张亚平院士JMCB获人类大脑转录组进化研究进展

  人类在进化过程中，脑的大小和复杂程度得到了极大得增加。脑的结构使得人类有着区别于其他物种的极高的认知能力，比如语言能力、抽象思考能力等等。转录后修饰，如RNA编辑、可变剪切等能够由相同的DNA序列生成不同的RNA，进而翻译成不同的蛋白质构体，是扩大蛋白质多样性的重要机制。随着二代测序发展，转录后修饰等已成为当今研究热点。

  为了充分地评估转录后修饰在人脑在进化中的作用，中国科学院昆明动物研究所张亚平课题组吴东东、叶凌群等对人脑的多个不同区域做了深度转录测序，详细分析了可变剪切、RNA编辑、长链非编码RNA和年轻新基因的表达等。研究发现，神经系统并未展示出较高程度的转录复杂度，但是神经系统尤其是壳核（putamen）中存在非常高的RNA编辑活性，揭示了这个区域对于人的进化中潜在的重要作用。同时，发现了脑中的可变剪切和RNA编辑之间具有显著的关联，RNA编辑酶降低表达后，可变剪切事件也就增多，表明可变剪切和RNA编辑的分子机制之间可能存在竞争关系。另外基于此数据，进一步分析了人类新基因的表达模式，发现这些新基因不仅在新皮质中高表达，在其它脑组织中同样有一些富集，尤其是壳核（putamen）组织中富集大量新基因。

  该项研究结果在线发表于Journal of Molecular Cell Biology。原文摘要：

Integrative analyses of RNA-editing, alternative splicing, and expression of young genes in human brain transcriptome by deep RNA-sequencing

Next-generation RNA-sequencing has been successfully used for identification of transcript assembly, evaluation of gene expression levels, and detection of post-transcriptional modifications. Despite these large-scale studies, additional comprehensive RNA-seq data from different subregions of the human brain are required to fully evaluate the evolutionary patterns experienced by the human brain transcriptome. Here, we provide a total of 6.5 billion RNA-seq reads from different subregions of the human brain. A significant correlation was observed between the levels of alternative splicing and RNA-editing, which might be explained by a competition between the molecular machineries responsible for the splicing and editing of RNA. Young human protein-coding genes demonstrate biased expression to the neocortical and non-neocortical regions during evolution on the lineage leading to humans. We also found that a significantly greater number of young human protein-coding genes are expressed in the putamen, a tissue that was also observed to have the highest level of RNA-editing activity. The putamen, which previously received little attention, plays an important role in cognitive ability, and our data suggest a potential contribution of the putamen to human evolution.