Evolution of Multi-Regional Transcriptional Architecture in Human and Non-Human Primate Brains

Phenotypic differences between human and non-human primate brains have been described at structural and functional levels. However, the underlying transcriptional events have remained elusive. Here, we deep sequenced mRNAs and small non-coding RNAs from 16 brain regions of chimpanzees and rhesus macaques, and compared those to the complementary human BrainSpan dataset. We found substantial species differences, including 19.2% of mRNAs and 15.8% of miRNAs displaying human-specific expression. mRNA and miRNA we also organized into conserved and species-specific co-expression modules. Analyses of regional patterns, revealed that the striatum, followed by the medio-dorsal nucleus of the thalamus and certain neocortical areas, had the highest number of human-specific changes. Annotation of human-specific transcriptional changes revealed affected many functional categories including transcriptional regulation, cell adhesion and dopaminergic neuromodulatory system. This study provides a comprehensive resource on the human and non-human primate brain transcriptomes and insights into species-specific transcriptional programs underlying phenotypic differences. Human samples are deposited under the dbGaP study phs000755.v1.p1.