Multiple sclerosis, a perplexing autoimmune disease affecting 2.9 million individuals, has long been a subject of scientific inquiry, with many researchers speculating that the Epstein-Barr virus plays a crucial role in triggering the condition. However, the intricate nature of the disease persists as nearly everyone encounters the virus at some point in life.

A groundbreaking study has recently delved into the skeletal remains of a lost nomadic tribe from 5,000 years ago, providing insights into the genetic mutations that may offer a solution to the paradoxical relationship between the virus and the autoimmune disorder.

The finding is part of a larger, unprecedented effort to understand how the evolutionary past has shaped the health of living people. Researchers are analyzing thousands of genomes of people who lived between Portugal and Siberia and between Norway and Iran roughly 3,000 to 11,000 years ago. They hope to trace the genetic roots of not only multiple sclerosis but also diabetes, schizophrenia and many other modern illnesses.

“We are taking ancient human genomics to a whole new level,” said Eske Willerslev, a geneticist at the University of Copenhagen who led the effort.

The researchers published the multiple sclerosis study as well as three other papers on the genetics and health of ancient peoples this month in the journal Nature.

For more than a decade, Willerslev and other researchers have been pulling DNA from ancient human bones. By comparing the surviving genetic material with that of living people, the scientists have been able to track some of the most significant migrations of people across the world.

The Movement of Farmers From What Is Now Turkey Across Europe

For example, they have chronicled the movement of farmers from what is now Turkey across Europe starting about 8,000 years ago. These early farmers encountered European hunter-gatherers who had lived on the continent for more than 30,000 years. In some places, hunter-gatherer DNA vanished from skeletons after the arrival of the farmers, suggesting violent conflicts. In other places, the two populations mingled enough to produce later generations with a mixed ancestry.

Thousands of years passed before the next big migrational shift. About 5,000 years ago, European DNA began to show the genetic signatures of a group of pastoralists, called the Yamnaya, who lived on the steppes that stretch from Ukraine to Kazakhstan.

The Yamnaya traveled on horses and in wagons across hundreds of miles of grassland, herding cows, goats and sheep along the way. Even without farms or cities, they prospered for centuries, burying their dead with gold and jewelry.

In the Bronze Age, the Yamnaya expanded their territory, sweeping through much of Asia as well as Europe. Willerslev and his colleagues have found that once in Europe, the group often wiped out the farmers it encountered, although they also had peaceful relations in some places.

Today, people in northern Europe can trace most of their ancestry to the Yamnaya. Farther south, Yamnaya ancestry is less common. People there instead have more ancestry from Near East farmers and Europe’s earlier hunter-gatherers.

Willerslev and his colleagues wondered what kind of genetic variations each ancient group carried and how those variations affected their health. To find out, the researchers studied some of their living descendants.

They took advantage of UK Biobank, a huge database of DNA and medical information. Most of the 433,395 volunteers whom the scientists studied were born in Britain, but 24,511 were born in other countries.

The researchers were able to tie thousands of genetic variants in the database to increased risks for a wide range of diseases. They then compared the volunteers’ DNA with the genetic fragments from ancient skeletons.

Hunter-Gatherers From Western Europe

One analysis found that hunter-gatherers from Western Europe carried many of the variants that raise the risk for high cholesterol, high blood pressure and diabetes. Another showed that ancient Near East farmers carried a high burden of variants linked to anxiety and other mood disorders.

These findings don’t necessarily mean that these ancient people suffered from these conditions. Genetic variants lay the trap, but it’s often the environment that springs it.

Diabetes, for example, has become increasingly common in the modern world, in part because of the cheap, sugar-loaded food that makes up an increasing part of our diet. In earlier centuries, high-risk genes for diabetes may not have had the opportunity to give rise to the disease.

In some cases, Willerslev and his colleagues found, these genetic variants provided ancient peoples with a survival advantage.

The variants that raise the risk of multiple sclerosis, for example, became steadily more common among the Yamnaya. The nomads who carried them appear to have had more offspring than those who didn’t.

“These variants that are causing the high risk of multiple sclerosis today must in the past have had a benefit,” Willerslev said.

The new studies give some strong hints about what that benefit is. Some of the skeletons contained DNA not just from humans, but also from disease-causing viruses and bacteria. Many of these pathogens did not appear among hunter-gatherers or even among the earliest farmers in Europe. But the Yamnaya remains contained the genetic signatures of a number of pathogens, including the one that caused plague.

“These variants seem to give some kind of protection from infectious diseases,” Willerslev said. A number of studies on multiple sclerosis suggest that the variants that raise the risk of the disease also make the immune system’s attack against viruses and bacteria more aggressive.

Willerslev and his colleagues argued that the Yamnaya were more vulnerable to animal diseases than previous humans were. The Yamnaya depended on animals for meat and milk and were in constant contact with their herds as they moved across the steppes.

Those conditions provided a new opportunity for diseases to jump to humans. In response, the Yamnaya evolved immune-related genes that helped them fend off the new enemies. “They’ve made a really, really compelling case,” Yassine Souilmi, a genomicist at the University of Adelaide in Australia, said of Willerslev and his colleagues. “I’ll be shocked if further experimental testing doesn’t match their conclusions.”