MicroRNA Expression and Regulation in Human, Chimpanzee, and Macaque Brains

被引:92
作者
Hu, Hai Yang [1 ]
Guo, Song [1 ]
Xi, Jiang [1 ]
Yan, Zheng [1 ]
Fu, Ning [2 ]
Zhang, Xiaoyu [3 ]
Menzel, Corinna [4 ]
Liang, Hongyu [3 ]
Yang, Hongyi [3 ]
Zhao, Min [3 ]
Zeng, Rong [2 ]
Chen, Wei [4 ,5 ]
Paeaebo, Svante [6 ]
Khaitovich, Philipp [1 ,6 ]
机构
[1] Chinese Acad Sci, Key Lab Computat Biol, CAS MPG Partner Inst Computat Biol, Shanghai, Peoples R China
[2] Chinese Acad Sci, Key Lab Syst Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China
[3] NE Forestry Univ, Coll Life Sci, Harbin, Peoples R China
[4] Max Planck Inst Mol Genet, Berlin, Germany
[5] Berlin Inst Med Syst Biol, Max Delbruck Ctr Mol Med, Berlin, Germany
[6] Max Planck Inst Evolutionary Anthropol, Leipzig, Germany
来源
PLOS GENETICS | 2011年 / 7卷 / 10期
关键词
PRIMATE GENE-EXPRESSION; TRANSCRIPTION FACTORS; TARGET PREDICTION; PREFRONTAL CORTEX; DNA-SEQUENCES; HUMAN GENOME; ALIGNMENT; PATHWAYS; PATTERNS; TOOL;
D O I
10.1371/journal.pgen.1002327
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
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页数:14
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