5000-year-old remains reveal plague’s genetic secrets

The remains of a 5000-year-old man have been discovered to house the oldest known strain of Yersinia pestis, the bacteria responsible for bubonic plague, aka the Black Death.

“What’s most astonishing is that we can push back the appearance of Y. pestis 2,000 years farther than previously published studies suggested,” says Ben Krause-Kyora, head of the Ancient DNA Laboratory at the University of Kiel in Germany, and senior author on a paper describing the research in Cell Reports.

The genome of the bacteria reveals that the hunter-gatherer’s plague would have been less contagious, and less deadly, than the famous bubonic plague of the 14th century.

“What’s so surprising is that we see already in this early strain more or less the complete genetic set of Yersinia pestis, and only a few genes are lacking,” says Krause-Kyora.

Skull bones of the man buried in riukalns latvia around 5000 years ago 1 credit dominik goldner bgaeu berlin
Skull of a man who died 5,000 years ago with the plague. Image credit: Dominik Göldner, BGAEU, Berlin

“But even a small shift in genetic settings can have a dramatic influence on virulence.”

Crucially, the Yersinia pestis found in the ancient man lacked the gene that allowed fleas to transmit the disease, preventing it from spreading so quickly. The development of this gene was responsible for the reach and severity of the Black Death.

The body of the dead man – a 20 to 30-year-old called “RV 2039” – was first uncovered in the late 1800s at a site called Riņņukalns in present-day Latvia, and then went missing for almost a century before reappearing in the collection of German anthropologist Rudolph Virchow. He was one of four skeletons found in the same area, thought to belong to the same social group.

Y. pestis was found in his bloodstream, leading researchers to conclude he most likely died from the disease. However, because he had a high quantity of bacteria in his bloodstream at the time of his death, the course of the disease was likely slow – in rodent studies, high bacterial loads of Y. pestis are associated with less aggressive infections.

The Riņņukalns site, a Stone Age shell midden on the banks of the Salaca River near the outflow from Lake Burtniek. Image credit: Harald Lübke, ZBSA, Schloss Gottorf

The people he was buried near were not infected, suggesting the disease did not surge through the community. These conclusions – that this early form of the disease was slow moving and not highly contagious – challenge prevailing theories about the development of civilisation in Eurasia, which suggest that the plague evolved in high-density megacities of 10,000 people or more near the Black Sea. Instead, this early version was found in a low-density hunter-gatherer community, long before the growth of cities.

“While we can’t run experiments today with these ancient strains, we can get valuable information on what virulence factors were acquired and when. It can tell us about the development and evolution of disease which are important for us today,” says Ashley Franks, a microbiologist at La Trobe University who was not involved in the study.

“We have limited knowledge about the microbes associated with hunter-gatherers from the past,” Frank says. “Disease has always been a persistent threat to people and there has been an evolutionary struggle for people to survive. The development into our modern lifestyle has outpaced evolution so having a good understanding of drivers of change is important.”

The authors say that examining the history of Y. pestis could also potentially shed light on human genomic history.

“Different pathogens and the human genome have always evolved together. We know Y. pestis most likely killed half of the European population in a short time frame, so it should have a big impact on the human genome,” says Krause-Kyora. “But even before that, we see major turnover in our immune genes at the end of the Neolithic Age, and it could be that we were seeing a significant change in the pathogen landscape at that time as well.”

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