What do a thousand-year-old human from the Black Sea region and modern HIV medicine have in common?
A great deal, as a new study from the University of Copenhagen shows.
18 to 25 percent of the Danish population carry a genetic mutation that can make them resistant or even immune to HIV. This knowledge is used to develop modern therapies against the virus.
Until now, it was unknown where, when, and why the mutation occurred. Using state-of-the-art DNA technology, researchers have now solved this genetic puzzle.
"It turned out that the variant originated in an individual who lived in an area near the Black Sea 6,700 to 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 a coincidence and very fascinating that a genetic variation that arose thousands of years ago also protects against a modern virus like HIV."
900 skeletons analyzed
To find out where and when the mutation originated, the researchers first analyzed the genomes of 2,000 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.
"Based on this extensive dataset, we can determine where and when the mutation originated. For a period, the mutation is completely absent, but then it suddenly appears and spreads incredibly quickly. Combined with our knowledge of human migration at the time, we can also determine the region from which the mutation originated," explains first author Kirstine Ravn, senior researcher at CBMR.
This allowed the researchers to locate the mutation in a human 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 that the mutation arose and spread rapidly because it provided an advantage to our ancestors:
"People with this mutation had better survival rates, likely because it weakened the immune system at a time when humans were exposed to new pathogens," explains Leonardo Cobuccio, co-first author and postdoc at CBMR. He and Kirstine Ravn elaborate:
Fascinatingly, variation disrupts the immune system. While this sounds negative, it was likely advantageous. 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 leads to patient death. As humans transitioned from hunter-gatherer lifestyles to densely populated agricultural societies, the pressure from infectious diseases increased, and a more balanced immune system may have been advantageous.
Journal
Cell
DOI
10.1016/j.cell.2025.04.015
