The largest genetic database of ancient humans yet is shedding new light on some modern medical conditions, such as multiple sclerosis (MS), as well as why there is variation among people when it comes to other heritable traits, such as height.
One of the findings is that the genes behind MS may have become more common because they helped people resist infections passed on from animals.
Other findings include explanations for why Alzheimer’s disease is more common in some groups than others and why people from northern Europe tend to be taller than those from the south of the continent.
“Things going on thousands of years ago can have really profound effects on the health and longevity of people living in the present,” says Evan Irving-Pease at the University of Copenhagen in Denmark.
The genes of people with ancestry from Europe and west Asia have been shaped by three large waves of migration. Modern humans living a hunter-gatherer lifestyle first arrived in these regions about 45,000 years ago. There was then a wave of farmers from the Middle East about 11,000 years ago, followed by a further influx of livestock herders from the Eurasian steppe, now called the Yamnaya people.
To understand how these mass movements shaped modern medical conditions, Irving-Pease’s team has been analysing bone and teeth samples from nearly 5000 ancient remains found in museum collections in Europe and west Asia, with the oldest being 34,000 years old.
The latest research reports on the first batch of samples to be analysed, based on about 1600 individuals. The team compared these indiviuals with genetic data from 410,000 people from a huge medical dataset called UK Biobank, analysing only white participants in order to select those with European ancestry.
The team started by focusing on MS, an autoimmune condition that occurs when the immune system starts attacking nerves, often leading to progressive disability. Previous studies have found 233 genetic variants that are linked to a higher risk of MS.
Among modern people in the UK, those with a higher genetic risk of MS have more ancestry from the Yamnaya, the results show. The team also found that some of these MS-predisposing genetic variants first arose in the Yamnaya and became more frequent in their descendants as they spread west through Europe.
Given that some of the 233 variants that are linked to MS also affect the immune system, coupled with the Yamnaya having lived among animals, the researchers concluded that the genes behind MS probably helped the Yamnaya fend off bacteria and viruses that can spread to people from animals. The team has also previously shown that a few of the MS risk variants are linked with partial resistance to tuberculosis.
In another paper, the researchers have shed light on how our ancestry affects our genetic risk for Alzheimer’s disease. People today are more likely to have a gene called ApoE4, which leads to a higher risk of developing Alzheimer’s, if they have more ancestry from the first hunter-gatherer populations of Europe.
An alternative variant of this gene, called ApoE2, which results in a lower risk of Alzheimer’s, seems to have arisen in the incoming Yamnaya people, perhaps because it gave protection against malaria or an unknown viral infection, the researchers write in their paper.
The Alzheimer’s-protecting variant doesn’t give a reproductive advantage, so it wouldn’t have been selected for by evolution for its effects on dementia, given that the condition generally occurs long after people would have had any children, says Benjamin Trumble at Arizona State University, who was not involved in any of the research.
“The cool thing about this paper is they’re looking back deeper into time and they’re saying what may have been advantageous or disadvantageous then,” says Trumble. “Too often we focus on modern environments and we say [a certain gene] is purely deleterious. We have to think about what the selective pressures were at various points in time.”
A further finding from the analysis is that among people living in Europe, those with more Yamnaya ancestry tend to be taller, which may explain why people in northern Europe, on average, have a higher stature than those in southern Europe.
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