How did the plague play (and continue to play) an important role in human evolution?

At the height of the pandemic, the plague decimated half the population of Europe. As DNA analysis of medieval plague victims and their lucky survivors has shown, the terrible pandemic of that time continues to affect modern humans today. Moreover, this is not because the Black Death pathogen is still active and poses a terrible threat. It is because the deadly epidemic that killed at least one-third of the population of medieval Europe triggered processes in our immune systems that continue hundreds of years later. Moreover, these changes are not always beneficial in the long run. Although the genes that have evolved in us since then increase our resistance to the plague, scientists have found that they are also associated with an increased risk of autoimmune diseases such as Crohn’s disease or rheumatoid arthritis. Thus, pandemics of the past may unexpectedly affect future generations.

The plague epidemic, which peaked in the mid-14th century, can rightly be considered one of the darkest episodes in human history. The Black Death killed tens, if not hundreds, of millions of people in Europe, Asia, and Africa. The bacterium Yersinia pestis causes the plague, which was transmitted to humans by fleas, and rats were thought to be the carriers of these plague-infected fleas. Rats were considered to be the main culprits of the epidemic, when in fact they were only the primary means of transmission, and after that the disease began to spread from person to person without the help of rats. There were no cures for the plague at the time, and it is doubtful that anything could have been done, as sometimes less than a day passed between the onset of symptoms and death.

Serious infectious diseases such as the plague serve as one of the most powerful forces of natural selection, especially in humans. For example, sickle cell anemia (an inherited genetic abnormality in which red blood cells are crescent-shaped) is an unpleasant disease in itself, but it also provides some protection against an even more serious disease – malaria. It turns out that people with sickle cell anemia have a better chance of surviving a malaria infection and having their own children who inherit the genetic disorder, along with better protection against malaria. Thus, over time, in areas where malaria epidemics are common, there will be an increased population with this DNA abnormality. In this case, an international team of researchers led by geneticists Jennifer Clance of McMaster University in Canada and Tauras Vilgalis of the University of Chicago (the results of their research were published in the journal Nature) decided to understand exactly how the plague affected the human genome.

According to researchers, many DNA samples from plague burials were heavily contaminated. We explain quickly, simply, and clearly what happened, why it matters, and what happens next. The number of offers should remain: episodes. End of story. Podcast advertising. “When a pandemic of this magnitude occurs, killing 30% to 50% of the population, people are inevitably selected for protective alleles (different forms of the same gene). People who are more susceptible to the circulating pathogen will die,” explains Hendrik Poinar, an evolutionary geneticist at McMaster University. “Even a small advantage can mean the difference between life and death. And those who survive and are of reproductive age will pass on their genes through inheritance.” Because the plague was so widespread that the dead had to be buried in mass graves (and the locations of these burials are well known), scientists have never been short of material to study the remains. Researchers have focused their attention on a century-long period that includes the time before the epidemic, its active phase, and some time after its end.

Burial in a plague cemetery in London. A total of one hundred human DNA samples were selected from individuals who died in London and various regions of Denmark. They were divided into three groups: those who died before the epidemic (their remains were buried in one of London’s mass graves), those who died during the epidemic, and those who survived the epidemic but later died of other causes. According to geneticist Luis Barreiro of the University of Chicago, who was also involved in the project, the DNA samples were of poor quality and heavily contaminated with inclusions of other DNA fragments. So the scientists focused on small regions of the genome, identifying a total of about 350 specific genes previously known to be associated with the immune system. From these genes, they then identified 350 variations that were prevalent in Londoners after the epidemic. After comparing the genomes of medieval Europeans, scientists identified four plague-related genes whose selection and fixation occurred at a rate unprecedented in human history before and after the Black Death epidemic. These genes were responsible for producing proteins that protected the body from pathogen invasion, and people with one or more of these genetic variants appeared to have a greater chance of surviving the plague.

To confirm their theories about medieval DNA, the scientists grew colonies of human cells with different genetic profiles under laboratory conditions and then infected them with Yersinia pestis, the bacterium that causes the plague. The experiment confirmed that previously identified genes reappeared in the most disease-resistant colonies. Specifically, the experiment showed that people with two identical copies of the ERAP2 gene had a 40-50% greater chance of surviving a plague infection than those with a different paired allele. Time passed, epidemics of the plague occurred several times, but they gradually weakened, and humanity moved on, unaware that its genome contained both a panacea for the plague bacterium and a slow-acting mine. The thing is, some of the genetic variations that saved our ancestors from the plague are now associated with an increased risk of autoimmune disease. In the Middle Ages, it was a matter of survival, and our genome set genetic priorities “without any thought or consultation with us. “Perhaps this risk [of developing autoimmune disease] did not play a significant role during the years of the plague epidemic,” David Enard, an associate professor in the Department of Ecology and Evolutionary Biology at the University of Arizona who was not involved in the study, wrote in a commentary on the new research. “The urgency of the survival problem essentially made such a trade inevitable.” According to him, similar “deals that our genome made” most likely took place during other epidemics, so traces of them can still be found in the genome of modern humans.