Researchers map 7,000-year-old genetic mutation that protects against HIV

GENETICS Modern HIV medicine is based on a common genetic mutation. Now, researchers have traced where and when the mutation arose – and how it protected our ancestors from ancient diseases
Illustration of DNA
“It’s almost coincidental and very fascinating that a genetic variation that arose thousands of years ago also protects against a modern virus like HIV,” says researcher behind new study. Illustration: William Brøns Petersen

What do a millennia-old human from the Black Sea region and modern HIV medicine have in common?

Quite a lot, it turns out, according to new research from the University of Copenhagen.

18-25 percent of the Danish population carries a genetic mutation that can make them resistant or even immune to HIV. This knowledge is used to develop modern treatments for the virus.

Until now, it was unknown where, when, or why the mutation occurred. But by using advanced DNA technology, researchers have now solved this genetic mystery.

HIV and resistance

HIV (human immunodeficiency virus) destroys white blood cells that defend the body against infections. Untreated HIV leads to AIDS.

The genetic mutation that protects against HIV is found in the so-called CCR5 gene. Carriers of the mutation lack a receptor – a kind of “door” – on their cells that the virus uses to infect the body. This missing receptor can make a person resistant or even immune to HIV.

Today, HIV is treated with medication that makes it difficult for the virus to replicate. The medicine cannot completely eliminate HIV but can suppress it, so the disease is not felt.

Sources: Statens Serum Institut, AIDS-Fondet, and Professor Simon Rasmussen, CBMR

“It turns out that the variant arose in one individual who lived in an area near the Black Sea between 6,700 and 9,000 years ago,” says Professor Simon Rasmussen from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen, corresponding author of a new study mapping the mutation. He adds:

“HIV is a relatively new disease – less than 100 years old – so it’s almost coincidental and very fascinating that a genetic variation that arose thousands of years ago also protects against a modern virus like HIV.”

Analyzed 900 skeletons

To determine where and when the mutation arose, researchers first mapped it by analyzing the genetic material of 2,000 living people worldwide. They then developed a new AI-based method to identify the mutation in ancient DNA from old bones.

The researchers examined data from over 900 skeletons dating from the early Stone Age to the Viking Age.

“By looking at this large dataset, we can determine where and when the mutation arose. For a period, the mutation is completely absent, but then it suddenly appears and spreads incredibly quickly. When we combine this with our knowledge of human migration at the time, we can also pinpoint the region where the mutation originated,” explains first author Kirstine Ravn, senior researcher at CBMR.

Thus, the researchers were able to locate the mutation in a person from the Black Sea region up to 9,000 years ago – an individual from whom all carriers of the mutation descend.

Was an advantage back then

But why do so many Danes carry a millennia-old genetic mutation that protects against a disease that didn’t exist back then?

The researchers believe the mutation arose and spread rapidly because it gave our ancestors an advantage:

People with this mutation were better at surviving.
Postdoc Leonardo Cobuccio

“People with this mutation were better at surviving, likely because it dampened the immune system during a time when humans were exposed to new pathogens,” explains Leonardo Cobuccio, co-first author and postdoc at CBMR. He and Kirstine Ravn elaborate:

“What’s fascinating is that the variation disrupts an immune gene. It sounds negative, but it was likely beneficial. An overly aggressive immune system can be deadly – think of allergic reactions or severe cases of viral infections like COVID-19, where the immune system often causes the damage that kills patients. As humans transitioned from hunter-gatherers to living closely together in agricultural societies, the pressure from infectious diseases increased, and a more balanced immune system may have been advantageous.”

Read the study “Tracing the evolutionary history of the CCR5delta32 deletion via ancient and modern genomes”.

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