Abstract
BackgroundThe remarkable abilities of the human brain are distinctive features that set us apart from other animals. However, our understanding of how the brain has changed in the human lineage remains incomplete, but is essential for understanding cognition, behavior, and brain disorders in humans. Here, we compared the expression trajectory in brain development between humans and rhesus macaques (Macaca mulatta) to explore their divergent transcriptome profiles.ResultsResults showed that brain development could be divided into two stages, with a demarcation date in a range between 25 and 26 postconception weeks (PCW) for humans and 17-23PCWfor rhesus macaques, rather than birth time that have been widely used as a uniform demarcation time of neurodevelopment across species. Dynamic network biomarker (DNB) analysis revealed that the two demarcation dates were transition phases during brain development, after which the brain transcriptome profiles underwent critical transitions characterized by highly fluctuating DNB molecules. We also found that changes between early and later brain developmental stages (as defined by the demarcation points) were substantially greater in the human brain than in the macaque brain. To explore the molecular mechanism underlying prolonged timing during early human brain development, we carried out expression heterochrony tests. Results demonstrated that compared to macaques, more heterochronic genes exhibited neoteny during early human brain development, consistent with the delayed demarcation time in the human lineage, and proving that neoteny in human brain development could be traced to the prenatal period. We further constructed transcriptional networks to explore the profile of early human brain development and identified the hub gene RBFOX1 as playing an important role in regulating early brain development. We also found RBFOX1 evolved rapidly in its non-coding regions, indicating that this gene played an important role in human brain evolution. Our findings provide evidence that RBFOX1 is a likely key hub gene in early human brain development and evolution.ConclusionsBy comparing gene expression profiles between humans and macaques, we found divergent expression trajectories between the two species, which deepens our understanding of the evolution of the human brain.
Highlights
The remarkable abilities of the human brain are distinctive features that set us apart from other animals
By comparing gene expression profiles between humans and macaques, we found divergent expression trajectories between the two species, which deepens our understanding of the evolution of the human brain
Human brain transcriptome data were used in this study, including RNA-sequencing (RNA-seq) and microarray data across multiple brain regions downloaded from the Allen Brain Atlas [24, 25] (Table 1; Additional file 1: Table S1 ~ Table S2)
Summary
The remarkable abilities of the human brain are distinctive features that set us apart from other animals. Based on compelling differences in cognitive and behavioral capacities, but relatively close phylogenetic relationship between humans and nonhuman primates (NHPs) [4,5,6], recent comparative analyses have provided a novel strategy to study humanspecific neurodevelopment [7,8,9]. Earlier research noted that neurodevelopmental timing is impacted by different developmental rates and life history strategies [2]. These differences in neurodevelopmental timing among species, called heterochrony, have long been considered a crucial impetus for evolution [17,18,19]. Humans have an unusually extended childhood and slow rate of neurodevelopment (known as neoteny) relative to other animals, which is considered a possible mechanism for human brain evolution [18, 20]. Extending comparative analysis to the prenatal stages is necessary for exploring the features of neurodevelopment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
