Health
How the bubonic plague rewired the human immune system
Written by David CoxFunctional support person
Getty ImagesBubonic plague is still found in scattered locations around the world, but thanks to modern antibiotics, it is much easier to treat than it used to be. However, the disease may still leave its mark on humanity.
under the microscope plague bacterium There's nothing particularly special about it. This is a pretty standard shape for bacteria, and it's kind of short. rounded stick – and relatively motionless. But it is the cause of the disease that once occurred. wiped out one-third of Europe's population and caused millions of deaths worldwide.
Even today, just hearing the word bubonic plague tends to evoke both fear and fascination. The disease is now rarely seen in the United States or Europe, largely because lifestyle changes have made it easier to prevent infected fleas from transmitting the disease to humans. Even if that happened, Can be treated relatively easily with antibiotics, save lives. However, incidents still occur.
Recently, a man living in Oregon, USA, I contracted bubonic plague from my pet cat.. This isn't all that surprising to evolutionary geneticist Paul Norman, who studies bubonic plague at the University of Colorado Anschutz.
“There's more. There is a small outbreak of plague in the United States.” he says. The virus is still circulating in wild animals such as squirrels and prairie dogs, he added. Seven cases of human plague are reported each year in the United States., but the number of deaths was much lower, at just 14 between 2000 and 2020. In some parts of the world, such as Madagascar, the disease is more common.
However, although relatively rare compared to the past, bubonic plague has left its mark on humanity and may still be present in the genomes of people living today.
plague bacterium It is thought to have plagued humanity for thousands of years.Bacterial DNA evidence found Discovered in a 4,000-year-old skeleton. However, in the early 1300s, a type of this bacterium exploded across Europe as the Black Death.It is believed that He was born in a village around the Chui Valley in what is now Kyrgyzstan.and possibly earlier, it was transmitted to humans via fleas from infected marmots. spread to Europe along the Silk Road trade routes.
AlamyThe Black Death is believed to have killed approximately 50 million Europeans by the mid-1300s, according to estimates based on historical records and writings. Recent research into agricultural activities at the time (which would have been drastically reduced given the high number of deaths) suggests that: The casualties everywhere may not have been so dramatic., Some regions have been devastated by the disease, while others are largely unaffected.However, for centuries, the plague is estimated to have caused at least one death. 200 million people.
The plague outbreak was so devastating that researchers have long wondered whether it left any lasting imprint on the human immune system. In particular, one theory suggests that the Black Death may have been widespread enough during his 14th century to produce a form of natural selection. The idea was that some of the surviving individuals could pass on genetic peculiarities that helped them to future generations.
“The Black Death put enormous pressure on Europe's population,” Norman says. “It was persistent and harmful, and anyone who had a slight advantage genetically in that situation would have been more likely to survive.”
However, until relatively recently, it was almost impossible to collect any kind of data to answer this question. Sequencing DNA from the skeletons of ancient plague victims found in mass graves is notoriously difficult, with scientists often working with the tiniest fragments of highly contaminated DNA. There is a need.
Pontus Skoglund, a Swedish geneticist who heads the Ancient Genomics Laboratory at the Francis Crick Institute in London, said: “The vast majority of DNA actually comes from soil and bacteria that invaded a person's skeleton after death.'' That often turns out to be the case.”
However, experts have discovered parts of the skeleton where intact human DNA is definitely still found.called bone maze, it is located within the inner ear and is one of the densest parts of the human body. “This is the most successful place to extract DNA,” Norman said. “This is a very small bone that is still protected in the skull specimen. We don't want to do anything too gross, but you have to really drill into the skull to get that bone out, but the leg bone Things like that are very porous and bacteria can get in there. It's much easier to get in there.”
Over the past three years, this research has helped provide new insights into who survived past plague outbreaks and why.
regulation of immunity
The human leukocyte antigen (HLA) system is composed of a group of genes that encode proteins on the surface of cells and plays an important role in regulating immune responses. According to recent research, Asymptomatic coronavirus patients benefited from genetic lottery This means they have certain HLA variants that act as a natural defense against viruses.
“The role of HLA genes is to identify foreign invaders into the body and instruct the immune system to seek out and destroy cells infected with pathogen proteins,” Norman says. “Relatively rare variants of these genes may help some people survive the pandemic, and if the death toll from COVID-19 had been much higher, humans would not have these The frequency of the variant would have been much higher.”
In 2021, Norman and his colleagues demonstrated that HLA variants likely exist. played a role in determining who survived medieval plague outbreaks. Researchers investigated a 16th century mass grave of plague victims in the German town of Ellwangen and sequenced the genomes of 36 human bones. Comparing them with the DNA of people living in Ellwangen today, they found that the town's 21st century residents had subtle differences in various HLA genes that may have made their ancestors more resistant. It has been found. plague bacterium.
Two years ago, an international group of researchers tried to find out Genetic samples were collected from the remains of around 500 people in cemeteries across London and Denmark who died before, during and after the 14th century pandemic to discover how the Black Death affected human immunity. investigated.
In particular, they looked at patterns associated with a gene called ERAP2, which encodes a protein known to help humans attack immune cells. plague bacterium and other pathogens. However, one mutant of ERAP2 produces a more restricted form of the protein, while another produces the full size protein.
The study showed that medieval Londoners and Danes who carried the latter ERAP2 variant were twice as likely to have survived the Black Death. By the end of the 14th century, researchers found that 50% of Londoners and 70% of Danes surveyed carried the variant.
But we still need to learn more. Professor Skoglund said the researchers looked at people living across Europe at the time of the Black Death and for centuries afterward to see if adaptations like the ERAP2 variant were truly widespread and hardwired into our DNA. They say thousands more genomes need to be studied from people who
“Genes that were protective against this outbreak may have increased their frequency considerably after such an event,” he says. “But this may be just a matter of a few generations.”
Getty ImagesSkoglund even wonders if diseases such as smallpox, which are even more persistent and virulent than the plague, could cause deaths. hundreds of millions of peoplemay have had a major impact on the formation of the modern immune system.
But the plague has a special charm, and studying how it affected our distant ancestors can provide valuable information. “Examining how plague evolves and why certain strains were more lethal is important to understanding the evolution of potentially problematic strains.” says Hendrik Poynar, an evolutionary biologist at McMaster University.
Skoglund points to research he conducted on plague victims found in Somerset and Cumbria, England. From about 4000 years ago when plague bacterium The ability to transmit by fleas had not yet developed.
“Looking at the DNA, we see that this bacterium lacks the genetic components that allow it to be transmitted by fleas,” he says. “But evolving it has had a dramatic impact on human health. But how evolution has dealt with problems in the past, and we've learned how to fight those diseases thousands of years ago. We can also learn from how we came up with the biological mechanisms, which is very important. We can use that to help develop vaccines and medicines today.”
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