The population of Europe has been replaced by migrants three times in the past 45,000 years. New research shows that the current risk of developing various diseases varies according to how much of a person’s DNA originates from the various prehistoric migrants.
The first population in the territory now called Europe was replaced 45,000 years ago, when hunter-gatherers replaced the Neanderthals.
A similar process recurred 10,000 years ago, when Neolithic people replaced the hunter-gatherers after migrating across Eurasia from what is now called the Middle East.
However, the dominance of this Neolithic population did not last as long, being replaced again about 5,000 years ago, when the nomadic Yamnaya migrated westward from the Pontic Steppe (now Ukraine, southwestern Russia and western Kazakhstan).
Every time the original population was replaced, the overall population genetics changed. The population was completely replaced in some places, leading to a drastic change in population genetics, and the migrants mixed with the original inhabitants in other places, leading to more modest changes.
Now a new study shows that the legacy of these major ancient population replacements is still in the DNA of modern Europeans today and influences their risk of developing various diseases.
“The study is part of a larger study that aimed to understand how much of the DNA of modern people in Europe derives from hunter-gatherers, Neolithic people and the Yamnaya – and to what extent this varies between countries. We also wanted to determine how this affects the observable difference in the risk of various hereditary and infectious diseases between European countries,” explains a researcher involved in the study, Evan Irving-Pease, Assistant Professor, Section for Molecular Ecology and Evolution, Globe Institute, University of Copenhagen.
The research has been published in Nature.
Analysed huge quantity of data
The researchers used data from two main sources. The UK Biobank provided 400,000 samples containing information on the ancestry of nearly 400,000 present-day people living in the United Kingdom and 23,000 people living elsewhere in Europe.
The researchers also performed paleogenomic analysis on 1,600 ancient genomes from teeth or petrous bones of people who lived in Europe millennia ago.
Some of these people were the original hunter-gatherers, some were migrating Neolithic people and some were Yamnaya from the Pontic Steppe.
The researchers examined each of the genomes of the 400,000 samples to determine which parts of the modern DNA came from the hunter-gatherers, the Neolithic people and the Yamnaya.
“In addition, we also had these people’s medical history and could thereby determine whether some genetic variants are associated with an increased risk of developing various diseases. This enabled us to determine the prehistoric population origin for any predisposition to disease,” says Evan Irving-Pease.
Increased risk for multiple sclerosis originated from Eurasian Steppe populations
The study shows that the genomes of present-day Europeans differ considerably in the extent to which they originate from the various prehistoric populations.
People in northern Europe owe much of their ancestry to the Yamnaya, whereas people in southern Europe have much more DNA from Neolithic people.
The study also shows that the risk of various diseases can be directly traced back to the genetic predisposition from these prehistoric populations.
For example, the Yamnaya introduced genetic variants associated with a higher risk of multiple sclerosis.
This means that people of northern European origin have a greater risk of developing multiple sclerosis than people of southern European origin, who do not have as much Yamnaya DNA in their genome.
Nevertheless, the researchers found that these genetic variants are not inherently negative despite being associated with a higher risk of multiple sclerosis. They protected the Yamnaya from infection, which was probably quite prevalent since they had close contact with the animals they herded.
“These genetic variants make people more resistant to infections, but they also increase the risk of developing multiple sclerosis, an immune disorder that attacks the body when the immune system has no infections to attack. In the past two centuries, the advantage of being protected against infection has not been as great, so the increased risk of developing multiple sclerosis remains as the legacy of the Yamnaya,” explains Evan Irving-Pease.
May lead to improved treatment
Another finding was that the present-day Europeans who have inherited much DNA from the prehistoric hunter-gatherers have the highest risk of developing diabetes and Alzheimer’s disease. The more DNA from hunter-gatherers, the greater the risk.
In contrast, people with much of their DNA from the Neolithic people have an increased risk of developing mood disorders, including anxiety and depression. This applies especially to people living in countries in southern Europe.
“The broad conclusion is that the genetic legacy of populations that have prevailed in Europe for the past 15,000 years continue today – affecting people’s appearance but also the risk of developing various diseases and disorders,” says Evan Irving-Pease.
He explains that the new knowledge may also be useful in determining how to treat the people who have these diseases.
For example, some small trials have tried to treat people with multiple sclerosis with parasites from pigs to force the immune system to concentrate on killing the parasites rather than attacking the body itself. However, the results of these trials were not as positive as had been hoped.
“But now that we have found that the genetic variants associated with multiple sclerosis originate from the Yamnaya and we know that they did not herd pigs but did herd cattle, it might make more sense to try to treat people with multiple sclerosis with parasites from cattle. This is a specific suggestion for a treatment based on data from this study,” concludes Evan Irving-Pease.
“The selection landscape and genetic legacy of ancient Eurasians” has been published in Nature. The project was supported by the Lundbeck Foundation, the Wellcome Trust, the Carlsberg Foundation, the Danish National Research Foundation, the University of Copenhagen, Ferring Pharmaceuticals A/S, a COREX European Research Council Synergy grant, Riksbankens Jubileumfond, the OAK Foundation, the United States National Institute of General Medical Sciences, a Vallee Scholar Award, the United States National Institutes of Health, a Villum Young Investigator Grant, the European Research Council under the European Union’s Horizon Europe programme and the Novo Nordisk Foundation.
