The Grapevine

Bubonic Plague Wasn't Always So Deadly: The Mutation That Made The Disease So Lethal

Death
If it weren't for two little mutations, the plague would look very different. Pixabay public domain

High school history books often have an entire chapter devoted to the Black Death, the then-mysterious plague that swept across Europe in the 14th Century. Thanks to modern scientists and historians, we now know that the cause of the devastation was most likely bubonic plague, a bacterial infection caused by Yersinia pestis. Researchers believed they had a reasonable handle on how the plague spread across the world, when it first manifested, and how it was contagious. New evidence has emerged, though, and it revealed that plague has been around for more than twice as long as previously thought, and that it wasn’t always transferred through rats — it was predominantly spread by human-to-human contact.

A Dangerous Mutation

The research revealed that a genetic mutation allowed Y. pestis to survive in the gut of fleas, and it may have happened sometime around the 1st millennium BC. Scientists got a hold of 101 adults dating from the Bronze Age, found across Eurasia, and analyzed DNA extracted from their teeth. Seven of the subjects had Y. pestis bacteria in their DNA, and the oldest one had died 5,783 years ago — previously, molecular evidence of the bacteria had not been obtained from skeletal material older than 1,500 years.

Six of the sampled were also missing two key genetic factors found in modern strains of plague. Researchers discovered that a “virulence gene” called ymt and a mutation in an “activator gene” called pla were both missing from the samples. The ymt gene keeps bacteria from being destroyed by the toxins in flea guts and also causes the flea to starve and frantically bite anything it can get a hold of, spreading the plague. The pla mutation allows Y. pestis to spread across tissues, so a localized lung infection of pneumonic plague can infect the blood and lymph nodes.

The team concluded that without these genetic components, the earliest strains of plague couldn’t have been carried by fleas, or cause bubonic plague. This meant that the early plague was transferred between humans, and was mainly manifested in the lungs.

A Perfect Storm

This ancient plague strain was significantly less deadly than the one that ripped through Europe a couple thousand years later, but with just one mutation and the perfect conditions, Y. pestis became a much more dangerous bacteria.

“Among our samples, the mutated plague strain is first observed in Armenia in 951 BC, yet it is absent in the next most recent sample from 1686 BC — suggesting bubonic strains evolve and become fixed in the late 2nd and very early 1st millennium BC,” said Dr. Marta Mirazon-Lahr, from Cambridge’s Leverhulme Centre for Human Evolutionary Studies (LCHES) and co-author of the study in a press release.

Mirazon-Lahr did point out, though, that the 1686 BC sample was from the mountains near Mongolia, a significant distance from Armenia. It was possible that the plague had a longer history in the Middle East, and that it was the movement of people during the 1st millennium BC that exported it.

The right conditions were crucial for the plague to survive and spread the way it did.

“Every pathogen has a balance to maintain,” said co-author Professor Robert Foley, also from Cambridge’s LCHES. “If it kills a host before it can spread, it too reaches a ‘dead end.’ Highly lethal diseases require certain demographic intensity to sustain them.

Foley said that the early pneumonic plague was likely more adapted for the Bronze Age population, but as Eurasian societies grew more complex, trading routes and movement started to favor the deadlier form of plague.

“The Bronze Age is the edge of history, and ancient DNA is making what happened at this critical time more visible,” Foley said.

Study lead author Professor Eske Willerslev, added: “These results show that the ancient DNA has the potential not only to map our history and prehistory, but also discover how disease may have shaped it.”

Source: Rasmussen S, Allentoft M, Nielsen K, Orlando L, Sikora M, Sjogren K, et al. Early Divergent Strains of Yersinia pestis in Eurasia five thousand years ago. Cell. 2015.

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