Ancient DNA traces origins of MS to 5,000-year-old migrations

Researchers have created the world’s largest ancient human gene bank by analyzing the bones and teeth of nearly 5,000 people who lived in Western Europe and Asia 34,000 years ago.

By sequencing ancient human DNA and comparing it to modern samples, the international team of experts mapped the historical spread of genes – and diseases – over time as populations migrated.

The “amazing” results were revealed in four groundbreaking research papers published in the same issue Nature and provide a new biological understanding of debilitating disorders.

The outstanding study involved a large international team led by Professor Eske Willerslev at the Universities of Cambridge and Copenhagen, Professor Thomas Werge at the University of Copenhagen and Professor Rasmus Nielsen at the University of California, Berkeley, and involved contributions from 175 researchers from around . the globe.

The new study found that genes that significantly increase the risk of developing multiple sclerosis (MS) were introduced into northwestern Europe about 5,000 years ago by sheep and cattle herders who migrated from the east. Image credit: SayoStudio

Scientists found:

• The surprising origins of neurodegenerative diseases, including multiple sclerosis
• Why Northern Europeans today are taller than Southern Europeans
• How the great migration about 5,000 years ago introduced risk genes into the population of northwestern Europe – leaving a legacy of higher rates of MS today
• Carrying the MS gene was one advantage at the time as it protected ancient farmers from contracting infectious diseases from their sheep and cattle
• Genes known to increase risk of diseases such as Alzheimer’s and type 2 diabetes identified in hunter-gatherers
• Future analysis hopes to reveal more about the genetic markers of autism, ADHD, schizophrenia, bipolar disorder and depression

Northern Europe has the highest prevalence of multiple sclerosis in the world. A new study has found that genes that significantly increase the risk of developing multiple sclerosis (MS) were introduced to northwestern Europe about 5,000 years ago by sheep and cattle herders who migrated from the east.

By analyzing the DNA of ancient human bones and teeth found at documented sites across Eurasia, the researchers traced the geographic spread of MS from its origins in the Pontic Steppe (an area spanning parts of present-day Ukraine, Southwestern Russia, and the Western Kazakhstan region ).

They found that the genetic variants associated with MS risk “traveled” with the Yamnaya people – pastoralists who migrated over the Pontic Steppe into Northwestern Europe.

These genetic variations provided a survival advantage to the Yamnaya people, likely protecting them from infection from their sheep and cattle. But they also increased the risk of developing MS.

“It must have been a distinct advantage for the Yamnaya people to carry the risk genes for multiple sclerosis, even after their arrival in Europe, despite the fact that these genes undoubtedly increased the risk of developing MS,” said Professor Eske Willerslev, jointly at the Universities of Cambridge and Copenhagen and Fellow of St John’s College, expert in ancient DNA analysis and Director of the project.

He added: “These results change our view of the causes of multiple sclerosis and have implications for how it is treated.”

The age of the samples ranges from the Mesolithic and Neolithic to the Bronze Age, the Iron Age and the Viking period to the Middle Ages. The oldest genome in the dataset comes from an individual who lived about 34,000 years ago.

The findings provide an explanation for the ‘North-South Gradient’, in which there are about twice as many modern-day MS cases in northern Europe as in southern Europe, which has long been a mystery to researchers.

Genetically, the Yamnaya people are believed to be the ancestors of the current inhabitants of much of Northwestern Europe. Their genetic influence on the current southern European population is much weaker.

Previous studies have identified 233 genetic variants that increase the risk of developing MS. These variants, which are also influenced by environmental and lifestyle factors, increase the risk of disease by about 30 percent. The new research found that this modern MS genetic risk profile is also present in bones and teeth thousands of years old.

“These results surprised us all. They provide a giant leap forward in our understanding of the evolution of MS and other autoimmune diseases. Showing how our ancestors’ lifestyles affected modern disease risk just highlights how much we are recipients of ancient immune systems in a modern world,” said Dr William Barry, a postdoctoral fellow in the Department of Zoology at the University of Cambridge and co-author of the paper.

Multiple sclerosis is a neurodegenerative disease in which the body’s immune system mistakenly attacks the “insulation” that surrounds the nerve fibers of the brain and spinal cord. This causes flare-ups of symptoms, known as relapses, as well as long-term degeneration, known as progression.

Professor Lars Fugger, co-author of the multiple sclerosis study, professor and consultant physician at the John Radcliffe Hospital, University of Oxford, said: “This means we can now understand and aim to treat multiple sclerosis as it is in fact: the result of a genetic adaptation to certain environmental conditions that occurred in our prehistory.”

Professor Astrid Iversen, another co-author based at the University of Oxford, said: “We now live very different lives to our ancestors in terms of hygiene, diet and medical treatment options and this combined with our evolutionary history means we can be more vulnerable to certain diseases than our ancestors, including autoimmune diseases like MS.”

The new findings were made possible by analyzing data held in a unique gene bank of ancient DNA created by researchers over the past five years with funding from the Lundbeck Foundation.

This is the first gene bank of its kind in the world. It has already enabled exciting new insights into areas from ancient human migrations to genetically determined risk profiles for developing brain disorders.

By analyzing the bones and teeth of nearly 5,000 ancient humans, held in museum collections across Europe and West Asia, the researchers created DNA profiles ranging from the Mesolithic and Neolithic to the Bronze Age, Iron Age and Viking period to the Middle Ages. They compared ancient DNA data with modern DNA from 400,000 people living in Britain, held in the UK Biobank.

“Creating a gene bank of ancient DNA from people of Eurasia’s past was a colossal project, involving collaboration with museums across the region,” said Willerslev.

He added: “We have demonstrated that our gene bank works as a precision tool that can give us new insights into human disease when combined with analyzes of current human DNA data and inputs from many other research fields. That in itself is amazing and there is no doubt that it has many applications beyond MS research.”

The team now plans to investigate other neurological conditions, including Parkinson’s and Alzheimer’s, and psychiatric disorders, including ADHD and schizophrenia.

They have received requests from disease researchers around the world for access to the ancient DNA profiles and eventually aim to make the gene bank open access.

The research was funded by an 8 million euro grant from the Lundbeck Foundation and was carried out at the Lundbeck Foundation Center for Geogenetics at the University of Copenhagen.

Jan Egebjerg, Director of Research at the Lundbeck Foundation, said: “The rationale for awarding such a large research grant to this project, as the Lundbeck Foundation did in 2018, was that if it all worked, it would represent a ground-breaking means of obtaining a deeper understanding of how the genetic architecture underlying brain disorders has evolved over time; And brain disorders are our particular area of ​​focus.”

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