Understanding the tuberculosis genome

A large international team of researchers set out to uncover the reasons for the global success of a tuberculosis strain, hoping to better understand, and consequently better combat, this resilient human pathogen.

Tuberculosis – a serious disease of the lungs and other organs – is caused by a group of infectious bacterial pathogens collectively known as the Mycobacterium tuberculosis Complex (MTBC). Human-infecting MTBC strains are classified into seven lineages that vary in their distribution and the breadth of their host range. 

Out of the seven, lineage 4 shows the highest global spread, infecting various human populations, and it is this lineage that this team of researchers scrutinizes. 

They compared 72 published lineage 4 genomes, and based on their variability, divided them into ten distinct sublineages¹. Then, they selected a unique set of genomic identifiers for each of the 10 sublineages, and screened over 3000 lineage 4 genomes isolated from patients around the world, and assigned each isolate to one of the ten.

They mapped each sublineage to the countries it was found in. They discovered that the different sublineages showed different geographical distributions. 

Some sublineages were globally spread (“generalists”), while others were more locally restricted (“specialists”).

Analysis of their genomes reveals that the generalists had a higher variation in the targets of the human immune system they harbour, allowing them to infect a wider range of genetically variable human hosts, whereas the specialists had less variation and were more adapted to a specific population – reflecting different evolutionary strategies.

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