Plague resistance genes in Black Death survivors are dangerous for their descendants

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 Plague resistance genes in Black Death survivors are dangerous for their descendants

Survivors of the Black Death epidemic passed down plague-resistant genes to their descendants. But these genes may make modern carriers more susceptible to certain autoimmune diseases, a new study of ancient DNA suggests.

The Black Death, a 14th-century bubonic plague pandemic caused by the bacterium Yersinia pestis, claimed the lives of between 30% and 50% of Europe's population in just five years. After the pandemic, Europe saw plague outbreaks that broke out every few years. However, as a rule, each subsequent outbreak claimed fewer lives than the previous one.

It is possible that the mortality rate has decreased due to evolutionary changes in the bacterium Y. pestis or European cultural practices related to hygiene. But the improved survival rate may also reflect the rapid natural selection caused by the pandemic. The scientists hypothesized that in this scenario, people with plague resistance genes survived more often and thus passed those genes on to the next generation at a faster rate. .

To test this idea, the researchers collected more than 500 DNA samples from the remains of people who died before, during, or shortly after the Black Death. swept through England and Denmark. Their results, published Wednesday, October 19 in the journal Nature, support the idea that the plague caused certain versions of genes to become more common in later generations.

” “People who had these alleles, these mutations, were more likely to survive and pass these mutations on to the next generation,” — said Luis Barreiro, co-author and principal investigator at the University of Chicago's Evolutionary Immunogenomics Laboratory.

For their analysis, the researchers extracted DNA from remains buried in London's East Smithfield plague pits, a roughly 2-acre cemetery that was used for mass graves between 1348 and 1350. They collected 318 samples from Smithfield and elsewhere in London. and 198 samples from five locations in Denmark. The DNA was obtained from people who died 500 years before the start of the Black Death epidemic. and up to 450 years after its end, and many of these samples were obtained from time periods closest to this event.

“This is the first study of ancient DNA that focuses on such a precise and narrow span of time,” — said David Enard, assistant professor of ecology and evolutionary biology at the University of Arizona, who was not involved in the study.

The DNA was heavily damaged and mixed with other environmental DNA, including those left behind by microbes, so the team decided to only study small sections of the genome, Barreiro told Live Science. They focused on about 350 specific genes known to be involved in the immune system, and also on some 500 wider regions of the genome previously associated with immune disorders.

Among the genes associated with immunity, the team identified 245 gene variants — that is, specific “flavors” different genes — which became significantly more common among Londoners after the epidemic. Four of these were also found in samples from Denmark.

A wide range of genes work together to elicit an immune response against pathogens such as Y. pestis. It follows that many of these genes were subject to natural selection during the deadly bubonic plague pandemic. It also makes sense, he says, that samples from England and Denmark might show different patterns of variation in these genes.

The team then wanted to understand whether and how the genes they marked protect people from the plague. To do this, they collected immune cells called macrophages from living people, analyzed their genetic makeup, and then exposed those cells to Y. pestis in Petri dishes.

One gene — ERAP2 — proved to be a key weapon in the arsenal of immune cells.

At least in petri dishes, macrophages carrying two copies of the version of ERAP2 that became more common after the Black Death killed Y. pestis is more efficient than macrophages with or without one copy of the gene variant. ERAP2 contains instructions for making a protein that helps immune cells display particles of foreign invaders, such as bacteria, on their surface. This raises a “red flag” to other immune cells, calling on them to help fight the virus.

Macrophages also release substances called cytokines to rally the immune system to fight. The team found that the array of cytokines released by cells varies depending on what versions of the ERAP2 gene they carry.

These findings may indicate that the post-plague version of ERAP2 did indeed give carriers an advantage over the Black Death, although studies in lab cups do not fully reflect what happens to humans, Barreiro noted.

However, this protection against the plague could be expensive. According to a 2016 report in the journal Clinical and Translational Gastroenterology, the version of ERAP2 that protects against Y. pestis is a known risk factor for Crohn's disease. The study authors noted that other genetic variants noted in the new study are associated with an increased risk of autoimmune diseases, including rheumatoid arthritis and lupus.

just didn't matter during the Black Death — the urgency of the pandemic could make a compromise inevitable”, — Enard wrote in a comment published in Nature. Similar compromises likely took place during other historical outbreaks, before and after the Black Death, Enard said, so echoes of these events may still reverberate in the DNA of modern people.

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