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4,000-Year-Old DNA Reveals Oldest Plague Cases Found in Britain

Levens Park ring cairn in Cumbria, UK.
Levens Park ring cairn in Cumbria, UK. To the right of the solitary large boulder is a circular penannular ring with three ~4,000 year old female inhumation burials, one of which carried Yersinia pestis DNA sequenced in the present study. Credit: Ian Hodkinson
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A study has found DNA evidence of the plague in 4,000-year-old skeletal remains, the oldest evidence of the plague in Britain to date. The research is published in Nature Communications.

The plague throughout history

The plague – known during an infamous 14th-century outbreak as the “Black Death” – is one of the deadliest diseases in human history. It is caused by the bacterium Yersinia pestis and infects many other animal species such as fleas, whose bites are one of the main routes of transmission to humans.

The plague was estimated to be responsible for over 50 million deaths in Europe in the Middle Ages. Today, outbreaks occasionally occur in parts of Africa, Asia and the western United States, though early treatment with antibiotics is effective at treating the infection.

Previous research has identified the presence of a strain of the plague in several Eurasian individuals dating from 2,500–5,000 years ago. The strain – known as LNBA – was likely to have spread into central and western Europe around 4,800 years ago. However, no examples in Britain had been identified before this period.

Now, researchers from the Francis Crick Institute, the University of Oxford, the Levens Local History Group and the Wells and Mendip Museum have used genome sequencing to suggest that this strain of Yersinia pestis may have also spread to Britain during this time.

Genetic clues from skeletal remains

The researchers analyzed human remains, collecting skeletal samples from 34 individuals across two sites in Britain – a mass burial site in Charterhouse Warren, Somerset, and a ring cairn monument in Levens, Cumbria.

Samples of teeth from the skeletal remains were drilled in specialist clean room facilities to expose the dental pulp – the innermost layer of the tooth – which can contain the remnants of DNA from infectious diseases.

Genome sequencing of these samples revealed the presence of Yersinia pestis in 3 of the 34 individuals, with radiocarbon dating suggesting that all 3 individuals were likely to have lived around the same time. Two of the cases were in children, estimated to be 10–12 years old when they died, and the other case was a woman aged 35–45.

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All three cases were found to lack two key genes – yapC and ymt – which are found in later strains of the plague. These genes play an important role in infection transmission via fleas, making it unlikely that this plague strain was spread via this vector.

Nonetheless, as DNA from disease-causing organisms can degrade very quickly in samples that might be incomplete or eroded, it is possible that more individuals from the same burial sites may also have been infected with this strain. One of the burial sites – Charterhouse Warren – doesn’t match other sites from the same period, as the individuals there seem to have died from trauma rather than an outbreak, though the researchers hypothesize that they may also have been infected when they died.

“The ability to detect ancient pathogens from degraded samples, from thousands of years ago, is incredible,” said Pooja Swali, first author of the study and PhD student at the Francis Crick Institute. “These genomes can inform us of the spread and evolutionary changes of pathogens in the past, and hopefully help us understand which genes may be important in the spread of infectious diseases. 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.”

An “evolutionary arms race”

“This research is a new piece of the puzzle in our understanding of the ancient genomic record of pathogens and humans, and how we co-evolved,” said Dr. Pontus Skoglund, group leader of the Ancient Genomics Laboratory at the Francis Crick Institute.

“We understand the huge impact of many historical plague outbreaks, such as the Black Death, on human societies and health, but ancient DNA can document infectious disease much further into the past. Future research will do more to understand how our genomes responded to such diseases in the past, and the evolutionary arms race with the pathogens themselves, which can help us to understand the impact of diseases in the present or in the future,” he added.

Reference: Swali P, Schulting R, Gilardet A, et al. Yersinia pestis genomes reveal plague in Britain 4000 years ago. Nat Commun. 2023;14(1):2930. doi: 10.1038/s41467-023-38393-w

This article is a rework of a press release issued by the Francis Crick Institute. Material has been edited for length and content.