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June 17, 2024

Ancient DNA Reveals Surprising European Origins of Multiple Sclerosis

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Jan 13, 2024

The origins of multiple sclerosis (MS), a debilitating neurological disease that affects nearly 1 million people in the United States, have long eluded scientists. But new research published this week in the journal Nature may finally unravel part of this medical mystery.

Analyzing DNA from over 4,500 ancient human remains across Europe and Asia, an international team led by researchers at Cambridge University discovered that genetic variants that increase MS risk arose among Steppe pastoralists in Eastern Europe and Russia around 5,000 years ago. These variants were then spread farther west in subsequent millennia by migrant farmers and herders.

Ancient Genomes Point to Steppe Origin

By sequencing full genomes from Bronze Age individuals spanning 8,000 years of Eurasian history, researchers assembled the largest genomic time transect of prehistoric humans to date. This allowed them to trace changes in gene frequency over time and space.

They found that genetic risk factors for not only MS, but also type 1 diabetes and rheumatoid arthritis, originated in groups such as the Yamnaya, who lived on the Steppe grasslands north of the Black Sea during the Copper Age and derived significant ancestry from Eastern Hunter Gatherers.

“It’s quite incredible that we can now directly reconstruct the population movements and mixing that happened thousands of years ago and trace how that impacts disease risk today,” said senior author Professor Eske Willerslev from the Lundbeck Foundation GeoGenetics Centre.

Bronze Age Migrations Spread MS Genes Westward

The Steppe groups played a key role in reshaping European ancestry after 3000 BC. As the Yamnaya and their descendants migrated west into Central Europe and then Northwestern Europe, they transmitted genetic variants that now predispose over 100 million European descendants to autoimmune diseases like MS.

“We show that processes starting with the Bronze Age Yamnaya expansions resulted in the evolution and continental-scale spread of genes that now make such a large proportion of European-ancestry groups vulnerable to specific diseases,” explained first author Dr Fernando Racimo.

In contrast, East Asians and closely related groups have an independently derived and more protective set of alleles that may buffer them against MS.

MS Genes Also Protect Against Infections

While detrimental today, the authors speculate these disease risk variants were likely beneficial in prehistory. Many arose due to strong selective pressures from epidemic pathogens, which have been a predominant cause of mortality throughout human evolution.

“It seems that as populations moved across Eurasia and adapted to new environments over thousands of years, certain genetic variants provided protection against ancient diseases but predisposed people to autoimmune conditions later in life,” said senior author Professor Richard Durbin.

Uncovering these complex evolutionary tradeoffs helps explain perplexing modern health disparities between and within populations.

What This Means for MS Today

These revelations around MS genetics may someday impact treatment strategies.

“If we can understand which components of the immune system go wrong first in MS, we may be able to stop the condition in its tracks by developing immunotherapies that target these specific immune pathways,” noted Professor James Pickett, Head of Research at the UK MS Society.

But genetics are only part of the puzzle ??? MS likely arises from a combination of genetic and environmental triggers. Smoking, low Vitamin D levels, obesity, Epstein-Barr Virus infection, and other external factors that have increased with modern lifestyles also influence MS risk.

“This study illustrates how modern genomics can reconstruct the deep history embodied in our DNA,” said Dr. Eric Lander, President and Founding Director of the Broad Institute of MIT and Harvard. “A deeper understanding of inherited disease risks allows us to better appreciate human diversity.”

Timeline of MS Genetic Origins and Spread

Date Event
8,000 years ago Genetic risk factors for MS first emerge in Eastern European Steppe pastoralists
5,000 years ago As Yamnaya expand westward into Europe, they transmit MS genetic variants and admixture to local farmer groups
3,000 years ago Bronze Age migrations continue spreading MS genes throughout Western Europe
100 years ago Neurologist Jean-Martin Charcot first clinically describes MS in 1868
Present Nearly 1 million individuals affected by MS in United States and over 2.8 million cases worldwide

Next Steps

Researchers plan to study individuals from different eras in Britain to analyze when and how MS risk alleles arrived in that area, which has among the highest prevalence today.

Scientists will also use similar techniques exploring ancient genomes to uncover the deep histories of other major diseases like cancer. Such evolutionary analyses can provide new insights to guide future drug development and personalized medicine strategies.

Ultimately, a holistic approach combining cutting-edge genomics with epidemiology, immunology and clinical research will be key to cracking the MS puzzle. This unprecedented peek into our prehistoric past is merely the first step on a long journey towards understanding and curing this complicated autoimmune illness.

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AiBot scans breaking news and distills multiple news articles into a concise, easy-to-understand summary which reads just like a news story, saving users time while keeping them well-informed.

To err is human, but AI does it too. Whilst factual data is used in the production of these articles, the content is written entirely by AI. Double check any facts you intend to rely on with another source.

By AiBot

AiBot scans breaking news and distills multiple news articles into a concise, easy-to-understand summary which reads just like a news story, saving users time while keeping them well-informed.

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