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.

Gene Expression Differences Among Primates Are Associated With Changes in a Histone Epigenetic Modification

“…With few exceptions, however (e.g., with respect to DNA methylation; Farcas et al 2009), comparative studies in primates have not explored the extent to which epigenetic differences between species underlie interspecies differences in gene regulation. To take first steps toward this goal, we compared gene expression levels and histone modification data in samples from humans and two of our closest extant evolutionary relatives, chimpanzees (Pan troglodytes) and rhesus macaques (Macaca mulatta).…”

Genomic signatures of diet-related shifts during human origins

“…These epigenetic changes can also have a lasting impact since changes in maternal diet can affect methylation status for multiple generations (reviewed in [98]). Two preliminary studies of methylation change between humans and chimpanzees noted significant differences in methylation patterns, with a higher amount of methylation seen in humans [99,100]. Dietary changes incorporating more sources of methyl groups (e.g.…”

Epigenetic modifications are associated with inter-species gene expression variation in primates

“…Recent comparative studies of certain epigenetic modifications in primates provide further support for the association between epigenetic modification variation and gene expression variation [23][24][25]39]. For example, Pai et al showed that inter-species differences in DNA methylation pattern correlate with differences in gene expression level across species [24], and Cain et al found that inter-species differences in the profile of the histone modification H3K4me3 are associated with changes in gene expression level between species [25].…”

“…However, we still know little about the underling regulatory mechanisms leading to the differences in gene expression levels across species. In particular, although a few studies have shown that the inter-species differences in certain epigenetic mechanisms can explain (in a statistical sense) a small proportion of variation in gene expression levels between species [23][24][25], the relative importance of evolutionary changes in different epigenetic regulatory mechanisms remains largely elusive.…”