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Sequencing Study Reveals Oldest Plague Cases in Britain

Arnold Böcklin: Die Pest (1889)

NEW YORK  Researchers have identified plague-causing Yersinia pestis bacteria in 4,000-year-old human remains of two children and a woman — the oldest known plague cases in Britain.

For a study appearing in Nature Communications on Tuesday, researchers from the Francis Crick Institute and the University of Oxford studied skeletal remains of 34 individuals across the two sites: a mass burial in Charterhouse Warren in Somerset and a ring cairn monument in Levens in Cumbria.

They recovered DNA from skeletal remains by drilling into teeth and extracting dental pulp, which is known to trap DNA remnants of pathogens.

Next, the researchers screened the samples for Yersinia pestis, identifying bacterial DNA in the remains of two children estimated to have been aged 10 to 12 years old when they died, and a woman between 35 and 45 years old. All of them lived around the same time, radiocarbon dating analysis revealed.

They used Illumina NovaSeq platforms to generate direct shotgun sequencing data from the children's samples that were found at Charterhouse Warren. The woman's sample recovered from Levens Park was not amenable to shotgun sequencing, the authors noted. However, DNA libraries from all three individuals were subjected to a couple of rounds of hybridization capture with an in-solution target enrichment approach using Y. pestis RNA baits from Daicel Arbor Biosciences.

The Y. pestis samples belonged to a Late Neolithic and Bronze Age (LNBA) lineage that was known to have caused plague across Eurasia in the period between 4700 and 2800 before present (BP).

"Human movements associated with the expansion of Bell Beaker cultures introduced steppe-derived ancestries to Britain and intensified links with continental Europe from around 4400 years BP, opening the possibility that Bronze Age groups from north-western Europe were also affected by LNBA lineages of Yersinia pestis," co-corresponding and lead author, Pooja Swali, a postdoctoral researcher at the Crick Institute, wrote along with her colleagues.

The authors feel that this lineage could have been widespread across Britain after the westward expansion of populations from the Eurasian steppe.

While they couldn't detect the pathogen in other skeletal remains, it's possible that Y. pestis DNA might have been eroded or degraded in those samples, they noted.

The Y. pestis genomes had undergone changes and lacked yapC and ymt genes that are known to be found in later strains of plague. The ymt gene is also known to play an important role in plague transmission via fleas, leading the researchers to hypothesize that the LNBA strain was likely not transmitted via fleas, unlike later plague strains such as the one that caused the Black Death.

Meanwhile, they noted that the samples from the Charterhouse Warren site didn't match other funeral sites from the time period and that individuals buried at the site appeared to have died from trauma and not due to a plague outbreak.

The findings from studies such as this one can inform researchers about how pathogens evolved over time and could aid in identifying the genes that make pathogens more virulent, the authors said.

"We see that this Yersinia pestis lineage, including genomes from this study, loses genes over time, a pattern that has emerged with later epidemics caused by the same pathogen," Swali said in a statement.

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