Differentially Evolutionary Pathways and Their Interactions in Genes Expressed in Brain of Human and Macaque

Abstract

As the key organ that separates humans from non-human primates, the brain has continuously evolved to adapt to the changes of environments and climates. Although human shares 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 non-human primates in the context of evolution will provide insights into the development, functionality, and diseases of the human nervous system. 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 evolutionary features of pathways enriched in genes expressed in the human brain and the macaque brain. 31 differentially expressed evolutionary pathways were identified in the brains of humans and macaques, among which included those related to neurological diseases, signal transduction, immunological response, and metabolic processes. By analyzing differentially expressed genes in brain regions or development stages between humans and macaques, 10 pathways and 4 pathways were found to have evolutionary distinctions, respectively. We further performed crosstalk analysis of pathways in order to obtain an intuitive correlation between the pathways, of which is helpful in understanding the mechanisms 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.