Bubonic Plague Had Lasting Impact on Human Immunity Genes

Examination of the remains of 36 bubonic plague victims from a 16th century mass grave in Germany has revealed evidence that evolutionary adaptive processes, driven by the disease, may have conferred immunity on later generations of people from the region.

"We found that innate immune markers increased in frequency in modern people from the town compared to plague victims," said Paul Norman from the University of Colorado School of Medicine, joint-senior author of the study published today in Molecular Biology and Evolution.

The researchers collected DNA samples from the inner ear bones of individuals in the mass grave in Ellwangen, Germany. Then they took DNA samples from 50 current residents of the town. They compared their frequency spectra—the distribution of gene variants in a given sample—for a large panel of immunity-related genes.

Among the current inhabitants, the team found evidence that a pathogen, likely Yersinia pestis, which causes bubonic plague, prompted changes in the allele distribution for two innate pattern-recognition receptors and four Human Leukocyte Antigen molecules, which help initiate and direct immune response to infection.

"We propose that these frequency changes could have resulted from Y. pestis plague exposure during the 16th century," Norman said. The findings are the first evidence that evolutionary processes, prompted by Y. pestis, may have been shaping certain human immunity-relevant genes in Ellwangen and possibly throughout Europe for generations, Norman explained.

And since the plague tormented Europe for nearly 5,000 years, the study suggests that these immunity genes may have been pre-selected in the population long ago but recently became selected through epidemic events.

"Although the lethality of the plague is very high without treatment it remains likely that specific individuals are protected from, or more susceptible to, severe disease through polymorphism in the determinants of natural immunity," the study said. "In this case, any change in allele frequencies that occurred during a given epidemic crisis could be evident as genetic adaptation and detectable in modern day individuals."