The depth of tuberculosis

3 minute read

Via a reader: BBC is reporting that tuberculosis may have arisen in hominids as early as 3 million years ago.

Until now, scientists had believed the disease arose a few tens of thousands of years ago and then spread rapidly around the world.
But investigation of a rare tuberculosis-causing bacterium isolated from patients in East Africa suggests the roots of the disease go back much further.
Molecular analysis suggests that the East African samples and the commoner strains are all descended from a more ancient bacterial species that emerged in Africa as long as three million years ago.

The research is a paper by M. Cristina Gutierrez and colleagues to appear in the first issue of PLoS Pathogens. Here's the abstract:

The highly successful human pathogen Mycobacterium tuberculosis has an extremely low level of genetic variation, which suggests that the entire population resulted from clonal expansion following an evolutionary bottleneck around 35,000 y ago. Here, we show that this population constitutes just the visible tip of a much broader progenitor species, whose extant representatives are human isolates of tubercle bacilli from East Africa. In these isolates, we detected incongruence among gene phylogenies as well as mosaic gene sequences, whose individual elements are retrieved in classical M. tuberculosis. Therefore, despite its apparent homogeneity, the M. tuberculosis genome appears to be a composite assembly resulting from horizontal gene transfer events predating clonal expansion. The amount of synonymous nucleotide variation in housekeeping genes suggests that tubercle bacilli were contemporaneous with early hominids in East Africa, and have thus been coevolving with their human host much longer than previously thought. These results open novel perspectives for unraveling the molecular bases of M. tuberculosis evolutionary success.

And the relevant portion about the history of the pathogen:

Given previous studies that estimated the age of M. tuberculosis to be approximately 35,000 y based on bacterial synonymous substitution rates of 0.0044 0.0047 per site per million years [11,26,27], we estimated that the minimal time needed to accumulate the observed amount of synonymous divergence in the tubercle bacilli species was between 2.6 and 2.8 million y. As both smooth bacilli and M. tuberculosis are isolated from human tuberculosis cases, the most parsimonious hypothesis is that the last common ancestor of the tubercle bacilli species could already have caused human tuberculosis. Therefore, our results change the current paradigm of the recent origin of tuberculosis [7] by suggesting that its causative agent is as old as 3 million years. Tuberculosis could thus be much older than the plague [1], typhoid fever [6], or malaria [28], and might have already affected early hominids. Consistent with this speculative scenario, nearly all smooth tubercle bacilli isolated so far come from East Africa, a region where early hominids were present 3 million years ago [29]. The distribution of diversity between the variable smooth tubercle bacilli from Djibouti and the uniform worldwide MTBC is remarkably reminiscent of the distribution of human genetic diversity among world populations, with larger genetic distances observed within Africa [30]. Our findings thus suggest that, similarly to humans [31], tubercle bacilli emerged in Africa and then underwent early diversification followed by much more recent expansion of a successful clone to the rest of the world, possibly coinciding with the waves of human migration out of Africa. However, we cannot exclude the possibility that the geographical confinement of the smooth bacilli to Africa reflects failure to recognize smooth isolates found elsewhere as being genuine tubercle bacilli (Gutierrez et al. 2005:e5, citations in original).

Personally, I wonder whether this may be a more common pattern: ancient human diseases with African origins spreading to other continents, developing greater virulence, and then returning to Africa wiping out (or in rare cases exchanging genetic material with) autochthonous African strains.

By the way, am I the only one who's tired of reading BBC stories on evolution that include gratuitous still shots from Walking with Cavemen?


Gutierrez MC, Brisse S, Brosch R, Fabre M, Omaïs B, Marmiesse M, Supply P, Vincent V. 2005. Ancient Origin and Gene Mosaicism of the Progenitor of Mycobacterium tuberculosis. PLoS Pathogens 1:e5.