A new study led by researchers at the University of Tartu has revealed that the plague, often remembered as a single catastrophic event known as the Black Death, actually had a much longer and more complex history in Europe. The research, published in the Proceedings of the National Academy of Sciences, examined DNA from the plague bacterium, Yersinia pestis, preserved in human remains found at 11 archaeological sites across Estonia, Russia, England, the Netherlands, and Switzerland. The samples span from the 14th to the 18th centuries, covering most of what historians call the Second Plague Pandemic, a period of recurring outbreaks that followed the Black Death. By reconstructing 26 genomes of Yersinia pestis, the researchers found that the plague repeatedly re-emerged in different parts of Europe over several centuries, creating new reservoirs in nature. One of the study’s key findings was evidence of a major expansion of plague lineages around 1450–1500, during which the bacterium diversified into three major branches. These branches may have established new reservoirs in wild rodent populations. The researchers suggest that climatic changes, such as the Great Renaissance Drought, could have played a role in this spread. The study introduced a new method for linking historical plague outbreaks to recovered genomes. This method improves the accuracy of dating by analyzing the position of plague genomes on the bacterium’s evolutionary tree. Using this approach, the researchers were able to narrow the likely dates of many samples and place them in a clearer historical context. They used these improved dates to reassess 64 previously published and 11 newly sequenced plague genomes, connecting them to known historical outbreaks. The study also highlights how human activity influenced the spread of plague. Newly analyzed genomes provide additional evidence for outbreaks linked to major conflicts like the Thirty Years' War (1618–1648) and the Great Northern War (c. 1700–1721). The researchers found that plague often spread along the same routes used by armies, refugees, and traders. For instance, in Tallinn, plague caused significant casualties among Swedish and Russian troops and civilians during the 1710 siege. Understanding how the plague re-emerged after the Black Death, persisted for centuries, and eventually disappeared from Europe can help scientists better grasp the long-term dynamics of infectious diseases. The study was a collaborative effort involving researchers from across Europe, including the University of Cambridge and institutions in the Netherlands and Switzerland. By combining ancient DNA analysis, archaeology, history, and radiocarbon dating, the team has created the most detailed genetic map of the Second Plague Pandemic to date.