The 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. Results 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. 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.

中文翻译：

---

人脑发育过程中表达轨迹的演变和转变。


人类大脑的非凡能力是我们区别于其他动物的独特特征。然而，我们对人类谱系中大脑如何变化的理解仍然不完整，但对于理解人类的认知、行为和大脑疾病至关重要。在这里，我们比较了人类和恒河猴（Macaca mulatta）大脑发育的表达轨迹，以探索它们不同的转录组谱。结果显示，大脑发育可分为两个阶段，人类的划分日期为受孕后25至26周（PCW），恒河猴的划分日期为17-23PCW，而不是广泛用作统一划分的出生时间。跨物种神经发育的时间。动态网络生物标志物（DNB）分析显示，这两个分界日期是大脑发育过程中的过渡阶段，此后大脑转录组谱经历了以 DNB 分子高度波动为特征的关键转变。我们还发现，人类大脑早期和晚期大脑发育阶段（由分界点定义）之间的变化明显大于猕猴大脑。为了探索早期人类大脑发育过程中时间延长的分子机制，我们进行了表达异时性测试。结果表明，与猕猴相比，更多的异时基因在人类早期大脑发育过程中表现出幼态持续状态，这与人类谱系中延迟的分界时间一致，并证明人类大脑发育中的幼态持续状态可以追溯到产前时期。 我们进一步构建了转录网络来探索人类早期大脑发育的概况，并确定了中枢基因RBFOX1在调节早期大脑发育中发挥着重要作用。我们还发现RBFOX1在其非编码区快速进化，表明该基因在人类大脑进化中发挥了重要作用。我们的研究结果证明 RBFOX1 可能是早期人类大脑发育和进化的关键枢纽基因。通过比较人类和猕猴之间的基因表达谱，我们发现这两个物种之间存在不同的表达轨迹，这加深了我们对人类大脑进化的理解。