Have an Autoimmune Disease? Blame the Black Death

Summary

The video explores the fascinating genetic legacy of the Black Death, showing how survivors of the plague passed down gene variants that offered immune protection at the cost of increasing susceptibility to autoimmune diseases. Researchers identified specific genetic traits, like the ERAP2 gene variant, which helped protect against the plague but is also linked to conditions such as Crohn's disease. This phenomenon, known as antagonistic pleiotropy, reveals how evolutionary advantages can come with unforeseen drawbacks, providing a complex picture of human survival and adaptation throughout history.

Takeaways

• 😀 The Black Death was one of the deadliest pandemics in history, killing over 25 million people across Europe, the Middle East, and North Africa.
• 😀 Genetic variants that helped survivors of the Black Death have been passed down to their descendants, with some of these variants now linked to autoimmune diseases.
• 😀 Researchers investigated DNA samples from historical graves in Europe to identify gene variants that might have offered protection during the plague.
• 😀 A key gene, ERAP2, was found to have two variants—type A, which produces more immune-boosting protein, and type B, which produces less effective proteins.
• 😀 The type A variant of ERAP2 increased survival rates during the plague by enhancing immune responses and limiting inflammation, providing a 40% survival advantage.
• 😀 While the type A variant helped protect against the plague, it is also associated with autoimmune diseases like Crohn's disease, showing the trade-off between disease protection and autoimmune risk.
• 😀 The phenomenon of **antagonistic pleiotropy** explains how a genetic trait beneficial in one context (e.g., plague survival) can have harmful effects in another (e.g., autoimmune diseases).
• 😀 A 2023 study confirmed that genes which protect against infectious diseases may simultaneously increase vulnerability to autoimmune diseases, highlighting a long-term evolutionary trade-off.
• 😀 Researchers found that these genetic changes likely began to emerge around the Bronze Age, coinciding with the rise of cities, increased travel, and domesticated livestock, which exposed people to more pathogens.
• 😀 The genetic legacy of pandemics like the Black Death is still influencing human health today, showing how our evolutionary adaptations to historical threats can have unintended consequences.

Q & A

What was the significance of the Black Death in terms of genetic evolution?

The Black Death acted as a massive natural selection event, killing millions of people while allowing survivors with specific genetic advantages to pass on their genes. These advantages may have included stronger immune responses, which are now reflected in certain genetic variants in modern populations.

How did researchers identify genetic variants associated with survival during the Black Death?

Researchers analyzed DNA samples from people who lived before, during, and after the Black Death. They focused on immune-related genes and identified variants that became more common post-plague, suggesting they had a protective effect against the disease.

Which gene was identified as playing a key role in survival during the Black Death?

The gene *ERAP2* was identified as crucial. People with a variant of this gene that produced more of the gene’s protein were 40% more likely to survive the plague.

How does *ERAP2* function in the immune system?

*ERAP2* helps immune cells identify and clear pathogens, while also modulating inflammation. It plays an essential role in training immune cells to recognize and respond to foreign invaders.

What is antagonistic pleiotropy, and how does it relate to *ERAP2*?

Antagonistic pleiotropy occurs when a gene has both beneficial and harmful effects. In the case of *ERAP2*, the variant that helped protect against the Black Death is also linked to autoimmune diseases like Crohn's disease and lupus, showing how genetic advantages can come with long-term risks.

What autoimmune diseases are associated with the *ERAP2* type A variant?

The *ERAP2* type A variant, which provided protection against the plague, is now linked to autoimmune diseases such as Crohn’s disease, lupus, and rheumatoid arthritis.

What does the 2023 study reveal about the relationship between immunity and autoimmune diseases?

The 2023 study found that genetic variants offering protection from infectious diseases often increase vulnerability to autoimmune diseases. It suggests an evolutionary trade-off between the benefits of infectious disease resistance and the risks of developing autoimmune conditions.

How does the evolution of immunity tie to the rise of cities and livestock in the Bronze Age?

The development of cities, increased travel, and the domestication of livestock during the Bronze Age exposed people to more pathogens. This led to the selection of genetic traits that offered protection against infections, but these same traits could later increase the risk of autoimmune diseases.

What evolutionary trade-off does the study suggest regarding genetic survival traits?

The study suggests that genetic variants that help humans survive infectious diseases, such as those related to *ERAP2*, can come at the cost of increasing susceptibility to autoimmune diseases, demonstrating a balancing act in human genetic evolution.

What role does basic hygiene and understanding of bacteria play in the context of the Black Death?

While 14th-century victims of the Black Death did not have knowledge of bacteria or hygiene, modern understanding of these topics could have helped prevent the spread of the disease. The podcast SciShow Tangents, referenced in the script, explores these topics in a more lighthearted way.