Over time, as more and more myelin is removed, nerves can no longer transmit their signals, leading to mental and physical symptoms.

These symptoms include vision problems, a loss of sensation, and muscle weakness. As the disease progresses, disability becomes steadily more pronounced.

Scientists still do not know why people develop MS, and currently, there is no cure.

However, a fascinating recent study sheds some light on the evolution of the genetic underpinnings of the condition and may, in the future, help move toward better treatments.

Although scientists are still working on understanding the precise reasons why MS affects some people, genetic risk factors play a role.

The picture is complex, though. Not everyone with a gene variant associated with MS develops the condition. For instance, the gene variant with the strongest link to MS — called HLA-DRB1*15:01 — increases the risk threefold, but so far our understanding of genetic risk factors only explains around 30% of an individual’s risk of MS.

So, it seems that environmental factors, including infection, might trigger events within the body that eventually lead to MS in people with a genetic susceptibility. However, as it stands, there are many gaps in our understanding.

To investigate, the researchers compared around 410,000 genetic samples from UK Biobank participants who identified as “white British” with almost 5,000 ancient specimens.

These ancient DNA samples came from the bones and teeth of people living in Asia and Western Europe up to 34,000 years ago.

With these data, they could map the genesis and journey of MS risk variants through human populations. They first spotted the most significant MS risk gene variants — HLA-DRB1*15:01 — in an Italian Neolithic individual who lived around 5,800 Before the Common Era (BCE).

Starting around 5,300 BCE, it increased in prevalence within the Yamanya people. The Yamanya lived in steppe regions in modern-day Ukraine, southwest Russia, and Western Kazakhstan.

Experts consider the Yamanya to be the genetic ancestors of modern inhabitants of North-Western Europe.

These early livestock herders moved steadily west into Europe, bringing HLA-DRB1*15:01 in tow. This helps explain why, even today, people in Northern Europe have a greater risk of developing MS than other populations.

Evolution selects for genetic variants that confer specific traits that are favorable for the survival of an organism and its ability to reproduce.

One might imagine that a gene that trebles your risk of developing a debilitating and potentially fatal illness like MS would not be selected for. So, why did the prevalence of this genetic variant increase in the Northern European population, and then persist for millennia?

The authors of the study suggest that when HLA-DRB1*15:01 arrived on the scene, it may have imparted some benefits to these ancient people.

They explain that during the late Neolithic and Bronze Age, infectious disease risk increased. This was partly due to increasing population density.

At the same time, the Yamanya’s close contact with livestock opened them up to a suite of novel pathogens that humans would rarely have encountered before humans domesticated animals.

As the researchers explain, this increased contact with new and old pathogens would have meant that some variants in genes responsible for controlling the immune system could have conferred an evolutionary advantage they previously had not. There may also have been multiple potential effects of these genetic variants over an individual’s lifetime.

Beyond HLA-DRB1*15:01, the scientists investigated a range of other MS-associated gene locations, finding that many were also linked to “protection against a wide range of infectious challenges.”

In conclusion, a significant change in these people’s lifestyle resulted in an increased exposure to pathogens, leading to an increased prevalence of MS risk variants in Northern European populations, as it confered protection to infection by these pathogens.

“These results astounded us all. They provide a huge leap forward in our understanding of the evolution of MS and other autoimmune diseases. Showing how the lifestyles of our ancestors impacted modern disease risk just highlights how much we are the recipients of ancient immune systems in a modern world.”

Dr. Sy told MNT he was most excited about the complex implications about the genes highlighted in the study. “As these risk genes appear to affect the immune system, this study adds to the hypothesis that genes which confer an advantage in fighting infections also increase the risk of autoimmune disease,“ he noted.

Dr. Giesser has worked with people with MS since the 1980s. She explained that: “[n]erve damage in MS is caused by an attack on the immune system on the central nervous system.“

“Much of the immune system is under genetic control, and so any new insights into the genetic blueprint for MS will enable further understanding of how this process is triggered and may lead to more precise and effective therapies,” she added.

“Understanding the origins of MS may one day help identify MS earlier and more effectively prevent any damage to the central nervous system,“ Dr. Sy also noted.

The authors hope these genetic insights will help shape future medical interventions for these difficult-to-treat conditions.