title: The emergence of latent infection in the early evolution of Mycobacterium tuberculosis.
abstract: Mycobacterium tuberculosis has an unusual natural history in that the vast majority of its human hosts enter a latent state that is both non-infectious and devoid of any symptoms of disease. From the pathogen perspective, it seems counterproductive to relinquish reproductive opportunities to achieve a détente with the host immune response. However, a small fraction of latent infections reactivate to the disease state. Thus, latency has been argued to provide a safe harbour for future infections which optimizes the persistence of M. tuberculosis in human populations. Yet, if a pathogen begins interactions with humans as an active disease without latency, how could it begin to evolve latency properties without incurring an immediate reproductive disadvantage? We address this question with a mathematical model. Results suggest that the emergence of tuberculosis latency may have been enabled by a mechanism akin to cryptic genetic variation in that detrimental latency properties were hidden from natural selection until their expression became evolutionarily favoured.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia Evolution and Ecology Research Centre, University of New South Wales, Sydney 2052, Australia rebecca.chisholm@unsw.edu.au.
authors.forename: Rebecca H
authors.identifier: 0000-0002-7830-793X
authors.initials: RH
authors.lastname: Chisholm
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia Evolution and Ecology Research Centre, University of New South Wales, Sydney 2052, Australia.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Tanaka
mesh_terms: D058345:Asymptomatic Infections; D056084:Genetic Fitness; D006801:Humans; D008957:Models, Genetic; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity* / Q000502:physiology*; D014376:Tuberculosis / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission; D014774:Virulence
keywords: adaptive dynamics; cryptic genetic variation; latency; niche construction; virulence