Ancient DNA tests idea that allergies are due to our dirtier past

Immunity genes forged in a germ-filled past are often blamed for causing our bodies to overreact to harmless triggers like pollen or food. But the evolution is perhaps not so one-sided.

Some infection-fighting genetic variants that have spread over the past 10,000 years appear reduce the risk of asthma and other allergiesand not increase it, the researchers report April 14 in a preprint published on bioRxiv.org.

This finding challenges a long-held idea that modern allergies are simply the price we pay for an immune system adapted to a dirtier past. This idea is “too simplistic,” says Will Barrie, an evolutionary geneticist at the University of Cambridge in England, who was not involved in the research.

The hypothesis developed from observations that many genetic variants that help fight infection are also involved in autoimmune diseasesin which the immune system goes haywire and mistakenly attacks healthy tissues in the body. But determining when these variants increased in frequency — and thus whether protection against past infections actually came at the cost of higher autoimmune risk today — has been difficult without ancient DNA data sets spanning major transitions in human history.

Recently, these datasets have become large enough that researchers can confidently track genetic changes throughout the Stone Age, the Stone Age. rise of agriculture and subsequent periods. For example, a recent analysis of the human genome of 15,836 individuals who lived between 18,000 and 200 years ago identified hundreds of genetic variants shaped by natural selection after the transition to agriculture transformed people’s diets, environments and lifestyles.

Many of these changes were linked to immune function, reinforcing the idea that pathogens became dominant evolutionary forces as people evolved into denser societies, researchers report April 15 in Nature. But that study failed to show how these ancient immune adaptations shape disease risk today, leaving the hypothesis about past germs and modern allergies or asthma largely untested.

To probe this hypothesis, Harvard geneticist Javier Maravall López and his colleagues integrated the Nature the study’s ancient DNA datasets with modern genetic studies of disease risk. A clear trend in the data showed that humans retained and transmitted genetic variants that helped protect them from tuberculosis, influenza and intestinal pathogens and, as expected, these same variants also tended to increase the risk of developing immune-mediated diseases such as inflammatory bowel disease.

But rather than simply making the immune system more responsive overall, evolution appears to have tweaked different parts of it in different ways.

As researchers have discovered, many genetic changes that increased in frequency after the advent of agriculture appear to have strengthened the body’s first lines of defense, particularly in tissues that come into direct contact with microbes, such as the lungs and intestines, helping to block or clear infections more effectively. At the same time, some changes reduced the activity of signaling molecules closely linked to allergic inflammation, helping to curb excessive reactions to harmless substances.

Together, the authors say, these changes could help explain how, even in a world teeming with microbes, natural selection has favored genes that confer protection against infection while also reducing the risk of asthma and other allergic diseases. But this conclusion, and the research it is based on, has not yet been peer-reviewed. And Barrie offers another way to interpret the results.

It’s possible, he says, that in ancient hunter-gatherer populations, evolution rewarded rapid, aggressive immune responses to survive constant infections, even though those responses also increased the risk of harmful inflammation. Only later, as lifestyles and disease exposures changed with the rise of agriculture, were other adaptations able to temper some of these responses.

Older DNA from prehistory could help determine when these changes occurred and whether they occurred in distinct phases. But if Barrie’s hunch is correct, the new results might not show that evolution solved infection and allergy in one fell swoop. Instead, they could reflect successive series of compromiseswhich overlapped over time as environments changed, leaving today’s immune system a patchwork shaped by different eras.

From this perspective, Barrie says, “it’s not surprising that our immune system has not achieved the right balance in the modern environment.”