MRC National Institute for Medical Research, London
Science for Health
Sebastien Gagneux group
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Population genomics and ecology of Mycobacterium tuberculosis
We have previously shown that Mycobacterium tuberculosis, the causative agent of human tuberculosis (TB) consists of genetically distinct strain lineages that are associated with different regions of the world. Understanding the forces that shape this variation is crucial for the development of improved diagnostics, drugs, and vaccines against TB. We are using large-scale DNA sequencing of M. tuberculosis clinical strains to address this question.
Recent data from 89 genes in 108 strains has shown that the genetic distance between two human strains of M. tuberculosis can be as pronounced as the distance between a human strain and M. bovis, which is a classical animal pathogen. These data also support an 'out-of-and-back-to-Africa' scenario for the evolutionary history of human TB. According to this scenario, M. tuberculosis originated in Africa and spread out of Africa together with ancient migrations of modern humans. More recently, the evolutionary 'modern' lineages of M. tuberculosis expanded as a result of the strong human population increases in Europe, India, and China, and spread globally following waves of colonization, trade, and conquest.
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Global phylogeny of M. tuberculosis based on 89 gene sequences in 108 strains.
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(A) Different M. tuberculosis lineages accompanied the 'Out-of-Africa' migrations of modern humans ~50,000 years ago. (B) Recent gobal spread of the 'modern' M. tuberculosis lineages as a consequence of colonisation, trade, and conquest.
Selected publications
- Comas, I; Chakravartti, J; Small, PM; Galagan, J; Niemann, S; Kremer, K; Ernst, JD and Gagneux, S (2010)
Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved.
Nature Genetics 42, 498-503 PubMed abstract - Borrell, S and Gagneux, S (2009)
Infectiousness, reproductive fitness and evolution of drug-resistant Mycobacterium tuberculosis.
International Journal of Tuberculosis and Lung Disease 13, 1456-1466 PubMed abstract - Comas, I and Gagneux, S (2009)
The past and future of tuberculosis research.
PLoS Pathogens 5, e1000600 PubMed abstract - Hershberg, R; Lipatov, M; Small, PM; Sheffer, H; Niemann, S; Homolka, S; Roach, JC; Kremer, K; Petrov, DA; Feldman, MW and Gagneux, S (2008)
High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography.
PLoS Biology 6, 2658-2671 PubMed abstract
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