MBE Advance Access published online on October 27, 2009
Molecular Biology and Evolution, doi:10.1093/molbev/msp261
Research Article |
Bacterial genetic signatures of human social phenomena among M.tuberculosis from an Aboriginal Canadian population
1 School of Medicine, Division of Infectious Diseases, Stanford University, Stanford, California, United States of America
2 Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
3 Department of Biology, Stanford University, Stanford, California, United States of America
Caitlin Pepperell is the corresponding author: Stanford University School of Medicine, Division of Infectious Diseases, Beckman Center, room B239, 279 Campus Drive, Stanford, California USA 94305-5323, 650-723-7026, pepperc{at}stanford.edu
Received for publication July 7, 2009. Revision received October 16, 2009. Accepted for publication October 19, 2009.
Despite a widespread global distribution and highly variable disease phenotype, there is little DNA sequence diversity among isolates of Mycobacterium tuberculosis. In addition, many regional population genetic surveys have revealed a stereotypical structure in which a single clone, lineage or clade makes up the majority of the population. It is often assumed that dominant clones are highly adapted; that is, the overall structure of M.tb populations is the result of positive selection. In order to test this assumption, we analyzed genetic data from extant populations of bacteria circulating in Aboriginal communities in Saskatchewan, Canada. Demographic parameters of the bacterial population were estimated from archival epidemiological data collected over 
130 years since the onset of epidemic tuberculosis in the host communities. Bacterial genetic data were tested against neutral theory expectations and the local evolutionary history of M.tb investigated by phylogenetic analysis. Our findings are not consistent with positive selection on the bacterial population. Instead, we uncovered founder effects persisting over decades, and barriers to gene flow within the bacterial population. Simulation experiments suggested that a combination of these neutral influences could result in the stereotypical structure of M.tb populations. Some aspects of population structure were suggestive of background selection and data were on the whole consistent with combined effects of population bottlenecks, subdivision and background selection. Neutral phenomena, namely bottlenecks and partitions within populations, are prominent influences on the evolution of M.tuberculosis and likely contribute to restricted genetic diversity observed within this species. Given these influences, a complex evolutionary model will be required to define the relative fitness of different M.tb lineages and, ultimately, to uncover the genetic basis for its success as a pathogen.
Key Words: Mycobacterium tuberculosis • founder effect • genetic drift • population subdivision • background selection • Aboriginal