Accelerated evolution of oligodendrocytes in human brain

Recent discussions of human brain evolution have largely focused on increased neuron numbers and changes in their connectivity and expression. However, it is increasingly appreciated that oligodendrocytes play important roles in cognitive function and disease. Whether both cell types follow distinctive evolutionary trajectories is not known. We examined the transcriptomes of neurons and oligodendrocytes in the frontal cortex of humans, chimpanzees, and rhesus macaques. We identified human-specific trajectories of gene expression in oligodendrocytes and show that oligodendrocytes have undergone accelerated gene expression evolution in the human lineage. The signature of acceleration is enriched for cell type-specific expression alterations in schizophrenia. These results underscore the importance of oligodendrocytes in human brain evolution. We compared the cell-type specific transcriptome profiling of sorted nuclei from humans to chimpanzees, our closest extant relative, using rhesus macaque as an outgroup. We analyzed genome-wide expression levels in adult human Brodmann area 46 (BA46, 27 individuals), and the homologous regions of chimpanzee (11 individuals), and rhesus macaque (15 individuals). Cell-type specific whole transcriptome data was obtained using fluorescence-activated nuclei sorting (FANS) with antibodies to either NeuN or OLIG2 to isolate neurons (NeuN) or oligodendrocytes (OLIG2) and their precursors, respectively.