Understanding the diversity of DNA methylation in Mycobacterium tuberculosis

Although strains exhibit genomic homology of >99%, there is considerable variation in the phenotype. The underlying mechanisms of phenotypic heterogeneity in are not well understood but epigenetic variation is thought to contribute. At present the methylome of has not been completely characterized. We completed methylomes of 18 () clinical isolates from Malawi representing the largest number of genomes to be completed in a single study using Single Molecule Real Time (SMRT) sequencing to date. We replicate and confirm four methylation disrupting mutations in lineages of . For the first time we report complete loss of methylation courtesy of C758T (S253L) mutation in the gene of Indo-oceanic lineage of . We also conducted a genomic and methylome comparison of the Malawian samples against a global sample. We confirm that methylation in is lineage specific although some unresolved issues still remain.