Evolution of regulatory signatures in primate cortical neurons at cell-type resolution

Significance The cerebral cortex of the human brain is a highly complex, heterogeneous tissue that contains many cell types that are exquisitely regulated at the level of gene expression by noncoding regulatory elements, presumably in a cell-type–dependent manner. However, assessing the regulatory elements in individual cell types is technically challenging, and therefore most of the previous studies on gene regulation were performed with bulk brain tissue. Here we analyze two major types of neurons isolated from the cerebral cortex of humans, chimpanzees, and rhesus macaques, and report complex patterns of cell-type–specific evolution of the regulatory elements in numerous genes. Many genes with evolving regulation are implicated in language abilities as well as psychiatric disorders.