By sequencing ancient human DNA and comparing it to modern samples, an international team of researchers has managed to map the historical evolution of genes during migrations, revealing the origins of some modern-day diseases. Their work was revealed in four papers published in the journal Nature.
a. The modern-day geographical distribution of MS in Europe, based on prevalence data (cases per 100,000) from a specific reference. b. The estimate of steppe ancestry in modern samples as determined by another study. c. A model of European prehistory onto which reference samples were projected using non-negative least squares (NNLS) for population painting. d. The same data as in c, but represented spatially. Samples are shown as vertical bars indicating their admixture estimate from six ancestries: EHG (green), WHG (pink), CHG (yellow), farmer (ANA + Neolithic; blue), steppe (cyan), and an outgroup (ancient Africans; red). The diagram shows population expansions and includes recent non-reference admixed populations from the Denmark time transect. Credit: Nature
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Ancient genes associated with MS migrated with populations
To do this, the 175 researchers from various European and American universities analyzed the bones and teeth of around 5,000 people who lived in Western Europe and Asia 34,000 years ago up to the Middle Ages and compared them with the modern DNA of around 400,000 people from the UK Biobank. This bank of ancient human genes, the largest in the world, has helped explain the origins of certain neurodegenerative diseases, starting with multiple sclerosis (MS).
In fact, the research team discovered that the genes that significantly increase a person’s risk of developing multiple sclerosis were introduced to northwestern Europe around five millennia ago by the Yamnaya people, cattle breeders who migrated from the Pontic steppe now Eastern Europe.
“These genetic variants associated with the risk of multiple sclerosis traveled with these people to northwestern Europe. They must have given them a survival advantage and probably protected them from infections from their sheep and cattle, but at the same time increased their risk of developing MS,” the study authors write in a press release.
According to them, this could explain the “observed north-south gradient in the incidence of multiple sclerosis”, with twice as many cases in northern Europe as in southern Europe, which has long been a mystery to science.
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Alzheimer’s risk genes attributed to hunter-gatherers
According to the team, this work may also provide a better understanding of how migration may have affected the prevalence of other neurodegenerative diseases, such as Alzheimer’s, which affects Europeans more than the rest of the world. “The genes known to increase the risk of diseases such as Alzheimer’s and type 2 diabetes have been attributed to hunter-gatherers,” but more research is needed to know the full story.
“Showing how the lifestyle of our ancestors affected the risk of modern diseases only highlights the extent to which we are the beneficiaries of an ancient immune system in a modern world,” the researchers conclude. Based on this gene bank, they now plan to study other neurological conditions, such as Parkinson’s disease, and psychiatric conditions, such as ADHD, schizophrenia, and depression.
References
Barrie, W., Yang, Y., Irving-Pease, E.K. et al. Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations. Nature 625, 321–328 (2024). https://doi.org/10.1038/s41586-023-06618-z
