Researchers have compiled the largest database of ancient genomes to date from the ancient DNA of more than 1,600 people from the Stone Age to the Bronze Age. The data can be used to reconstruct migrations and trace lineages. Additionally, they provide unique insights into the origins of modern diseases. According to this, northern Europeans, for example, inherited certain genes that increase the risk of multiple sclerosis from pastoral peoples who came to Europe from the Pontic-Caspian steppes around 5,000 years ago.
The current genetic diversity of the West Eurasian population probably goes back to three major migration movements in the past: The first hunters and gatherers came to Europe around 45,000 years ago. They were partially displaced around 11,000 years ago by Neolithic farmers from the Middle East. Around 5,000 years ago, nomadic sheep and cattle herders from the Pontic-Caspian steppe began to settle large parts of Europe. The legacy of these three ethnic groups can still be seen in varying proportions in our genomes today. However, where exactly which genes come from and how they affect has only been partially researched so far.
Database of ancient genomes
An international research team led by Eske Willerslev from the University of Cambridge has now compiled the largest database of ancient human genomes to date. To do this, the researchers sequenced 317 genomes from people who lived in Europe and Asia up to 34,000 years ago and whose remains are now kept in museums. They combined this data with 1,347 previously published sequences of prehistoric genomes. For comparison, the team also included modern genomes in the analysis.
These data not only make it possible to trace the lineages of today's West Eurasian population well into the past. They also provide information about the origins of many of today's characteristics - from body size to susceptibility to certain diseases. “Creating a gene bank with ancient DNA from the ancient inhabitants of Eurasia was a huge project that required collaboration with numerous museums,” says Willerslev. “Our gene bank functions as a precision tool that can provide us with new insights into human diseases when combined with analyzes of present-day human DNA and contributions from various other research areas.”
MS risk genes earlier beneficial
Among other things, the data provides an explanation for why people of northern European descent have a significantly higher risk of developing multiple sclerosis (MS) than people from other parts of the world. A look at the ancient genomes shows that corresponding risk genes for this neurodegenerative autoimmune disease were already present in the shepherds from the Yamnaya culture, who originally herded their sheep and cattle in the Pontic-Caspian steppe in the area of the Black and Caspian Seas and around migrated to Eastern and Northern Europe 5000 years ago.
“It must have been a clear advantage for the Yamnaya to carry the MS risk genes even after they arrived in Europe, although these genes undeniably increased their risk of MS,” explains Willerslev. The researchers suspect that the corresponding gene variants ensured that the shepherds' immune systems were better equipped to combat infections that can be transmitted from cattle and sheep to people. Shepherds with these gene variants therefore had a survival advantage despite the increased risk of MS. “This means that we can now try to understand and treat MS for what it actually is: the result of a genetic adaptation to certain environmental conditions that occurred in our prehistory,” says co-author Lars Fugger from the University of Oxford.
Inherited traits
In the future, the team would like to investigate the evolutionary basis of other neurological diseases. In further studies that were published in the journal Nature at the same time as the MS study, the researchers have already reported numerous additional findings. They found that gene variants known to increase the risk of diseases such as Alzheimer's and type 2 diabetes can be traced back to early hunter-gatherers. Today, this genetic heritage is most widespread in the genomes of Eastern European people.
Even traits that are not associated with disease can be traced back to our ancestors thousands of years ago. Northern Europeans not only inherited MS risk genes from the Yamnaja, but also height genes, which explain why northern Europeans are typically taller than southern Europeans. “The lifestyle of people in the Eurasian region over the last 10,000 years has resulted in a genetic inheritance that impacts their present-day descendants, both in terms of their physical appearance and their risk of developing a range of diseases get sick,” summarizes co-author Evan Irving-Pease from the University of Copenhagen.
Sources: Morten Allentoft (University of Copenhagen, Denmark) et al., Nature, doi: 10.1038/s41586-023-06865-0; Evan Irving-Pease (University of Copenhagen, Denmark) et al., Nature, doi: 10.1038/s41586-023-06705-1; William Barrie (University of Cambridge, UK) et al., Nature, doi: 10.1038/s41586-023-06618-z; Morten Allentoft (University of Copenhagen, Denmark) et al., Nature, doi: 10.1038/s41586-023-06862-3