Plague Gene Evolution: How One Mutation Fueled Centuries of Death
Uncover the evolution of the bubonic plague and how a single gene mutation shaped centuries of death. This study explores the role of the pla gene, revealing its impact on the plague’s virulence and persistence throughout history’s deadliest pandemics. Researchers discovered that fewer pla gene copies correlated with longer infections, impacting mortality rates and transmission. This investigation into ancient and modern strains delivers critical insights for global health. News Directory 3 highlights the study’s findings, underscoring the importance of understanding pathogen evolution. Discover what future research reveals about the plague’s long-term threat.
Plague’s Path: Gene Changes Impact Virulence and Persistence
Updated May 30, 2025
A new study published in Science sheds light on how the bubonic plague bacterium, Yersinia pestis, adapted over centuries. Researchers from McMaster University and France’s Institut Pasteur examined how a single gene influenced the plague’s virulence and its ability to persist, offering insights into pandemic evolution and the plague’s persistence.
The Black Death, caused by the same bacteria as the Plague of Justinian, remains history’s deadliest pandemic, killing 30 to 50 percent of Europe, Western Asia, and Africa’s populations. While the third plague pandemic, originating in China in 1855, is now controlled by antibiotics, cases still occur in regions like Madagascar and the Democratic Republic of Congo. Understanding plague virulence and persistence is crucial for global health.
Hendrik Poinar,co-senior author and director of the McMaster Ancient DNA Center,said this research directly examines changes in an ancient pathogen to understand what drives the virulence,persistence,and extinction of pandemics. The study focuses on the pla gene, a high copy component of Y. Pestis, which aids the bacterium in evading the immune system and spreading through the body.
Genetic analysis revealed that the number of copies of the pla gene decreased in later outbreaks, reducing mortality by 20 percent and extending the infection period in mice models. Conversely, a high copy number of the pla gene resulted in a more virulent disease that killed hosts more quickly. Scientists found a striking similarity between modern and ancient strains, with autonomous evolution leading to similar reductions in pla in later stages of the first and second pandemics.
Researchers propose that when the gene copy number dropped and infected rats lived longer, they could spread the infection farther, ensuring the pathogen’s reproductive success. Poinar suggests that the reduction of pla may reflect changes in rodent and human population sizes and densities. Black rats in cities likely acted as “amplification hosts,” maintaining high pathogen levels due to their susceptibility to Y. pestis and proximity to humans.
“The reduction of pla may reflect the changing size and density of rodent and human populations,” Poinar said.
Despite the advantage of extended infection, the pla-reduced strains eventually went extinct, indicating further shifts in the host-pathogen relationship.The team identified three contemporary strains with pla depletion in samples from the third pandemic, preserved at the Institut Pasteur.
Javier Pizarro-Cerdá, co-senior author and director of the yersinia Research Unit at the Institut Pasteur, emphasized the importance of international collaboration in finding these unique bacterial samples. Guillem Mas fiol, co-lead author, noted the opportunity to experimentally test a feature first observed in extinct plague strains in living contemporary bacterial strains.
Ravneet Sidhu, co-lead author, cautioned that most strains circulating today in Africa, South America, and India remain highly virulent, responsible for massive mortality.
What’s next
Further research will focus on understanding the factors that led to the extinction of the less virulent strains and the implications for current plague outbreaks, particularly in regions were the disease remains a persistent threat. Monitoring plague virulence and persistence remains crucial for global health security.