Oldest pathogen genome reveals cause of devastating pandemics

Distinct versions of the same bacterial pathogen, Yersinia pestis, caused two of the world’s most devastating plagues, the Black Death and Plague of Justinian - each responsible for killing as many as half the people then in Europe.

The research, by an international collaboration of scientists including Australians, used miniscule DNA fragments from the 1500-year-old teeth of two victims of the Justinian plague, to produce the oldest pathogen genomes obtained.

“We discovered that the bacterium responsible for the Plague of Justinian, which jumped from rats to humans and killed many millions of people in the sixth century, faded out on its own,” said Professor Edward Holmes, from the University of Sydney’s School of Biological Sciences.

Professor Edward Holmes.

The findings give a new historical perspective on the plagues and could lead to a better understanding of the dynamics of modern infectious disease.

Little has been known about the origins or cause of the enigmatic Justinian Plague, which helped bring an end to the Roman Empire. It killed virtually half the world’s human population as it spread across Asia, North Africa, Arabia and Europe.

The samples came from plague victims who are believed to have died in the final stages of the epidemic when it reached southern Bavaria in Germany sometime between 541 and 543.

The scientists reconstructed the oldest pathogen genome ever obtained and compared it to a database of Y. pestis genomes of more than a hundred contemporary strains.

They found that the Justinian outbreak was an evolutionary ‘dead-end’ and distinct from strains involved in the Black Death and other plague pandemics.

A third pandemic, likely to be a descendant of the Black Death strain, started in Yunnan in China in 1855 and spread globally, killing more than 12 million people in China and India alone.

Dave Wagner, an associate professor in the Center for Microbial Genetics and Genomics at Northern Arizona University, said, “We know the bacterium Y. pestis has jumped from rodents into humans throughout history, and rodent reservoirs of plague still exist today in many parts of the world. Fortunately, we now have antibiotics that could be used to effectively treat plague, which lessens the chances of another large-scale human pandemic.”

Two unanswered questions remain: why was the Justinian Plague so remarkably virulent and what caused it to die out?

“This study raises intriguing questions about why a pathogen that was both so successful and so deadly died out. One testable possibility is that human populations evolved to become less susceptible,” said Professor Holmes.

The study was published in Lancet Infectious Disease.