DNA Methylation Assessed by SMRT Sequencing Is Linked to Mutations in Neisseria meningitidis Isolates

Aims: The extent and functional consequences of DNA methylation in the human pathogen Neisseria meningitidis is incompletely characterized. Materials & methods: We applied SMRT sequencing (Pacific Biosciences) to assess the genome-wide DNA modification profiles of two closely related N. meningitidis strains. Results: Our results revealed high divergence in DNA methylation predominantly driven by phase variability, represented by the discovery of one novel strain-specific target motif AC6mACC of the DNA methyltransferase modA12. We detected clear biases in the positional distribution of methylated target sites and prominent colocalization of methylated bases with Single Nucleotide Polymorphisms (SNPs) in a collection of N. meningitidis genomes. Conclusions: These findings suggest more diverse roles of DNA methylation and Restriction-Modification systems in the evolution of prokaryotic genomes.