How the “Black Death” Left Its Genetic Mark on Future Generations | eKathimerini.com

Many Europeans carry genetic mutations that protected their ancestors from bubonic plague, scientists reported Wednesday in the journal Nature.

When the Black Death swept Europe in 1348, the bacterial infection killed large swarms of humans across the continent and fueled the strongest pulse of natural selection ever measured in humans, the new study says.

It turned out that certain genetic variants made people much more likely to survive the plague. However, this protection came at a price: People who inherit the plague-resistant mutations are at higher risk for immune disorders such as Crohn’s disease.

“These are the unfortunate side effects of long-term selection for protection,” said Hendrik Poinar, a geneticist at McMaster University in Canada and author of the new study.

Bubonic plague is caused by Yersinia pestis, a type of bacteria transmitted by fleas. Although the plague had been infecting humans for thousands of years, it struck medieval Europe with an intense ferocity that has led scientists to question whether the Black Death had altered Europe’s genetic makeup.

“We would expect a big shift,” Poinar said.

The idea makes fundamental evolutionary sense: if many organisms die off, the survivors will pass on mutations that protected them from death. For example, during the Industrial Revolution, the peppered moth changed from a light mottled color to a dark one. This shift was fueled by the coal smoke blackening the trees on which the moths rested. Dark moths were better at hiding from birds and survived to pass on their genes.

When the Black Death struck, there were no evolutionary biologists to document its effects. In the 1990s, some scientists looked for clues by examining the DNA of living Europeans. A mutation in a gene called CCR5 is present in 10% of Europeans, but is rare in other people. In 1998 researchers suggested that the gene may have provided protection during the Black Death.

However, later research showed that it was impossible to rule out that the CCR5 mutation spread in response to another disease at a different time in history. “It’s something that a lot of people talk about, but it’s very difficult to demonstrate,” said Luis Barreiro, a population geneticist at the University of Chicago and author of the new study.

Instead of studying living people, Barreiro, Poinar and their colleagues examined the DNA of people who lived centuries ago and extracted genetic material from human remains buried in three London cemeteries. They found DNA fragments in 318 skeletons that had lived between 1000 and 1500. The remains included 42 Black Death victims.

Comparing the bones from before and after the plague, the scientists found a striking difference in DNA: hundreds of mutations in genes involved in immunity became more common after the epidemic.

This shift alone was not evidence that the mutations conferred an evolutionary advantage. Biologists have long known that mutations can occur more frequently in a population thanks to the vagaries of history – a process called genetic drift.

It can be difficult to determine whether a shared mutation is due to genetic drift or natural selection. One way to tell the difference is by speed: under extreme conditions, natural selection can cause a mutation to spread much faster than genetic drift.

To compare natural selection and genetic drift, Barreiro and his colleagues went back for another look at Londoners’ DNA. They took advantage of the fact that large parts of our DNA do not contain working genes. Mutations hitting these sections are unlikely to cause any damage. They are also unlikely to bring any benefit. They only spread thanks to gene drift.

Barreiro and his colleagues found that some of these neutral mutations became more common after the Black Death. But 35 of the mutations in immune genes spread much faster than the neutral ones – so fast that only natural selection could be responsible for their success.

For another test, the scientists repeated their experiment, this time in Denmark.

They found DNA in the skeletons of 198 Danes who lived between 850 and 1800. Mutations in immune genes also spread rapidly in Denmark after the Black Death, they found. When the scientists lined up the mutations from the London and Denmark samples, they found four that had spread to both populations. These four mutations spread so quickly in London and Denmark that they must have provided impressive protection against the plague.

The researchers found that carrying two protective versions of a gene called ERAP2, for example, meant humans had a 40 percent chance of surviving the Black Death — the largest evolutionary advantage ever found in humans, Barreiro said.

“It’s actually shocking,” said David Enard, an evolutionary biologist at the University of Arizona who was not involved with the new study.

Enard said the study was particularly compelling because the scientists ruled out genetic drift. “What really gives this study its power has to do with this whole approach of making careful comparisons,” he said.

ERAP2 makes a protein involved in the immune response to invading bacteria and viruses. When an immune cell swallows a pathogen, it presents proteins from the invader on its surface. They serve as an alarm for the rest of the immune system. ERAP2’s job is to cut off parts of the foreign proteins to prepare them for their presentation.

Billions of people have a version of the ERAP2 gene with a mutation that makes cells unable to make its protein. But people with this version of the gene don’t suffer any major damage. That’s most likely because humans have many other genes that help present foreign proteins to the immune system.

During the Black Death, Barreiro and his colleagues found that natural selection favored the working version of ERAP2. To better understand why, they mixed Yersinia bacteria with immune cells from people with both versions of the gene.

The researchers found that having two functioning copies of ERAP2 enabled the immune cells to wipe out the bacteria. Without them, the cells did a much worse job.

But this version of the gene also increases the risk of Crohn’s disease, a condition in which the immune system attacks friendly bacteria in the gut and causes harmful inflammation. Barreiro said it’s possible ERAP2 is doing its job too well, sounding the alarm to friends and foes alike. The other mutations he and his colleagues identified from ancient DNA have also been linked to immune disorders.

Barreiro and his colleagues continue to study the genes that favored evolution during the Black Death, not only to understand this chapter in history, but also to understand the genes themselves. The fact that they have undergone such intense natural selection most likely makes them important in the fight against disease – and perhaps not just the plague.

“That was important in the past and will most likely be important today,” Barreiro said.

This article originally appeared in The New York Times.