Methylation in Mycobacterium tuberculosis is lineage specific with associated mutations present globally

Jody Phelan, Paola Florez De Sessions, Leopold Tientcheu, Joao Perdigao, Diana Machado, Rumina Hasan, Zahra Hasan, Indra L. Bergval, Richard Anthony, Ruth McNerney, Martin Antonio, Isabel Portugal, Miguel Viveiros, Susana Campino, Martin L. Hibberd, Taane G. Clark

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
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Abstract

DNA methylation is an epigenetic modification of the genome involved in regulating crucial cellular processes, including transcription and chromosome stability. Advances in PacBio sequencing technologies can be used to robustly reveal methylation sites. The methylome of the Mycobacterium tuberculosis complex is poorly understood but may be involved in virulence, hypoxic survival and the emergence of drug resistance. In the most extensive study to date, we characterise the methylome across the 4 major lineages of M. tuberculosis and 2 lineages of M. africanum, the leading causes of tuberculosis disease in humans. We reveal lineage-specific methylated motifs and strain-specific mutations that are abundant globally and likely to explain loss of function in the respective methyltransferases. Our work provides a set of sixteen new complete reference genomes for the Mycobacterium tuberculosis complex, including complete lineage 5 genomes. Insights into lineage-specific methylomes will further elucidate underlying biological mechanisms and other important phenotypes of the epi-genome.

Original languageEnglish
Article number160
Pages (from-to)160-167
Number of pages7
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

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