Wang Xiaotong, Li Qiye, Lian Jinmin, Li Li, Jin Lijun, Cai Huimin, Xu Fei, Qi Haigang, Zhang Linlin, Wu Fucun, Meng Jie, Que Huayong, Fang Xiaodong, Guo Ximing, Zhang Guofan
Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.
BMC Genomics. 2014 Dec 16;15(1):1119. doi: 10.1186/1471-2164-15-1119.
Studies of DNA methylomes in a wide range of eukaryotes have revealed both conserved and divergent characteristics of DNA methylation among phylogenetic groups. However, data on invertebrates particularly molluscs are limited, which hinders our understanding of the evolution of DNA methylation in metazoa. The sequencing of the Pacific oyster Crassostrea gigas genome provides an opportunity for genome-wide profiling of DNA methylation in this model mollusc.
Homologous searches against the C. gigas genome identified functional orthologs for key genes involved in DNA methylation: DNMT1, DNMT2, DNMT3, MBD2/3 and UHRF1. Whole-genome bisulfite sequencing (BS-seq) of the oyster's mantle tissues revealed that more than 99% methylation modification was restricted to cytosines in CpG context and methylated CpGs accumulated in the bodies of genes that were moderately expressed. Young repeat elements were another major targets of CpG methylation in oysters. Comparison with other invertebrate methylomes suggested that the 5'-end bias of gene body methylation and the negative correlation between gene body methylation and gene length were the derived features probably limited to the insect lineage. Interestingly, phylostratigraphic analysis showed that CpG methylation preferentially targeted genes originating in the common ancestor of eukaryotes rather than the oldest genes originating in the common ancestor of cellular organisms.
Comparative analysis of the oyster DNA methylomes and that of other animal species revealed that the characteristics of DNA methylation were generally conserved during invertebrate evolution, while some unique features were derived in the insect lineage. The preference of methylation modification on genes originating in the eukaryotic ancestor rather than the oldest genes is unexpected, probably implying that the emergence of methylation regulation in these 'relatively young' genes was critical for the origin and radiation of eukaryotes.
对多种真核生物DNA甲基化组的研究揭示了系统发育群体之间DNA甲基化的保守和不同特征。然而，关于无脊椎动物尤其是软体动物的数据有限，这阻碍了我们对后生动物DNA甲基化进化的理解。太平洋牡蛎基因组的测序为在这个模型软体动物中进行全基因组DNA甲基化分析提供了机会。
对太平洋牡蛎基因组的同源搜索确定了参与DNA甲基化的关键基因的功能直系同源物：DNMT1、DNMT2、DNMT3、MBD2/3和UHRF1。牡蛎外套膜组织的全基因组亚硫酸氢盐测序（BS-seq）显示，超过99%的甲基化修饰仅限于CpG背景下的胞嘧啶，且甲基化的CpG在中等表达基因的基因体内积累。年轻的重复元件是牡蛎中CpG甲基化的另一个主要靶点。与其他无脊椎动物甲基化组的比较表明，基因体甲基化的5'端偏向以及基因体甲基化与基因长度之间的负相关可能是仅限于昆虫谱系的衍生特征。有趣的是，系统发育地层分析表明，CpG甲基化优先靶向起源于真核生物共同祖先的基因，而不是起源于细胞生物共同祖先的最古老基因。
对牡蛎DNA甲基化组与其他动物物种的比较分析表明，DNA甲基化特征在无脊椎动物进化过程中总体上是保守的，而一些独特特征是在昆虫谱系中衍生出来的。甲基化修饰对起源于真核生物祖先而非最古老基因的基因的偏好是出乎意料的，这可能意味着这些“相对年轻”基因中甲基化调控的出现对真核生物的起源和辐射至关重要。
