Melanie Karniewich ’25
When the human body reacts to something foreign, the immune response will likely ensure that the human body is unharmed. For example, when receiving a vaccine, the body remembers the virus being injected and will know how to fight it off the next time. A recent study identified traces of immune genes associated with the Black Death from the 1300s in current genetic makeup through comparison of variations from before and after the Black Death pandemic. Researchers from various institutions posed the hypothesis that past pandemics caused evolution in immune response genes—natural selection within the population—that may reduce susceptibility to subsequent outbreaks.
The researchers obtained information from NCBI Sequence Read Archive for the immune genes from two sources, 318 people from London and 198 people from Denmark who died from the Black Death. Samples collected were all from the time before, during, and after the Black Death was there; the researchers found 245 variations between the pre- and post-pandemic samples (only from London). If the scientists were to assume that these gene variants result in greater immunity to Yersinia pestis (the bacteria responsible for the Black Death), it would not be as widespread as among those who died from the pandemic in London but more widespread in subsequent generations, consistent with hypothesis of becoming more immune over time. Therefore, they continued to look for genes that followed the specific pattern related to immunity. They found 35 of these variations and then compared these to the Denmark group, which had four variations. When compared to 206 ancient immune-related genes, the test subjects’ genes had similarities in their DNA, which indicates increased immunity to present-day diseases. This also is suggestive of a higher risk for those with the protective allele to be affected by autoimmune diseases like Crohn’s disease (protein ERAP2). Specifically, the researchers suggest that those with the protective allele are about 40% more likely to survive the Black Death, but because the ERAP2 protein is present in the protection allele, there is also an increased risk of autoimmune disease.
The researchers observed positive selection conferring greater immunity to the Black Death in post-pandemic DNA samples, possibly suggesting a broader impact of past pandemics on our genetic makeup. The researchers also believe that this is only one proven example among pandemics that have possibly influenced human immune responses, which could be further investigated in future studies.
 J. Klunk, T.P. Vilgalys, C.E. Demeure, et al., Evolution of immune genes is associated with the Black Death. Nature 611, 312-319 (2022). Doi: doi.org/10.1038/s41586-022-05349-x