Bubonic Plague Family Tree Sheds Light on the Risk of New Outbreaks

The Black Death and the Justinian Plague arose separately from the same pathogen. Could a new strain emerge in the future?

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A scientist examines a 1500-year-old tooth from a Justinian plague victim in the lab. Image: McMaster University

Meet the Plague of Justinian, the Black Death’s older, but equally fatal cousin. Arriving in Constantinople around 540 AD, it killed up to 100 million people, contributed to the fall of the Roman Empire, and lingered for two centuries. And then it disappeared. 

In a paper published yesterday in The Lancet Infectious Diseases, scientists have reconstructed the genome of this ancient pathogen for the first time. The Black Death and the Justinian plague each emerged separately from the same fatal bacterium, Yersinia pestis

Because of their similar symptoms, scientists have always linked the earlier plague with the Black Death, but they have never determined conclusively how the two pandemics were related. Some studies have even suggested that the Justinian plague was a flu virus. 

Part of the difficulty in pinning down the first plague's origin is that finding remains of people who died of the Justinian plague can be quite difficult—while scientists could turn to the meticulous government property records of the locations of mass gravesites of Black Death victims, no such records exist for the prior plague. Undeterred, Dave Wagner, a biologist and Northern Arizona University and a coauthor of the paper, worked with colleagues including German archaeologists and found fragments of Y. pestis in human remains from a 6th century cemetery in Bavaria, Germany. 

Modern plague strains trace their lineage to the Black Death, so the scientists wondered, is the Justinian Plague the same bug? 

Bubonic Plague Family Tree Sheds Light on the Risk of New Outbreaks
Scientists analyzed teeth from two sets of remains from this grave site in a Bavarian cemetery. Image: M. Harbeck / University of Munich

To find out how this Justinian strain fits in to the plague family tree, they needed the whole genome. “We can use [DNA sequencing] techniques to travel deeper and deeper in time to reveal the genomes of ancient pathogens,” says Hendrik Poinar, an evolutionary geneticist at McMaster University in Canada and another co-author.  "If the Black Death and the Justinian are related," he says, "are these separate emergences or is there something inherent in the physiology of the bug that allows it to re-emerge?"

Poinar's lab analyzed teeth from two Bavarian corpses buried around 504 AD and 533 AD. In ancient skeletal remains, the best place to find genetic evidence of the pathogen that killed the person is in their teeth. “A tooth is like a safe,” says Poinar. But not an impermeable safe; teeth also contain symbiotic bacteria, soil fungi, other pathogens, and the individual’s own DNA. So the researchers removed the crown, ground up the tooth pulp, and searched for fragments of the ancient plague genome amid the gunk.

Luckily, they retrieved enough fragments to piece together the whole genome of the pathogen responsibile for the Justinian Plague. Then, they compared that reconstructed genome with the Black Death and modern strains. 

Bubonic Plague Family Tree Sheds Light on the Risk of New Outbreaks
Scientists analyzed this ancient tooth from the remains of a Justinian plague victim unearthed in Germany looking for plague DNA. Image: McMaster University

Their findings revealed that, though it emerged first, the Justinian Plague died out and is only a distant cousin to the Black Death and the strains the later pandemic birthed. The Justinian Plague is most closely related to two strains long known to have persisted in Chinese rodent populations, suggesting that like the Black death it originated in Asia and traveled to Europe likely via the busiest trade route, the Silk Road. But for some reason the Black Death was much more successful in that it survived and continued to spread. Based on the researchers' lineage analyses and previous studies, it jumped from Europe to the Mediterranean and Africa before retracing its steps back to China. 

And there it spawned a third pandemic—rats helped to spread this form of plague around the globe via human shipping routes, which is where we get the modern strains that occassionaly infect people today. 

Francois Balloux, a geneticist at University College London, notes that it's not that rare for a two strains to appear on the same "clade" or branch of a pathogen family tree, but what makes one strain more likely to linger through time while another dies out is an interesting question. "There’s no clear obvious candidate of what mutations could make a strain more successful or more virulent," says Balloux. Wagner and Poinar looked for genes that might instill increased virulence, but didn't come up with any major contenders. 

Environmental factors may play a role in determining the lifecycle of a plague, as rainfall tends to have a significant affect on rodent populations. The authors note that climate may have influenced the boom and bust of the Justinian plague. Heavy rain seasons preceeded all three plague pandemics, and by each plague's end, climate had stabilized. But, without evidence to suggest that climate shifts were more severe at the end of the Justinian plague, environmental factors alone can't adequately explain why the strain vanished. 

Wagner also points out that human movement increased between each pandemic. By the time of the third pandemic, steamboat technology allowed humans to travel the globe, which is exactly how modern strains arrived in Madagascar, where nonnative rat populations are more widespread. In the US, low levels of plague do still cycle through native rodent populations, a relic of that third pandemic. But the US Centers for Disease Control and Prevention routinely screens prairie dogs and other rodents in the southwest in case anything out of the ordinary emerges.

The fact that the two ancient plagues emerged separately over time means a new form of plague could arise in the future. "It is worrying," says Balloux. With modern travel, a new strain of plague might find it much easier to hop around the globe. But the last hundred years has seen improvements in hygiene, availability of antibiotics, and decreases in urban rat populations.

“Could there be another pandemic? Certainly,” says Wagner. “But, we don’t think those conditions are ripe in too many places in the world.” So, we're not in for Monthy Python scenario anytime soon. 

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