Network-based analysis reveals genetic diversity of human-brain expressed genes with high evolutionary rates

Introduction Comparing the gene expression profiles of human and non-human primate brains can provide essential insights to understand the structural and functional disparities between these species, as well as the origins of many diseases. In recent years, the availability of genomic and transcriptomic data of the human brain has made it feasible to explore the evolutionary features of the brain-expressed genes at the molecular level on a large scale. Analyses of human and non-human primate brain cell-type-specific expressed genes with elevated evolutionary rates can uncover the genetic and functional diversity intrinsic to the human brain. Methods In this study, we try to explore the genetic diversity of the human brain by analyzing genes with divergent evolutionary rates in human and macaque brains, as well as in the human lineage. Results We identified 450 genes with high evolutionary rates between human and macaque, and 534 genes between human populations. Topological characteristics showed that these genes had lower protein-protein interaction network node degree. We also found that pathways related to neurological diseases, immune, metabolism, and signaling transduction were enriched in the genes of high evolutionary rates between human and macaque. We further identified 97 and 137 potential genes with differential evolution features between and within species. Discussion Our results reveal the genetic diversity of evolutionarily variable specific-expressed genes in the human brain and provide complementary findings for human brain evolution at the transcriptional level.