Scientists have warned that a strain of the bubonic plague which could be as deadly as the Black Death could return without notice.
Researchers examined the Plague of Justinian, which struck in the sixth century and is estimated to have killed between 30 and 50 million people - virtually half the world's population - and the Black Death, which hit around 800 years later and killed 50 million people across Europe in just 14 years.
The study, which examined DNA fragments from the teeth of two 1,500-year-old victims of the Justinian plague, found that the plague was brought on by a different strain to that which caused the Black Death.
The Justinian strain died off and vanished from the earth. However, the strain which resulted in the spread of the Black Death rose again and caused another plague in the 1800s
Scientists now say the study suggests another plague similar to the Black Death could return to earth in the future. Both the Justinian and Black Death diseases were caused by the Yersinia Pestis bug, which can be spread by fleas from rats to humans.
Northern Arizona University's Dr Dave Wagner 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.
"If the Justinian plague could erupt in the human population, cause a massive pandemic, and then die out, it suggests it could happen again.
"Fortunately we now have antibiotics that could be used to effectively treat plague, which lessens the chances of another large-scale human pandemic."
The study, published in the journal The Lancet Infectious Diseases, described the strain responsible for the Justinian plague an evolutionary "dead end" having disappeared completely off the earth having spread across Asia, North Africa, Arabia and Europe.
It is also said to have helped bring an end to the Roman Empire.
The plague that emerged in the 19th century pandemic, which spread across the globe from Hong Kong, was likely to be descendant of the more successful Black Death strain.
Hendrik Poinar, associate professor and director of the McMaster Ancient DNA Centre, said: "The research is both fascinating and perplexing, it generates new questions which need to be explored, for example why did this pandemic, which killed somewhere between 50 and 100 million people die out?"
The scientists said human responses to modern infectious diseases is a direct outcome of lessons learned from previous pandemics.
Edward Holmes, an NHMRC Australia Fellow at the University of Sydney said: "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."
"Another possibility is that changes in the climate became less suitable for the plague bacterium to survive in the wild," added Wagner.