Genetic changes that predispose people to developing multiple sclerosis (MS) first emerged among herding populations who migrated to Eastern Europe thousands of years ago and then spread across the continent, new research has found.
Researchers think these genetic variations may have helped turbocharge the immune system, making it easier to fight off infections, but in modern times, these once-advantageous changes may instead lead to autoimmune diseases like MS.
“These results astounded us all. They provide a huge leap forward in our understanding of the evolution of MS and other autoimmune diseases,” William Barrie, PhD, a postdoctoral researcher at the University of Cambridge and co-author of the study, said in a university news story.
The study, “Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations,” was published in Nature.
Certain genetic variations associated with increased MS risk
In MS, the body’s immune system mistakenly launches an attack targeting healthy parts of the brain and spinal cord. While the causes of MS aren’t fully understood, it’s been established that certain genetic variations are associated with an increased risk of MS.
MS is much more common in northern Europe than in southern parts of the continent, and variations in genetics among ethnic groups are thought to be one of the reasons. However, it hasn’t been clear why some northern European populations would have more MS risk genes.
To find out, scientists conducted detailed genetic analyses using samples from ancient human bodies found in Europe dating back as far as 34,000 years ago.
“Creating a gene bank of ancient DNA from Eurasia’s past human inhabitants was a colossal project, involving collaboration with museums across the region,” said Eske Willerslev, a professor at Cambridge and study co-author.
“We’ve demonstrated that our gene bank works as a precision tool that can give us new insights into human diseases, when combined with analyses of present-day human DNA data and inputs from several other research fields. That in itself is amazing, and there’s no doubt it has many applications beyond MS research,” Willerslev added.
These results astounded us all. They provide a huge leap forward in our understanding of the evolution of MS and other autoimmune diseases.
From these analyses, the team deduced that many genetic variants associated today with a high risk of MS first appeared in the Pontic-Caspian steppe, which is a region of eastern Europe including parts of modern-day Ukraine, as well as southwest Russia and western Kazakhstan. The MS-associated variants became common among a herding group known as the Yamnaya people.
Over the years, the Yamnaya migrated north and west, and many people in modern-day northern Europe have genetic ancestry that traces back to these ancient herders. Thus, the findings provide a general timeline for how these MS risk genes appeared and spread to parts of the continent where the disease is now common.
“While 5,000 years ago farmer ancestry predominated across Europe, a relatively diverged genetic ancestry arrived with the steppe migrations around this time,” the scientists wrote.
“These results address the long-standing debate around the north-south gradient in MS prevalence in Europe and indicate that the steppe ancestry gradient in modern populations … across the continent may cause this phenomenon,” they noted.
Genetic variants may have helped ancestors fight off infections
Many of these MS risk variants affect genes that are part of the immune system, and specifically help the body to fend off infections and parasites. Because the Yamnaya were herders, these genetic variations may have helped make their immune systems more powerful, so they were better at fighting off infections that they could have picked up from their animals.
“It must have been a distinct advantage for the Yamnaya people to carry the MS risk genes, even after arriving in Europe, despite the fact that these genes undeniably increased their risk of developing MS,” Willerslev said.
This could also help to explain why MS has become more common in recent years. With rapid improvements in sanitation over the last century, our immune systems no longer have to deal with many of the infections and parasites that plagued our ancestors. In people with a genetic predisposition toward more immune activity, this could plausibly set the stage for autoimmune diseases.
“The fine balance of genetically driven cell functions within the immune system, which are needed to combat a broad repertoire of pathogens and parasites without harming self-tissue, has been met with new challenges, including a potential absence of requirement,” the researchers wrote.
Willerslev said, “These results change our view of the causes of multiple sclerosis and have implications for the way it is treated.”
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January 12, 2024 at 11:19PM
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Ancient DNA reveal how MS risk genes spread across Europe - Multiple Sclerosis News Today
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