David Gokhman of the Weizmann Institute of Science explores how changes in gene regulation shaped recent human evolution. His team used massively parallel reporter assays in skeletal and neural cells to test 71,443 genetic variants that distinguish Neanderthals and Denisovans from modern humans, building a catalog that reveals hundreds of noncoding variants that alter gene expression. The work uncovers evolutionary trends and examples of convergent evolution, including an enhancer of KDM8, a gene involved in tumor progression, that was completely silenced in both archaic and modern human lineages through different mechanisms: motif disruption in Neanderthals and Denisovans, and hypermethylation in modern humans. Gokhman also introduces a way to reconstruct anatomical profiles from DNA sequence and methylation, using it to model Denisovan anatomy and scan the fossil record. The results suggest that the Harbin and Dali fossils were likely Denisovans, while Kabwe may have been related to the ancestor of Neanderthals and Denisovans, helping to clarify the regulatory changes underlying human evolution. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 41195]