He Libo, Liang Xinyu, Wang Qian, Yang Cheng, Li Yongming, Liao Lanjie, Zhu Zuoyan, Wang Yaping
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Immun Ageing. 2022 Jun 2;19(1):28. doi: 10.1186/s12979-022-00285-w.
Grass carp are an important farmed fish in China that are infected by many pathogens, especially grass carp reovirus (GCRV). Notably, grass carp showed age-dependent susceptibility to GCRV; that is, grass carp not older than one year were sensitive to GCRV, while those over three years old were resistant to this virus. However, the underlying mechanism remains unclear. Herein, whole genome-wide DNA methylation and gene expression variations between susceptible five-month-old (FMO) and resistant three-year-old (TYO) grass carp were investigated aiming to uncover potential epigenetic mechanisms.
Colorimetric quantification revealed that the global methylation level in TYO fish was higher than that in FMO fish. Whole-genome bisulfite sequencing (WGBS) of the two groups revealed 6214 differentially methylated regions (DMRs) and 4052 differentially methylated genes (DMGs), with most DMRs and DMGs showing hypermethylation patterns in TYO fish. Correlation analysis revealed that DNA hypomethylation in promoter regions and DNA hypermethylation in gene body regions were associated with gene expression. Enrichment analysis revealed that promoter hypo-DMGs in TYO fish were significantly enriched in typical immune response pathways, whereas gene body hyper-DMGs in TYO fish were significantly enriched in terms related to RNA transcription, biosynthesis, and energy production. RNA-seq analysis of the corresponding samples indicated that most of the genes in the above terms were upregulated in TYO fish. Moreover, gene function analysis revealed that the two genes involved in energy metabolism displayed antiviral effects.
Collectively, these results revealed genome-wide variations in DNA methylation between grass carp of different ages. DNA methylation and gene expression variations in genes involved in immune response, biosynthesis, and energy production may contribute to age-dependent susceptibility to GCRV in grass carp. Our results provide important information for disease-resistant breeding programs for grass carp and may also benefit research on age-dependent diseases in humans.
草鱼是中国重要的养殖鱼类，受到多种病原体的感染，尤其是草鱼呼肠孤病毒（GCRV）。值得注意的是，草鱼对GCRV表现出年龄依赖性易感性；也就是说，一岁以下的草鱼对GCRV敏感，而三岁以上的草鱼对该病毒具有抗性。然而，其潜在机制仍不清楚。在此，研究了易感的五个月龄（FMO）和抗性的三岁龄（TYO）草鱼之间全基因组范围内的DNA甲基化和基因表达变化，旨在揭示潜在的表观遗传机制。
比色定量分析表明，TYO鱼的整体甲基化水平高于FMO鱼。两组的全基因组亚硫酸氢盐测序（WGBS）揭示了6214个差异甲基化区域（DMR）和4052个差异甲基化基因（DMG），大多数DMR和DMG在TYO鱼中呈现高甲基化模式。相关性分析表明，启动子区域的DNA低甲基化和基因体区域的DNA高甲基化与基因表达相关。富集分析表明，TYO鱼中的启动子低甲基化DMG在典型免疫反应途径中显著富集，而TYO鱼中的基因体高甲基化DMG在与RNA转录、生物合成和能量产生相关的术语中显著富集。对相应样本的RNA测序分析表明，上述术语中的大多数基因在TYO鱼中上调。此外，基因功能分析表明，参与能量代谢的两个基因具有抗病毒作用。
总体而言，这些结果揭示了不同年龄草鱼之间全基因组范围内的DNA甲基化变化。参与免疫反应、生物合成和能量产生的基因中的DNA甲基化和基因表达变化可能导致草鱼对GCRV的年龄依赖性易感性。我们的结果为草鱼抗病育种计划提供了重要信息，也可能有益于人类年龄依赖性疾病的研究。
