Genetics uncovers the earliest cases of plague

  • Teeth from a group of five thousand year-old skeletons reveal the earliest known cases of plague.
  • This predates any earlier examples by almost three thousand years.
  • This early strain of the disease could have led to the mass migrations of Bronze Age Europe.

New DNA research has uncovered the oldest known cases of plague in humans–Bronze Age people from across Europe and Asia, from as early as 4,800 years ago.

These new cases are almost 3,000 years older than the previous examples of plague from historical records.

“This study changes our view of when, and how plaque influenced human populations and opens new avenues for studying the evolution of diseases,” says co-author Eske Willerslev, from the Centre for GeoGenetics, at the University of Copenhagen, Denmark, in a press release.

The research is published in the open-access journal Cell.

Bronze Age Europe was a wash with migrants

In a previous study of ancient European genomics, Willerslev and colleagues showed just how mobile the inhabitants of Bronze Age Europe actually were.

Waves of migrants entered and moved around Europe between 1,500 and 3,000 years ago. And it’s these migrations that sowed the seeds of Europe’s demographic makeup today.

But why was Bronze Age Europe on the move?

Disease was a possible answer, with people either fleeing from an epidemic themselves, or taking advantage of recently decimated populations, moving into new territories whilst they had the opportunity.

But without any evidence of disease from this time, they couldn’t know for sure.

Bronze Age DNA held some answers

Willerslev and colleagues analysed the teeth of 101 Bronze Age individuals, sequencing their genome. They saw that seven of them were infected with a strain of the Yersinia pestis bacterium–the deadly bacteria that causes plague.

This dates the earliest known cases of plague to 2,794 BC. That is 3,300 years before any historical recordings of the disease.

The disease itself is now believed to be almost 6,000 years old. More specifically, the last common ancestor of all known strains of Y. pestis is now believed to be 5,783 years old.

According to the new study, it is therefore plausible that Bronze Age Europeans were migrating as a direct result of these plague outbreaks, and that these migrations helped to spread the disease across Europe.

“One of the most deadly bacteria ever encountered by humans”

This ancient strain of Y. pestis was somewhat underdeveloped in comparison with its more modern relative, the deadly virulent Black Death, which decimated Europe in the 1300s, wiping out somewhere between 30 and 50 per cent of the population at that time.

Animation to show the spread of bubonic plague, a.k.a The Black Death, throughout Europe in the 1300s.

Animation showing the spread of bubonic plague, a.k.a The Black Death, throughout Europe in the 1300s. (Credit: Wikipedia)

But in the oldest Bronze Age samples, Y. pestis had not yet developed two of the key genetic characteristics that would turn it into what the scientists refer to as “one of the most deadly bacteria ever encountered by humans.”

One of these genetic variants–the Yersinia murine toxin–protects the pathogen inside the flea gut, thereby allowing it to be spread by fleas. The other gene prevents the human immune system from recognising Y. pestis, allowing it to go undetected in the human body.

According to the new study, these key characteristics were not likely to have been fully developed until the beginning of the 1st millennium BC, at which point Y. pestis had turned into the more virulent pathogen that we recognise today.

 

The Y. pestis bacterium was found in seven Bronze Age skeletons from Eurasia. The map above shows the locations. The bacterium became virulent after developing two genetic characteristics around 1000 BC: development of Yersinia murine toxin (ymt) that allowed it to be carried by fleas, and another genetic variant that enabled the bacterium to hide from the human immune system defences. (Illustration: Rasmussen et al. Cell/2015).

The Y. pestis bacterium was found in seven Bronze Age skeletons from Eurasia. The map above shows the locations. The bacterium became virulent after developing two genetic characteristics around 1000 BC: development of Yersinia murine toxin (ymt) that allowed it to be carried by fleas, and another genetic variant that enabled the bacterium to hide from human immune system defences. (Illustration: Rasmussen et al. Cell/2015).

A new understanding of this deadly disease

In a press release, lead-author Simon Rasmussen, associate professor at the Technical University of Denmark, says that the new results “changes the historical understanding of this extremely important human pathogen.”

Documenting the evolution of this pathogen into a virulent, flea-borne strain that would ultimately lead to the bubonic plague will help scientists to understand how this, and other pathogens, may develop in the future.

“The underlying evolutionary mechanisms that facilitated the evolution of Y. pestis are still present today, and learning from this will help us understand how future pathogens may arise or develop increased virulence,” says Rasmussen.

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Photo Credit: Flickr themostinept

 

Time for a bit more? Read on…

Looking for more reading on this topic? First off, why not try reading the original open-access scientific article.

If that is a step too far, then try the original press release form EurekAlert.

Check out the lead scientist Simon Rasmussen and co-author Eske Willerslev’s research profiles to read more about their research interests.

 

Simon Rasmussen, Morten Erik Allentoft, Kasper Nielsen, Ludovic Orlando, Martin Sikora, Karl-Göran Sjögren, Anders Gorm Pedersen, Mikkel Schubert, Alex Van Dam, Christian Moliin Outzen Kapel, Henrik Bjørn Nielsen, Søren Brunak, Pavel Avetisyan, Andrey Epimakhov, Mikhail Viktorovich Khalyapin, Artak Gnuni, Aivar Kriiska, Irena Lasak, Mait Metspalu, Vyacheslav Moiseyev, Andrei Gromov, Dalia Pokutta, Lehti Saag, Liivi Varul, Levon Yepiskoposyan, Thomas Sicheritz-Pontén, Robert A. Foley, Marta Mirazón Lahr, Rasmus Nielsen, Kristian Kristiansen, & Eske Willerslev (2015). Early Divergent Strains of Yersinia pestis in Eurasia 5,000 Years Ago Cell, 163 (3) : http://dx.doi.org/10.1016/j.cell.2015.10.009

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2 responses to “Genetics uncovers the earliest cases of plague

  1. Nice article, the only thing that gave me pause was this line:

    “This dates the earliest known cases of plague to 2,794 BC. That is 3,300 years before any historical recordings of the disease.”

    I checked the summary of the original paper which had:

    “We report the oldest direct evidence of Yersinia pestis identified by ancient DNA in human teeth from Asia and Europe dating from 2,800 to 5,000 years ago…Our results show that plague infection was endemic in the human populations of Eurasia at least 3,000 years before any historical recordings of pandemics”

    The reason I’m confused is because Thucydides, who lived in the 450-400 BC range, reported what seems to be a plague. Perhaps this study deals with a specific type of plague, or what Thucydides reports on is only a plague colloquially, being in fact scientifically different?

    Like

    • Interesting question! It would be useful to hear from a medical historian who could perhaps clarify if this is one particular strain, or a terminology issue?

      Like

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