A recent study published last year in the journal Cell has identified the ancient origins of a genetic mutation that confers resistance to HIV, and how it first appeared in an individual who lived near the Black Sea between 6,700 and 9,000 years ago. Named CCR5 delta 32, the uncommon genetic variant disables a key immune protein used by a large majority of strains of the HIV virus to enter human cells and therefore “locks out” the virus in individuals who carry two copies of the mutation.
Reconstructed Viking village featuring traditional buildings and artifacts that illustrate daily life and culture in the Viking age. Credit: Paolo Ghedini
HIV is a relatively new disease. It was only identified in the last century, but the genetic mutation that defends against it has existed for thousands of years. The international research team, led by Professor Simon Rasmussen and senior researcher Kirstine Ravn of the University of Copenhagen’s Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), confirmed this through the analysis of over 3,000 genomes of ancient and modern humans. The study used a new AI-based method to detect the mutation in the often degraded DNA of ancient bones.
The researchers analyzed DNA from more than 900 ancient people, ranging from the early Mesolithic era to the Viking era. They found that the CCR5 delta 32 mutation emerged abruptly and rapidly spread in human populations, particularly after humans transitioned from a nomadic hunter-gatherer lifestyle to more densely settled agricultural societies. That shift in lifestyle likely put humans in contact with new pathogens, imposing evolutionary pressure that favored individuals 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 of the study and postdoctoral researcher at CBMR, in a statement. “While it might sound negative that the variation disrupts an immune gene, it was probably beneficial. An overly aggressive immune system can be ᴅᴇᴀᴅly — think of allergic reactions or severe cases of viral infections like COVID-19, where the immune system often causes the damage that kills patients.”
Layout featuring a colorized 3D print of an HIV virus particle (purple with green surface proteins). Micrograph captured at the NIAID Integrated Research Facility in Fort Detrick, Maryland. Credit: NIAID, CC BY 2.0
CCR5, the protein affected by the mutation, helps direct immune cells to areas of inflammation within the body. Disabled by the delta 32 mutation, however, it becomes harder for HIV to infect these cells. This discovery has already been put to use in medicine: scientists have used the protective properties of the mutation to successfully treat a handful of HIV patients.
One of the most fascinating findings of the research is that every modern carrier of this mutation, found in approximately 10 to 16 percent of Europeans, and up to 25 percent of Danes, probably descends from that single individual living around the Black Sea thousands of years ago. Previous hypotheses had suggested that the mutation had spread in response to more recent events such as the Black Death or Viking-era pandemics. The new genetic evidence, however, defies such a supposition and shows that the mutation became widespread between 8,000 and 2,000 years ago, long before such events.
The study redefines our understanding of how humans have learned to live with disease and demonstrates the power of combining ancient DNA and modern technology to uncover hidden pages of human history.
More information: Ravn, K., Cobuccio, L., Muktupavela, R. A., Meisner, J., Danielsen, L. S., Benros, M. E., … Rasmussen, S. (2025). Tracing the evolutionary history of the CCR5delta32 deletion via ancient and modern genomes. Cell. doi:10.1016/j.cell.2025.04.015University of Copenhagen’s Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR)
