Friday, August 19, 2005

Origins of tuberculosis

The open-access journal group Public Library of Science will launch a new journal, PLoS Pathogens, in September. A preview article talks about the suprisingly homogeneous genomes of tuberculosis baccili.

The tuberculosis complex (approximately equivalent to genus) consists of 6 clone groups, of which M. Tuberculosis is the most commonly encountered in human disease. In contrast to other microbial complexes, this family shows extremely little inter-species variation, and almost no evidence of lateral gene exchange, leading to the suggestion that they all clonal progeny of a single, recent, highly successful ancestor.

In 1997, a novel tuberculosis isolate from Africa was described as having features of a possible ancestor baccilus. In the current work, the authors report 37 additional isolates of this smooth tubercule baccilus, enough to characterize them as a single species (with variance distances more common of microbes "in the wild") and a direct ancestor pool for all the modern, highly homogeneous pathogens.

The story gets pretty interesting in the discussion section. They point out a parallel between human genetic diversity (also at its apex in East Africa) and that of the tuberculosis progenitor. The two species were in prolonged contact, and may have exerted selection on each other prior to the emergence of modern pathogen (I mean the baccilus, of course), and even that they may have migrated out of Africa together. This last point would require more precise dating- the molecular clock data (difficult to make precise) for the tuberculosis bottleneck falls at 30,000 years ago, at which point the migrations of H. Sapiens which populated the rest of the world were already long gone. Still, it's interesting that the clone-like Mycobacterium which causes leprosy worldwide also appears to have originated in Eastern Africa Conceivably leprosy's forbears also made use of the greater palette of host genomes in East Africa during its emergence. See Carl Zimmer at the Loom (link below) for other examples of this.

For the purpose of fighting the disease it is always enormously helpful to find an outgroup, and an outgroup with variation amounts to a gold mine. The selection events which gave rise to such a homogeneous group can be read out by comparing with the ancestral gene pool. This may give insight into how tuberculosis persists for so long in human tissue, for example.

Wikipedia on tuberculosis is here. Additional open-access work on the ancestral TB strain is here .

UPDATE: Carl Zimmer at the Loom puts tuberculosis in context with other human pathogens, all of which likely shaped the modern H. Sapiens.

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