About 1,500 years ago, frequent outbreaks of the world's first known plague
, caused by the bacterium Yersinia pestis, killed more than 25 million people and sickened many others in the Mediterranean basin with "flu-like" symptoms. The pandemic, which was called the Justinian Plague after the sixth-century Byzantine emperor Justinian I, lasted to the mid-eighth century.
Now, researchers in Germany have sequenced the genome of the Y. pestis strain that they believe caused the Justinian Plague but hasn't been seen since, according to a new study published in the journal Molecular Biology and Evolution
Variations of Y. pestis are thought to have caused at least three known plague pandemics. The Justinian plague was the first, and the Black Death
, a pandemic that emerged in the Middle Ages and killed up to half of the European population, was the second. The third plague pandemic began in late 19th-century China, giving rise to many of the subsequent plagues that exist
The newly sequenced genome reveals that the Y. pestis strain linked to the Justinian Plague indeed differs from the strain linked to the Black Death. (A genome of the Y. pestis strain
behind the Black Death was published in a separate study in 2011.)
Therefore, "this study provides a better understanding of the history and the biology of the disease," said Michal Feldman, a researcher at the Max Planck Institute and the University of Tubingen in Germany, who served as first author of the study.
"We still do not know why the Justinian plague suddenly vanished," Feldman said. "The bacterium causing the Black Death and the Justinianic one is the same bacterium, Y. pestis, and this was already reported on in previous studies. However, the strains of the bacteria -- you can also call them variations if you like -- causing the two pandemics were different, and the Justinianic strain is extinct today."
Old bones hold new clues
The researchers examined the skeletons of two Justinian plague victims. The remains were unearthed in 1966 among several hundred other skeletons in a large medieval cemetery in rural southern Germany.
"A communal burial indicates simultaneous death, or death close in time of those interred, and could therefore also indicate that an epidemic occurred," said Andreas Rott, a researcher at the State Collection of Anthropology and Palaeoanatomy in Munich, Germany, and a co-author of the study.
The teeth of the plague victims, a man and a woman, were analyzed and used to extract DNA samples. The researchers separated the human DNA from bacterial DNA in order to sequence the Y. pestis genome.
After analyzing the reconstructed genome, the researchers found clues that this ancient strain of Y. pestis might have had Chinese origins, which was also found in a 2014 study
from a separate research team.
Additionally, the new findings provide evidence that the Justinian plague hit rural Germany. "But more data is needed to determine the rate in which the disease had spread," Feldman said.
"How the pathogen reached southern Germany is at present unknown. Possibly, it traveled across the Alps from the Mediterranean or from France and western Germany. It could have also traveled up the Danube [River] from the east," Feldman said. "The exact trade routes that the disease traveled in are a subject of debate among scholars. It was transmitted either by people or by rats that were 'traveling' with cargo."
'Always good to have more ancient genomes'
Between 1,000 and 2,000 plague cases caused by Y. pestis are reported to the World Health Organization
each year, according to the Centers for Disease Control and Prevention
. The three most endemic countries are Madagascar
, the Democratic Republic of Congo and Peru.
In the United States, 15 people were infected
with the bubonic plague
last year, and about four of them died.
Antibiotics and antimicrobials are often used to treat the plague. However, with further research, many scientists think that the genomes of ancient pathogens could lead to improved treatments to eliminate plague-related deaths.
"I think it's interesting and always good to have more ancient genomes," said Hendrik Poinar, a molecular evolutionary geneticist and biological anthropologist at McMaster University in Canada, who was not involved in the new study.
More genomes could allow scientists to better detect any small changes in the evolution of a pathogen that may affect how quickly it can spread and cause disease, Poinar said. "Those sorts of things are critical for understanding eradication in currently plague-hit areas, such as Madagascar."