Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system, destroying the insulating layer of neurons in the brain and spinal cord, the myelin sheath, causing a series of symptoms such as neuritis, ophthalmoplegia, and limb paralysis, and the condition often worsens over time.
Data show that there are currently 2.9 million ms patients in the world, but the specific cause of the disease is not yet known in the academic community, and there is no ideal method.
A 2022 Science article showed that the common human herpesvirus, Epstein-Barr virus, is responsible for almost all cases of MS. Epstein-Barr virus can cause the immune system to attack nerves, causing symptoms such as fatigue, fever, pharyngitis, and even difficulty walking or speaking. The vast majority of people have been infected with the virus at some point in their lives and carry these latent people for a long time or even for life.
A recent study published in Nature suggests that the fossilized bones of a nomadic tribe in the steppes of West Asia 5,000 years ago reveal the genetic roots of multiple sclerosis. The genetic mutations possessed by the owners of the bones are likely to protect them from pathogens carried by animals, but it also makes their immune systems more sensitive, making their offspring prone to uncontrolled autoimmune reactions.
A skeleton from more than 4,000 years ago found in Bulgaria.
This work is part of a large-scale study of the human genome. The entire project team had the ambition of understanding how past evolution has shaped human health; The researchers were analyzing thousands of human genomes that lived between Portugal and Siberia and between Norway and Iran between 11,000 and 3,000 years ago.
Not only did they trace the origins of MS, but they also looked for the genetic origins of diabetes, psychiatric disorders, and many other modern diseases, "taking ancient human genomics to a whole new level."
Eske Willerslev, a geneticist at the University of Copenhagen who led the project, said they had been extracting DNA from ancient human bones for more than a decade. By comparing the genetic material that has survived to the present day with that of modern humans, scientists have traced some of the most important human migrations that have occurred around the world.
For example, early farmers migrated from what is now Turkey to Europe about 8,000 years ago and encountered hunter-gatherers who had been living in Europe for more than 30,000 years. After the arrival of the farmers, the DNA of the hunter-gatherers disappeared in some places (their genetic information could not be found in the fossil bones), indicating a violent conflict between the two sides; In other places, the two clans were mixed, leaving behind mixed-race offspring.
About 5,000 years ago, another great migration took place: the Yamnaya, a Western Asian nomadic people who originally lived in the steppes of the Ukrainian-Kazakh region, entered the heart of Europe and spread their DNA there.
Although there were no farms and no cities, the community prospered for centuries. When they crossed the grassland, they rode large horses and chariots, grazed cattle and sheep along the way, and buried the dead with ** and jewelry. The Yannayas of the Bronze Age expanded their territory and swept through much of Asia and Europe.
Willeslev and his colleagues found that the Yannayas often exterminated the local peasants they encountered when they arrived in Europe, and of course, in some areas, the two sides maintained peaceful relations.
The lineage of the peoples of modern northern Europe was largely inherited from the Yannaya; However, the Yannaya ancestry is less common in the south, where the local population is more likely to inherit the lineage of Near Eastern farmers and early European hunter-gatherers.
Willerslev et al. wanted to know what kind of genetic variation each ancient group carried and how they affected their health.
To find out, the research team analysed the surviving descendants of these ancient people.
Using volunteer information from the UK Biobank, they linked thousands of genetic variants to an increased risk of multiple diseases, and then compared the volunteers' DNA with genetic fragments from fossil bones.
One analysis found that hunter-gatherers from Western Europe carried many variants that increase the risk of high cholesterol, high blood pressure, and diabetes. Another study showed that ancient Near Eastern farmers carried variants associated with mood disorders such as anxiety.
These findings do not mean that these ancients suffered more prevalent disease infestations due to more dangerous genes. Because genes only load the gun, the environment pulls the trigger.
For example, diabetes is becoming more prevalent today, in part because cheap, high-sugar foods are making up an increasing part of modern people's diets. Centuries ago, genes that were at high risk of diabetes might not have had a chance to cause disease at all.
Willeslev and his colleagues have even found that these mutations, which appear to be unfavorable at the moment, provided the ancients with a survival advantage in certain circumstances.
For example, as the Yannaya people have become more prevalent in carrying mutations that increase the risk of multiple sclerosis, the group appears to have left more descendants than other nomads who do not carry mutations of their kind.
Today's variants that cause a high risk of MS must have had benefits in the past.
And the team said that some of the bones they analysed contained not only human DNA, but also DNA from disease-causing viruses and bacteria, many of which were not found in hunter-gatherer groups, such as the bacteria that caused plague, and were not even associated with Europe's earliest farmers — whose genetic signatures were found in the bones of the Yannaya people.
These variants appear to provide protection against infectious diseases.
Many studies on multiple sclerosis have shown that variants that increase the risk of developing the disease also make the immune system more responsive to pathogen attacks.
Willerslev et al. argue that the Yannaya are more susceptible to animal diseases than earlier populations such as hunter-gatherers – they rely on livestock for meat and milk, and have frequent contact with cattle and sheep as they cross the steppe – and therefore face a greater risk of contagion. The Yannayas have evolved sharper immune-related genes to defend against special enemies.
Lars Fugger, an expert on multiple sclerosis at the University of Oxford, who works with Willerslev, said MS may not have become common until recent decades. In today's environment, there are fewer infectious diseases than in past centuries, and strong immune systems are more likely to malfunction and attack one's own people.
Humans live in a very clean environment. The balance no longer exists.
Understanding the evolutionary roots of multiple sclerosis can guide scientists in creating better**. Currently, the only effective way to do MS is to take medications that suppress the immune system.
According to Fuggel, "we should not just suppress it, but reveal the principle of imbalance in more detail, and then rebalance it." ”
In addition to multiple sclerosis, the research team has begun to do similar analyses for other diseases, such as psychosis and psoriasis.
Of course, at the moment they rely heavily on data from the UK Biobank, so the findings will be largely limited to the genes that influence the health of Nordic people. Lluis Quintana-Murci, an evolutionary geneticist at the Institut Pasteur (who was not involved), said: "It would be great if similar studies were carried out in other parts of the world. ”
*: World Science.
Original title: In the fossilized bones of a nomadic tribe in the steppes of West Asia 5,000 years ago, they found the root of an autoimmune disease....New discoveries in Nature.
Editor: artistet
*The content represents the author's views only.
It does not represent the position of the Institute of Physics of the Chinese Academy of Sciences.
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