Ancient remains provide clues to the mysteries of multiple sclerosis

Multiple sclerosis, an autoimmune disease that affects 2.9 million people, presents a biological conundrum.

Researchers believe the disease is triggered by a virus, Epstein-Barr, which causes the immune system to attack nerves and can make patients struggle to walk or talk. But the virus cannot be the whole story; Most people get it at some point in their lives.

A new study has found a possible solution to this paradox in the skeletal remains of a lost tribe of nomads who herded cattle in Asia 5,000 years ago. The nomads carried genetic mutations that likely protected them from pathogens carried by their animals, but also made their immune systems sensitive.

These genes made their descendants prone to an excessive immune response.

The finding is part of an effort to understand how the evolutionary past has shaped the health of living people. Researchers analyze thousands of genomes from people who lived between Portugal and Siberia and between Norway and Iran 3,000 to 11,000 years ago. They also hope to trace the genetic roots of diabetes, schizophrenia and other modern conditions.

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

For more than a decade, Willerslev and others have extracted DNA from ancient human bones. By comparing genetic material with that of living people, scientists have tracked some of the most important migrations of people around the world.

About 5,000 years ago, European DNA began to show the genetic signatures of shepherds living in steppes from Ukraine to Kazakhstan, called yamna. In the Bronze Age, the yamna spread throughout much of Asia and Europe. Today the people of northern Europe can trace most of their ancestry to the Yamna.

Further south, people have more lineage from Near Eastern farmers and European hunter-gatherers.

Willerslev's team wondered what genetic variations each ancient group carried and how they affected their health. To find out, the team studied their living descendants.

They turned to the UK Biobank, a huge database of DNA and medical information. Most of the 433,395 volunteers were born in Britain, but 24,511 were born in other countries.

The researchers linked thousands of genetic variants in the database to increased risks of various diseases. They then compared the volunteers' DNA with genetic fragments from ancient bones.

An analysis found that hunter-gatherers in Western Europe carried many of the variants that increase the risk of high cholesterol, hypertension and diabetes. Another showed that ancient farmers in the Near East carried variants linked to mood disorders.

Variants that increase the risk of multiple sclerosis have become increasingly common among the Yamna.

Some of the skeletons contained DNA not only from humans, but also from disease-causing viruses and bacteria. Many of these pathogens did not appear among hunter-gatherers or early farmers in Europe. But the yamna remains contained the genetic signatures of several pathogens, such as the one that caused the plague.

The team believes that the Yamna were more vulnerable to animal diseases than previous humans. The Yamna depended on animals for meat and milk and were in constant contact with their flocks.

These conditions allowed a new way for diseases to reach humans. In response, the Yamna developed genes related to the immune system that helped them defend themselves against new enemies.

By: CARL ZIMMER