Health and Wellness 8 min read

Evolutionary ‘Volume Knob’: Scientists Discover the Genetic Mechanism Behind the Plague’s Centuries-Long Persistence and Eventual Extinction

Published on September 20, 2026

To see if these historical patterns are still relevant today, the researchers turned to the vast collection of modern Y. pestis isolates housed at the Institut Pasteur. Javier Pizarro-Cerdá, co-senior author and director of the Yersinia Research Unit and the WHO Collaborating Centre for Plague at the Institut Pasteur, noted the difficulty of the task.

"Thanks to our international collaborators who monitor local epidemics of plague worldwide, we were able to find the unique bacterial samples used for this project, akin to finding of three rare needles in a haystack," Pizarro-Cerdá says.

Among the thousands of modern samples, the team identified three contemporary strains from Vietnam that exhibited the same pla depletion seen in the dying days of the ancient pandemics. This discovery provided a rare opportunity to test ancient theories on living bacteria.

Guillem Mas Fiol, a postdoctoral researcher at the Institut Pasteur and co-lead author of the study, emphasized the importance of this bridge between the past and present. "One of the most interesting aspects of our research was the possibility to explore a feature first observed in extinct plague strains, that could, for the first time, be experimentally tested in living contemporary bacterial strains," he says.

Despite the fascinating discovery of these lower-virulence strains, the researchers issued a stark reminder that the plague remains a formidable foe. While the Vietnamese samples show that the bacterium is still capable of "turning down the volume" on its lethality, the majority of the world’s current plague reservoirs do not share this trait.

"Although our research sheds light on an interesting pattern in the evolutionary history of plague, the majority of strains which continue to circulate today in Africa, South America and India are the more virulent ones," says Ravneet Sidhu, a PhD candidate at the McMaster Ancient DNA Centre and co-lead author. "These are the ones that were previously responsible for massive mortality."

The study concludes that the history of the plague is not a straight line of increasing or decreasing lethality, but rather a complex dance between a pathogen and its hosts. By understanding the genetic "switches" like the pla gene, scientists can better predict how modern pathogens might evolve as they move through human and animal populations. The persistence of the plague for over 1,500 years serves as a testament to the bacterium’s adaptability—and a warning that even the most ancient of killers can still find ways to survive in the modern world.

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