ABOVE: Excavation (between 1885 and 1892) of the Kara-Djigach A.S. Leybin, August 1886

In the foothills of the Tian Shan mountains in what is now Kyrgyzstan, tombstones in the Kara-Djigach cemetery with Syriac inscriptions showed that the village’s death rate skyrocketed over a two-year period. Phil Slavin, a historian at the University of Stirling in Scotland, says that “out of a total of 467 stones that are precisely dated to the period between 448 and 1345, 118 actually turned out to be dated to the years 1338 [and] 1339.”

An 1890 publication covering the tombstones drew Slavin into their mystery, he said in a press briefing yesterday. Ten of the gravestones from those two years had longer inscriptions memorializing the persons and their cause of death—pestilence. This made Slavin wonder whether the site might help settle a long debate about the origins of the Black Death pandemic that arrived in Europe around 1347 CE. Knowing he’d have little chance of finding enough written historical evidence to test the idea, he sought help from archaeogeneticists Johannes Krause at the Max Plank Institute for Evolutionary Anthropology and Maria Spyrou at the Eberhard Karls University of Tübingen, both in Germany.

The results of their analysis, published today (June 15) in Nature, implicate an ancient strain of the bacterium Yersinia pestis as the likely source of the Black Death pandemic, which Spyrou says killed half of Europe’s population in the decade after it arrived in the Black Sea region. The research also puts the village’s outbreak near the epicenter of a phylogenetic diversification, called a polytomy, where the bacterium’s lineage split into four new branches. “So it’s really like the big bang . . . of plague that we have there; the strain that gave rise to the majority of strains that are circulating in the world today,” Krause said in the briefing. Although it was already known that Y. pestis underwent an explosive radiation, the timing of it has been debated.

ancient tombstone of someone who died of plague
The headstone of one Kara Djigach plague victim (whose DNA was not sequenced in this work) The inscription translation says: “In the Year 1649 [1338 CE], and it was the Year of the Tiger. This is the tomb of the believer Sanmaq. [He] died of pestilence”
A.S. Leybin, August 1886

Y. pestis has caused three plague pandemics; the Black Death was the second. The new research sheds light on the mysteries of when the second plague pandemic emerged and the timing of the bacterium’s diversification.

The Kara-Djigach village appears to have been a trading community with around 1,000 people at the time of its local plague epidemic, Slavin says. DNA analyses conducted on teeth extracted from seven of the deceased humans revealed that three carried DNA matching Y. pestis, and two of those genomes were of relatively high quality and were used for the majority of the study’s analyses. Spyrou says that the researchers could distinguish the ancient bacterial DNA from modern versions because they lacked signature patterns common in contemporary strains. The team was able to reconstruct the entire genome of the ancient Y. pestis strain and connect it phylogenetically to modern lineages. “So the fact that, first of all, we have these patterns that are indicative of old DNA, and second, we also see a genome that is ancestral to all the modern diversity are two main indications that what we are dealing with is really an ancient bacterial strain,” she says.

See “Bronze Age Plague Sequenced

After establishing that the ancient strain of Y. pestis was ancestral to the four branches that arose from the “big bang,” the researchers conducted a phylogenetic analysis with known modern and historical variants to estimate a time period over which the bacterium’s diversification could have emerged. That showed the split occurred in the first half of the fourteenth century, leaving open the possibility that the big bang occurred before the village experienced its epidemic, and perhaps in a different location.

The researchers then compared variants that still circulate from a fifth branch called branch zero that is ancestral to the ancient strain identified in this study. They compared modern-day branch zero variants of Y. pestis found in nearby rodent populations and their parasites to the Y. pestis from the ancient cemetery, and they closely matched, suggesting the Black Death could have originated in the same vicinity. “So we find the ancient evidence as well as the modern evidence, and, at the same time, we have also witnessed fantastic tombstones that even tell us when it happened,” Krause says.

All told, the study authors say their evidence supports the notion that the Black Death originated from Central Asia and counters other theories, such as the East Asia hypothesis, which postulates that Y. pestis swept into Europe from China. Their results also narrow the timeline of the big bang compared to other recent studies, which have suggested that the bacterium’s phylogenetic split could have occurred more than a century before the second plague pandemic. 

Javier Pizarro-Cerdá, a microbiologist at Institut Pasteur who was not involved with this research, says he agrees with the findings. “The question that they ask is, ‘Branch zero is still living today, and we’re going to investigate where its strains are located.’ And boom—they found out that they are there,” within 50 to 100 kilometers of the burial site, he says. “This is why this is a major paper—because it really locates in time and in space, the origin of this major diversity of Yersinia pestis.” 

The findings don’t show exactly how the bacterium spread from Central Asia to Europe, but it may have been carried along passages used for commerce, the study’s authors write. Slavin describes the Kara Djigach village as “a trading community that was situated at the very heart of those long distance inland trade routes, commonly known as the Silk Road.” Artifacts found at the site, including pearls that would have likely been harvested in the Pacific or Indian Oceans and coins minted as far away as northern Iran lend weight to the notion that trade might have carried local microbes to far-flung regions.

It’s not known what caused Y. pestis to branch so suddenly. The bacterium’s mutation rate, which Spayou estimates at a single mutation every 5 to 20 years, pales in comparison to how quickly SARS-CoV-2 variants pop up. Y. pestis lineages that existed between the 600 years that spanned the first and second plague pandemics seem to have remained in rodent populations, Spayou writes in an email to The Scientist. Krause says that because the bacterium was hidden from humans for 600 years, nobody had immunity, leaving conditions ripe for the “perfect storm of that pandemic.”

See “Predicting Future Zoonotic Disease Outbreaks

Y. pestis still causes plague in humans today, but on much a smaller scale compared to the fourteenth century. According to the World Health Organization, between 2010 and 2015, there were about 3,200 cases and almost 600 deaths globally, but antibiotics are an effective treatment if an infection is caught early enough. 

Krause notes that the plague bacterium has long resided in animals in the Tian Shan mountain region, and we still don’t understand much about pathogens in animal reservoirs, leaving us ill-equipped to predict the next spillover event. “I think we really have to increase our efforts to understand the diversity of pathogens in animal reservoirs—to monitor them.”