Doctoral Dissertation Research: Genetics of hominin brain evolution

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Paleoanthropology uses the fossil record to work out how and when the defining characteristics of humans, such as large-brains, upright walking, extended juvenile period, and increased longevity, evolved. Advances in molecular biology now make it possible to investigate how the genes of our forbearers might have been modified to generate these defining characteristics. This project focuses on the evolution of a gene (NR2C1) potentially involved in early brain development, and will compare the activity of human versus non-human ape versions of the gene in mouse cells. The data that are generated will advance our understanding of the unique molecular interactions at play in the evolution and development of the modern human brain. In addition, the project has broader impacts to society that include potential pharmacological applications, generation of new, shared genetic data, training of a non-traditional, female graduate student, and public science education and outreach. Nuclear receptor genes are implicated in the control of growth and development, hormone regulation and behavior. Preliminary evidence suggests that one of these genes, NR2C1, has undergone positive selection in the human lineage. In this six-month study, copies of NR2C1 will be generated for modern humans and chimpanzees, and predicted/reconstructed for a last common ancestor (LCA) of chimpanzees/bonobos and modern humans. These three different gene variants will be inserted into mouse embryonic stem cells that have had NR2C1 knocked down, allowing quantification of the transcriptional and regulatory functions of NR2C1. These methods will allow the investigators to analyze how alterations to the modern human version of NR2C1 may have resulted in the morphological or functional changes we see in the modern human brain. Data on the locations and timing of primate amino acid substitutions for all 48 primate nuclear receptor genes will be generated and will be of interest to the general public and to researchers in biological anthropology, evolutionary biology, medical genetics, neuroscience, and pharmacology. The graduate student researcher, who has years of experience as a biology teacher, is dedicated to providing well-designed student and public education about evolutionary processes.