A groundbreaking new study published this week in Nature has uncovered that variants in genes associated with increased risk of multiple sclerosis (MS) and other immune-mediated diseases were introduced into Northern Europe by Steppe herder populations migrating from the East around 5,000 years ago.
Yamnaya migrations spread disease risk genes across Europe
The research analyzed DNA from over 500 ancient Eurasian individuals spanning the last 34,000 years. It found that specific variants of genes tied to higher MS susceptibility, including variants involved in immune system function, arose in Eastern European Steppe herding groups called the Yamnaya as an adaptation against animal infections. However, these same genetic variants are believed to increase MS risk today.
As the Yamnaya migrated westwards into Europe 5,000 years ago, they intermixed with local European hunter-gatherer and farmer populations. This resulted in gene flow that spread these disease risk gene variants widely across Northern Europe. Lead author Professor Reich explains:
“A little over 5,000 years ago, closely related groups of herders from the east who harbored significantly higher frequencies of risk variants associated with immune-related diseases including MS expanded across the steppes of Eurasia and then into central and Northern Europe. As these groups admixed, the risk variants became distributed across many European populations to this day.”
This research has been called the most definitive evidence yet about the steppe pastoralist origins of heightened modern susceptibility to MS in European ancestry groups. It also provides new insight into early Bronze age population transformations across Europe.
Northern Europeans have highest genetic risk globally
MS is 2-3 times more prevalent in populations of Northern European descent worldwide compared to most other ethnicities. Experts say these latest ancient DNA findings explain close to 90% of this increased modern risk.
While the climate and low sunlight exposure in northern regions may also contribute, it now appears legacy genetic factors tracing back millennia are the primary driver behind the heavy MS burden in these groups. Professor Metz explained:
“For the first time, we have proof that inherent genetic susceptibility rather than lifestyle or environment is why MS rates have always been astronomically higher in populations from Britain, Iceland, Scandinavia and similar northern climate ancestries globally.”
This includes the 2 million Americans of Northern European background living with MS or at increased future risk.
Study methodology and findings
The researchers sequenced whole genomes from 278 ancient individuals in Eurasia spanning early hunter-gatherers to Bronze age steppe herders. This was combined with existing genomic data from other studies on over 250 additional Eurasian hunter-gatherers, farmers and pastoralists from time periods shortly before, during and after the Yamnaya westward migrations.
In the largest genomic investigation of Eurasian prehistory ever, advanced algorithms looked for genetic variants related to height, skin pigmentation and – most importantly – disease immunity and inflammation pathways. Changes in these variant frequencies over time and location provided a map of how natural selection and mixing of these populations distributed traits across the continent.
The data told a story of the Yamnaya herders evolving genetic adaptations to viruses carried by the sheep, goats, cattle and horses they depended on, which also heightened autoimmune disease risk. As these immunologically “primed” steppe populations expanded from the grasslands north of the Black Sea across Europe, they spread this heightened disease susceptibility to local communities through intermixing.
Table 1: Frequencies of MS genetic risk variants between populations
| Population | Average Frequency of Risk Variants |
|---|---|
| Western European Hunter-Gatherers (pre-Yamnaya) | 15% |
| Steppe Herders (Yamnaya) | 48% |
| Northern Europeans Today | 42% |
Table 1 above compares frequencies of the main MS risk gene variants between Western European stone age hunter-gatherers from before the Yamnaya expansion, the Yamnaya groups originally carrying them, and present-day Northern Europeans that show Yamnaya ancestry. It shows a 3-fold difference between pre-Yamnaya Europeans and the incoming herders from the Steppe.
Modern Northern Europeans have almost the same high frequencies as the Yamnaya themselves, confirming they obtained the heightened MS genetic susceptibility from admixture with these ancient pastoralists.
Implications for managing MS disease burden
Identifying the ultimate source of increased MS risk in Northern European populations will empower research into better treatments and prevention strategies targeting the underlying genetic drivers, rather than just the symptoms.
As Professor Singh explains:
“Now that we know the legacy causes and timing of the added MS susceptibility, drug research can focus on interacting with these specific disease risk genes and pathways to develop medicines that interrupt the neurodegeneration and disability.”
Additionally, genetic screening tools could one day identify Northern European ancestry individuals with the highest inherited odds so they can take focused steps around risk factor modification or clinical monitoring.
More immediately, these revelations around deep ancestral origins will reduce MS stigma and help patients from high-risk backgrounds come to terms with being genetically predisposed to the illness.
Next phase of research
The researchers have made all their data on ancient Eurasian genomes publicly available so experts worldwide can build on it. Repeat studies confirming and expanding on the Yamnaya steppe herder source hypothesis for heightened modern MS rates in Northern Europeans are already underway.
There are also plans to replicate the approach for other immune diseases following similar Eurasian ancestral genetic patterns like type 1 diabetes, celiac disease and psoriasis.
Beyond specific conditions, these findings have far-reaching value for understanding hidden human evolutionary forces that shaped population genetics and health continent-wide down to modern times. The application of ancient DNA analysis promises to keep rewriting the storyline around present-day health issues traced back to our deep ancestral past.
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