Inference of Bacterial Microevolution Using Multilocus Sequence Data

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Abstract
We describe a model-based method for using multilocus sequence data to infer the clonal relationships of bacteria and the chromosomal position of homologous recombination events that disrupt a clonal pattern of inheritance. The key assumption of our model is that recombination events introduce a constant rate of substitutions to a contiguous region of sequence. The method is applicable both to multilocus sequence typing (MLST) data from a few loci and to alignments of multiple bacterial genomes. It can be used to decide whether a subset of isolates share common ancestry, to estimate the age of the common ancestor, and hence to address a variety of epidemiological and ecological questions that hinge on the pattern of bacterial spread. It should also be useful in associating particular genetic events with the changes in phenotype that they cause. We show that the model outperforms existing methods of subdividing recombinogenic bacteria using MLST data and provide examples from Salmonella and Bacillus. The software used in this article, ClonalFrame, is available from http://bacteria.stats.ox.ac.uk/.