Institute for Human Genetics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Leibniz Institute for Resilience Research, 55122, Mainz, Germany.
Sci Data. 2024 May 28;11(1):545. doi: 10.1038/s41597-024-03380-3.
Human and non-human primates have strikingly similar genomes, but they strongly differ in many brain-based processes (e.g., behaviour and cognition). While the functions of protein-coding genes have been extensively studied, rather little is known about the role of non-coding RNAs such as long non-coding RNAs (lncRNAs). Here, we predicted lncRNAs and analysed their expression pattern across different brain regions of human and non-human primates (chimpanzee, gorilla, and gibbon). Our analysis identified shared orthologous and non-orthologous lncRNAs, showing striking differences in the genomic features. Differential expression analysis of the shared orthologous lncRNAs from humans and chimpanzees revealed distinct expression patterns in subcortical regions (striatum, hippocampus) and neocortical areas while retaining a homogeneous expression in the cerebellum. Co-expression analysis of lncRNAs and protein-coding genes revealed massive proportions of co-expressed pairs in neocortical regions of humans compared to chimpanzees. Network analysis of co-expressed pairs revealed the distinctive role of the hub-acting orthologous lncRNAs in a region- and species-specific manner. Overall, our study provides novel insight into lncRNA driven gene regulatory landscape, neural regulation, brain evolution, and constitutes a resource for primate's brain lncRNAs.
人类和非人类灵长类动物的基因组惊人地相似,但它们在许多基于大脑的过程(例如行为和认知)中存在强烈差异。虽然已经广泛研究了蛋白质编码基因的功能,但对于非编码 RNA(如长非编码 RNA(lncRNA))的作用了解甚少。在这里,我们预测了 lncRNA 并分析了它们在人类和非人类灵长类动物(黑猩猩、大猩猩和长臂猿)不同大脑区域的表达模式。我们的分析确定了共享的直系同源和非直系同源 lncRNA,显示出在基因组特征上存在显著差异。对人类和黑猩猩共享直系同源 lncRNA 的差异表达分析显示,在皮质下区域(纹状体、海马体)和新皮质区域存在明显不同的表达模式,而在小脑体中保持均匀表达。lncRNA 和蛋白质编码基因的共表达分析显示,与黑猩猩相比,人类新皮质区域的共表达对比例巨大。共表达对的网络分析以区域和物种特异性的方式揭示了具有枢纽作用的直系同源 lncRNA 的独特作用。总的来说,我们的研究为 lncRNA 驱动的基因调控景观、神经调节、大脑进化提供了新的见解,并为灵长类动物的大脑 lncRNA 构成了资源。