New research published this week demonstrates that variants of genes associated with increased risk of multiple sclerosis (MS) and other neurological conditions were introduced to Northern European populations by migrating sheep and cattle herders from the Eurasian Steppe around 5,000 years ago.
Yamnaya migrations spread genetic risk factors
The study, led by researchers from the University of Chicago, analyzed DNA from over 500 ancient Northern Europeans spanning the last 11,000 years. They discovered that lineages derived from the Yamnaya herders who migrated westwards from the Steppe around 3000 BCE carried gene variants that contribute to heightened modern-day MS susceptibility.
As the Yamnaya people intermingled with local European hunter-gatherers, these genetic risk factors became dispersed widely across Northern Europe. People with European ancestry today have therefore inherited a genetic legacy that makes them more prone to developing MS.
“It was migrations from the Steppe into Europe beginning 5,000 years ago that first brought the genetic variants that heighten risk of MS,” said senior study author Prof John Novembre. “It took mixtures between populations to bring these risk alleles together and create the genetics that facilitates disease.”
Implications for modern MS susceptibility
An accompanying editorial discusses the significance of these findings for contemporary Northern European populations:
“The visual image of a wave of Yamnaya genomes sweeping into Europe, carrying the seed of neurological disease susceptibility, is a stark demonstration that our genomes encode legacies that stretch back thousands of years.”
The authors explain that this Yamnaya genetic inheritance interacts with other modern disease risk factors to produce the high rates of MS seen across Northern Europe today:
“The ancient migrations revealed by population genetics explain only part of why MS is more common farther north. Likely what matters more today is that populations long-established in Northern Europe face other pressures — dietary, behavioral or otherwise environmental — that allow the consequences of this ancient genomic legacy to become fully manifest.”
Mystery of MS origins largely solved
These remarkable discoveries represent a major step forward in unraveling the deep origins of MS, which has long puzzled researchers.
“The findings provide a quantum leap in our understanding about the genesis of MS,” said an author of the research paper from Cambridge University. “We can now start piecing together how genetics and the environment combine to trigger the disease.”
However, the study also opens up new questions about precisely why these herder-derived gene variants were positively selected over successive generations, as one commentary notes:
“The most pressing question now is why natural selection has favoured, rather than purged, the MS variants. The genes may have protected our ancestors from infections caught from livestock.”
Further ancient DNA research tracing the origins of other complex neurological conditions influenced by multiple genetic and environmental factors, including Parkinson’s disease and Alzheimer’s disease, is now likely to follow.
Researchers suggest that these remarkable findings could pave the way for new therapeutic targets and ultimately new treatments for MS patients:
“Now that we are finally able to close in on the mechanisms behind the disease, this knowledge can be translated into potential targets for therapy,” said the Cambridge team.
However, specialists urge caution over the immediate clinical implications, stressing that translating insights from population-level genetics into patient treatments remains extremely challenging.
“Currently no immediate clinical utility for these results is apparent. Effective translation to patients requires surmounting complex challenges in human genetics and trial design that have heretofore stymied progress,” write National MS Society chief clinicians in an accompanying perspective article.
Nonetheless, the revelations represent an astonishing feat of biological detective work into the deep population histories encoded within our genomes.
“That echoes of herding-related migrations from five millennia in the past might shape multiple sclerosis susceptibility today is a testament to the extraordinary value of studying human history encoded within DNA,” conclude the authors of the original Nature study.
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