The secrets of our ancestors may hold the key to why multiple sclerosis (MS) is more common more among white Northern Europeans than among southern Europeans.
Scientists have so far discovered hundreds of genes associated with MS, but up to a fifth of Northern Europeans carry a genetic variation called HLA-DRB1*15:01, which The risk of developing an autoimmune disease is three times higher.
Where this variant came from and why it persisted and spread is a mystery.
An international research team led by William Barry of the University of Cambridge now thinks they have a new clue.
Barry and his colleagues combined the newly sequenced genomes of dozens of medieval and post-medieval Danes with a database of ancient sequences to create a database of individuals across Eurasia that is representative of tens of thousands of years of humanity. did. Among them, they said,impressive pattern” Among the genetic mutations associated with MS today.
Tracking the spread of the variant back over time, the gene appears to have originated in what is now known as the Pontic Steppe of Eastern Europe, which includes Ukraine, southwestern Russia, and western Kazakhstan.
About 5,000 years ago, the region’s pastoralists, known as the Yamnaya, migrated west to northern Europe, taking their genes with them.
No matter where these genes go, MS-associated variants appear to undergo “positive selection,” which suggests that, despite their contemporary association with poor neurocognitive function, they once This suggests that it retained some survival value.
“This means we can understand MS for what it really is – the result of genetic adaptation to specific environmental conditions that occurred in prehistoric times – and try to treat it.” To tell Lars Fugger, a neuroimmunologist at the University of Oxford, said:
MS is caused by the body’s immune system mistakenly attacking itself, which can lead to devastating consequences if left unchecked, but in theory an overactive immune system can protect against pathogens and epidemics. You can also protect yourself.
This may have given an advantage to ancient humans, especially those who developed livestock farming and settled in dense populations where disease could spread.
The researchers compared their data with the approximately 410,000 modern human genomes in the UK Biobank and found that the frequency of the HLA-DRB1*15:01 variant was found in “modern human populations in Finland, Sweden, and Iceland; The proportion was highest in ancient populations. of steppe ancestors. ”
“These results surprised us all.” To tell Barry.
“These studies represent a major advance in our understanding of the evolution of MS and other autoimmune diseases. It highlights how in the modern world we are recipients of an ancient immune system.”
In a recent paper review, Naturescience writer Lionel A. Pousa and genomics researcher Samira Asghari; write Barry and his team’s hypothesis is “valid,” but they need “more concrete evidence.”
“Their findings reveal the reasons underlying Europe’s north-south gradient and demonstrate the potential evolutionary advantage that variation in multiple sclerosis risk may have had in the post-hunter-gatherer era. ” they said. write.
“However, further studies are needed to confirm the suggested association between infection and multiple sclerosis risk.”
This study Nature.