Evolutionary Changes in Pathways and Networks of Genes Expressed in the Brains of Humans and Macaques

As the key organ that separates humans from nonhuman primates, the brain has continuously evolved to adapt to environmental and climatic changes. Although humans share most genetic, molecular, and cellular features with other primates such as macaques, there are significant differences in the structure and function of the brain between humans and these species. Thus, exploring the differences between the brains of human and nonhuman primates in the context of evolution will provide insights into the development, functionality, and diseases of the human central nervous system (CNS). Since the genes involved in many aspects of the human brain are under common pressures of natural selection, their evolutionary features can be analyzed collectively at the pathway level. In this study, the molecular mechanisms underlying human brain capabilities were explored by comparing the evolution features of pathways enriched in genes expressed in the human brain and the macaque brain. We identified 31 pathways with differential evolutionary properties, including those related to neurological diseases, signal transduction, immunological response, and metabolic processes. By analyzing genes differentially expressed in brain regions or development stages between humans and macaques,  9 and 4 pathways with differential evolutionary properties were detected, respectively. We further performed crosstalk analysis on the pathways to obtain an intuitive correlation between the pathways, which is helpful in understanding the mechanisms of interaction between pathways. Our results provide on a comprehensive view of the evolutionary pathways of the human CNS and can serve as a reference for the study of human brain development.