Protective genes during the Black Death may now increase autoimmune disorders - Harvard Health

Protective genes during the Black Death may now increase autoimmune disorders – Harvard Health

Will the COVID-19 pandemic alter the genes — and the health — of future generations?

A colorful twisted DNA strand with a spotlight on a mutated gene on a hazy purple background

Most people alive today have only witnessed one pandemic: COVID-19. But pandemics are not new; medical historians have documented nearly 20 major pandemics over the past 1,500 years. And while the past few years have been difficult, they pale in comparison to the mid-1300s, when the pandemic dubbed the Black Death was raging and those infected generally died.

The Black Death decimated up to half the population of Europe, the Middle East and Africa. Now, scientists are wondering if survivors of this pandemic had a genetic advantage that allowed them to avoid infection, and if so, what lessons might be learned for survivors of our current pandemic?

Surviving the Black Death: Chance or Genes?

In the 1300s, people did what they could to avoid infection. This mostly meant trying to separate the sick from the healthy. But there seemed to be a lot of luck as to who was infected, who lived and who died. The cause of this plague was entirely mysterious to those who experienced it. Much later, researchers learned that a bacterium, Yersinia pestiswas the cause, most likely spreading from flea rodents to humans.

Recently, researchers extracted DNA from the bones of people who perished during the Black Death era and compared it to those who survived this pandemic. They found important differences: Survivors were more likely to carry genes that helped their immune system fight infection. So maybe surviving the Black Death wasn’t so random after all.

But the researchers also noticed other remarkable things:

  • Infection-fighting genes have increased dramatically in the general population within a few generations. A change of this magnitude in a population in such a short time is almost unheard of.
  • People today living with autoimmune diseases such as rheumatoid arthritis or lupus are more likely to carry these same infection-fighting genes than people without autoimmune diseases. It appears that the genes that helped some of our ancestors avoid dangerous infection in the 1300s may now be a risk factor for autoimmune diseases.

Understanding Selective Pressure: Evolution’s Action Arm

An evolutionary process called selective pressure encourages the survival of favorable genes in a population and discourages unfavorable genes. If a living organism survives long enough to pass on favorable genes to the next generation, the species benefits by avoiding potential extinction.

A good example of selective pressure is antibiotic resistance. Let’s say you are being treated with an antibiotic for pneumonia caused by bacteria. The antibiotic is meant to kill bacteria so you can recover. But a few bacteria may have a genetic mutation or variation that allows them to survive and thrive despite antibiotic treatment.

As their bacterial brethren are wiped out, the resistant ones thrive, multiply, and pass their genetic information – including the genes that determine antibiotic resistance – to later generations of bacteria. In this example, the antibiotic treatment applies selective pressure that encourages (selects) the development of resistant bacteria: great for bacteria, although bad, of course, if you are the person with pneumonia.

Selective pressure has led to adaptations like the ability of chameleons to escape predators by changing color; desert plants able to thrive with minimal water; and humans with our big brains, opposable thumbs, and even our ability to digest milk. Variants of COVID-19 are another good example: mutations allow the coronavirus responsible for our current pandemic to survive despite vaccinations and antiviral treatments.

The Black Death: Beneficial Genes and Downstream Consequences

In humans, genetic changes of this type typically take hundreds of years. The genetic impact of the Black Death was much faster, probably because the pandemic was so large and killed so many people before they have reached childbearing age. Those with favorable genes made up such a large proportion of survivors that the gene pool of the population changed rapidly.

Obviously, however, beneficial genes that take hold in a population can come at a price. We don’t yet know why the genes that helped protect against the Black Death might increase the risk of autoimmune disease. Perhaps they carry instructions for a particularly vigorous immune system that is able to fight off a dangerous infection, but is also imprecise in its attack or prone to overreacting, leading to the friendly fire of autoimmune disease.

A benefit at a particular time and place may have a price for future generations. For example, genes that cause red blood cells to take on a sickle shape help people resist malaria infection. Inheriting sickle cell genes from one parent can be protective, but inheriting sickle cell genes from both parents causes sickle cell anemia, a life-threatening condition on its own.

Will COVID-19 alter the genes of the world’s population?

Given the history of the Black Death, you may be wondering: will the COVID-19 pandemic have a large impact on the genetic make-up of the world’s population through selective pressure? Experts think that’s unlikely. Even though COVID-19 has killed millions around the world, most of its victims were older. Selective pressure is most powerful when applied to a population before reproductive age, as described above.

And curiously, certain genes associated with the risk of developing severe COVID seem to decrease the risk of certain autoimmune diseases. For now, why this might be remains a mystery.

The bottom line

Surviving the Black Death was no easy feat and probably owed more to genetics than anything else. But genetic variations good for our ancestors may be much less beneficial now. This new knowledge about the Black Death and how selective pressure can contribute to future diseases could prove useful to our descendants as they deal with their own pandemics.

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