Drivers and sites of diversity in the DNA adenine methylomes of 93 <i>Mycobacterium tuberculosis</i> complex clinical isolates.

ABSTRACT: This study assembles DNA adenine methylomes for 93 Mycobacterium tuberculosis complex (MTBC) isolates from seven lineages paired with fully-annotated, finished, de novo assembled genomes. Integrative analysis yielded four key results. First, methyltransferase allele-methylome mapping corrected methyltransferase variant effects previously obscured by reference-based variant calling. Second, heterogeneity analysis of partially active methyltransferase alleles revealed that intracellular stochastic methylation generates a mosaic of methylomes within isogenic cultures, which we formalize as 'intercellular mosaic methylation' (IMM). Mutation-driven IMM was nearly ubiquitous in the globally prominent Beijing sublineage. Third, promoter methylation is widespread and associated with differe

SUBMITTER: Modlin SJ 

PROVIDER: S-EPMC7591249 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature