MicroRNA expression and regulation in human, chimpanzee, and macaque brains.
MicroRNA expression and regulation in human, chimpanzee, and macaque brains.
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DOI：
10.1371/journal.pgen.1002327
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发表时间：
2011-10
期刊：
影响因子：
4.5
通讯作者：
Khaitovich P
中科院分区：
文献类型：
--
作者：
Hu HY;Guo S;Xi J;Yan Z;Fu N;Zhang X;Menzel C;Liang H;Yang H;Zhao M;Zeng R;Chen W;Pääbo S;Khaitovich P
在其他因素中，人类进化谱系上基因表达的变化被认为在人类特异性表型的建立中起重要作用。然而，这些表达变化背后的分子机制在很大程度上是未知的。在这里，我们探讨了microRNA（miRNA）在调节成年人，黑猩猩和恒河猴的基因表达差异中的作用，在两个大脑区域：前额叶皮层和小脑。使用高通量测序，miRNA微阵列和Q-PCR的组合，我们已经表明，在325种表达的miRNA中，高达11%的人和黑猩猩之间存在显著差异，而人和猕猴之间的差异高达31%。测量人类和黑猩猩大脑中的mRNA和蛋白质表达，我们发现miRNA和靶基因表达差异之间存在显著的负相关关系，解释了2%-4%的mRNA和4%-6%的蛋白质表达差异。值得注意的是，显示人类特异性表达的miRNA定位于神经元和参与神经功能的靶基因。神经功能的富集以及miRNA驱动的对人类进化谱系的调节，通过在两个神经母细胞瘤细胞系中预测的miRNA靶点的实验验证得到进一步证实。最后，我们在5种人类特异性表达的miRNA之一miR-34 c-5 p的上游区域鉴定了正选择的特征。这表明miR-34 c-5 p表达变化发生在人类和尼安德特人谱系分裂之后，并且具有适应性意义。总之，这些结果表明，miRNA表达的变化可能有助于人类认知功能的进化。人类在基因组序列水平上与猿和猴子非常相似，但在认知能力方面仍然非常不同。人类的认知如何在如此短的进化时间内进化？在众多假说中，影响数百个靶基因的几个关键调控因子的表达进化被认为是一种可能的解决方案。在这里，我们通过研究一种特定类型的调节RNA，microRNA（miRNA）的表达差异及其对人类，黑猩猩和恒河猴大脑中基因表达谱的影响来验证这一观点。我们的研究结果表明，在mRNA和蛋白质表达水平上，miRNA表达的变化在人脑和非人灵长类动物脑之间的基因表达差异的建立中发挥了相当大的作用。此外，我们发现的迹象表明，一些人类特异性的基因表达谱所造成的miRNA表达差异可能与人类特异性功能的进化。
Among other factors, changes in gene expression on the human evolutionary lineage have been suggested to play an important role in the establishment of human-specific phenotypes. However, the molecular mechanisms underlying these expression changes are largely unknown. Here, we have explored the role of microRNA (miRNA) in the regulation of gene expression divergence among adult humans, chimpanzees, and rhesus macaques, in two brain regions: prefrontal cortex and cerebellum. Using a combination of high-throughput sequencing, miRNA microarrays, and Q-PCR, we have shown that up to 11% of the 325 expressed miRNA diverged significantly between humans and chimpanzees and up to 31% between humans and macaques. Measuring mRNA and protein expression in human and chimpanzee brains, we found a significant inverse relationship between the miRNA and the target genes expression divergence, explaining 2%–4% of mRNA and 4%–6% of protein expression differences. Notably, miRNA showing human-specific expression localize in neurons and target genes that are involved in neural functions. Enrichment in neural functions, as well as miRNA–driven regulation on the human evolutionary lineage, was further confirmed by experimental validation of predicted miRNA targets in two neuroblastoma cell lines. Finally, we identified a signature of positive selection in the upstream region of one of the five miRNA with human-specific expression, miR-34c-5p. This suggests that miR-34c-5p expression change took place after the split of the human and the Neanderthal lineages and had adaptive significance. Taken together these results indicate that changes in miRNA expression might have contributed to evolution of human cognitive functions. Humans are remarkably similar to apes and monkeys on the genome sequence level but remain remarkably distinct with respect to cognitive abilities. How could human cognition evolve within such a short evolutionary time? Among many hypotheses, evolution in expression of a few key regulators affecting hundreds of their target genes was proposed as one possible solution. Here, we tested this notion by studying expression divergence of a specific type of regulatory RNA, microRNA (miRNA), and its effect on gene expression profiles in brains of humans, chimpanzees, and rhesus macaques. Our results indicate that changes in miRNA expression have played a considerable role in the establishment of gene expression divergence between human brains and brains of non-human primates at both mRNA and protein expression levels. Furthermore, we find indications that some of the human-specific gene expression profiles caused by miRNA expression divergence might be associated with evolution of human-specific functions.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
14.9
作者：
Griffiths-Jones, S
通讯作者：
Griffiths-Jones, S
Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ
影响因子：
14.8
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.