Guest seminar: "Human evolution through the lens of gene regulation" with dr. David Gokhman

On Thursday, October 17, at 11.00 a.m., a guest seminar on "Human evolution through the lens of gene regulation" will take please in the Institute of Genomics at the University of Tartu (Riia 23b, room 105) by Dr David Gokhman from the Weizmann Institute of Science in Israel.

David Gokhman is a trained evolutionary biologist. He did his undergraduate studies in chemistry and biology, as well as his MSc and PhD at the Department of Genetics at the Hebrew University of Jerusalem. David conducted a postdoc at Stanford University after which he joined the faculty of the Weizmann Institute in 2021. His research group focuses on the analysis of how gene expression regulation shaped human evolution and disease, by comparative approaches with our closest extinct (such as Neandertals and Densiovans) and living (such as chimpanzees and other great apes) relatives. He is visiting the Institute of Genomics as the opponent for the PhD defense of Danat Yermakovich

Abstract of the guest seminar:

Changes to gene regulation are key drivers of human evolution. However, our understanding of which regulatory changes shaped human adaptations, and how, remains extremely limited. Here, we employed massively parallel reporter assays in skeletal, adipose, skin, and neural cells to uncover the functional effect of each of the 71,443 variants distinguishing Neanderthals and Denisovans from modern humans, as well as the 541,851 variants distinguishing all human lineages from other great apes. We found that 15% of the variants arose in active enhancers and promoters, and that 20% of them altered human expression levels. To identify the genes affected by these expression-altering variants, we generated human-chimp hybrid cells, a powerful system to detect expression differences driven in cis by nearby variants. Synergizing these approaches, we found three body parts that likely experienced unique selective pressures: the face, vocal tract, and cerebellum. Interestingly, we detected several examples of convergent evolution between modern and archaic humans. For example, both lineages completely silenced the activity of an enhancer of KDM8, a gene involved in tumor progression, but archaic humans achieved this through motif disruption, while modern humans achieved this through hypermethylation. Finally, we focused on two regions, and using CRISPR/Cas9 and mouse models, we discovered that they likely played a key role in shaping human-specific traits. These include a single-nucleotide substitution that doubled the expression of EVC, a key regulator of facial development, and a variant that silenced IRF4, a regulator of skin pigmentation. Overall, this work synergizes two powerful systems – reporter assays and human-chimp hybrids – to generate the first catalog of functionally important noncoding variants in deep and recent human evolution, and to elucidate their role in human adaptations.

You can also join the seminar via Zoom

Join Zoom Meeting
https://ut-ee.zoom.us/j/99789590450?pwd=la9SvIlGsMam7kUnjg022H07JGFAW3.1

Meeting ID: 997 8959 0450
Passcode: 644413