Researchers at the Francis Crick Institute have identified three 4,000-year-old British cases of Yersinia pestis, the bacteria causing the plague – the oldest evidence of the plague in Britain to date, reported in a paper published today in Nature Communications.

Working with the University of Oxford, the Levens Local History Group and the Wells & Mendip Museum, the team identified two cases of Yersinia pestis in human remains found in a mass burial in Charterhouse Warren in Somerset and one in a ring cairn monument in Levens in Cumbria.

They took small skeletal samples from 34 individuals across the two sites, screening for the presence of Yersinia pestis in teeth. This technique is performed in a specialist clean room facility where they drill into the tooth and extract dental pulp, which can trap DNA remnants of infectious diseases.

They then analysed the DNA and identified three cases of Yersinia pestis in two children estimated to be aged between 10-12 years old when they died, and one woman aged between 35-45. Radiocarbon dating was used to show it’s likely the three people lived at roughly the same time.

The plague has previously been identified in several individuals from Eurasia between 5,000 and 2,500 years before present (BP), a period spanning the Late Neolithic and Bronze Age (termed LNBA), but hadn’t been seen before in Britain at this point in time. The wide geographic spread suggests that this strain of the plague may have been easily transmitted.

This strain of the plague – the LNBA lineage – was likely brought into Central and Western Europe around 4,800 BP by humans expanding into Eurasia, and now this research suggests that it extended to Britain.

Using genome sequencing, the researchers showed that this strain of the Yersinia pestis looks very similar to the strain identified in Eurasia at the same time.

The individuals identified all lacked the yapC and ymt genes, which are seen in later strains of plague, the latter of which is known to play an important role in plague transmission via fleas. This information has previously suggested that this strain of the plague was not transmitted via fleas, unlike later plague strains such as the one that caused the Black Death.

Because pathogenic DNA – DNA from bacteria, protozoa, or viruses which cause disease – degrades very quickly in samples which might be incomplete or eroded, it’s also possible that other individuals at these burial sites may have been infected with the same strain of plague.

The Charterhouse Warren site is rare as it doesn’t match other funeral sites from the time period – the individuals buried there appear to have died from trauma. The researchers speculate that the mass burial wasn’t due to an outbreak of plague but individuals may have been infected at the time they died.

Pooja Swali, first author and PhD student at the Crick, said, “The ability to detect ancient pathogens from degraded samples, from thousands of years ago, is incredible. 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.”

Pontus Skoglund, group leader of the Ancient Genomics Laboratory at the Crick, said,

“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.”

“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.”

Bibliographic information:

Yersinia pestis genomes reveal plague in Britain 4,000 years ago, Nature Communications (30-May-2023), DOI: 10.1038/s41467-023-38393-w

Press release from the Francis Crick Institute.

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Researchers studied more than 600 genome sequences of Yersinia pestis, the bacterium that causes plague.

Seeking to better understand more about the origins and movement of bubonic plague, in ancient and contemporary times, researchers at McMaster University, University of Sydney and the University of Melbourne, have completed a painstaking granular examination of hundreds of modern and ancient genome sequences, creating the largest analysis of its kind.

Despite massive advances in DNA technology and analysis, the origin, evolution and dissemination of the plague remain notoriously difficult to pinpoint.

The plague is responsible for the two largest and most deadly pandemics in human history. However, the ebb and flow of these, why some die out and others persist for years has confounded scientists.

In a paper published today in the journal Communications Biology, McMaster researchers use comprehensive data and analysis to chart what they can about the highly complex history of Y. pestis, the bacterium that causes plague.

The research features an analysis of more than 600 genome sequences from around the globe, spanning the plague’s first emergence in humans 5,000 years ago, the plague of Justinian, the medieval Black Death and the current (or third) Pandemic, which began in the early 20^th century.

“The plague was the largest pandemic and biggest mortality event in human history. When it emerged and from what host may shed light on where it came from, why it continually erupted over hundreds of years and died out in some locales but persisted in others.   And ultimately, why it killed so many people,” explains evolutionary geneticist Hendrik Poinar, director of McMaster’s Ancient DNA Centre.

Poinar is a principal investigator with the Michael G. DeGroote Institute for Infectious Disease Research and McMaster’s Global Nexus for Pandemics & Biological Threats.

The team studied genomes from strains with a worldwide distribution and of different ages and determined that Y. pestis has an unstable molecular clock. This makes it particularly difficult to measure the rate at which mutations accumulate in its genome over time, which are then used to calculate dates of emergence.

Because Y. pestis evolves at a very slow pace, it is almost impossible to determine exactly where it originated.

Humans and rodents have carried the pathogen around the globe through travel and trade, allowing it to spread faster than its genome evolved. Genomic sequences found in Russia, Spain, England, Italy and Turkey, despite being separated by years are all identical, for example, creating enormous challenges to determining the route of transmission.

