Study shows that Bubonic Plague had a long-term impact on immune gene expression

Researchers investigating the remains of 36 bubonic plague victims from a 16^th-century mass burial in Germany have discovered the first indication that evolutionary adaptation mechanisms triggered by the disease may have conferred immunity on subsequent generations from the region.

Image Credit: University of Colorado Anschutz Medical Campus

We found that innate immune markers increased in frequency in modern people from the town compared to plague victims. This suggests these markers might have evolved to resist the plague.”

Paul Norman, PhD, Study Joint-Senior Author and Associate Professor, Division of Biomedical Informatics & Personalized Medicine, University of Colorado School of Medicine

The research, conducted in collaboration with the Max Planck Institute in Germany, was published online recently in the journal Molecular Biology and Evolution.

The DNA samples were taken from the inner ear bones of those buried in a mass grave in Ellwangen, a southern German city that had bubonic plague epidemics in the 16^th and 17^th centuries. They then collected DNA samples from 50 present town residents.

They examined frequency spectra—the distribution of gene variations in a particular sample—for a wide panel of immune-related genes.

Immunity-relevant genes shed light

The researchers discovered evidence that a pathogen, most likely Yersinia pestis, which causes bubonic plague, caused changes in the allele distribution of two innate pattern-recognition receptors and four Human Leukocyte Antigen molecules, which help start and coordinate immune responses to infection. A variant version of a gene is referred to as an allele.

We propose that these frequency changes could have resulted from Y. pestis plague exposure during the 16th century.”

Paul Norman, PhD, Study Joint-Senior Author and Associate Professor, Division of Biomedical Informatics & Personalized Medicine, University of Colorado School of Medicine

The findings provide the first evidence that Y. pestis-induced evolutionary processes have been changing some human immunity-relevant genes in Ellwangen and perhaps throughout Europe for generations.

And, given that the plague haunted Europe for approximately 5,000 years, the study shows that these immunity genes were pre-selected in the population a long time ago but were just recently chosen via epidemic occurrences.

“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. 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,” the study notes.

“Survival of the fittest” underscored

Later simulations revealed that these allele frequency shifts were most likely caused by natural selection.

I think this study shows that we can focus on these same families of genes in looking at immunity in modern pandemics. We know these genes were heavily involved in driving resistance to infections.”

Paul Norman, PhD, Study Joint-Senior Author and Associate Professor, Division of Biomedical Informatics & Personalized Medicine, University of Colorado School of Medicine

The study also shows that, so far, no matter how lethal a pandemic is, there are always survivors.

“It sheds light on our own evolution. There will always be people who have some resistance. They just don’t get sick and die, and the human population bounces back,” said Norman.

Still, he does not want the incorrect message to be sent, especially in the Covid-19 time.

“I wouldn’t want to discourage anyone from taking a vaccine for the current pandemic. It’s a much safer bet than counting on your genes to save you,” concluded Norman.