Technology VarSome.com Research Brief

Ancient DNA Confirm First Pandemic's Pathogen

Jason Armstrong | September 8, 2025

The Plague of Justinian (541-750 CE) has long been described as the first recorded pandemic. Contemporary descriptions report a sudden and devastating outbreak that spread across the Byzantine Empire, killing tens of millions. Historians have long suspected Yersinia pestis, the bacterium responsible for later, infamous plagues, but direct evidence at the heart of the outbreak had been missing. Two new studies now provide that evidence and set the pandemic within a broader evolutionary context.

Contemporary Accounts

We have several historical sources that detail the Plague of Justinian. Procopius of Caesarea, a chief historian of the era, records that an epidemic began in Pelusium, Egypt, around 541 CE¹. He writes that it marched across Egypt and through Palestine before reaching Constantinople by the spring of 542 CE, noting it spread “as if fearing lest some corner of earth might escape it.”

Early symptoms were deceptively mild; a low-grade fever that gave little hint of what was to come. Within days, however, victims developed swollen lymph nodes in the groin, armpits, or thighs, known as buboes, followed by coma, delirium, vomiting of blood, and sudden death.

By early 542 CE, the disease had reached Constantinople, where it raged for four months. Procopius cites peak daily death tolls of up to 10,000 and describes the collapse of burial systems, causing bodies to be piled up in the streets before being tossed onto boats for disposal.

This vivid account, along with other contemporary reports, convinced historians that the First Pandemic was attributed to bubonic plague, caused by the bacterium Y. pestis. However, this has never before been confirmed by biological evidence.

The Jerash Evidence

Adapa et al. (2025) examined human remains from a mass grave dated to 550-660 CE in Jerash, Jordan, just 200 miles (330km) from Pelusium². The grave, found in a disused Roman hippodrome, contained around 230 individuals interred rapidly, suggesting a crisis event.

Using proteomic screening and ancient DNA techniques, the researchers identified Y. pestis from the teeth of five individuals. Genome sequencing revealed nearly identical strains, consistent with a single circulating lineage causing a sudden outbreak. The strains carried key virulence factors like Ymt, Pla, and the F1 capsule gene, all associated with flea-borne transmission and epidemic potential.

Previous genetic evidence for Y. pestis has been found in Western European burial sites thousands of miles from the epicentre of the First Pandemic. But this is the first time genomic evidence of bubonic plague, dated to the correct period, has been recovered from the Eastern Mediterranean. The Jerash findings, therefore, provide the missing link between historical accounts of the pandemic's origin and direct biological evidence at its ground zero.

The conversion of a civic structure, such as a hippodrome, into a mass grave in Jerash points to rapid mortality overwhelming normal burial practices. This archeological context reinforces the historical record, and the genetic uniformity across recovered genomes further suggests a swift, localised outbreak within the city.

Plague in Deep Time

Dutta et al. (2025) placed the Jerash genomes into a broader analysis of 326 Y. pestis strains spanning prehistory to the modern day³. Their phylogenomic study found that plague-causing lineages did not descend from a single ancestor. Instead, they arose independently from entrenched reservoirs across Eurasia.

Ancient strains recovered from Neolithic and Bronze Age sites show that Y. pestis was already circulating millennia before the Justinian outbreak. The pathogen’s history shows repeated spillover into humans, occasionally triggering pandemics.

The study also found that plague genomes from the First Pandemic and the Black Death’s later outbreaks (14th to 18th centuries) have so far been recovered only from human remains, not from animals or the environment. This suggests that these outbreaks were largely sustained by human-to-human transmission, in contrast to today, where Y. pestis is mostly maintained in reservoirs such as rodents, fleas, and soil.

Unlike pathogens such as SARS-CoV-2, Y. pestis does not follow a single, steady evolutionary clock. Its history shows long periods of dormancy in environmental reservoirs, punctuated by bursts of genetic change during human outbreaks. This pattern helps explain its recurring but unpredictable nature.

Connecting the Findings

Together, these studies resolve long-standing uncertainty about the Plague of Justinian and expand our understanding of the plague’s broader history.

Adapa et al. provide direct proof that Y. pestis was present at the epicentre of the First Pandemic.
Dutta et al. show that the Jerash strain fits into a much deeper and more complex evolutionary history, where pandemics emerge repeatedly from regional reservoirs rather than a single lineage.

Both studies highlight the role of human society – dense urban centers, trade networks, and mobility – in amplifying outbreaks. Jerash was a thriving city of the Byzantine Empire, and its fate illustrates how interconnected infrastructure made populations both prosperous and vulnerable.

Implications

These findings have two main implications. First, they close a major historical gap by confirming the microbial cause of the first recorded pandemic, linking written accounts to genetic evidence. Second, they remind us that plague is not only a past catastrophe but a continuing biological risk. This disease still circulates in animal reservoirs worldwide, with sporadic human cases reported each year. And while antimicrobial resistance (AMR) is rarely reported in Y. pestis, it highlights the importance of surveillance.

This research also underlines a broader principle: pandemics emerge where entrenched pathogens and human behaviour meet. In the 6th century, it was dense cities and trade routes. Today, urban populations are denser, and global trade and travel routes are more extensive, while other factors, such as intensive farming, climate change, and AMR, add further risk.

Conclusion

Ancient DNA has provided the first direct evidence that Yersinia pestis caused the Plague of Justinian at its epicenter, while global phylogenomic analysis frames plague as a recurrent threat shaped by human society and ecological persistence. These studies show how genomic evidence can bridge archeology, history, and epidemiology, reshaping our understanding of past pandemics and their relevance to the present.