-level approaches to identify cellular processes that are modulated by proto-genes. The data generated during the course of this project may also reveal whether and how genomic context influences the functional potential of proto-genes as they emerge de novo in non-genic sequences. 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.