title: High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography.
abstract: Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC). However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data. We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events. We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. Our findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis described here, could contribute to the emergence and spread of drug-resistant tuberculosis.
authors.affiliation: Department of Biology, Stanford University, Stanford, California, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Hershberg
authors.forename: Mikhail
authors.initials: M
authors.lastname: Lipatov
authors.forename: Peter M
authors.initials: PM
authors.lastname: Small
authors.forename: Hadar
authors.initials: H
authors.lastname: Sheffer
authors.forename: Stefan
authors.initials: S
authors.lastname: Niemann
authors.forename: Susanne
authors.initials: S
authors.lastname: Homolka
authors.forename: Jared C
authors.initials: JC
authors.lastname: Roach
authors.forename: Kristin
authors.initials: K
authors.lastname: Kremer
authors.forename: Dmitri A
authors.initials: DA
authors.lastname: Petrov
authors.forename: Marcus W
authors.initials: MW
authors.lastname: Feldman
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
mesh_terms: D001483:Base Sequence; D030541:Databases, Genetic; D003710:Demography; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004641:Emigration and Immigration; D040961:Genetic Drift; D016680:Genome, Bacterial; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D018088:Tuberculosis, Multidrug-Resistant / Q000235:genetics