I am part of the 5-10% of the population that are affected by autoimmune disease, but that just means that I'm surviving the plague and you're not.
Autoimmune conditions occur when the body's immune system mistakenly attacks the body; this is because when the hyperactive immune system is not exposed to pathogens, it begins attacking the body's own tissues (Cleveland Clinic). What if I told you that having an autoimmune disease is a survival adaptation to the Bubonic Plague?
The black plague acted as a bottleneck natural selection effect. In a 2022 study, DNA was taken from individuals who died shortly before, during, and after the plague from cemeteries in London and Denmark. The ERAP2 gene was identified to have a protective allele mutation in individuals who died in the later months/after the plague- homozygous individuals for the allele were roughly 40% more likely to survive the plague than those who were not (Klunk et al., 2022). This positive adaptation came with the consequence of selection of overactive immune systems: great for fighting off the bubonic plague, but kind of terrible the rest of the time. The ERAP2 gene is vital in producing & regulating immune responses against pathogens, however, following the lineage of the mutant variant has directed researchers to higher susceptibility to autoimmune disease & chronic inflammatory conditions (Klunk et., 2022).
What I take away from this is that my immune system might overreact to everything, but if history repeats itself, im surviving the plague and you're...not.
Cleveland Clinic. Autoimmune diseases. Cleveland Clinic Health Library. Updated October 22, 2024. Accessed December 1, 2025. https://my.clevelandclinic.org/health/diseases/21624-autoimmune-diseases
Klunk, J., Vilgalys, T. P., Demeure, C. E., Cheng, X., Shiratori, M., Madej, J., Beau, R., Elli, D., Patino, M. I., Redfern, R., DeWitte, S. N., Gamble, J. A., Boldsen, J. L., Carmichael, A., Varlik, N., Eaton, K., Grenier, J. C., Golding, G. B., Devault, A., Rouillard, J. M., … Barreiro, L. B. (2022). Evolution of immune genes is associated with the Black Death. Nature, 611(7935), 312–319. https://doi.org/10.1038/s41586-022-05349-x
What a beautiful, phenomenal, insightful post Sophia, your wit and intelligence never fail to amaze me. What a cool trade off you've written about! It reminds me of some of the evolutionary trade-offs we studied way back in Gen Bio II such as offspring quantity / litter size vs. parental investment, specialization vs generalization, and reproductive activity vs lifespan in fruit flies. My question for you - is your trade-off worth it? One one hand, it seems having to deal with autoimmune flare-ups would be an inconvenience, especially in the modern world in which it seems unlikely that a plague-level pathogen would come rolling around anytime soon. On the other hand, according to the CDC, there are actually a handful cases of the plague in humans every year in the southwestern US (even some fairly recently in Colorado!) so perhaps your evolutionary advantage will prove itself use in the near future! #spooky
ReplyDeleteWho would have thought an autoimmune disease would be an adaption from the plague. For the presence of ERAP2 gene I wonder based off the levels of expression if it can play any factor in the severity of a autoimmune disease. In relation to that does that gene have a association to certain types of autoimmune disorders?
ReplyDeleteThis is a super cool fun fact I never would've thought to look up... let alone research! One question that comes to my mind is if there is a correlation between ERAP2 and specific diseases/conditions, or if the enhancing effect applies to any and all diseases/conditions. (is there a "link" between anything or is there just an overarching effect?) Also, was the ERAP2 gene a result of those who did survive the plague, or was it present before and just helped carriers have a better rate of survival.
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