Where Did the Multiple Sclerosis Genes Originate?

A global team of 175 researchers has mapped the historical dissemination of genetic traits and their associated diseases. They discovered that genetic variations linked to an increased risk of multiple sclerosis traveled alongside the Yamnaya people, known for establishing the pit grave culture. These pastoralists, who moved into Northwestern Europe, were primarily cattle herders.

Multiple sclerosis (MS) is characterized as an autoimmune disorder that gradually damages the myelin sheath surrounding nerves, resulting in progressive motor impairment. The geographic birthplace of MS can be traced back to the Pontic Steppe, encompassing regions of present-day Ukraine, southwestern Russia, and western Kazakhstan, where the initial mutation likely occurred, introducing genes that heightened disease susceptibility.

Researchers hypothesize that these disease-related genes were once advantageous for health. They suggest that these genes initially offered the Yamnaya a survival edge, protecting them from diseases contracted from livestock.

"Carrying these genes must have conferred a distinct advantage to the Yamnaya, even after their arrival in Europe, despite the increased risk of developing multiple sclerosis," stated Professor Eske Willerslev, the project leader.

Prior genetic investigations indicated that the Yamnaya are the ancestors of many modern populations across Northwestern Europe. This new insight clarifies why multiple sclerosis cases are most concentrated in the northern regions of the continent and explains the observed "north-south gradient," where the incidence of MS is approximately doubled in northern Europe compared to the south—a long-standing conundrum for researchers.

Changing Perspectives on Multiple Sclerosis

This research also pinpointed the timeline for when these new genetic variations emerged in northern Europe, occurring around 5,000 years ago. These findings alter our understanding of the origins of multiple sclerosis and could influence future therapeutic strategies. They emphasize that the primary cause of the disease is genetic.

"This means we can now comprehend and address multiple sclerosis for what it truly is: a genetic condition shaped by our environmental adaptations throughout prehistory," explained Prof. Lars Fugger, co-author of the study and consultant at John Radcliffe Hospital, University of Oxford.

This phenomenon is not isolated; several other conditions are recognized as evolutionary adaptations. Examples include cystic fibrosis, sickle cell anemia, and hemochromatosis.

Previously conducted studies on multiple sclerosis failed to clarify its causes, with 233 genetic variants identified that elevate the risk of developing MS by approximately 30%.

Other Genetic Insights

It appears that the genetic makeup of the Yamnaya may also contribute to the taller stature of Northern Europeans compared to individuals from other parts of the continent. The studies published in “Nature” have also illuminated other diseases beyond multiple sclerosis. For instance, it has been found that Southern Europeans show a genetic predisposition to bipolar affective disorder, while Eastern Europeans face an increased genetic risk for Alzheimer’s disease and type 2 diabetes.

The research team is eager to further explore the prehistoric origins of additional neurological disorders. They aspire that continued DNA analysis of ancestral remains will enhance our understanding of conditions like Parkinson's and Alzheimer's, alongside various mental health issues such as ADHD, bipolar disorder, autism, depression, and schizophrenia.

The first video, "CARTA: Ancient DNA and Human Evolution – Johannes Krause," delves into the implications of ancient DNA studies on our understanding of human evolution and its relevance to modern health issues.

The second video, "Lecture | Genetic History of Europe Adaptation and Migration in Prehistory | Johannes Krause," discusses the historical genetic migrations in Europe and their impact on contemporary health conditions.