PacBio sequencing of human fecal samples uncovers the DNA methylation landscape of 22 673 gut phages

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 (2120x, 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. Graphical Abstract

Automated summary

This study used PacBio sequencing to reveal the DNA methylation landscape of gut phages. The research found that methylation plays an important role in the taxonomy and interaction with hosts of phages, and also discovered the presence of restriction-modification systems in some phage genomes, which aid in evading clearance by the host.