A study led by researchers at the University of Tartu is revealing new details about how plague persisted after the Black Death. By analyzing Yersinia pestis DNA preserved in archaeological human bones, scientists reconstructed how the disease spread, evolved and returned long after the first pandemic had passed.

Ancient DNA reveals centuries of plague outbreaks

The research team reconstructed 26 plague genomes from human bones discovered at 11 archaeological sites in Estonia, Russia, England, the Netherlands and Switzerland. The samples date from the 14th to the 18th centuries, covering much of the period known as the Second Plague Pandemic.

Genetic evidence suggests that plague did not simply survive in one location. Instead, it repeatedly spread outward from a single source and resurged in different parts of Europe over hundreds of years. These movements may have created several new sources where the bacterium could persist.

Estonia was repeatedly affected. Researchers found evidence of multiple plague introductions into the region during most of the Second Plague Pandemic. Estonia’s connections with other parts of Europe may therefore have helped the disease travel long distances.

One of the most striking patterns appeared between about 1450 and 1500. During this period, the plague lineage expanded significantly and split into three important branches. These lineages may have contributed to the establishment of new reservoirs in wild rodent populations, which serve as natural hosts for Y. pestis.

Climate may also have influenced this expansion. Researchers cite the Renaissance drought as one possible contributing factor. Studies of modern plague systems indicate that climate changes can significantly affect outbreaks among wild rodents.

“We found evidence of repeated introductions of plague into Estonia already from the late 14th century and identified several previously unknown genetic lineages in both urban and rural areas,” said lead author Professor Kristina Tambets.

How scientists dated ancient plague outbreaks

A major challenge in studying historical pandemics is determining exactly when ancient infectious diseases occurred.

During the coronavirus pandemic, genome sequences were usually linked to precise dates, allowing scientists to track individual variants in detail. Ancient disease samples rarely contain such precise timestamps. Archaeological sites are often dated using radiocarbon techniques, which can produce time ranges spanning decades or even more than a century.

“In the case of COVID-19, scientists were able to reconstruct the prevalence of individual strains very well because the genome had precise timestamps. For historical pandemics, these timestamps are often missing or can cover more than 100 years, which limits the ability to interpret genetic data,” explained lead author Dr. Marcel Keller.

To address this problem, the team developed a method to narrow broad archaeological dating ranges. The researchers examined where individual plague genomes appeared on the bacterium’s evolutionary tree and used that information to improve the estimated ages of many samples.

This approach allowed the researchers to place ancient plague infections on a more accurate historical timeline.

The team then applied the improved dating method to 64 previously published plague genomes and 11 newly sequenced genomes. The study represents the first systematic attempt to connect nearly all currently available plague genomes from the 14th to the 18th centuries with outbreaks described in historical records.

Historian and corresponding author Professor Philip Slavin said: “We were able to improve the dating intervals for many of the samples, and as a result we were able to link them to specific plague waves and epidemics recorded by chroniclers in their respective towns and regions.”

War and migration helped spread plague across Europe

The genetic record also shows how strongly human activity influenced the spread of plague.

Newly analyzed genomes provide further evidence linking plague outbreaks to the Thirty Years’ War, fought from 1618 to 1648, and the Great Northern War, which took place around 1700 to 1721. Armies, displaced people, refugees and traders frequently traveled along the same routes, creating opportunities for disease to move between regions.

“During periods of conflict, it splits into new branches and spreads along routes traveled by troops and displaced populations,” said lead author Dr. Christiana L. Scheib.

The findings add new details to the plague outbreak associated with the Great Northern War. During the Siege of Tallinn in 1710, the disease killed Swedish and Russian soldiers as well as civilians.

Taken together, the evidence shows that plague was much more than a single medieval catastrophe. It remained a recurring danger for generations, returning repeatedly to communities across Europe.

Why the history of plague still matters

Although plague is no longer a major public health threat in Europe, Y. pestis has not disappeared from the world. The bacterium still lives in natural rodent habitats in some regions.

Researchers say that understanding how plague took hold after the Black Death, persisted for centuries and eventually disappeared from Europe could help scientists better understand the long-term behavior of infectious diseases.

By linking ancient genomes to recorded outbreaks and animal sources, researchers can study how diseases originate, spread, become established and persist over long periods. This knowledge could also improve modern disease surveillance and efforts to monitor areas where plague remains endemic.

Reconstructing the Second Plague Pandemic with ancient DNA

The project brought together researchers and evidence from several countries and scientific disciplines. Samples and expertise were provided by collaborators across Europe, including scientists at the University of Cambridge and research partners in the Netherlands and Switzerland.

By combining ancient DNA analysis, archaeology, historical records and radiocarbon dating, the researchers created the most comprehensive genetic picture of the Second Plague Pandemic to date.

The findings reveal that plague crossed borders multiple times, evolved into new lineages, followed human movements and continued to shape Europe for centuries after the Black Death itself ended.