October 2022

Over the summer, researchers announced that they’d identified the source of a deadly pandemic. This might sound like another story on COVID-19 – but in fact, the research did not focus on bats in China circa 2019, but on tombstones in Kyrgyzstan circa 1340. The Black Death, an outbreak of bubonic plague, killed perhaps as much as 60% of the population of Western Europe and Asia in less than 10 years. Bubonic plague is caused by the bacteria Yersinia pestis, which can spread through flea bites that transmit the microbe from one infected animal to another, as well as directly from person to person. This pandemic pestilence still lurks in rodents and other small animals around the world today, but now we treat the disease with antibiotics and understand its transmission well enough to tamp down outbreaks. However, many questions about the plague’s deadliest epidemic in the Late Middle Ages remain – mysteries to which ancient graves seemed to hold clues…

Where's the evolution?

The cemeteries near Lake Issyk-Kul in modern-day Kyrgyzstan were first excavated in the late 1800s. Researchers had long suspected that bubonic plague was responsible for many of the dead – and the new research further buttressed this idea. An unusually large number of burials dated to 1338 and 1339, just before the Black Death in Europe, and some of the tombstone inscriptions specify the cause of death to be a “pestilence.” To get more direct evidence, scientists searched for ancient DNA in the excavated human remains and found what they were looking for: genetic sequences from Y. pestis, clear evidence of bubonic plague.

Timing-wise, it seemed plausible that the plague epidemic rattling ancient Kyrgyzstan in 1338 and 1339 had simply spread westward, sparking the Black Death in Europe, Western Asia, and North Africa in 1346, but the evidence was circumstantial.  A more definitive answer would require evolutionary reasoning.

The researchers gathered Y. pestis DNA sequences from other places and times – including other ancient DNA sequences that were clearly part of the Black Death and sequences from modern strains of Y. pestis. They used these to build an evolutionary tree, or a phylogeny, showing how all the different strains are related to one another. The tree supported previous research, which found that there are several different modern strains (branches 0, 1, 2, 3, and 4 on the tree below), with the Black Death sequences (in blue below) all clustered on a single branch. The Black Death sequences, as well as those from later outbreaks in Europe (in green below), are all very closely related and are, in fact, each other’s closest relatives. This suggests that the Black Death and those later outbreaks of bubonic plague were not caused by multiple invasions of slightly different strains of Y. pestis from different areas, but a single event where a lineage of sparked a pandemic and then stuck around, continuing to diversify.

Remarkably, the evolutionary analysis placed the Y. pestis DNA sequence from the Kyrgyzstan graves (in pink above) at a central node of the tree, in between branches 2, 3, 4, and the Black Death sequences. This means the Y. pestis DNA from the Kyrgyzstan graves exactly matched the sequence that we we would expect the evolutionary ancestor of the Black Death strain (as well as the ancestor of branches 2, 3, and 4) to have. This is strong evidence that the lineage of Y. pestis that caused the Black Death passed through the communities around Lake Issyk-Kul before reaching Europe, in a sort of ‘prequel’ plague.

To try to figure out where the plague strain might have been before infecting people near Lake Issyk-Kul, the researchers searched for Y. pestis DNA sequences that branched off the tree before the Kyrgyzstan plague sequence arose. These represent other descendants of the ancient Y. pestis lineage (the ‘pre-prequel’ plague) that gave rise to the Kyrgyzstan plague. They are shown as the black 0.ANT strains on the tree above. These sequences – the modern descendants of the pre-prequel Y. pestis lineage – mainly came from wild animals very near the Kyrgyzstan site. This suggests that the Kyrgyzstan plague may have arisen locally, spilling over from local populations of marmots into the human population, and from there moving west.

Since the Kyrgyzstan site is also close to ancient trade routes between Eastern Asia and Europe, the researchers further hypothesize that trade may have played a role in spreading this strain of Y. pestis from Kyrgyzstan to Europe and North Africa, where it sparked a pandemic causing at least 10 times more deaths than COVID-19 has so far. Evolutionary theory can help us understand the circumstances that led to past pandemics, with the hope that we can use this knowledge to better prevent them in the future.