Norovirus, commonly known as winter vomiting disease, is caused by a virus and spreads mainly during the winter months. The illness lasts for a couple of days and provides only short-term immunity, meaning the same person can fall ill several times in quick succession. However, some people do not get sick thanks to a specific genetic variant.
“The genes we inherit influence how susceptible we are to different diseases. An important factor is so-called histo-blood group antigens. These are sugar molecules on our mucous membranes that play a key role in how viruses and bacteria can attach to our cells. In the case of norovirus, it’s the cells in the intestinal lining,” says Johan Nordgren.
For these sugar molecules to form, an enzyme called FUT2 is required. The production of this enzyme is controlled by a gene of the same name. Those who do not fall ill have a gene variant that renders the enzyme non-functional – and without sugar molecules on the cell surface, the virus cannot enter. But how did this gene variant spread?
Historical spread
Hugo Zeberg, senior lecturer in genetics at Karolinska Institutet and affiliated with the Max Planck Institute for Evolutionary Anthropology in Leipzig, led the study.
“We wanted to trace the historical spread of the gene variant,” he says in a press release.
To trace its spread, the researchers analysed the genomes of 4,343 ancient humans from the past 10,000 years. The gene variant arrived in Europe with early farmers from present-day Turkey around 8,000 years ago and then spread gradually. In early agricultural societies, stomach viruses spread far more than when people lived in smaller groups. The researchers’ findings suggest that this new disease environment drove up the frequency of the gene variant, as it protects against norovirus and gave carriers the advantage of avoiding illness.
Using questionnaires and genetic material from biobanks containing 700,000 modern individuals, the researchers found that people with the gene variant rarely suffered from stomach bugs, especially if they had two copies – one from each parent.
"Mini-guts"
To confirm their findings, they also used human “mini-guts”, so-called intestinal organoids. Mini-guts that did not express these sugar molecules (two copies of the gene variant) were fully protected against infection with norovirus.
However, protection against norovirus comes at a cost. Modern biobanks show an increased risk of stomach ulcers and gallstones among carriers of the gene variant. According to the researchers, this may be linked to stress and high fat intake, which were likely less common in the lives of early farmers.
As for the clinical relevance of the results, the researchers believe that knowing the gene variant provides full protection can help in risk assessments. In Sweden, an estimated 20 per cent of the population have two copies.
“But my chief interest is in evolutionary science. Prehistoric DNA is a time machine that allows us to replay evolution and see how genetic mutations can be tied to events in the human environment,” says Hugo Zeberg.
LiU researcher Johan Nordgren has recently been granted SEK 5,400,000 from the Swedish Research Council to continue the studies. The new project is called Evolutionary History of Blood Group Antigens and Their Impact on Disease Today.
“We want to increase understanding of the relationship between these blood group antigens and diseases – both historically and today. We will investigate how viruses can spread from animals to humans, why rotavirus vaccines work differently in different parts of the world, and why certain populations have an increased risk of specific diseases,” he says.
Article: Natural selection of a virus-protective FUT2 variant following the transition to agriculture, Johan Nordgren, Richard Ågren, David Hu Ziliang, Magdalena Neijd, Ainash Childebayeva, Kay Prüfer, Marie Hagbom, Lennart Svensson and Hugo Zeberg. Molecular Biology and Evolution, online 24 October 2025, doi: 10.1093/molbev/msaf243.
