Do you suffer from an autoimmune disease? Chances are the origins lie in the Black Death, the pandemic that wiped out more than half of all Europeans in the Middle Ages.
In the Middle Ages, the Black Death (now known as the Bubonic Plague) killed tens of millions of victims in Europe and Asia – then half the population – in five years. Only people with a good immune system had a chance of surviving the disease. Now it turns out that this selection pressure — the effect of natural selection — was so great that we are still experiencing its effects even today, say researchers at the University of Chicago and McMaster University. Nature.
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Undetected attack
The bubonic plague is caused by the bacteria Yersinia pestis. It can attack the body without the immune system noticing – until it’s too late. Yet there are people whose immune system recognizes the pathogen well and catches it in time. The researchers wanted to find out why.
The team, led by Luis Barreiro, analyzed DNA samples from a total of more than 200 human remains from graves in London and Denmark. Among them were people who died before the pandemic, victims of the plague (see photo above this article) and survivors of the disease, who only died in the period after.
Good luck and bad luck
The researchers focused on a set of three hundred genes involved in the immune system, such as the gene ERAP2. There are two different variants of this: if you owned the variant rs2549794 in the Middle Ages, you were lucky. This variant provides an active ERAP2 protein that sits on the outside of a macrophage, a large immune cell. Thanks to the protein, the macrophage can easily find and eliminate the plague bacteria.
The proud owners of the gene variant mentioned were about 40 percent more likely to survive the bubonic plague. The other variant of the ERAP2 gene leads to a non-functional ERAP2 protein. You were unlucky with that.
Hyperactive immune system
Many carriers of the rs2549794 variant thus survived the Black Death. As a result, the gene variant appeared in more and more people in subsequent generations, and it is still the most common variant today. Unfortunately, a well-functioning ERAP2 protein increases the chance that you will get an autoimmune disease, in which immune cells attack your own body; an example is Crohn’s disease. This is because the protein makes the immune system hyperactive. During the Middle Ages this was an advantage, now it is just playing tricks on us.
It is possible that even more gene variants have emerged due to the selection pressure of infectious diseases in the past. They can still leave a mark on our health today. This could have been positive (better control of pathogens) or negative (leading to autoimmune diseases). The next project of Barreiro and colleagues is therefore to screen the entire package of immunity genes of people from the Middle Ages and compare it with the same genes of modern people.
Immunologist Tom Ottenhoff of the Leiden University Medical Center speaks of a wonderful study. “The findings demonstrate that high-mortality infections likely had a significant impact on the natural selection of the most genetically protected individuals in the population. And thus on the genetic makeup of the people who survived this epidemic. Also the downside of this, the increased risk of autoimmune diseases, comes out well.”
Bronnen: Nature, University of Chicago Medical Center via EurekAlert!, McMaster University via EurekAlert!
Beeld: Museum of London Archaeology (MOLA)