NOMIS researcher James Noonan and colleagues published their findings in a Jan. 12, 2021, Proceedings of the National Academy of Sciences of the United States of America (PNAS) article, revealing new details about how evolutionary innovations impact enhancer function and offer new candidates to study the emergence of uniquely human neural traits. Noonan is co-leader of the NOMIS project Deciphering the Evolutionary Origins of Human Brain Uniqueness.
In human evolution, researchers have theorized that adaptations which altered regulatory function underlie the emergence of uniquely human traits, such as the expansion of our cerebral cortex. Despite keen interest, finding these key branching points between humans and other primates has remained technically challenging. Severin Uebbing, Jake Gockley, et al. use massively parallel reporter assays to probe the effects of more than 32,000 human-specific genetic substitutions on regulatory function in neural stem cells. Focusing on two classes of regulatory elements thought to exhibit novel regulatory activities in humans—human accelerated regions (HARs) and human gain enhancers (HGEs)—the authors find that more than 30% of active HARs and HGEs differ functionally between humans and chimpanzees. Within HARs and HGEs that exhibit human-specific regulatory activity, the study identifies more than 400 specific sequence changes that influence each other in both additive and non-additive ways to alter regulatory function and potentially shape human evolution. The findings both reveal new details about how evolutionary innovations impact enhancer function and offer new candidates to study the emergence of uniquely human neural traits, according to the authors. — T.J.
Read the PNAS article: Massively parallel discovery of human-specific substitutions that alter enhancer activity
