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

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

From genetic studies we know that there is there was stable crossbreeding between wise man and Neanderthals approximately between 50,000 and 45,000 years ago. Neanderthals went extinct about 41,000 years ago.but some of their DNA survives in modern humans of non-African descent, making up 1 to 2 percent of the genome.

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

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

Neanderthals and X. sapiens there were different versions PIEZO1a gene critical for oxygen transport in the blood. The researchers analyzed DNA from modern humans and Neanderthals and modeled differences in the PIEZO1 protein to understand how the two variants might interact. They also studied human red blood cells in the laboratory, using chemical treatments to mimic the effect of the Neanderthal variant.

They discovered that the Neanderthal variant, V1leads to the formation of red blood cells, which bind oxygen more strongly compared to X. sapiens option, V2. V1 is dominant, so the person who inherits both V1 And V2 will have red blood cells with such a high affinity for oxygen.

This means that the fruit descended from Neanderthals and X. sapiens interbreeding could have evolved in both Neanderthal and Neanderthal man. X. sapiens mother. But according to the study, problems could arise in the next generation. Hybrid mother with V1 And V2 carrying a fetus with two copies V2 she would have a higher affinity for oxygen than her fetus, so she would deliver less oxygen through the placenta. This may impair fetal growth and increase the risk of pregnancy loss.

Eppenberger and his colleagues declined to be interviewed, but in the paper they argue that this incompatibility would have caused the Neanderthal population to experience reduced reproductive output. “Over millennia of coexistence, even low levels of gene flow from modern humans to Neanderthals could have led to gradual reproductive deficits that worsened over generations,” they write.

This wouldn't be such a problem for X. sapiens the team suggests it was much larger. Neanderthal DNA may have spread through the population through fathers, but V1 the variant would be quickly eliminated by natural selection. This could explain why nuclear DNA from Neanderthals survives in modern humans, but mitochondrial DNA, inherited only from the mother, does not.

Although not derived from Neanderthal DNA, the researchers also note that some mutations in PIEZO1 with a similar effect do occur today and may cause some cases of unexplained pregnancy loss due to a similar mismatch between mother and fetus.

Sally Wasef at Queensland University of Technology in Brisbane, Australia, says the discovery of second-generation delayed incompatibility is a “good discovery.” “Even small impacts on reproduction can push small groups below replacement levels, which can lead to population declines and, in unstable conditions, a spiral of extinction,” she says.

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

Les Laurits from the University of Copenhagen in Denmark say a variety of factors likely contributed to the Neanderthal extinction, including climate change, the emergence of modern humans, the small size of the Neanderthal community, the emergence of new diseases and genetic incompatibility.

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

“I think more work is needed to say conclusively 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, this mutation played in the extinction of the Neanderthals.”

Neanderthals, early humans and rock art: France

Take a fascinating journey through time, exploring key Neanderthal and Upper Palaeolithic sites in the south of France, from Bordeaux to Montpellier, with New Scientist's Kate Douglas.