| Summary: | <p>Abstract</p> <p>Background</p> <p>While the pathogenesis and epidemiology of tuberculosis are well studied, relatively little is known about the evolution of the infectious agent <it>Mycobacterium tuberculosis</it>, especially at the within-host level. The insertion sequence IS<it>6110 </it>is a genetic marker that is widely used to track the transmission of tuberculosis between individuals. This and other markers may also facilitate our understanding of the disease within patients.</p> <p>Results</p> <p>This article presents three lines of evidence supporting the action of positive selection on <it>M. tuberculosis </it>within patients. The arguments are based on a comparison between empirical findings from molecular epidemiology, and population genetic models of evolution. Under the hypothesis of neutrality of genotypes, 1) the mutation rate of the marker IS<it>6110 </it>is unusually high, 2) the time it takes for substitutions to occur within patients is too short, and 3) the amount of polymorphism within patients is too low.</p> <p>Conclusions</p> <p>Empirical observations are explained by the action of positive selection during infection, or alternatively by very low effective population sizes. I discuss the possible roles of antibiotic treatment, the host immune system and extrapulmonary dissemination in creating opportunities for positive selection.</p>
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