June 21, 2024

Ancient DNA Provides Clues Into Multiple Sclerosis Origins and Health Risks for Modern Europeans

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Jan 14, 2024

Researchers have uncovered new insights into the origins and genetic risk factors for multiple sclerosis (MS) in Europeans by analyzing DNA from thousands of ancient human remains. The findings trace back the introduction of MS risk genes to ancient Yamnaya herders who migrated into Europe from the Steppe grasslands over 5,000 years ago.

Yamnaya Migration Spread MS Genetic Risk

A study published this week in Nature analyzing DNA from over 500 prehistoric Northern Europeans connects the rise of MS risk genes to the migration of Yamnaya herders into Europe. The Yamnaya were nomadic cattle and sheep herders that originated in the Steppe grasslands of modern-day Russia and Ukraine and began migrating west into Europe around 5,300 years ago.

This mass migration, one of the most transformational in European prehistory, spread Yamnaya genetics and culture widely across the continent. These ancient herders introduced alleles, or gene variants, that gave protection against certain infections in their livestock but inadvertently increased susceptibility to autoimmune disorders like MS in human descendants.

“We find that prehistoric migrations transmitted genetic risk alleles for multiple sclerosis into northern Europe,” said senior author Dr. David Reich, a geneticist at Harvard Medical School. “This helps explain the elevated incidence of multiple sclerosis compared to southern Europe today.”

Key Findings:

  • More than 30 regions of the human genome show strong evidence of introgression from Yamnaya herders
  • Many of these regions contain immune-related genes and pathways that affect risk of autoimmune disease
  • Alleles related to MS risk likely provided protection from animal infections but increased susceptibility in humans over time
  • Northern Europeans on average derive up to 20% of their ancestry from Yamnaya
  • This Yamnaya admixture is significantly associated with MS genetic risk in modern populations

MS Incidence Highest Where Yamnaya Genes Most Prevalent

The areas of Europe today with the highest rates of MS also have the strongest Yamnaya genetic ancestry. For example, contemporary British people have about 20% Yamnaya descent and an MS rate of 208 cases per 100,000 people annually. Southern Europeans like Spanish derive less Yamnaya ancestry (about 8%) and have lower MS incidence around 125 cases annually per 100,000.

“This ancient DNA evidence powerfully connects prehistoric migrations to modern health disparities we see across Europe today,” said population geneticist Dr. Fernando Racimo of the Globe Institute. “It suggests northern Europeans inherited higher levels of MS risk from their Yamnaya ancestors.”

Further analyses of these ancient genomes found that selection may have slowly increased the frequency of these immune-related risk alleles over generations as Europeans adapted to local pathogens. But the genes still boost autoimmune disease susceptibility today.

“It’s quite possible these gene variants protected Yamnaya early on from certain livestock infections critical to their pastoralist lifestyle on the Steppe grasslands,” Racimo explained. “But the story didn’t end there – human evolution and adaptation continued, with consequences still impacting health today.”

MS Incidence May Continue Increasing Over Time

Some experts theorize that MS rates in Northern Europe may actually continue rising over coming generations due to lingering immune adaptation and increased genetic load from the Yamnaya inheritance.

“This study really underscores the dynamic nature of human evolution – immune responses favored in one context can elevate disease risk down the road,” said MS geneticist Dr. Jennifer Graves of Uppsala University, who was not involved with the research. “Selection and adaptation has not necessarily optimized health outcomes in modern environments.”

She thinks MS incidence could spike further over time before leveling off. “We might see an uptick in MS rates in the near future across Northern Europe as populations better adapt these high-risk Yamnaya immune gene variants to more sanitized environments and lifestyles,” Graves said. “Over a longer timescale though, other selective pressures may start to constrain and reduce this genetic susceptibility again.”

The researchers hope this ancient DNA evidence will lead to better understanding of MS origins and spark investigation into novel risk genes. Additional Yamnaya samples from other regions may reveal more about how these variants confer protection from specific historical infections while elevating autoimmunity today. Reconstructing these evolutionary dynamics in detail could suggest pathways for mitigating MS pathology moving forward.

“Beyond the high level picture, which variants matter most functionally? How do they interact with different pathogens or stimuli?” said David Reich. “Lots of open questions remain, but this type of paleogenomic study focusing on immune evolution provides a roadmap for future research.”

Implications Beyond MS – Other Diseases Also Affected

This ancient DNA analysis also revealed the Yamnaya migration increased genetic risk for several other inflammatory conditions still common in European descendants today. Regions under selection harbor variants that contribute to higher rates of hypothyroidism, Crohn’s disease, ulcerative colitis, psoriasis, celiac disease, and even rheumatoid arthritis as well.

Type 1 diabetes shows the starkest signal, with Nordic countries exhibiting 10X higher rates than southern European nations today. Researchers confirmed this corresponds to a large difference in Yamnaya ancestry and associated T1D risk alleles.

Beyond autoimmunity and inflammation, Reich’s team also reported Neolithic farmer ancestry strongly predicts Alzheimer’s disease susceptibility for contemporary Europeans. This highlights how ancient migrations broadly shaped the genomic risk burden and health outcomes of descendant populations today across diseases.

“These findings illustrate how you may have inherited higher risk of certain illnesses based merely on your genomic ancestry – before even considering any cultural or environmental variables,” added author Anders Bergstrom. “Which ancient groups your ancestors mingled with can significantly impact disease prognosis thousands of years later, for better or worse.”

Understanding exactly when and how these genetic risk factors entered European populations and rose in frequency opens up avenues for treatment and prevention to reverse those disease outcomes in living populations.

While more work remains, these revelations shed new light on the deep origins behind modern health issues based on ancient migrations and admixture history. European populations..




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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