The analysis conducted by Pepperell and her colleagues 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.
|Contact: Caitlin Pepperell|
University of Wisconsin-Madison