Human-specific features of special gene expression and regulation in eight brain regions. Human-specific features of special gene expression and regulation in eight brain regions

Despite the substantial efforts made to compile the molecular maps of the human brain, they do not fully inform us of the features unique to humans. Yet, identification of these features might help us to understand both the evolution and nature of the human cognitive traits. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions of humans, chimpanzees, gorillas, gibbon and macaques. Integrated analysis of these data revealed existence of 1,851 human-specific transcriptome differences affecting one or multiple brain regions, in contrast to 240 chimpanzee-specific ones. More than a half of these differences represented elevated expression in human hippocampus, while the rest affected microglial functions in neocortex. Analysis of predicted regulatory interactions driving these differences revealed role of transcription factors in species-specific transcriptome changes, while epigenetic modifications were linked to spatial expression differences conserved across species. Overall design: Transcriptome across eight brain regions (dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, anterior cingulate cortex, premotor cortex, primary visual cortex, striatum, hippocampus, cerebellum) of humans, chimpanzees, gorillas and gibbon were measured using RNA-seq.

尽管学界已为构建人类大脑分子图谱付出了大量努力，但现有图谱仍未能完整揭示人类独有的大脑特征。而对这些独有特征的识别，将有助于我们理解人类认知特质的演化历程与本质属性。本研究通过分析人类、黑猩猩、大猩猩、长臂猿及猕猴八个脑区的基因表达（gene expression）与H3K27ac染色质修饰（chromatin modification）数据，对该问题展开了探究。对上述数据的整合分析显示，共存在1851种人类特异性转录组（transcriptome）差异，这些差异可影响一个或多个脑区；与之相对的是仅240种黑猩猩特异性转录组差异。其中超过半数的差异表现为人类海马体的基因表达上调，剩余差异则与新皮层中小胶质细胞的功能相关。针对驱动这些差异的预测调控互作进行分析后发现，转录因子在物种特异性转录组变化中发挥了关键作用；而表观遗传修饰则与跨物种保守的空间表达差异存在关联。实验整体设计：本研究采用RNA测序（RNA-seq）技术，对人类、黑猩猩、大猩猩与长臂猿的8个脑区——背外侧前额叶皮层、腹外侧前额叶皮层、前扣带回皮层、运动前皮层、初级视觉皮层、纹状体、海马体及小脑——的转录组进行了检测。