Tuberculosis (TB) is a wildly successful pathogen, if your goal is to infect up to two billion people in every corner of the world, with a new infection of a human host every second.

A new analysis of dozens of tuberculosis genomes gathered from around the world has shed some light on how it evolves to resist countermeasures - it that marches in lockstep with human population growth and history, evolving to take advantage of the most crowded and wretched human conditions.

The analysis reveals that tuberculosis experienced a 25-fold expansion worldwide in the 17th century, a time when human populations underwent explosive growth and European exploration of Africa, the Americas, Asia and Oceania was at its peak.

TB is only transmitted by people, and the organism cannot survive in the environment. It thrives, however, in the crowded conditions of prisons, refugee camps and slums, and TB populations tend to be dominated by the bacteria "lucky" enough to land in those environments.

Geographic and genetic structure of global sample of M.tb genomes. A) Maximum clade credibility phylogeny inferred from genome-wide M.tb SNP data using BEAST [83]. Tips are colored by the geographic origin of the M.tb isolate (see key). Descriptions of the 48 M.tb isolates shown here are in Table S1. B) Countries of origin for M.tb isolates used in this study are shown as colored dots on global map. One dot is shown per country but some countries were represented by >1 M.tb isolate. Colors correspond to global regions (see key). C) Phylogeny of global human populations from [91], based on Y chromosome data. Tips are colored according to the same scheme as the M.tb phylogeny (A). Credit and link: 

"The timing is coincident with expansion, urbanization and colonial migrations of global human populations," explains lead author Caitlin S. Pepperell,  professor of medicine and medical microbiology at University of Wisconsin-Madison. "These findings suggest that much of the current TB pandemic has its origins in historical events of the last three centuries." 

The analysis focused on the role of natural selection, looking at patterns of genetic diversity among 63 TB and related pathogenic mycobacterial genomes gathered from around the globe. 

The study shows a highly constrained bacterial genome, with most deleterious mutations quickly discarded. This was especially true for genes essential for causing disease, protein translation and the trafficking and metabolism of inorganic ions, which help control the interaction between the TB pathogen and its human host.

The bacterium's "defense" genes, on the other hand, showed a high degree of tolerance for beneficial mutations, which may play a role in evolution of drug resistance and evasion of the human immune system.

Pepperell notes, "Evolutionary theory predicts that Mycobacterium tuberculosis populations should be vulnerable to extinction. Yet it is obviously highly prevalent. It must have some incredibly clever strategies and tricks to hang on."

As a result, the explosive spread of TB parallels the growth of human populations and takes every advantage of a world where most people live in crowded and impoverished conditions.

The study, according to Pepperell, should help other researchers home in on genes that may be good candidates for targeting with new drugs, and aid disease control strategies that accommodate or even co-opt the bacterium's evolution and help drive its extinction.

Citation: Pepperell CS, Casto AM, Kitchen A, Granka JM, Cornejo OE, et al. (2013) The Role of Selection in Shaping Diversity of Natural M. tuberculosis Populations. PLoS Pathog 9(8): e1003543. doi:10.1371/journal.ppat.1003543