USF and FAU researchers identify bacterium behind 1,500-year-old pandemic mystery.
For the first time, scientists have obtained direct genomic evidence of the bacterium responsible for the Plague of Justinian, the earliest known pandemic in recorded history. The outbreak, which struck the Eastern Mediterranean nearly 1,500 years ago, has now been firmly tied to Yersinia pestis, the pathogen that causes plague.
An international team led by researchers at the University of South Florida and Florida Atlantic University, working with partners in India and Australia, identified Y. pestis in human remains from a mass grave at the ancient city of Jerash in Jordan, close to the heart of the pandemic. This pivotal discovery confirms the bacterium’s role in the Justinian Plague (AD 541–750), resolving a mystery that has lingered for centuries.
Filling historical gaps with genetic proof
For hundreds of years, scholars debated the origins of the catastrophic outbreak that killed tens of millions, reshaped the Byzantine Empire, and altered the trajectory of Western history. Although written accounts hinted at plague, no biological proof had been available, leaving a critical gap in the narrative of pandemics.
Now, two newly released papers led by USF and FAU provide that missing proof, offering fresh insight into one of humanity’s most transformative health crises. The findings also highlight plague’s continued presence today: although uncommon, Y. pestis still circulates globally. In July, a resident of northern Arizona died from pneumonic plague, the deadliest form of the disease and the first U.S. fatality since 2007, followed just a week later by a confirmed case in California.
“This discovery provides the long-sought definitive proof of Y. pestis at the epicenter of the Plague of Justinian,” said Rays H. Y. Jiang, PhD, lead PI of the studies and associate professor with the USF College of Public Health. “For centuries, we’ve relied on written accounts describing a devastating disease, but lacked any hard biological evidence of plague’s presence. Our findings provide the missing piece of that puzzle, offering the first direct genetic window into how this pandemic unfolded at the heart of the empire.”
Evidence of widespread mortality
The Plague of Justinian was first documented in Pelusium (modern-day Tell el-Farama) in Egypt, before sweeping across the Eastern Roman, or Byzantine, Empire. Although remnants of Y. pestis had been detected in small villages in western Europe thousands of miles away, no genetic evidence had ever been uncovered within the empire itself or close to the pandemic’s center.
“Using targeted ancient DNA techniques, we successfully recovered and sequenced genetic material from eight human teeth excavated from burial chambers beneath the former Roman hippodrome in Jerash, a city just 200 miles from ancient Pelusium,” said Greg O’Corry-Crowe, PhD, co-author and a research professor at FAU Harbor Branch Oceanographic Institute and a National Geographic Explorer.
The arena had been repurposed as a mass grave during the mid-sixth to early seventh century, 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 within the Byzantine Empire between AD 550-660. That genetic uniformity suggests a rapid, devastating outbreak consistent with historical descriptions of a plague causing mass death.
“The Jerash site offers a rare glimpse of how ancient societies responded to public health disasters,” said Jiang. “Jerash was one of the key cities of the Eastern Roman Empire, a documented trade hub with magnificent structures. That a venue once built for entertainment and civic pride became a mass cemetery in a time of emergency shows how urban centers were very likely overwhelmed.”
Broader evolutionary patterns
A companion study, also led by USF and FAU, places the Jerash discovery into a wider evolutionary context. By analyzing hundreds of ancient and modern Y. pestis genomes — including those newly recovered from Jerash — the researchers showed that the bacteria had been circulating among human populations for millennia before the Justinian outbreak.
The team also found that later plague pandemics, from the Black Death of the 14th century to cases still appearing today, did not descend from a single ancestral strain. Instead, they arose independently and repeatedly from longstanding animal reservoirs, erupting in multiple waves across different regions and eras. This repeated pattern stands in stark contrast to the SARS-CoV-2 pandemic (COVID-19), which originated from a single spillover event and evolved primarily through human-to-human transmission.
Together, the landmark findings reshape the 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 repeating biological events driven by human congregation, mobility and environmental change — themes that remain relevant today.
Shared humanity across pandemics
“This research was both scientifically compelling and personally resonant. It offered an extraordinary opportunity to delve into the study of human history through the lens of ancient DNA at a time when we ourselves were living through a global pandemic,” said O’Corry-Crowe. “Equally profound was the experience of working with ancient human remains — individuals who lived, suffered, and died centuries ago — and using modern science to help recover and share their stories. It’s a humbling reminder of our shared humanity across time and a moving testament to the power of science to give voice to those long silent.”
While very different from COVID-19, both diseases highlight the enduring link between connectivity and pandemic risk, as well as the reality that some pathogens can never be fully eradicated.
“We’ve been wrestling with plague for a few thousand years, and people still die from it today,” Jiang said. “Like COVID, it continues to evolve, and containment measures evidently can’t get rid of it. We have to be careful, but the threat will never go away.”
Building on the Jerash breakthrough, the team is now expanding its research to Venice, Italy, and the Lazaretto Vecchio, a dedicated quarantine island and one of the world’s most significant plague burial sites. More than 1,200 samples from this Black Death-era mass grave are now housed at USF, offering an unprecedented opportunity to study how early public health measures intersected with pathogen evolution, urban vulnerability, and cultural memory.
Reference: “Genetic Evidence of Yersinia pestis from the First Pandemic” by Swamy R. Adapa, Karen Hendrix, Aditya Upadhyay, Subhajeet Dutta, Andrea Vianello, Gregory O’Corry-Crowe, Jorge Monroy, Tatiana Ferrer, Elizabeth Remily-Wood, Gloria C. Ferreira, Michael Decker, Robert H. Tykot, Sucheta Tripathy and Rays H. Y. Jiang, 31 July 2025, Genes.
DOI: 10.3390/genes16080926
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