MicroRNA expression and regulation in human, chimpanzee, and macaque brains

Hai Yang Hu, Song Guo, Jiang Xi, Zheng Yan, Ning Fu, Xiaoyu Zhang, Corinna Menzel, Hongyu Liang, Hongyi Yang, Min Zhao, Rong Zeng, Wei Chen, Svante Pääbo, Philipp Khaitovich

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere1002327
JournalPLoS Genetics
Volume7
Issue number10
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

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