CAREER: Transcriptional Regulation of Primate Gene Expansions

University Of California-Davis, Davis CA

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 aims to identify what makes us uniquely human by comparing newly decoded primate genomes. Finding genetic differences may offer insights into the origins of increased human brain size and cognitive ability versus other great apes. These same genes may also explain trait differences and susceptibility to diseases observed across modern humans today. By exploring these questions, this project will provide early research experiences to high school and undergraduate students, imbuing them with the confidence and skills to continue on in STEM-related fields. Ultimately, these efforts will contribute to a more diverse future generation of scientists. American Rescue Plan funding of this project provides support for this investigator at a critical stage in her career. Directed studies in primates have identified gene expansions likely contributing to human brain evolution; however, there are few studies of duplicated cis-regulatory elements, which can impact many genes. The research goal of this project is to narrow in on functional noncoding elements within structurally-variant loci that drive differences in gene expression across primates by: (1) identifying changes in duplicated elements that may lead to altered gene regulation between primate species; (2) characterizing alterations in chromatin contacts resulting from structural variants between primate species; and (3) interrogating gene regulation and chromatin interactions across diverse human structural haplotypes. This study will employ innovative experimental and computational genomic approaches and leverage thousands of primate sequencing datasets. Results from this project will point to exciting candidate genes driving species innovation and diversity, and provide functional targets for future in vivo studies. Ultimately, this work has the potential to expand understanding of how structural variation contributes to primate evolution and diversity. Further, the methods employed can be applied broadly to other species. 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.