The most devastating pandemic in history viciously attacked Europe, Asia and Africa almost 700 years ago. The Black Death (Yersinia pestis), which reached London in the mid-13th century, killed more than 50 percent of the population in some of the most populous areas of that time.
An international team of scientists has searched ancient DNA to learn how our ancestors adapted to the virulent disease. What they found is that there were key genetic differences that determined who lived and who died. The problem is that, centuries later, those same advantages have ended up being counterproductive.
Experts from McMaster University, the University of Chicago and the Pasteur Institute analyzed and identified these protective genes. But, as they explain in a study published in the journal Nature, these defenses against the Black Death are now associated with a greater vulnerability to autoimmune diseases such as Crohn's disease and rheumatoid arthritis.
The work focused on a 100-year window before, during and after the pandemic. More than 500 samples of ancient genetic code were extracted and analyzed from the remains of people in London who had died before, died of, or survived the plague, including remains buried in the East Smithfield pits used for mass burials between 1348 and 1349.
In addition, additional evidence from buried remains at five other locations in Denmark was analyzed, looking for signs of genetic adaptation to plague. They thus managed to identify four genes, all involved in the production of proteins that defend our systems from invading pathogens, and found that some versions of these genes, called alleles, protected humans or made them susceptible to the plague.
Individuals with two identical copies of a particular gene, known as ERAP2, came through the pandemic at much higher rates than those with the opposite set of copies. That is, the researchers say, because the "good" copies were able to more efficiently neutralize the Yersinia pestis bacterium.
“When a pandemic of this nature occurs, killing 30 to 50 percent of the population, there is likely to be selection for protective alleles, meaning that people who are susceptible to the circulating pathogen will succumb. This slight advantage makes the difference between surviving or dying. And survivors who are of reproductive age will be able to pass on their genes,” explains evolutionary geneticist Hendrik Poinar of McMaster University.
Europeans living at the time of the Black Death were initially very vulnerable because they had not been exposed to Yersinia pestis in a long time. As waves of disease rolled on over several centuries, mortality rates decreased.
Specialists estimate that people with the ERAP2 protective allele were 40 to 50 percent more likely to survive than those without it. "This selective advantage is among the strongest ever detected in humans, demonstrating how a single pathogen can have such a strong impact on the evolution of the immune system," says geneticist Luis Barreiro of the University of Chicago.
Over time, our immune systems have evolved to respond in different ways to pathogens, to the point where what was once a protective gene against plague in the Middle Ages is now associated with autoimmune diseases, those in which the immune system becomes the aggressor, attacking and destroying the body's own healthy organs and tissues. “This is the balancing act on which evolution plays with our genome”, they conclude.
