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Plague Genomes Reveal How Pandemic Spread in 14th, 18th Centuries

NEW YORK – New plague genomes dating from around the time of the Black Death have given researchers a glimpse into how the pandemic spread across Europe.

The second plague pandemic began with the Black Death in the middle of the 14th century AD and persisted through the 18th century. Estimates suggest that the outbreak caused the deaths of up to 60 percent of the European population. But where the strain of Yersinia pestis that caused this pandemic originated has been unclear.

A team led by researchers at the Max Planck Institute for the Science of Human History analyzed human remains dating back to the time of the second plague pandemic to tease out remnants of the Y. pestis that infected individuals across Europe. Through their sequencing and phylogenetic analysis, the researchers found that Y. pestis likely entered through eastern Europe and that its genetic diversity remained low during the time of the Black Death. After then, the plague diversified to give rise to multiple disease branches. The findings were published today in Nature Communications.

"We have shown that extensive analysis of ancient Y. pestis genomes can provide unique insights into the microevolution of a pathogen over a period of several hundred years," senior author Johannes Krause, the director of the department of archaeogenetics at Max Planck, said in a statement.

The researchers searched for Y. pestis DNA within tooth samples collected at 10 archaeological sites across Europe that dated to the 14th to 17th centuries. For each sample that was putatively positive for the presence of Y. pestis, the researchers combined a Y. pestis whole-genome in-solution capture approach with sequencing to generate new Y. pestis genomes.

Using a maximum likelihood method, the researchers constructed a phylogenetic tree of these new and previously published plague samples. All the newly reconstructed plague genomes, the researchers noted, reside on the same branch and are situated near other samples from the second plague pandemic.

One isolate, hailing from Laishevo, Russia, appeared ancestral to the new Black Death-era samples from other parts of Europe and to previously published isolates from London and Bolgar City, Russia. This suggested to the researchers that this is the most ancestral form of the strain that entered Europe from the east.

All the Black Death-era isolates were highly similar. One of the new samples from an archaeological site in Nabburg did not differ from previously published Y. pestis genomes isolated from London and Barcelona. Likewise, other samples from Toulouse, Oslo, and Siena at first appeared to differ by a few SNPs, but when the researchers examined the sequences manually, they found the differences could be due to DNA damage or other, environmental contaminants.

After the Black Death, though, genetic diversity increased among Y. pestis samples and they split into multiple branches. This, the researchers noted, suggests that multiple reservoirs of the plague may have been established. However they noted that no modern descendants have been found, indicating that those reservoirs may have gone extinct.

Late in the second plague pandemic, these lineages lost a portion of the Y. pestis genome that includes two genes, mgtB and mgtC, that affect virulence. This same region was lost, the researchers noted, in an earlier plague pandemic, suggesting that the bacterium might have followed similar evolutionary paths in both outbreaks.

"Given that this deletion occurred in lineages from the first and second pandemic, both now extinct, determining how these genes impact maintenance in human and flea hosts would be an important area for future study," author Kirsten Bos, a research group leader at Max Planck, said.