Researchers find surprising links which show that Neandertal ancestry influences our immune system today in ways more nuanced than previously recognised.
Viruses account for an estimated 10-20% of the global disease burden. Many DNA viruses can persist in the body for a lifetime, and virus load varies greatly even among people without symptoms. Throughout human history, they have posed persistent and rapidly evolving threats, placing strong adaptive pressure on our immune system. Previous research has shown that many genetic variants involved in immunity bear the marks of these evolutionary battles - including signatures of natural selection and contributions from interbreeding with archaic humans. While Neandertal ancestry has previously been associated with beneficial effects in RNA virus defence, the new study highlights a contrasting trend for DNA viruses.
Because of past admixture with archaic humans, around 2% of the genomes of present-day non-Africans is composed of Neandertals DNA and an additional 2-4% of people in Oceania of Denisovan ancestry These introgressed sequences have shaped many biological traits, including immunity. But their role in defences against DNA viruses has remained largely unexplored.
Modern disadvantages don’t imply ancient harm
RNA and DNA viruses differ fundamentally in their biology - including infection strategies, tissue tropism, and the pace at which they evolve. These differences raise the possibility that the effects of archaic genetic variants on DNA and RNA virus response might differ. To investigate this, the team explored the contribution of archaic DNA - primarily Neandertal ancestry - to the DNA viral load of participants in the UK Biobank. By analysing viral sequences detected in large-scale genomic data, the researchers asked whether archaic variants correlate with the presence or quantity of common DNA viruses.
The study uncovered multiple associations between archaic DNA and the loads of Epstein-Barr virus (EBV), Human Herpesvirus 7 (HHV‑7), and anelloviruses of the Teno family. These viruses are widespread in humans and often persist as chronic infections. Overall, archaic DNA was disproportionally often associated with higher virus loads. These viruses often cause no symptoms, but the amount of viral DNA can reflect how effectively the immune system keeps them in check.
“Our results suggest that Neandertal-derived variants may not provide effective defense against several DNA viruses in people today,” said Michael Dannemann, a co-author of this study. “This stands in striking contrast to their previously reported beneficial effects on RNA virus immunity.” However, the researchers emphasise that these negative effects in present-day populations do not mean that the same variants were harmful to Neandertals themselves. “Viruses evolve extremely quickly,” noted Dannemann.
“The pathogenic landscape faced by Neandertals tens of thousands of years ago would have been vastly different from the one we face today. A variant that reduced viral burden in the past may increase it now.” Supporting this idea, the team identified genomic regions carrying archaic variants that show shifts in selective pressure over time, including signatures of more recent negative selection. These evolutionary signals align with the possibility that once-beneficial archaic alleles have become disadvantageous in today’s environments.
The findings highlight that archaic DNA in people today interacts with modern pathogens in distinct ways - and that its effects can differ sharply between virus classes. The work underscores that archaic genetic ancestry still influences our immune system today - but in ways more nuanced than previously recognised.
Read more: https://academic.oup.com/gbe/article/18/5/evag110/8664352
Genome Biology and Evolution
Meta-analysis
Not applicable
Archaic introgression shapes genetic variation at loci associated with DNA virus load in modern humans
28-Apr-2026
The authors declare no conflict of interest.