MBE Advance Access originally published online on August 18, 2004
Molecular Biology and Evolution 2004 21(12):2195-2201; doi:10.1093/molbev/msh234
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Research Article |
The Control of Copy Number of IS6110 in Mycobacterium tuberculosis
* School of Biotechnology & Biomolecular Sciences, University of New South Wales, Australia; Molecular & Computational Biology, University of Southern California, Los Angeles, California; Stanford University School of Medicine, Stanford, California
E-mail: m.tanaka{at}unsw.edu.au.
Insertion sequence (IS) elements are bacterial genes that are able to transpose to different locations in the genome. These elements are often used in molecular epidemiology as genetic markers that track the spread of pathogens. Transposable elements have frequently been described as "selfish DNA" because they facilitate their own transposition, causing damage when they insert into coding regions, while contributing little if anything to the bacterial host. According to this hypothesis, the expansion of copy number of insertion sequences is opposed by negative selection against high copy numbers. From an alternative point of view, we might expect IS elements to intrinsically regulate transposition within cells, thereby limiting damage to their bacterial host. Here, we report evidence that the copy number of IS6110 in Mycobacterium tuberculosis is controlled by selection against the element. We first construct 12 different models of marker change resulting from a combination of possible transposition functions and selective regimes. We then compute the Akaike Information Criterion for each model to identify the models that best explain data consisting of serial isolates of M. tuberculosis genotyped with IS6110. We find that the best performing models all include selection against the accumulation of copies. Specifically, our analysis points to the interaction of separate copies of the element causing lethal effects. We discuss the implications of these findings for genome evolution and molecular epidemiology.
Key Words: Mycobacterium tuberculosis • molecular epidemiogy • insertion sequence • transposition rate • regulation • Akaike information criterion
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