Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS Genet. 2011 Oct;7(10):e1002327. doi: 10.1371/journal.pgen.1002327. Epub 2011 Oct 13.

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

Author information

  • 1Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Chinese Academy of Sciences, Shanghai, China.

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.

PMID:
22022286
[PubMed - indexed for MEDLINE]
PMCID:
PMC3192836
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk