Ancient DNA has revealed the origins of multiple sclerosis in Europe

More than 1,600 ancient genomes have helped trace the roots of a number of genetic characteristics found in modern Europeans. The genomes show that many characteristics - including an increased risk of multiple sclerosis - were brought to Europe by people who migrated to the continent in three different waves starting about 45,000 years ago.
The results show that some of the regional differences in some characteristics are due to differences in migrant displacement patterns. This contradicts the idea that genetic differences arose mainly as a result of people adapting to conditions in certain places in Europe.
"It's a real tour de force," said Lluis Quintana-Mursi, a population geneticist at the Institut Pasteur in Paris, who was not directly involved in the study. He says the study provides unprecedented detail about how ancient ancestors can influence disease risk even today. "This is a wonderful example of how solving very basic fundamental anthropological and genomic questions can inform medicine," he says.
Europe was settled by anatomically modern humans in three main waves: hunter-gatherers reached Europe from Asia about 45,000 years ago; farmers arrived from the Middle East 11,000 years ago; and pastoralists - herders of animals - came from the steppes of Western Asia and Eastern Europe 5,000 years ago. Archaeologists and historians have hypothesized that these groups intermixed across the continent and that populations in particular locations developed different traits in response to the local environment.
But when geneticist Eske Willerslev of the University of Cambridge, UK, and his team began examining the genomes of ancient humans, they discovered that this was not the whole story. The researchers collected and sequenced DNA from 317 ancient skeletons found in Europe, most of which were between 3,000 and 11,000 years old. They then combined these sequences with existing genomic data from more than 1,300 other ancient Eurasians.
By comparing the remains' genetic markers, age and burial sites, the scientists were able to construct a European family tree and migration map that reveals how the genomic characteristics of a particular location changed as populations moved over time. This shows, for example, that the steppe herders mainly moved to the more northern parts of Europe, while the farmers from the Middle East - to the southern and western ones.
Some of these migrants have completely replaced existing populations. Denmark, for example, has undergone two major demographic transitions, each within just a few generations. Villerslev says that the archaeological evidence and the speed of the transition show that the newcomers killed all the natives, rather than driving them out or mixing with them.
Patterns of displacement mean that many modern Europeans carry some genetic roots from all three population waves, but the relative proportion of each varies by location, Villerslev says.
The researchers then compared the ancient genomes with those of 410,000 modern individuals whose genetic profiles are stored in the UK Biobank, a huge database of genetic and physical information. The data provide clear evidence that many traits originate directly from one of the three migration waves.
For example, modern northern Europeans are taller and lighter-skinned than their southern counterparts because they have more ancestors than the steppe herders. And people with the most hunter-gatherer ancestors, typically found in northeastern Europe, have variants that put them at higher risk for diabetes and Alzheimer's disease.
Surprisingly, one trait that appears to have had a strong evolutionary advantage is that associated with susceptibility to multiple sclerosis. This trait arrived in Europe with West Asian pastoralists and became even more widespread in northern Europe over the following millennia.
Today, multiple sclerosis is a devastating disease caused by an overactive immune system that attacks the nervous system. But this overpowered immune system, or the genetic variants associated with it, may have helped ancient people survive epidemics and common pathogens," says Villerslev. "This is the best explanation we can come up with," adds the scientist/BGNES