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Sequencing Study Tracks Roots of TB Emergence to East Africa

NEW YORK (GenomeWeb) – An international team led by investigators in the UK and Spain has garnered genetic evidence that the tuberculosis-causing pathogen Mycobacterium tuberculosis originated in Africa.

As they reported today in Current Biology, the researchers did genome sequencing on 66 M. tuberculosis complex (MTBC) isolates from Ethiopia and compared them with hundreds of previously sequenced MTBC isolates from around the world.

Based on the nature and diversity of the Ethiopian M. tuberculosis lineages, the team proposed that the bug has an East African origin — results that appear to contradict the so-called virgin soil theory which posits that TB was introduced by Europeans to previously unaffected populations in Africa.

"The diversity of M. tuberculosis complex in Ethiopia confirms the African origin of the disease and contradicts early notions that TB was not present in Africa before main European contact," first author Iñaki Comas, a genomics and health researcher at FISABIO Public Health in Spain, said in a statement. "However, it remains to be explained why high rates of infection among native people were observed after the contact."

Historical records suggest TB infections were once infrequent in Ethiopia and other parts of Africa, the researchers explained. And because infections jumped after exposure to Europeans, some suspected that the pathogen might have originated in another part of the world. Even so, several genetic studies, including a genomic comparison of smooth tubercle bacilli strains published in 2013, hint that M. tuberculosis emergence may have occurred in Africa.

To explore the roots of African TB in more detail, Comas and his colleagues delved into frozen M. tuberculosis samples collected in Ethiopia and genotyped for a prior study. They used the Illumina HiSeq 2000 to generate genome sequences for 66 of the isolates.

By analyzing these sequences alongside 219 MTBC isolates from around the world, the researchers found that Ethiopia is currently home to four M. tuberculosis lineages: a lineage known as L7 that's exclusive to Ethiopia; an L1 lineage frequently found in sites along the Indian Ocean; a Central Asian lineage called L3, which has also been detected in East Africa; and the Euro-American L4 lineage.

The team also saw numerous sub-lineages within L3 and L4, some of which matched MTBC sub-lineages elsewhere and others that seemed Africa-specific.

By looking more closely at the geographical distributions of various M. tuberculosis lineages and sub-lineages, as well as molecular dating information, the researchers concluded that MTBC likely emerged somewhere in East Africa thousands of years before European contact.

Even so, results from their phylogenetic analyses suggest that the arrival of new strains from other parts of the world may have altered existing MTBC lineages in ways that made them more dangerous to populations that had long-adapted to earlier forms of the bug.

"In place of a 'virgin soil' fostering the spread of TB in a previously naïve population," the authors wrote, "we propose that increased TB mortality in Africa was driven by the introduction of European strains of M. tuberculosis alongside expansion of selected indigenous strains having biological characteristics that carry a fitness benefit in the urbanized settings of post-colonial Africa."

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