Historical story

Immune system changes under pressure from epidemics

In the fourteenth century, Europe was ravaged by epidemics. Mihai Netea, researcher at Radboud UMC, discovered that this has left its mark in the DNA. Certain immune genes in Europeans and Roma gypsies have changed under the influence of the epidemics. But in people from Northwest India, where the Roma originated, the genes remained the same.

About a thousand years ago, the Roma gypsies migrated from northwestern India to Europe. They settled mainly in the southern countries and have since formed a separate population group there. Mihai Netea conducted his research among Romanians of European descent and Roma living in Romania but originally from India. “This is a special demographic situation that you don't easily find elsewhere,” he explains. “Two population groups live in the same region, but due to historical and social circumstances there has been little mixing. Although they have been living together for a thousand years, Romanians and Roma are genetically very different.”

High pressure

Netea and his colleagues from Groningen, Spain and Romania collected DNA from 100 Romanians, 100 Roma and 500 inhabitants of northwest India. “We found twenty genes in that DNA that have changed in both Romanians and Roma, but have remained the same in Indians. Three of those genes code for Toll-like receptors, receptors that play an important role in the defense against various bacteria, including the plague bacteria.”

Plague epidemics have probably put selection pressure on these genes. Netea:“Between 1300 and 1400, various plague epidemics raged in Europe. 25 to 35 percent of the population died. Only people with the right genes survived. There has also been a plague outbreak in India, but it came much later (around 1800) and 'only' 5 percent of the population died." In Europe there was much more pressure on the genes of the immune system to change than in India.

New medicines

We still benefit from the fact that the infection pressure in Europe has been so high, Netea thinks. “Europeans have become more resistant to it. You saw this, for example, when Europeans moved to America. In America many peoples lived in isolation and they were therefore much more susceptible to infections. The Europeans brought with them 'ordinary' infectious diseases, which they themselves were hardly bothered by. But among the isolated American peoples, for example the Native Americans, millions were killed.”

With this type of research, Netea and colleagues are trying to discover which factors play an important role in the defense against disease. And that can lead to the discovery of new drugs or treatments. Netea gives an example:“Under the influence of past epidemics, Europeans developed a variant of the CCR5 protein that makes them slightly more resistant to HIV. By blocking that protein, a new drug against HIV has been discovered.”

Look objectively

Unfortunately, the strong immune system of Europeans does not only have advantages. In Europe, autoimmune diseases, diseases in which the immune system attacks your own cells, are more common than in other areas. “That is the case if you only look at the numbers,” says Netea. But that's not entirely fair, he says. “Life expectancy is high in Europe, so there is more time to develop an autoimmune disease. If Africans lived to the same age as Europeans, I think you would see more autoimmune diseases there too.”

In order to gain more insight into these kinds of matters, Netea's research continues. In Romania and India, but also in Africa, for example. “We are now in contact with colleagues from Sudan and Tanzania, where situations exist that are comparable to Europeans and Roma. We want to expand the research. Now we've looked specifically at the immune system, but we're collecting the entire DNA. So soon we want to look very objectively at that DNA and determine which parts are under evolutionary pressure.”