Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK-Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China.
Center for Gut Microbiome Research, Department of Surgery, Med-X Institute, Department of High Talent, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Nucleic Acids Res. 2023 Dec 11;51(22):12140-12149. doi: 10.1093/nar/gkad977.
Gut phages have an important impact on human health. Methylation plays key roles in DNA recognition, gene expression regulation and replication for phages. However, the DNA methylation landscape of gut phages is largely unknown. Here, with PacBio sequencing (2120×, 4785 Gb), we detected gut phage methylation landscape based on 22 673 gut phage genomes, and presented diverse methylation motifs and methylation differences in genomic elements. Moreover, the methylation rate of phages was associated with taxonomy and host, and N6-methyladenine methylation rate was higher in temperate phages than in virulent phages, suggesting an important role for methylation in phage-host interaction. In particular, 3543 (15.63%) phage genomes contained restriction-modification system, which could aid in evading clearance by the host. This study revealed the DNA methylation landscape of gut phage and its potential roles, which will advance the understanding of gut phage survival and human health.
肠道噬菌体对人类健康有重要影响。甲基化在噬菌体的 DNA 识别、基因表达调控和复制中起着关键作用。然而，肠道噬菌体的 DNA 甲基化图谱在很大程度上是未知的。在这里，我们通过 PacBio 测序（2120×，4785 Gb），基于 22673 个肠道噬菌体基因组检测了肠道噬菌体的甲基化图谱，并展示了基因组元件中多样化的甲基化基序和甲基化差异。此外，噬菌体的甲基化率与分类群和宿主有关，温和噬菌体中的 N6-甲基腺嘌呤甲基化率高于毒性噬菌体，表明甲基化在噬菌体-宿主相互作用中具有重要作用。特别是，3543（15.63%）个噬菌体基因组含有限制-修饰系统，这有助于逃避宿主的清除。本研究揭示了肠道噬菌体的 DNA 甲基化图谱及其潜在作用，这将有助于深入了解肠道噬菌体的生存和人类健康。
