Fukuda Kei, Inoguchi Yukihiro, Ichiyanagi Kenji, Ichiyanagi Tomoko, Go Yasuhiro, Nagano Masashi, Yanagawa Yojiro, Takaesu Noboru, Ohkawa Yasuyuki, Imai Hiroo, Sasaki Hiroyuki
Division of Epigenomics and Development, Medical Institute of Bioregulation, and Epigenome Network Research Center, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
Cellular Memory Laboratory, RIKEN, Wako, Saitama 351-0198, Japan.
Hum Mol Genet. 2017 Sep 15;26(18):3508-3519. doi: 10.1093/hmg/ddx236.
Changes in gene expression resulting from epigenetic and/or genetic changes play an important role in the evolutionary divergence of phenotypes. To explore how epigenetic and genetic changes are linked during primate evolution, we have compared the genome-wide DNA methylation profiles (methylomes) of humans and chimpanzees, which have a 1.2% DNA sequence divergence, of sperm, the frontal cortices, B cells, and neutrophils. We revealed that species-specific differentially methylated regions (S-DMRs), ranging from several hundred base pairs (bp) to several kilo base pairs (kb), were frequently associated with sequence changes in transcription factor-binding sites and insertions of Alu and SVA retrotransposons. We then generated a reference macaque sperm methylome map and revealed, in sperm, that both human and chimpanzee S-DMRs arose more frequently owing to methylation loss rather than gain. Moreover, we observed that the sperm methylomes contained many more hypomethylated domains (HMDs), ranging from 20 to 500 kb, than did the somatic methylomes. Interestingly, the sperm HMDs changed rapidly during primate evolution; hundreds of sperm HMDs were specific to humans, whereas most somatic HMDs were highly conserved between humans and chimpanzees. Notably, these human-specific sperm HMDs frequently occurred in regions exhibiting copy number variations. Our findings indicate that primate evolution, particularly in the germline, is significantly impacted by reciprocal changes in the genome and epigenome.
由表观遗传和/或基因变化导致的基因表达改变在表型的进化分化中起着重要作用。为了探究在灵长类动物进化过程中表观遗传和基因变化是如何联系的，我们比较了人类和黑猩猩的全基因组DNA甲基化图谱（甲基化组），人类和黑猩猩的DNA序列差异为1.2%，比较的样本包括精子、额叶皮质、B细胞和中性粒细胞。我们发现，几百个碱基对（bp）到几千个碱基对（kb）范围内的物种特异性差异甲基化区域（S-DMRs）经常与转录因子结合位点的序列变化以及Alu和SVA逆转录转座子的插入有关。然后我们生成了一份猕猴精子甲基化组参考图谱，并发现，在精子中，人类和黑猩猩的S-DMRs更多是由于甲基化缺失而非增加而产生的。此外，我们观察到精子甲基化组比体细胞甲基化组含有更多的低甲基化结构域（HMDs），范围从20到500kb。有趣的是，精子HMDs在灵长类动物进化过程中变化迅速；数百个精子HMDs是人类特有的，而大多数体细胞HMDs在人类和黑猩猩之间高度保守。值得注意的是，这些人类特有的精子HMDs经常出现在表现出拷贝数变异的区域。我们的研究结果表明，灵长类动物的进化，尤其是在种系中，受到基因组和表观基因组相互变化的显著影响。
