A groundbreaking study published last year in the journal Cell has traced the ancient origins of a genetic mutation, known as CCR5 delta 32, that provides resistance to HIV. This rare genetic variant, which first appeared in an individual living near the Black Sea between 6,700 and 9,000 years ago, disables a key immune protein that most strains of the HIV virus use to infect human cells. Individuals carrying two copies of this mutation effectively “lock out” the virus, rendering them resistant to HIV infection.
Led by Professor Simon Rasmussen and senior researcher Kirstine Ravn from the University of Copenhagen’s Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), an international research team analyzed over 3,000 genomes from ancient and modern humans. Using a novel AI-based method to detect the CCR5 delta 32 mutation in the often-degraded DNA of ancient bones, the researchers studied genetic material from more than 900 individuals, spanning from the Mesolithic era to the Viking period.
The study revealed that the CCR5 delta 32 mutation emerged suddenly and spread rapidly in human populations, particularly as humans transitioned from nomadic hunter-gatherer lifestyles to settled agricultural communities. This shift likely exposed early humans to new pathogens, creating evolutionary pressure that favored those with the mutation. “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,” explained Leonardo Cobuccio, a co-author and postdoctoral researcher at CBMR. “While disrupting an immune gene might seem harmful, it was likely beneficial. An overly aggressive immune response can be deadly, as seen in severe allergic reactions or viral infections like COVID-19, where the immune system can cause fatal damage.”
The CCR5 protein, affected by the delta 32 mutation, normally directs immune cells to areas of inflammation in the body. When disabled by the mutation, it prevents HIV from infecting these cells, offering a natural defense against the virus. This discovery has already been applied in medical treatments, with scientists leveraging the mutation’s protective properties to successfully treat a small number of HIV patients.
Remarkably, the study found that every modern carrier of the CCR5 delta 32 mutation—present in approximately 10 to 16 percent of Europeans and up to 25 percent of Danes—likely descends from that single individual who lived near the Black Sea thousands of years ago. Earlier theories suggested the mutation spread in response to later events like the Black Death or Viking-era pandemics, but the new genetic evidence shows it became widespread between 8,000 and 2,000 years ago, long before these events.
This research reshapes our understanding of how humans have adapted to coexist with diseases and highlights the power of combining ancient DNA analysis with cutting-edge AI technology. By uncovering the ancient origins of the CCR5 delta 32 mutation, the study reveals a hidden chapter of human history, showing how a single genetic change from millennia ago continues to protect millions from HIV today.