Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity

Abstract

Plague is a pandemic human invasive disease caused by the bacterial agent Yersinia pestis. We here report a comparison of 17 whole genomes of Y. pestis isolates from global sources. We also screened a global collection of 286 Y. pestis isolates for 933 SNPs using Sequenom MassArray SNP typing. We conducted phylogenetic analyses on this sequence variation dataset, assigned isolates to populations based on maximum parsimony and, from these results, made inferences regarding historical transmission routes. Our phylogenetic analysis suggests that Y. pestis evolved in or near China and spread through multiple radiations to Europe, South America, Africa and Southeast Asia, leading to country-specific lineages that can be traced by lineage-specific SNPs. All 626 current isolates from the United States reflect one radiation, and 82 isolates from Madagascar represent a second radiation. Subsequent local microevolution of Y. pestis is marked by sequential, geographically specific SNPs.

Figure 1

Genomic maximum parsimony tree and divergence dates based on 1,364 non-repetitive, non-homoplastic SNPs from 3,349 coding sequences in 16 Y. pestis genomes (excluding FV-1). Black text: names of genomic sequences (Supplementary Table 1); Colored text: branch and population names. Grey: ranges of maximal and minimal dates of divergence for individual branches calculated with strict mutation rates of 2.9 × 10⁻⁹ and 2.3 × 10⁻⁸ per site per year (Supplementary Table 2). Comparable results were obtained using intergenic SNPs or a variable clock rate (Supplementary Table 2B).

Figure 2

Fully parsimonious minimal spanning tree of 933 SNPs for 282 isolates of Y. pestis colored by location. Large, bold text: Branches 1, 2 and 0. Smaller letters: populations (e.g. 1.ORI3). Lower case letters: nodes (e.g. 1.ORI3.a). Strain designations near terminal nodes: genomic sequences. Roman numbers: hypothetical nodes. Grey text on lines between nodes: numbers of SNPs, except that one or two SNPs are indicated by thick and thin black lines, respectively. Six additional isolates in 0.PE1 and 0.PE2b (blue dashes) were tested only for selected, informative SNPs.