Paris, October 8, 2008

Out of Mesopotamia : Evolutionary history of tuberculosis

The evolutionary timing and spread of the Mycobacterium tuberculosis complex (MTBC), one of the most successful groups of bacterial pathogens, remains largely unknown. Here, using mycobacterial tandem repeat sequences as genetic markers, we show that the MTBC consists of two independent clades, one composed exclusively of M. tuberculosis lineages from humans and the other composed of both animal and human isolates.

The latter also likely derived from a human pathogenic lineage, supporting the hypothesis of an original human host. Using Bayesian statistics and experimental data on the variability of the mycobacterial markers in infected patients, we estimated the age of the MTBC at 40,000 years, coinciding with the expansion of “modern” human populations out of Africa. Moreover, the diversification of the oldest EAI and LAM populations took place during plant and animal domestication. In the Fertile Crescent, 13,000 years ago, small nomadic hunter-gatherer groups were replaced by farming societies based on domesticated livestock and crops. This paramount event in human history was probably not without consequence for an epidemic, infectious disease such as tuberculosis, where crowded farming populations may have promoted high infection rates, bacterial spread and transition to new niches and animal hosts. Furthermore, coalescence analysis revealed a strong and recent demographic expansion in almost all M. tuberculosis lineages, which coincides with the human population explosion over the last two centuries. These findings thus unveil the dynamic dimension of the association between human host and pathogen populations.


Origin, Spread and Demography of the Mycobacterium tuberculosis Complex Thierry Wirth1,2, Falk Hildebrand1, Caroline Allix-Beguec3, Florian Wölbeling4, Tanja Kubica4, Kristin Kremer5, Dick van Soolingen5, Sabine Rüsch-Gerdes4, Camille Locht6,7, Sylvain Brisse8, Axel Meyer1, Philip Supply6,7, Stefan Niemann4 - Plos Pathogens – septembre 2008.
1 Lehrstuhl für Zoologie und Evolutionsbiologie, Department of Biology, University of Konstanz, Konstanz, Germany
2 École Pratique des Hautes Études, Muséum national d'Histoire naturelle, UMR-CNRS 5202, Département Systématique et Évolution, Paris, France
3 Institut Pasteur de Bruxelles, Laboratoire Tuberculose et Mycobactéries, Brussels, Belgium
4 Research Center Borstel, Department of Clinical Medicine, Borstel, Germany
5 National Institut of Public Health and Environment, Bilthoven, The Netherlands
6 INSERM U629, Lille, France
7 Institut Pasteur de Lille, Lille, France
8 Institut Pasteur, Genotyping of Pathogens and Public Health, Paris, France



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