A Millennia-Old Mutation with Modern Implications

A recent study conducted at the University of Copenhagen has uncovered the origins of a genetic mutation that provides resistance to HIV—a mutation that first appeared in a single individual near the Black Sea between 6,700 and 9,000 years ago. Today, this same mutation, known as CCR5Δ32, is carried by 18-25% of the Danish population and has played a crucial role in developing modern HIV treatments.

The CCR5Δ32 mutation deletes a small segment of the CCR5 gene, which encodes a protein on the surface of immune cells. HIV typically uses this protein as an entry point to infect the body, but the mutation disrupts the receptor, making it harder for the virus to take hold. While this protective effect against HIV was discovered decades ago, its ancient origins remained a mystery.  

By analyzing DNA from over 2,000 modern individuals and 900 ancient skeletons, researchers traced the mutation’s emergence to a single ancestor in the Black Sea region during the Neolithic period. Using AI-powered genetic analysis, they determined that the mutation spread rapidly, suggesting it provided a significant survival advantage long before HIV existed.  

Why did this mutation spread so widely? HIV has only been around for about a century, so why would a mutation that blocks it have been beneficial thousands of years ago? The researchers propose that CCR5Δ32 may have helped balance the immune system during a time of increasing infectious disease threats.  

As humans transitioned from hunter-gatherer lifestyles to settled farming communities, population density rose, and so did exposure to new pathogens. An overactive immune response could be deadly—much like the cytokine storms seen in severe COVID-19 cases. The mutation may have tempered excessive inflammation, giving carriers a better chance of survival during outbreaks.  

"This wasn’t about making the immune system stronger—it was about making it more controlled," explained Professor Simon Rasmussen, senior author of the study. "In an era of emerging diseases, a less aggressive immune response could have been the difference between life and death."  

The discovery not only solves a long-standing evolutionary puzzle but also reinforces the importance of studying ancient DNA. The same mutation that once helped Neolithic farmers survive is now the basis for HIV therapies, including the controversial (but groundbreaking) CCR5 gene-editing approach used in the "Berlin Patient," the first person cured of HIV.  

"This is evolution in action—a genetic fluke from the past turning out to be vital in the present," said Kirstine Ravn, lead researcher on the study. "It shows how much we can learn from our ancestors’ DNA."  

The study, published in Cell, marks a major step in understanding how human genetics and ancient diseases have shaped our biology. Future research could explore whether similar mutations exist for other modern viruses, hidden in the genomes of our distant ancestors.  

For now, the CCR5Δ32 mutation stands as a remarkable example of how the past continues to influence medicine today—one ancient gene at a time.