How did multiple sclerosis reach Europe?

In 2017, multiple sclerosis affected 110,000 people in France, and the number of new cases is estimated at about 5,000 annually. This autoimmune disease, which today affects more than 2.5 million people worldwide, especially in northern Europe, causes the immune system to attack the membrane covering that surrounds nerve cells in the brain and spine. The resulting lesions cause motor, cognitive and even visual disturbances. This disease, which appears on average around the age of 30, is the leading cause of severe disability of non-traumatic origin in young people. If current treatments only partially alleviate patients' symptoms, their effectiveness is very relative in the medium term, and does not prevent the disease from progressing. Moreover, a number of mysteries still surround multiple sclerosis, the most notable of which is the unequal distribution around the world, with twice as many cases recorded in northern Europe as in southern Europe. Recently, in order to better understand this neurological disease, an international team of 175 researchers, led by Eske Willerslev, from the University of Copenhagen, became interested in its genetic origins and geographical spread over time.

To do this, scientists used paleontological methods, which are increasingly used to understand the evolution of our immunity over time, our diseases, and human health, in a global way. From bones and teeth, they extracted, sequenced and analyzed ancient DNA from 86 people who lived across Eurasia, and combined it with 1,664 individuals analyzed in other studies – the oldest of which is 45,000 years old, the most recent dating back to the Middle East. Ages. Comparing this data with modern samples then allowed them to map the spread of local mutations in genes known to be responsible for certain diseases over time.

Northern Europe has the highest prevalence of multiple sclerosis in the world. However, maps by Eski Willerslev and his team show that mutations discovered in genes known to increase the risk of the disease were introduced into northern and western Europe about 5,000 years ago. They actually traveled among the Yamnaya people, pastoralists who migrated en masse from the east and the Pontic steppe (a region that today includes Ukraine, southwestern Russia, and western Kazakhstan). In these individuals, the genetic variants involved provided a selective advantage, presumably protecting them from infectious diseases carried and transmitted by their sheep and cattle. However, from a genetic point of view, the Yamnaya are estimated to be the ancestors of the current populations of much of northwestern Europe, and that their genetic influence on the southern populations is much less. This would explain the famous north-south gradient observed in the prevalence of MS in Europe.

Previous studies have already identified 233 genetic variants responsible for a 30% increase in the risk of developing multiple sclerosis, especially when associated with certain environmental or lifestyle factors. However, analysis of ancient DNA from individuals who lived in the Middle Ages has shown that these variants were already present in 1,000-year-old bones. For researchers, this discovery highlights how much our diseases today depend on the immune systems of our ancestors. Because our lifestyle is radically different from that of our ancestors, in terms of hygiene, diet and medicines, we may be more susceptible to certain diseases than they are.

In addition to this work, this consortium of researchers used a massive database of ancient DNA from more than 5,000 individuals. Using this, they traced genes known to play a role in the development of Alzheimer's and type 2 diabetes to hunter-gatherer societies. Furthermore, the team believes that future analyzes should shed light on genetic markers for autism, attention disorders, schizophrenia, bipolar disorders, and even depression. Many disorders that continue to greatly confound the medical profession. In the meantime, this work allows us to better understand the nature of multiple sclerosis: it is likely the result of genetic adaptation to certain environmental conditions dating back to prehistoric times. In doing so, they should help medical research develop more effective treatments.