Differentially evolutionary pathways and their interactions in genes expressed in brain of human and macaque

As the key organ that separates human from other non-human primates, brain has continuously evolved to adapt to the changes of environments and climates. Although human shares most genetic, molecular and cellular features with primates like macaque, there are significant differences in the structure and function in brain of human and these species. Thus, exploring the differences between brains of human and non-human primates in the context of evolution will provide insights into the development, function and diseases of human nervous system. Since the genes involved in many aspects of human brain are under common pressures of natural selection, their evolutionary features can be analyzed collectively at pathway-level. In this study, we tried to explore the molecular mechanisms underlying human brain by comparing the evolutionary features of pathways enriched in genes expressed in human brain and macaque brain. We identified 31 differentially evolutionary pathways in the brain of human and macaque, among which included those related to neurological diseases, signaling transduction, immune and metabolism. By analyzing differentially expressed genes in brain regions and development stages between human and macaque, we also found that ten and four pathways with evolutionary differences, respectively. We further performed crosstalk analysis of pathways to obtain an intuitive correlation between the pathways, which is helpful to understand the mechanism of interaction between pathways. Our results shed light on a comprehensive view of the evolutionary pathways of the human nervous system and provide a reference for the study of human brain development.