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

Jody Phelan¹, Paola Florez de Sessions², Leopold Tientcheu³

¹Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Scientific Reports

|January 11, 2018

Summary

This study characterizes the DNA methylome in Mycobacterium tuberculosis and M. africanum, revealing lineage-specific patterns linked to virulence and drug resistance. These findings offer new insights into the tuberculosis complex epi-genome.

Area of Science:

Epigenetics
Genomics
Microbiology

Background:

DNA methylation is a key epigenetic regulator of cellular processes.
The methylome of Mycobacterium tuberculosis complex is not well understood.
Epigenetic modifications may influence tuberculosis virulence, survival, and drug resistance.

Purpose of the Study:

To characterize the methylome across major lineages of Mycobacterium tuberculosis and M. africanum.
To identify lineage-specific methylated motifs and their association with methyltransferase function.
To provide new reference genomes for the Mycobacterium tuberculosis complex.

Main Methods:

Utilized PacBio sequencing technologies to identify DNA methylation sites.
Analyzed methylomes across four M. tuberculosis lineages and two M. africanum lineages.
Generated sixteen new complete reference genomes.

Main Results:

Discovered lineage-specific methylated motifs in M. tuberculosis and M. africanum.
Identified strain-specific mutations potentially causing loss of function in methyltransferases.
Revealed abundant global variations in methylomes.
Provided complete reference genomes for M. tuberculosis complex, including lineage 5.

Conclusions:

Lineage-specific methylomes provide insights into the Mycobacterium tuberculosis complex epi-genome.
Understanding these epigenetic patterns can elucidate biological mechanisms and phenotypes.
This research advances knowledge of tuberculosis pathogenesis and evolution.

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