Understanding the diversity of DNA methylation in Mycobacterium tuberculosis

Abstract

AbstractAlthoughMycobacterium tuberculosis (Mtb)strains exhibit genomic homology of >99%, there is considerable variation in the phenotype. The underlying mechanisms of phenotypic heterogeneity inMtbare not well understood but epigenetic variation is thought to contribute. At present the methylome ofMtbhas not been completely characterized. We completed methylomes of 18Mycobacterium tuberculosis(Mtb) clinical isolates from Malawi representing the largest number ofMtbgenomes 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 ofMtb. For the first time we report complete loss of methylation courtesy of C758T (S253L) mutation in theMamBgene of Indo-oceanic lineage ofMtb. We also conducted a genomic and methylome comparison of the Malawian samples against a global sample. We confirm that methylation inMtbis lineage specific although some unresolved issues still remain.