To better understand the molecular and cellular differences in brain organization between human and nonhuman primates, we performed transcriptome sequencing of 16 regions of adult human, chimpanzee, and macaque brains. Integration with human single-cell transcriptomic data revealed global, regional, and cell-type-specific species expression differences in genes representing distinct functional categories. We validated and further characterized the human specificity of genes enriched in distinct cell types through histological and functional analyses, including rare subpallial-derived interneurons expressing dopamine biosynthesis genes enriched in the human striatum and absent in the nonhuman African ape neocortex. Our integrated analysis of the generated data revealed diverse molecular and cellular features of the phylogenetic reorganization of the human brain across multiple levels, with relevance for brain function and disease.

Data was generated as part of the PsychENCODE Consortium, supported by MH103339, MH106934, and MH110926. Additional support was provided by the NIH grant MH109904, the Kavli Foundation, the James S. McDonnell Foundation, NSF grant BCS-1316829, and ERC Starting Grant 260372, and MICINN BFU2011-28549