Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients

Speciation is associated with substantial rewiring of the regulatory circuitry underlying the expression of genes. Determining which of these changes are biologically relevant and underlie the emergence of the human brain or its unique susceptibility to neural disease has been challenging. Here we annotate changes to gene regulatory elements at cell type resolution in the brains of multiple primate species spanning most of primate evolution. We identify a unique set of regulatory elements that emerged in hominins prior to the separation of humans and chimpanzees. We demonstrate that these hominin gains disproportionally affect oligodendrocyte function after postnatal development and are preferentially affected in the brains of autism spectrum disorder patients. Our data provide a roadmap of regulatory rewiring across primate evolution providing insight into the genomic changes that underlie the emergence of the brain and its susceptibility to neural disease. Overall design: ChIP-sequencing for H3K27ac, ATAC-sequencing and RNA-sequencing of primate brain samples