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The Black Death Sequencing Study Helps to Understand the Evolutionary Origins of Autoimmune Disease

TAIPEI, TAIWAN, Oct.31, 2022 - Scientists at the University of Chicago, McMaster University in Ontario and the Pasteur Institute in Paris discovered genetic traits that determined who survived the Black Death in the 14th century but are today associated with increased susceptibility to some autoimmune diseases. Their finding has been published in the journal Nature. It shows people with ERAP2 variants survived the 14th-century plague at much higher rates but raises the frequency of mutations detrimental in modern times.

The Black Death is the deadliest pandemic recorded in human history. It killed nearly 30% to 50% of people in Europe, the Middle East, and Africa. For a long period of time, scientists have been eager to find any clues in the genomes of survivors. Genomic technologies for analyzing ancient DNA have made it possible to research the legacies of pathogens in the genomes of people who died long ago.

For the study, more than 500 ancient DNA samples were collected from London and Denmark. The samples came from people who had either died before the plague, died from it or survived the Black Death. The team used targeted enrichment capture sequencing to profile 365 immune-related genes and nearly 500 sites linked to immune conditions in prior GWAS.

They found people who had two copies of the "good" ERAP2 gene had the ability to produce functional proteins—molecules that help the immune system recognize an infection. They also found that some of the same genetic variants identified as protective against the plague are associated with certain autoimmune disorders, such as Crohn’s disease, rheumatoid arthritis and lupus. In these diseases, the immune system that defends the body against disease and infection attacks the body’s own healthy tissues.

Our genome today is a reflection of our whole evolutionary history. Studies of ancient DNA could help a better understanding of the evolutionary origins of autoimmune disease. It will give us a new point of view on the risk of such diseases when a given population happens to carry specific disease-associated variants.


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