Ancient Human DNA Provides ‘Quantum Leap’ in Understanding Modern Disease
New research published this week in the journal Nature has uncovered important new insights into the genetic origins of multiple sclerosis (MS), showing how variants that may have initially evolved to fight ancient viral infections ended up predisposing some modern populations to the autoimmune disease.
Analyzing DNA from more than 500 ancient human remains across Europe and Central Asia spanning the last 35,000 years, an international team of scientists found evidence that current genetic risk factors for MS appeared in populations descended from Steppe pastoralists who lived about 5,800 years ago. These nomadic horseback riders from the Yamnaya culture likely picked up the disease variants from even earlier hunter-gatherers and farmers as they migrated west into Europe.
“This study provides a quantum leap in our understanding of MS genetics,” said senior study author Johannes Krause of the Max Planck Institute for Evolutionary Anthropology. “For the first time, we can connect the dots from modern risk variants to their origins thousands of years ago and begin to grasp the evolutionary forces that have shaped one of the most common neurological disorders.”
Ancient Adaptations Lead to Modern Susceptibility
The research team, including scientists from Cambridge University, Massachusetts General Hospital, and the Broad Institute of MIT and Harvard, reconstructed the largest genomic transect of Eurasian history to date. By comparing the genomes of these ancient individuals to those of nearly half a million modern people, they could precisely track changes in MS risk variants over time.
They found that three major variants emerged in a population known as Eastern Hunter Gatherers about 35,000 years ago, likely as an adaptation to fight off infections from ancient retroviruses or herpesviruses. These protective variants were then passed down and also picked up by early European Farmers migrating from Anatolia beginning 8,500 years ago.
| Origin of Key MS Risk Variants |
|—|
| 35,000 years ago | Appear in Eastern Hunter Gatherers as adaptation against viral infections |
| 8,500 years ago | Variants spread to early European Farmers migrating from Anatolia |
| 5,800 years ago | Further spread through Yamnaya Steppe pastoralists |
When the Yamnaya swept westward into Europe about 5,800 years ago, they carried these risk factors with them. The genes continued spreading among descendant Northern European populations over subsequent millennia to the point where they now explain why MS rates are up to 3 times higher among individuals with British, Scandinavian, and other North European ancestry compared to those with Southern European ancestry.
“It is striking how a genetic variant that likely contributed to survival from infections thousands of years ago has now become a major risk factor for MS,” said senior study author David Reich of Harvard Medical School. This illustrates the “flip-side of adaptation,” where genetic variants that were once beneficial become detrimental in different environments over time.
Implications for Prevention and Treatment
Experts say these findings represent an exciting advancement, providing clues about the mechanisms driving MS susceptibility that could open up avenues for treatment and prevention.
“If we know MS risk variants originated thousands of years ago to fight viruses, that tells us these same pathways could be targeted therapeutically,” said Dr. Jennifer Graves of University College London, who was not involved in the study. “This research also highlights the need to understand these variants in context – protective in the past, risky now – which cautions against quick fixes like deactivating or removing them.”
Additionally, the data offers a reminder that genetic risk is not absolute destiny. Lifestyle factors like smoking, low Vitamin D levels, obesity, and lack of exercise are all known to influence MS risk above and beyond genetics.
“Genetics loads the gun, but the environment pulls the trigger when it comes to this complex disease,” said Tim Coetzee, Chief Advocacy Officer at the National MS Society. “Knowing your ancestry can help understand genetic risk, while living a healthy lifestyle is key for everyone to lower risk.”
The researchers also aim to continue exploring how ancient environmental factors and microbes might have interacted with human genes related to MS over history. Graves said further insights “could open up an era of gene-environment prevention strategies tailored to an individual’s genomic ancestry to help neutralize disease risk passed down from our ancestors.”
Looking Ahead
Moving forward, experts say this research ushers in a new paradigm for investigating modern disease origins by tracing genetic changes over thousands of years of human history.
“Most disease genetics studies look at present day individuals and make inferences about history over relatively short timescales” said Iain Mathieson, population geneticist at the University of Pennsylvania who helped lead the new research. This can lead to incomplete or even misleading understandings of causality.
Instead, Mathieson emphasizes that directly observing how ancient DNA relates to modern disease risk represents a “paleogenomics” approach that can provide more definitive and temporally-grounded insights.
The team plans to expand this work by studying more diseases like type 2 diabetes and schizophrenia, aiming to reveal the deeper historical forces shaping genetic disease risk and why health issues concentrate in some populations more than others.
“We have this incredible resource now – the largest ancient DNA dataset ever – that allows us to directly watch genetic risk evolve over tens of thousands of years,” said Mathieson. Unlocking these historical trajectories promises to overhaul understanding of human disease and “open up completely new possibilities for prevention in the future.”
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