Investigating Regulatory Functions of Archaic Hominin Genetic Variants in Modern Human Genomes

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When the ancestors of people living today dispersed from their ancestral homeland between one hundred thousand and fifty thousand years ago, they interbred with now-extinct distant human relatives, such as Neanderthals. The resulting exchange of genetic material means that the modern human gene pool includes a small amount of Neanderthal genetic variation. In this project, researchers will examine how Neanderthal genetic variants that are present in living humans affect the degree to which a nearby gene is active, in a variety of different human cell types (e.g., skin cells, immune cells, liver cells, skeletal cells). Through the identification of functional variants and by the dissemination of such data to the public, the researchers will advance research and public understanding of the effects of evolutionary history and genetic variation on living human biology. The findings will help to characterize the functional and medical impacts of Neanderthal DNA sequences on human cell function. The investigators will also work with museums to develop exhibits that will highlight the practical importance of this field of research. Furthermore, this project will promote broader participation of women and underrepresented scholars in STEM research through student training and mentoring activities. Given recent advances in high throughput functional testing, the researchers will conduct experiments in which they investigate tens of thousands of Neandertal genetic variants and their human counterparts for their ability to regulate the expression of genes in a variety of human cell types. The researchers will follow up key findings from this approach by performing additional functional experiments on genetic base-pairs in specific cell types, to examine the functional effects of Neandertal genetic variants on gene expression and cell biology. Furthermore, by directly comparing previous correlational findings to the results acquired in a laboratory experimental context, this research will deepen the understanding of these commonly used genetic datasets. This project is supported by NSF Biological Anthropology with Human Networks & Data Science co-funds.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.