In Partial Fulfillment of the Requirements for the Degree

Doctor of Philosophy

in the School of Biological Sciences

Melanie Quiver

Defends her thesis:

Tissue specificity of recent human adaptation

Wednesday, January 14, 2026, at 2:00pm EST

Engineered Biosystems Building (EBB), 4029

Meeting Link: https://gatech.zoom.us/j/97915709747?pwd=uImJmbAhCSbC07LbBRL6Lbl7SayUlI.1

Meeting ID: 979 1570 9747

Passcode: 125135

Thesis Advisor:
Dr. Joseph Lachance, School of Biological Sciences, Georgia Institute of Technology

Committee Members:

Dr. Greg Gibson, School of Biological Sciences, Georgia Institute of Technology

Dr. I. King Jordan, School of Biological Sciences, Georgia Institute of Technology

Dr. John Lindo, Department of Anthropology, Emory University

Dr. Katrina Claw, Department of Biomedical Informatics, University of Colorado

Abstract

Human evolutionary history has been shaped by the interaction of regulatory genetic variation, population demography, and natural selection. By combining population branch statistics (PBS) with expression quantitative trait locus (eQTL) data from the Genotype-Tissue Expression (GTEx) project, I identify regulatory variants that show signatures of recent positive selection and demonstrate that eQTLs exhibit greater population differentiation than random genomic variants. These adaptive QTLs tend to affect fewer tissues than genome-wide variants, supporting the hypothesis that tissue pleiotropy limits adaptive change and highlighting sex-specific and diet-related tissues as recurrent targets of selection over the past ~100,000 years. This work also explores the evolutionary dynamics of disease-associated loci, focusing on prostate cancer risk variants in African populations. Although cancer-associated loci show substantial allele frequency divergence among Sub-Saharan African populations, there is little evidence for recent hard selective sweeps. Comparisons of X-linked and autosomal variation further reveal signatures of sex-biased demographic history. Finally, analyses of Human Accelerated Regions demonstrate pronounced tissue specificity, particularly in brain-related tissue. HAR eQTLs also exhibit reduced pleiotropy, reinforcing the broader conclusion that constraints on tissue breadth are a key feature of regulatory evolution across multiple evolutionary timescales, from human–chimpanzee divergence to recent human adaptation. Together, the results show that regulatory variation has played a central role in human evolution, but that its adaptive potential is constrained by pleiotropy and chromosomal context. Overall, this thesis integrates population genetics, functional genomics, and evolutionary theory to demonstrate how pleiotropy, tissue specificity, and demographic history shape regulatory evolution, human adaptation, and disease susceptibility.