To address the problem, researchers developed a new method for distinguishing specific populations of Y. pestis, enabling them to identify and date five populations throughout history, including the most famous ancient pandemic lineages which they now estimate had emerged decades or even centuries before the pandemic was historically documented in Europe.

“You can’t think of the plague as just a single bacterium,” explains Poinar. “Context is hugely important, which is shown by our data and analysis.”

To properly reconstruct pandemics of our past, present, and future, historical, ecological, environmental, social and cultural contexts are equally significant.

He explains that genetic evidence alone is not enough to reconstruct the timing and spread of short-term plague pandemics, which has implications for future research related to past pandemics and the progression of ongoing outbreaks such as COVID-19.

Bibliographic information:

Plagued by a cryptic clock: insight and issues from the global phylogeny of Yersinia pestis, Communications Biology (19-Jan-2023), DOI: 10.1038/s42003-022-04394-6

Press release from McMaster University, by Michelle Donovan.

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Multidisciplinary team studied ancient plague genomes

The Black Death, the biggest pandemic of our history, was caused by the bacterium Yersinia pestis and lasted in Europe between the years 1346 and 1353. Despite the pandemic’s immense demographic and societal impacts, its origins have long been elusive. Now, a multidisciplinary team of scientists, including researchers from the Max Planck Institute for Evolutionary Anthropology in Leipzig, the University of Tübingen, in Germany, and the University of Stirling, in the United Kingdom, have obtained and studied ancient Y. pestis genomes that trace the pandemic’s origins to Central Asia.

In 1347, plague first entered the Mediterranean via trade ships transporting goods from the territories of the Golden Horde in the Black Sea. The disease then disseminated across Europe, the Middle East and northern Africa claiming up to 60 percent of the population in a large-scale outbreak known as the Black Death. This first wave further extended into a 500-year-long pandemic, the so-called Second Plague Pandemic, which lasted until the early 19th century.

The origins of the Second Plague Pandemic have long been debated. One of the most popular theories has supported its source in East Asia, specifically in China. To the contrary, the only so-far available archaeological findings come from Central Asia, close to Lake Issyk Kul, in what is now Kyrgyzstan. These findings show that an epidemic devastated a local trading community in the years 1338 and 1339. Specifically, excavations that took place almost 140 years ago revealed tombstones indicating that individuals died in those years of an unknown epidemic or “pestilence”. Since their first discovery, the tombstones inscribed in Syriac language, have been a cornerstone of controversy among scholars regarding their relevance to the Black Death of Europe.

In this study, an international team of researchers analysed ancient DNA from human remains as well as historical and archaeological data from two sites that were found to contain “pestilence” inscriptions. The team’s first results were very encouraging, as DNA from the plague bacterium, Yersinia pestis, was identified in individuals with the year 1338 inscribed on their tombstones.

“We could finally show that the epidemic mentioned on the tombstones was indeed caused by plague”, says Phil Slavin, one of the senior authors of the study and historian at the University of Stirling, UK.

Researchers found the Black Death’s source strain

But could this have been the origin of the Black Death? Researchers have previously associated the Black Death’s initiation with a massive diversification of plague strains, a so-called Big Bang event of plague diversity. But the exact date of this event could not be precisely estimated, and was thought to have happened sometime between the 10^th and 14^th centuries. The team now pieced together complete ancient plague genomes from the sites in Kyrgyzstan and investigated how they might relate with this Big Bang event.

“We found that the ancient strains from Kyrgyzstan are positioned exactly at the node of this massive diversification event. In other words, we found the Black Death’s source strain and we even know its exact date [meaning the year 1338]”, says Maria Spyrou, lead author and researcher at the University of Tübingen.

But where did this strain come from? Did it evolve locally or did it spread in this region from elsewhere? Plague is not a disease of humans; the bacterium survives within wild rodent populations across the world, in so-called plague reservoirs. Hence, the ancient Central Asian strain that caused the 1338-1339 epidemic around Lake Issyk Kul must have come from one such reservoir.

“We found that modern strains most closely related to the ancient strain are today found in plague reservoirs around the Tian Shan mountains, so very close to where the ancient strain was found. This points to an origin of Black Death’s ancestor in Central Asia”, explains Johannes Krause, senior author of the study and director at the Max Planck Institute for Evolutionary Anthropology.

The study demonstrates how investigations of well-defined archaeological contexts, and close collaborations among historians, archaeologists and geneticists can resolve big mysteries of our past, such as the infamous Black Death’s origins, with unprecedented precision.

The source of the Black Death in 14th-century central Eurasia, Nature (15-Jun-2022), DOI: 10.1038/s41586-022-04800-3

Press release from the Max Planck Institute for Evolutionary Anthropology in Leipzig

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