The bacteria responsible for the Justinian Plague, the first recorded pandemic in history that struck the Byzantine Empire, has been discovered.

Researchers have discovered direct genomic evidence of the bacterium responsible for the Justinian Plague , the world’s first recorded pandemic , in the Eastern Mediterranean, where the outbreak was first described nearly 1,500 years ago. The landmark discovery, led by an interdisciplinary team from the University of South Florida and Florida Atlantic University (USA), with collaborators in India and Australia, identified Yersinia pestis , the microbe that causes the plague , in a mass grave in the ancient city of Jerash, Jordan, near the epicenter of the pandemic.

This groundbreaking discovery definitively links the pathogen to the Plague of Justinian , which marked the first pandemic (541–750 AD), solving one of history’s oldest mysteries. For centuries, historians have deliberated over the cause of the devastating outbreak that killed tens of millions of people, reshaped the Byzantine Empire, and altered the course of Western civilization. Despite circumstantial evidence, direct proof of the responsible microbe remained elusive —a missing link in the history of pandemics.

Two recently published articles in Genes , led by the University of South Florida and Florida Atlantic University, provide these long-sought answers and offer a new perspective on one of the most momentous episodes in human history. The discovery also underscores the current relevance of the plague : although rare, Y. pestis continues to circulate worldwide.

In July, a northern Arizona resident died from pneumonic plague, the deadliest form of Y. pestis infection, marking the first such death in the United States since 2007, and last week another person in California tested positive for the disease. "This discovery provides the long-sought definitive proof of the presence of Y. pestis at the epicenter of the Justinian Plague ," said Rays H.Y. Jiang, Ph.D., principal investigator of the studies and an associate professor in the USF College of Public Health.

"For centuries, we've relied on written accounts describing a devastating disease, but we've lacked solid biological evidence of the plague's presence. Our findings provide the missing piece of that puzzle, offering the first direct genetic window into how this pandemic developed in the heart of the empire," he added.

The Plague of Justinian first appeared in historical records from Pelusium (present-day Tell el-Farama) in Egypt, before spreading throughout the Eastern Roman, or Byzantine, Empire. Although traces of Y. pestis had been found thousands of miles away, in small villages across Western Europe, no evidence had ever been found within the empire itself or near the epicenter of the pandemic.

"Using specific ancient DNA techniques, we successfully recovered and sequenced genetic material from eight human teeth excavated from burial chambers beneath the ancient Roman hippodrome at Jerash, a city just 200 miles (320 kilometers) from ancient Pelusium," said Greg O'Corry-Crowe, Ph.D., co-author, a research professor at FAU's Harbor Branch Oceanographic Institute and a National Geographic Explorer.

The arena had become a mass grave between the mid-6th and early 7th centuries, when written accounts describe a sudden wave of mortality. Genomic analysis revealed that the plague victims carried nearly identical strains of Y. pestis, confirming for the first time that the bacterium was present in the Byzantine Empire between 550 and 660 AD. This genetic similarity suggests a rapid and devastating outbreak, consistent with historical descriptions of a plague that caused mass deaths.

Improve understanding of pandemics

A complementary study, also led by the universities, places the Jerash discovery in a broader evolutionary context. By analyzing hundreds of ancient and modern Y. pestis genomes, including those newly recovered from Jerash, the researchers showed that the bacterium had been circulating among human populations for millennia before the Justinian outbreak.

The team also found that subsequent plague pandemics , from the Black Death of the 14th century to the cases that continue to occur today, did not descend from a single ancestral strain. Instead, they arose independently and repeatedly from long-standing animal reservoirs, erupting in multiple waves in different regions and eras.

This repeated pattern contrasts sharply with the SARS-CoV-2 pandemic ( COVID-19 ), which originated from a single spillover event and evolved primarily through human-to-human transmission.

Together, these landmark findings redefine our understanding of how pandemics emerge, recur, and spread, and why they remain a persistent feature of human civilization. The research underscores that pandemics are not singular historical catastrophes, but rather repetitive biological events driven by human congregation, mobility, and environmental change—issues that remain relevant today.