Abstract
DNA methylation is an important epigenetic mark that contributes to various regulations in all domains of life. Giant viruses are widespread dsDNA viruses with gene contents overlapping the cellular world that also encode DNA methyltransferases. Yet, virtually nothing is known about the methylation of their DNA. Here, we use single-molecule real-time sequencing to study the complete methylome of a large spectrum of giant viruses. We show that DNA methylation is widespread, affecting 2/3 of the tested families, although unevenly distributed. We also identify the corresponding viral methyltransferases and show that they are subject to intricate gene transfers between bacteria, viruses and their eukaryotic host. Most methyltransferases are conserved, functional and under purifying selection, suggesting that they increase the viruses' fitness. Some virally encoded methyltransferases are also paired with restriction endonucleases forming Restriction-Modification systems. Our data suggest that giant viruses' methyltransferases are involved in diverse forms of virus-pathogens interactions during coinfections.