近日，国际著名杂志《基因组研究》Genome Research杂志在线刊登了了中科院上海生科院计算生物学研究所Philipp Khaitovich研究组的最新研究成果“Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques，”文章中，研究者发现人类大脑起源于皮质突触发育的延迟。
该研究团队结合芯片以及高通量测序技术，测量了不同年龄段的人、黑猩猩和恒河猴大脑和小脑皮质中基因的表达活性，分析了约12，000个基因的表达。结果发现，人类大脑皮质中有702个基因，其随着年龄变化的表达模式与其它两个物种不同。与之对应的是，黑猩猩中只拥有55个特有的表达模式。这些拥有人类特有表达模式的基因可分为5个不同的共表达模型。最显著的一类模型聚集了很多突触相关功能的基因，并显示出人类大脑皮质突触发育的一种长达5年的极度延迟。此结果通过电镜观察三个物种中7，000多个突触被证实。进一步的调控机制研究揭示了转录因子MEF2A有可能介导这一突触发育的延迟。
该研究得到国际同仁的高度肯定和好评，对理解人类大脑发育的进化以及进化调控机制具有重要意义。
该研究获得科技部、中国科学院、上海生命科学研究院、德国马普学会、德国联邦教育与研究部的经费资助。（生物谷Bioon.com）
doi:10.1101/gr.127324.111
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Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques
Xiling Liu1,8, Mehmet Somel1,2,8, Lin Tang1,3,8, Zheng Yan1, Xi Jiang1, Song Guo1, Yuan Yuan1,4, Liu He1,3, Anna Oleksiak1, Yan Zhang5, Na Li6, Yuhui Hu6, Wei Chen6,7, Zilong Qiu5,9, Svante Pääbo2,9 and Philipp Khaitovich1,2,9
Over the course of ontogenesis, the human brain and human cognitive abilities develop in parallel, resulting in a phenotype strikingly distinct from that of other primates. Here, we used microarrays and RNA-sequencing to examine human-specific gene expression changes taking place during postnatal brain development in the prefrontal cortex and cerebellum of humans, chimpanzees, and rhesus macaques. We show that the most prominent human-specific expression change affects genes associated with synaptic functions and represents an extreme shift in the timing of synaptic development in the prefrontal cortex, but not the cerebellum. Consequently, peak expression of synaptic genes in the prefrontal cortex is shifted from <1 yr in chimpanzees and macaques to 5 yr in humans. This result was supported by protein expression profiles of synaptic density markers and by direct observation of synaptic density by electron microscopy. Mechanistically, the human-specific change in timing of synaptic development involves the MEF2A-mediated activity-dependent regulatory pathway. Evolutionarily, this change may have taken place after the split of the human and the Neanderthal lineages.
