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Medieval Plague Genomes Help Retrace Pandemic's Routes

NEW YORK (GenomeWeb) – A team led by researchers at the University of Oslo has used medieval Yersinia pestis genome sequences, comparative genomics, phylogenetics, and bioinformatics to explore historical introduction and transmission patterns for the so-called Second Plague Pandemic, which stretched from the mid-14th century through the 19th century.

"We have reevaluated all medieval strains under the light of archeological and historical evidence to carefully discuss the involvement of different transmission routes during the Second Plague Pandemic," University of Oslo ecological and evolutionary synthesis researchers Barbara Bramanti and Nils Stenseth, the study's co-senior authors, and their colleagues wrote. 

As they reported online yesterday in the Proceedings of the National Academy of Sciences, the researchers sequenced the genomes of five Y. pestis isolates from Italy, France, Norway, and the Netherlands that were dated to the latter half of the 14th century. By comparing these isolates to Y. pestis isolates sequenced in the past, including other Second Plague Pandemic pathogens from the 14th to 18th century, the authors identified genetic results consistent with multiple introductions of the plague to Western Europe.

"Corroborated by historical and ecological evidence, the presented phylogeny, which includes our Y. pestis genomes, could support the hypothesis of an entry of plague into Western European ports through distinct waves of introduction during the Medieval Period, possibly by means of fur trade routes, as well as the recirculation of plague within the human population via trade routes and human movement," they wrote.

For their analysis, the researchers began with PCR-based screening for Y. pestis in dozens of tooth samples from burial sites in Italy and Norway. Together with Y. pestis-positive samples identified in France and the Netherlands in the past, they settled on a set of five isolates for targeted enrichment and sequencing at the University of Oslo.

Using a custom sequencing and analysis pipeline that relied on high-throughput Illumina HiSeq 2500 sequencing and mapping to a reference genome generated for the Y. pestis CO92 strain, the team generated sequences spanning 44 percent to more than 87 percent of the Y. pestis genome apiece at depths of threefold coverage or more.

The researchers then narrowed in on more than 2,800 plague pathogen SNPs, using the new genomes as well as126 present-day Y. pestis genomes and sequences from a handful of ancient Y. pestis isolates from the Bronze Age, First Plague ("Justinian Plague"), or Second Plague Pandemics. Their phylogenetic analyses, based on a subset of these variants, put the newly sequenced Y. pestis representatives in a cluster with other Second Plague isolates.

In particular, strains from southern France and Norway were genetically identical or very similar to previously described strains from the Black Death outbreak, pointing to a shared source. On the other hand, variants in the strains from Italy and the Netherlands appeared to be consistent with new introductions, the team reported.

Based on these and other findings, the authors concluded that the plague strain phylogeny "may be explained by independent introductions on the fur trade routes, a complex of interconnected maritime, riverine, and overland routes in Western Europe," consistent with the possibility that plague entered the region through successive and independent introductions.