Journal of Human Genetics (2013) 58, 446–454; doi:10.1038/jhg.2013.55; published online 6 June 2013
Regional DNA methylation differences between humans and chimpanzees are associated with genetic changes, transcriptional divergence and disease genes
Open
Kei Fukuda1, Kenji Ichiyanagi1, Yoichi Yamada2, Yasuhiro Go3, Toshifumi Udono4,5, Seitaro Wada6, Toshiyuki Maeda7, Hidenobu Soejima7, Naruya Saitou8, Takashi Ito9 and Hiroyuki Sasaki1
1Division of Epigenomics and Development, Medical Institute of Bioregulation, and Epigenome Network Research Center, Kyushu University, Fukuoka, Japan
2Faculty of Electrical and Computer Engineering, Institute of Science and Engineering, Kanazawa University, Kanazawa, Japan
3Molecular Biology Section, Department of Cellular and Molecular Biology, Primate Research Institute, Kyoto University, Inuyama, Aichi, Japan
4Sanwa Kagaku Kenkyusho Co., Ltd., Uto, Kumamoto, Japan
5Kumamoto Sanctuary, Wildlife Research Center, Kyoto University, Uto, Kumamoto, Japan
6Kyoto City Zoo, Okazaki Hoshojicho, Sakyo-ku, Kyoto, Japan
7Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan
8Division of Population Genetics, National Institute of Genetics, Mishima, Japan
9Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan
Correspondence: Dr K Ichiyanagi or Professor H Sasaki, Division of Epigenomics and Development, Medical Institute of Bioregulation, and Epigenome Network Research Center, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail: ichiyanagi@bioreg.kyushu-u.ac.jp or hsasaki@bioreg.kyushu-u.ac.jp
Received 13 March 2013; Revised 26 April 2013; Accepted 1 May 2013
Advance online publication 6 June 2013
Abstract
Changes in gene expression have been proposed to have an important role in the evolutionary changes in phenotypes. Interspecific changes in gene expression can result not only from genetic changes in regulatory regions but also from epigenetic changes in such regions. Here we report the identification of genomic regions showing differences in DNA methylation between humans and chimpanzees (termed S-DMRs for species-specific differentially methylated regions) on chromosomes 21 and 22. These regional methylation differences are frequently associated with genes, including those relevant to a disease, such as Alzheimer’s disease, diabetes mellitus or cancer. Methylation differences are often correlated with changes in promoter activity or alternative splicing. Comparative studies including other great ape species provide evidence for the contribution of genetic changes to some of these S-DMRs. Genetic changes responsible for the S-DMRs include gain or loss of CTCF-binding site and changes in CpG density in microsatellite repeats. Our results suggest that DNA methylation changes, often caused by small sequence changes, contribute to transcriptional and phenotypic diversification in hominid evolution.
Keywords: APP; CTCF; Epigenome; MN1; speciation
