Study Traces 10,000 Years of Human Immune System Evolution

Scientists from the Institut Pasteur, Université Paris Cité, the CNRS, and the Collège de France have used paleogenomics to trace the evolution of the human immune system over the past 10,000 years. By analyzing the genomes of more than 2,800 individuals who lived in Europe over the past ten millennia, the team was able to date the increase in frequency of most of the mutations that are advantageous in defending against pathogens to after the Bronze Age, 4,500 years ago.

In the 1950s, the geneticist J.B.S. Haldane attributed the maintenance or persistence of the mutation responsible for anomalies in red blood cells commonly observed in Africa to the protection these anomalies provided against malaria, an endemic infection claiming millions of lives. This theory suggests that pathogens are among humans' strongest selective pressures.

The scientists explained the "acceleration" in adaptation by the growth in the human population during this period and/or by strong selective pressures exerted by pathogens in the Bronze Age, probably linked to the spread of severe infectious diseases such as plague.

At the same time, the scientists also looked at the opposite situation: mutations whose frequency fell significantly over the past ten millennia. These mutations are likely subject to "negative" selection since they increase the disease risk. The team noted that, once again, these selection events mainly began in the Bronze Age.

Many of these disadvantageous mutations were also located in genes associated with the innate immune response, such as TYK2, LPB, TLR3 and IL23R, and have been confirmed in experimental research to have a deleterious effect in terms of infectious disease risk.

The results, published in the journal Cell Genomics, emphasize the value of adopting an evolutionary approach in research on genetic susceptibility to diseases and the identification of therapeutic targets. By understanding the history of our immune system, scientists can gain insight into the origins of disease and develop new treatments.