Characterization of DNA methylation in Malawian clinical isolates.

Background 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. Methods 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. Results We replicate and confirm four methylation disrupting mutations in 4 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 . Additionally, we report a novel missense mutation G454A (G152S) in the gene of the Euro-American lineage which could potentially be attributed to total disruption of methylation in the CCCG motif but partial loss in a partner motif. Through a genomic and methylome comparative analysis with a global sample of sixteen, we report previously unknown mutations affecting the locus in L6 isolates. We confirm that methylation in is lineage specific although some unresolved issues still remain