近日，國際著名雜志《基因組研究》Genome Research雜志在線刊登了了中科院上海生科院計算生物學(xué)研究所Philipp Khaitovich研究組的最新研究成果“Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques,，”文章中,，研究者發(fā)現(xiàn)人類大腦起源于皮質(zhì)突觸發(fā)育的延遲。
該研究團隊結(jié)合芯片以及高通量測序技術(shù),，測量了不同年齡段的人,、黑猩猩和恒河猴大腦和小腦皮質(zhì)中基因的表達活性，分析了約12,，000個基因的表達,。結(jié)果發(fā)現(xiàn)，人類大腦皮質(zhì)中有702個基因，其隨著年齡變化的表達模式與其它兩個物種不同,。與之對應(yīng)的是,，黑猩猩中只擁有55個特有的表達模式。這些擁有人類特有表達模式的基因可分為5個不同的共表達模型,。最顯著的一類模型聚集了很多突觸相關(guān)功能的基因,，并顯示出人類大腦皮質(zhì)突觸發(fā)育的一種長達5年的極度延遲。此結(jié)果通過電鏡觀察三個物種中7,，000多個突觸被證實,。進一步的調(diào)控機制研究揭示了轉(zhuǎn)錄因子MEF2A有可能介導(dǎo)這一突觸發(fā)育的延遲。
該研究得到國際同仁的高度肯定和好評,，對理解人類大腦發(fā)育的進化以及進化調(diào)控機制具有重要意義,。
該研究獲得科技部、中國科學(xué)院,、上海生命科學(xué)研究院,、德國馬普學(xué)會、德國聯(lián)邦教育與研究部的經(jīng)費資助,。（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.
