Using Paleogenomics to Elucidate 10,000 Years of Immune System Evolution

Published:10 Mar.2023 Source:Institut Pasteur

In the study led by the Institut Pasteur, published on January 13 in the journal Cell Genomics, the scientists analyzed the variability of the genomes of more than 2,800 individuals who lived in Europe over the past ten millennia -- a period covering the Neolithic, the Bronze Age, the Iron Age, the Middle Ages and the present. By reconstituting the evolution over time of hundreds of thousands of genetic mutations, the scientists initially identified mutations that rapidly increased in frequency in Europe, indicating that they were advantageous. These mutations that evolved under “positive” natural selection are mainly located in 89 genes enriched in functions relating to the innate immune response, including especially the OAS genes -- which are responsible for antiviral activity -- and the gene responsible for the ABO blood group system.

At the same time, the scientists also looked at the opposite situation, in other words, mutations whose frequency fell significantly over the past ten millennia. These mutations are probably subject to “negative” selection because they increase the risk of disease. Finally, the scientists explored the theory that the selection exerted by pathogens in the past gave an advantage to alleles conferring resistance to infectious diseases, but that in turn these alleles have increased the present-day risk of autoimmune or inflammatory disorders. By looking at the evolution of these mutations over time, they observed that those associated with an increased risk of inflammatory disorders -- including Crohn’s disease -- became more frequent over the past 10,000 years, while the frequency of those associated with a risk of developing infectious diseases decreased.