Adaptive sequence divergence forged new neurodevelopmental enhancers in humans.


Searches for the genetic underpinnings of uniquely human traits have focused on human-specific divergence in conserved genomic regions, which reflects adaptive modifications of existing functional elements. However, the study of conserved regions excludes functional elements that descended from previously neutral regions. Here, we demonstrate that the fastest-evolved regions of the human genome, which we term "human ancestor quickly evolved regions" (HAQERs), rapidly diverged in an episodic burst of directional positive selection prior to the human-Neanderthal split, before transitioning to constraint within hominins. HAQERs are enriched for bivalent chromatin states, particularly in gastrointestinal and neurodevelopmental tissues, and genetic variants linked to neurodevelopmental disease. We developed a multiplex, single-cell in vivo enhancer assay to discover that rapid sequence divergence in HAQERs generated hominin-unique enhancers in the developing cerebral cortex. We propose that a lack of pleiotropic constraints and elevated mutation rates poised HAQERs for rapid adaptation and subsequent susceptibility to disease.





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Publication Info

Mangan, Riley J, Fernando C Alsina, Federica Mosti, Jesús Emiliano Sotelo-Fonseca, Daniel A Snellings, Eric H Au, Juliana Carvalho, Laya Sathyan, et al. (2022). Adaptive sequence divergence forged new neurodevelopmental enhancers in humans. Cell, 185(24). pp. 4587–4603.e23. 10.1016/j.cell.2022.10.016 Retrieved from

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Riley Mangan


Doctor of Philosophy (Ph.D.) Student. Molecular Genetics and Microbiology. 
Program in Cell and Molecular Biology (CMB), 2018-2023

I was a graduate student in the lab of Craig B. Lowe, where I studied human evolutionary genomics. My work combined tools from evolutionary developmental biology, cell and molecular neuroscience, and comparative genomics to investigate how changes in gene regulation have led to human-unique disease susceptibility and derived traits.

Prior to joining Duke CMB, I worked for two years as a research technician in the laboratory of Dr. Sallie Permar at the Duke Human Vaccine Institute investigating a variety of topics related to mother to child transmission of HIV-1. In particular, I investigated the mechanism of interaction between the HIV-1 envelope and the extracellular matrix protein Tenascin-C, which has been previously identified as an innate, broadly HIV-neutralizing factor present in mucosal fluids.

After defending my dissertation in August 2023, I have since started a position as a postdoctoral associate in the lab of Manolis Kellis in the Computer Science and Artificial Intelligence Laboratory at the Massachusetts Institute of Technology and as a postdoctoral scholar at the Broad Institute of MIT and Harvard.

Doctor of Philosophy, 2023
Duke University (Durham, NC, USA)
Molecular Genetics and Microbiology

Bachelor of Science, 2016
Davidson College (Davidson, NC, USA)
Biology, Magna Cum Laude


Timothy E Reddy

Associate Professor of Biostatistics & Bioinformatics,

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