Ancient remains give clues to modern maladies
Prehistoric gene mutations helped humans survive but cause folks much misery today
Multiple sclerosis, an autoimmune disease that affects 2.9 million people, presents a biological puzzle.
Many researchers suspect that the disease is triggered by a virus, known as Epstein-Barr, which causes the immune system to attack the nerves and can leave patients struggling to walk or talk. But the virus can’t be the whole story, since nearly everyone is infected with it at some point in life.
A recent study found a possible solution to this paradox in the skeletal remains of a lost tribe of nomads who herded cattle across the steppes of western Asia 5,000 years ago. The nomads carried genetic mutations that most likely protected them from pathogens carried by their animals but also made their immune systems more sensitive. These genes, the study suggests, made the nomads’ descendants prone to a runaway immune response.
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 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.
Researchers published the multiple sclerosis study as well as three other papers on the genetics and health of ancient peoples in the journal Nature.
For more than a decade, Willerslev and other researchers have been pulling DNA from ancient human bones. By comparing 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.
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 swept 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 huntergatherers.
Willerslev wondered what kind of genetic variations each ancient group carried and how those variations affected their health. To find out, the researchers studied their living descendants.
They took advantage of
UK Biobank, a database of DNA and medical information. Most of the 433,395 volunteers that were 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.
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 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 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 the earliest farmers in Europe. But the Yamnaya remains contained the genetic signatures of many 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 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.
Those conditions provided an opportunity for diseases to jump to humans. In response, the Yamnaya evolved immune-related genes that helped them fend off the new enemies.
Dr. Lars Fugger, a multiple sclerosis expert at the University of Oxford who worked with Willerslev on the studies, said that the disease may not have become common until recently. In today’s environment, with less infectious disease than past centuries, he said, a strong immune system is more likely to misfire, attacking its own body.
“Many of us are living in an environment that is squeaky clean,” Fugger said. “The balance is no longer there.”
Researchers are analyzing other diseases, such as schizophrenia and psoriasis. “This is just the beginning,” Fugger said.