Neanderthal-human hybrids may have been struck by a genetic mismatch

Modern humans may have wiped out the Neanderthals – but not just through war or murder. A new study suggests that when the two species interbreed, a slow-acting genetic incompatibility increases the risk of pregnancy failure in hybrid mothers. A similar mismatch between mothers and fetuses may also help explain a subset of pregnancies that fail today.

We know from genetic studies that there was sustained interbreeding between A wise man and Neanderthals around 50,000 to 45,000 years ago. Neanderthals went extinct about 41,000 years ago, but some of their DNA persisted in modern humans of non-African ancestry, making up about 1 to 2 percent of the genome.

But mysteriously, none of the mitochondrial DNA in modern humans comes from Neanderthals. This form of DNA is carried by eggs but not by sperm; it is therefore always inherited from the mother.

Patrick Eppenberger of the University of Zurich, Switzerland, and colleagues have proposed a possible explanation for this. They suggest that Neanderthal women and H. sapiens the parents would have had a higher risk of pregnancy failure due to a mismatch between their genes and those of their fetus.

Neanderthals and H. sapiens had different versions of PIEZO1a gene essential for the transport of oxygen in the blood. The researchers analyzed modern human and Neanderthal DNA and modeled differences in the PIEZO1 protein to understand how the two variants would have interacted. They also studied human red blood cells in the laboratory, using chemical treatment to simulate the effect of the Neanderthal variant.

They discovered that the Neanderthal variant, V1red blood cells bind more strongly to oxygen than red blood cells. H. sapiens variant, V2. V1 is dominant, therefore a person who has inherited both V1 And V2 would have red blood cells with this high affinity for oxygen.

This means that a fetus from Neanderthals and H. sapiens interbreeding could have developed healthily in a Neanderthal or in H. sapiens mother. But according to the study, problems would have arisen in the next generation. A hybrid mother with V1 And V2 carrying a fetus with two copies of V2 would have had a higher affinity for oxygen than that of her fetus, so she would deliver less oxygen across the placenta. This could harm the growth of the fetus and increase the risk of miscarriage.

Eppenberger and his colleagues declined to be interviewed, but in a paper they argue that this incompatibility would have led the Neanderthal population to suffer a decline in reproductive capacity. “Over millennia of coexistence, even low levels of gene flow from modern humans to Neanderthal populations could have introduced progressive reproductive disadvantage, worsening over generations,” they write.

This would not be such a problem for the H. sapiens population because it was much larger, the team suggests. Neanderthal DNA could spread through the population via fathers, but the V1 This variant would be quickly eliminated by natural selection. This could explain why Neanderthal nuclear DNA persisted in modern humans, while mitochondrial DNA, inherited only from mothers, did not persist.

Although not from Neanderthal DNA, the researchers also note that some mutations in PIEZO1 with a similar effect are occurring today and could cause some cases of unexplained miscarriages due to a similar mismatch between mother and fetus.

Sally Wasef, of the Queensland University of Technology in Brisbane, Australia, says the discovery of second-generation delayed incompatibility is a “good idea.” “Even a minor impact on reproduction can push small groups below replacement level, which can trigger a decline in numbers and, in fragile contexts, a spiral of extinction,” she says.

“That being said, I would view this discovery as one piece of the puzzle rather than the whole story,” she says. “The effect is likely to be modest and will add to other ecological and social pressures. »

Laurits Skov, of the University of Copenhagen in Denmark, says several factors were likely involved in the disappearance of Neanderthals, including climate change, the arrival of modern humans, the small size of the Neanderthal community, the introduction of new diseases and genetic incompatibilities.

Skov also says he would be surprised if this difference in oxygen affinity was determined by a single mutation in the PIEZO1 gene, as the researchers suggest.

“I think more work is needed to conclusively determine what the impact of this particular mutation is – and what happens when the mother and fetus have different configurations,” he says. “Or what role, if any, did this mutation play in the extinction of Neanderthals.”

Neanderthals, ancient men and rock art: France

Embark on a captivating journey through time as you explore key Neanderthal and Upper Paleolithic sites in southern France, from Bordeaux to Montpellier, with New Scientist’s Kate Douglas.