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Correction: The Role of Selection in Shaping Diversity of Natural M. tuberculosis Populations

C. Pepperell,A. Casto,A. Kitchen,J. Granka,Omar E. Cornejo,E. Holmes,B. Birren,J. Galagan,M. Feldman

Published 2013 in PLoS Pathogens

ABSTRACT

Mycobacterium tuberculosis (M.tb), the cause of tuberculosis (TB), is estimated to infect a new host every second. While analyses of genetic data from natural populations of M.tb have emphasized the role of genetic drift in shaping patterns of diversity, the influence of natural selection on this successful pathogen is less well understood. We investigated the effects of natural selection on patterns of diversity in 63 globally extant genomes of M.tb and related pathogenic mycobacteria. We found evidence of strong purifying selection, with an estimated genome-wide selection coefficient equal to 29.5610 (95% CI 21.1610 to 26.8610); this is several orders of magnitude higher than recent estimates for eukaryotic and prokaryotic organisms. We also identified different patterns of variation across categories of gene function. Genes involved in transport and metabolism of inorganic ions exhibited very low levels of non-synonymous polymorphism, equivalent to categories under strong purifying selection (essential and translation-associated genes). The highest levels of nonsynonymous variation were seen in a group of transporter genes, likely due to either diversifying selection or local selective sweeps. In addition to selection, we identified other important influences on M.tb genetic diversity, such as a 25-fold expansion of global M.tb populations coincident with explosive growth in human populations (estimated timing 1684 C.E., 95% CI 1620–1713 C.E.). These results emphasize the parallel demographic histories of this obligate pathogen and its human host, and suggest that the dominant effect of selection on M.tb is removal of novel variants, with exceptions in an interesting group of genes involved in transportation and defense. We speculate that the hostile environment within a host imposes strict demands on M.tb physiology, and thus a substantial fitness cost for most new mutations. In this respect, obligate bacterial pathogens may differ from other host-associated microbes such as symbionts. 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 Editor: Christopher M. Sassetti, University of Massachusetts, United States of America Received November 7, 2012; Accepted June 24, 2013; Published August 15, 2013 Copyright: 2013 Pepperell et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by NIH grant 5K08AI67458-2 (to CSP). This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN266200400001C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: cspepper@medicine.wisc.edu

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