Phylogeography of <i>Francisella tularensis</i> : Global Expansion of a Highly Fit Clone

<jats:title>ABSTRACT</jats:title> <jats:p> <jats:italic>Francisella tularensis</jats:italic> contains several highly pathogenic subspecies, including <jats:italic>Francisella tularensis</jats:italic> subsp. <jats:italic>holarctica</jats:italic> , whose distribution is circumpolar in the northern hemisphere. The phylogeography of these subspecies and their subclades was examined using whole-genome single nucleotide polymorphism (SNP) analysis, high-density microarray SNP genotyping, and real-time-PCR-based canonical SNP (canSNP) assays. Almost 30,000 SNPs were identified among 13 whole genomes for phylogenetic analysis. We selected 1,655 SNPs to genotype 95 isolates on a high-density microarray platform. Finally, 23 clade- and subclade-specific canSNPs were identified and used to genotype 496 isolates to establish global geographic genetic patterns. We confirm previous findings concerning the four subspecies and two <jats:italic>Francisella tularensis</jats:italic> subsp. <jats:italic>tularensis</jats:italic> subpopulations and identify additional structure within these groups. We identify 11 subclades within <jats:italic>F. tularensis</jats:italic> subsp. <jats:italic>holarctica</jats:italic> , including a new, genetically distinct subclade that appears intermediate between Japanese <jats:italic>F. tularensis</jats:italic> subsp. <jats:italic>holarctica</jats:italic> isolates and the common <jats:italic>F. tularensis</jats:italic> subsp. <jats:italic>holarctica</jats:italic> isolates associated with the radiation event (the B radiation) wherein this subspecies spread throughout the northern hemisphere. Phylogenetic analyses suggest a North American origin for this B-radiation clade and multiple dispersal events between North America and Eurasia. These findings indicate a complex transmission history for <jats:italic>F. tularensis</jats:italic> subsp. <jats:italic>holarctica</jats:italic> . </jats:p>