Summary: Researchers have assembled the largest ancient human gene bank to date, analysing DNA from nearly 5,000 individuals. This resource reveals how migrations shaped the distribution of genes linked to modern diseases and offers fresh insight into the origins of conditions such as multiple sclerosis and other neurodegenerative disorders.
An international team compared genomes extracted from bones and teeth spanning up to 34,000 years with modern genetic datasets. Their analysis maps how disease-associated variants moved across Eurasia as human groups migrated, altered lifestyles, and adapted to new environments.
The results, presented across four papers in Nature, clarify long-standing questions about regional differences in disease prevalence and open new paths for research into neurological and psychiatric disorders.
Key Findings
- Genetic variants that increase multiple sclerosis (MS) risk spread into north-western Europe roughly 5,000 years ago with pastoralist migrations from the Pontic Steppe.
- Some variants that raise the risk of Alzheimer’s disease and type 2 diabetes can be traced to hunter-gatherer populations, showing how ancient lifestyles shaped modern disease susceptibility.
- Carrying MS-associated alleles was likely beneficial for early pastoralists because those alleles offered protection against infections shared with domesticated animals, despite increasing long-term autoimmune risk.
Source: University of Cambridge
About the dataset
The study created a unique archive of ancient human genomes by extracting DNA from almost 5,000 skeletal remains held in museum collections across western Europe and western Asia. Samples cover the Mesolithic and Neolithic periods through the Bronze and Iron Ages, the Viking era and the Middle Ages. The oldest genome in the collection dates to about 34,000 years ago.
Researchers compared these ancient genomes with modern genetic data — including around 400,000 contemporary samples from Britain — to trace the historical movement of disease-associated variants and to study how natural selection affected immune-related genes over millennia.
Research team and scope
The work was led by Professor Eske Willerslev (Universities of Cambridge and Copenhagen), Professor Thomas Werge (University of Copenhagen), and Professor Rasmus Nielsen (University of California, Berkeley). A total of 175 researchers from institutions around the world contributed to the project. Funding was provided by an €8M grant from the Lundbeck Foundation and the work was carried out at the Lundbeck Foundation GeoGenetics Centre.
Origins of multiple sclerosis risk
Multiple sclerosis is most common in northern Europe. The team found that the cluster of genetic variants that substantially elevates MS risk became common among Yamnaya-related steppe pastoralists and was introduced into north-western Europe during migrations approximately 5,000 years ago. These variants likely experienced positive selection in steppe populations and later in Europe, probably because they helped defend against pathogens associated with increased population density, animal domestication and changing diets.
The findings provide a genetic explanation for the long-observed North–South gradient in MS prevalence across Europe: populations in north-western Europe retain a stronger genetic legacy from steppe pastoralists than many southern populations, which helps account for higher regional MS rates today.
While these immune-related variants reduced vulnerability to certain infections in the past, they also predispose carriers to autoimmune reactions that can lead to MS in modern environments where infectious pressures and lifestyles are very different.
Broader implications
Beyond MS, the gene bank reveals that alleles associated with conditions such as Alzheimer’s disease and type 2 diabetes can be traced to distinct ancient groups, including hunter-gatherers. This highlights how diverse ancestral populations contributed different genetic risk profiles that persist in modern populations.
The resource will allow researchers to investigate other neurological and psychiatric disorders — including Parkinson’s disease, autism spectrum disorders, ADHD, schizophrenia, bipolar disorder and depression — by linking ancient genetic variation to present-day disease risk.
The Lundbeck Foundation GeoGenetics Centre – the resource underpinning the discoveries
The Lundbeck Foundation GeoGenetics Centre supported the construction of the first large-scale gene bank of ancient human DNA. For the first time, researchers can use a comprehensive, time-resolved dataset to study how selection, migration and changing lifestyles shaped the genetic architecture of disease over thousands of years. The team plans to make these data accessible to the research community, subject to governance and ethical oversight.
“Creating a gene bank of ancient DNA from Eurasia’s past inhabitants was a colossal endeavour requiring collaboration with museums and collections across the region,” said Professor Eske Willerslev. “Combined with modern genetic data and interdisciplinary expertise, this archive is a precision tool for discovering how ancient immune systems influence disease risk in today’s world.”
Funding and next steps
The project received financial support from the Lundbeck Foundation. The team is already fielding requests from disease researchers globally to use the ancient DNA profiles and aims to provide wider access in the future. Ongoing work will apply the gene bank to additional disorders and refine our understanding of how ancient adaptations interact with modern environments to shape health.
About this evolution, genetics, and neurology research news
Author: Jacqueline Garget
Source: University of Cambridge
Contact: Jacqueline Garget – University of Cambridge
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations” by William Barrie et al. Nature
Abstract
Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations
Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that is most prevalent in northern Europe. While many MS risk alleles are located in or near immune-related genes, the timing and pathways through which this inherited risk entered European populations were previously unclear. Using a large ancient genome dataset spanning the Mesolithic through the Bronze Age, together with new medieval and post-medieval genomes, the authors show that MS-associated genetic risk increased among pastoralist groups on the Pontic Steppe and entered Europe with Yamnaya-related migrations about 5,000 years ago. These immunogenetic variants then underwent positive selection in steppe and later European populations, likely driven by shifts in pathogen exposure, diet, lifestyle and population density. The study highlights the Neolithic and Bronze Age as critical periods that shaped modern immune responses and subsequent MS risk in changing environments.