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，张亚平院士课题组吴东东，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。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的潜在的重要作用。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。  

　　该项研究结果收录于Journal of Molecular Cell Biology在2015年出版的第4期专辑Collection: Innovative Methods and Techniques for Frontiers of Life Science，详情如下：

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

Abstract

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.

J Mol Cell Biol (2015)7 (4):314-325 first published online July 17, 2015 doi:10.1093/jmcb/mjv043

Keywords: RNA editing, human brain transcriptome, young gene, human brain evolution