Origin of multiple sclerosis is revealed by DNA analysis – 01/11/2024 – Science

DNA obtained from the bones and teeth of Europeans who lived up to 34,000 years ago is providing new insights into the origins of multiple sclerosis. According to a new study, genetic variants that now increase the risk of the disease have already served to protect humans from diseases transmitted by animals.

The findings resulted from research involving sequenced DNA from 1,664 people from various locations in Western Europe and Asia. These ancient genomes were then compared with modern DNA from the UK Biobank, which comprises around 410,000 people self-identified as white and British, and more than 24,000 others born in other countries, to identify changes over time.

Autoimmune, multiple sclerosis is a chronic disease of the brain and spinal cord in which the body mistakenly attacks itself.

Researchers have identified a pivotal migratory event about 5,000 years ago, in the Early Bronze Age, when a people of cattle herders called the Yamnaya moved into Western Europe from an area that includes modern Ukraine and southern Russia.

They carried genetic traits that at the time were beneficial, protecting against infections that could arise in their sheep and cattle. As health conditions improved over the millennia, these same variants increased the risk of multiple sclerosis. This helps explain, the researchers said, why northern Europeans have the highest prevalence of multiple sclerosis in the world, twice that of southern Europeans.

“We are a product of evolution that occurred in past environments, and in many ways we are not ideally adapted to the environment we have created for ourselves today,” said Rasmus Nielsen, a population geneticist at the University of California at Berkeley, one of the leaders of research published this Wednesday (10) in the journal Nature.

Around 11,000 years ago, farmers from the region of modern Turkey expanded into Western Europe, replacing hunter-gatherers. It was these farmers that the Yamnaya later replaced.

“The Yamnaya were Europe’s first true nomads. They used domesticated cattle and horses to access the interior of the Asian steppes, where there is little to eat or drink, so they carried everything with them in carts. Physically, they were extraordinarily large, which we can see by measuring skeletons and also genetically, and apparently quite violent,” said Cambridge University geneticist and study co-author William Barrie.

“We believe that much of the replacement that occurred involved war,” Nielsen added.

High Yamnaya-related ancestry exists in northern Europeans, peaking in Ireland, Iceland, Norway and Sweden and to a lesser extent in the south.

The findings highlight how genetic traits can shift from beneficial to deleterious as conditions evolve.

“The frequency of pathogenic infections increased during the Bronze Age, due to the proximity between people and their domestic animals, as well as increasing population density,” said Evan Irving-Pease, an expert in computational evolutionary biology at the University of Copenhagen and co-author of the research.

“It was only in the modern era, with widespread sanitation and medical care, that these genetic variants became surplus to our immunological needs, resulting in an increased risk of developing multiple sclerosis and other autoimmune diseases,” Irving-Pease added.

The findings could have implications for multiple sclerosis research and treatment.

“This changes our view of multiple sclerosis, helping us understand its origins. We can see the disease as the result of an immune system that evolved efficiently to deal with a range of infections in the human past, but which now exists in an environment very different. This difference between past and modern sanitary environments likely causes the overactive immune system. This implies that we should aim to recalibrate the immune system rather than suppress it,” said Barrie.

The research also shed light on other characteristics of Europeans.

Because the Yamnaya were genetically predisposed to be tall, present-day northern Europeans tend to be taller than southern Europeans, who have greater ancestry from Neolithic farmers who are genetically predisposed to be short.

Eastern Europeans have an elevated genetic risk of Alzheimer’s and type 2 diabetes, researchers have found. They also realized that lactose tolerance, the ability to digest the sugar in milk and other dairy products, emerged in Europe approximately 6,000 years ago.