MBE Advance Access published online on March 12, 2009
Molecular Biology and Evolution, doi:10.1093/molbev/msp046
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Research Article |
Differences in DNA Methylation Patterns and Expression of the CCRK Gene in Human and Non-human Primate Cortices
* Institute for Human Genetics, Johannes Gutenberg University, 55101 Mainz, Germany
Department of Neuropathology, Johannes Gutenberg University, 55101 Mainz, Germany
Biomedical Primate Research Center, 2280 GH Rijswijk, The Netherlands
Institute of Legal Medicine, Johannes Gutenberg University, 55101 Mainz, Germany
|| Department of Pediatrics, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
¶ Institute for Anthropology, Johannes Gutenberg University, 55099 Mainz, Germany
Corresponding author: Professor Thomas Haaf, Institute for Human Genetics, Bldg. 601, Johannes Gutenberg University, Langenbeckstrasse 1, 55131 Mainz, Germany. Tel.: +49 6131 175790; Fax: +49 6131 175690; Email: haaf{at}humgen.klinik.uni-mainz.de
Received for publication November 22, 2008. Revision received February 4, 2009. Revision received March 9, 2009. Accepted for publication March 9, 2009.
Changes in DNA methylation patterns during embryo development and differentiation processes are linked to the transcriptional plasticity of our genome. However, little is known about the evolutionary conservation of DNA methylation patterns and the evolutionary impact of epigenetic differences between closely related species. Here we compared the methylation patterns of CpG islands (CGIs) in the promoter regions of 7 genes in humans and chimpanzees. We identified a block of CpGs in the cell cycle related kinase (CCRK) gene that is more methylated in the adult human cortex than in the chimpanzee cortex and, in addition, it exhibits considerable intraspecific variation both in humans and chimpanzees. The species-specifically methylated region (SMR) lies between the almost completely methylated 5’ region and the completely demethylated 3’ region of the presumed CCRK CGI promoter. It is part of an Alu-Sg1 repeat that has been integrated into the promoter region in a common ancestor of humans and New World monkeys. This SMR is relatively hypomethylated in the rhesus monkey cortex and more or less completely methylated in the baboon cortex, indicating extraordinary methylation dynamics during primate evolution. The mRNA expression level of CCRK has also changed during the course of primate evolution. CCRK is expressed at much higher levels in human and baboon cortices, which display an average SMR methylation of 70% and 100%, respectively, than in chimpanzee and rhesus macaque cortices with an average SMR methylation of 35% and 40%, respectively. The observed evolutionary dynamics suggests a possibility that CCRK has been important for evolution of the primate brain.
Key Words: Alu insertion • CCRK • CpG island promoter • DNA methylation • epigenetic modification • primate cortex