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Open Access Highly Accessed Research article

Genome-wide DNA methylation analyses in the brain reveal four differentially methylated regions between humans and non-human primates

Jinkai Wang1, Xiangyu Cao12, Yanfeng Zhang12 and Bing Su1*

Author Affiliations

1 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 East Jiao-Chang Road, Kunming, Yunnan, 650223, People's Republic of China

2 Graduate School of Chinese Academy of Sciences, Beijing, People's Republic of China

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BMC Evolutionary Biology 2012, 12:144  doi:10.1186/1471-2148-12-144

Published: 16 August 2012

Abstract

Background

The highly improved cognitive function is the most significant change in human evolutionary history. Recently, several large-scale studies reported the evolutionary roles of DNA methylation; however, the role of DNA methylation on brain evolution is largely unknown.

Results

To test if DNA methylation has contributed to the evolution of human brain, with the use of MeDIP-Chip and SEQUENOM MassARRAY, we conducted a genome-wide analysis to identify differentially methylated regions (DMRs) in the brain between humans and rhesus macaques. We first identified a total of 150 candidate DMRs by the MeDIP-Chip method, among which 4 DMRs were confirmed by the MassARRAY analysis. All 4 DMRs are within or close to the CpG islands, and a MIR3 repeat element was identified in one DMR, but no repeat sequence was observed in the other 3 DMRs. For the 4 DMR genes, their proteins tend to be conserved and two genes have neural related functions. Bisulfite sequencing and phylogenetic comparison among human, chimpanzee, rhesus macaque and rat suggested several regions of lineage specific DNA methylation, including a human specific hypomethylated region in the promoter of K6IRS2 gene.

Conclusions

Our study provides a new angle of studying human brain evolution and understanding the evolutionary role of DNA methylation in the central nervous system. The results suggest that the patterns of DNA methylation in the brain are in general similar between humans and non-human primates, and only a few DMRs were identified.

Keywords:
DNA methylation; Brain evolution; Primates