title: Differences in DNA methylation patterns and expression of the CCRK gene in human and nonhuman primate cortices.
abstract: 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 seven 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.
authors.affiliation: Institute for Human Genetics, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Farcas
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schneider
authors.forename: Katrin
authors.initials: K
authors.lastname: Frauenknecht
authors.forename: Ivanela
authors.initials: I
authors.lastname: Kondova
authors.forename: Ronald
authors.initials: R
authors.lastname: Bontrop
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bohl
authors.forename: Bianca
authors.initials: B
authors.lastname: Navarro
authors.forename: Markus
authors.initials: M
authors.lastname: Metzler
authors.forename: Hans
authors.initials: H
authors.lastname: Zischler
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zechner
authors.forename: Angelika
authors.initials: A
authors.lastname: Daser
authors.forename: Thomas
authors.initials: T
authors.lastname: Haaf
mesh_terms: D000818:Animals; D001483:Base Sequence; D018899:CpG Islands / Q000235:genetics*; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D010215:Papio; D011401:Promoter Regions, Genetic; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase