Adaptive sequence divergence forged new neurodevelopmental enhancers in humans.

ABSTRACT: 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.

SUBMITTER: Mangan RJ 

PROVIDER: S-EPMC10013929 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature