A Single Gene Could Have Contributed to Neanderthals’ Extinction, Study Suggests

New research posits that a genetic incompatibility between female offspring of humans and Neanderthals and their children could have led to pregnancy complications and the eventual end of the species

October 30, 2025

A Neanderthal figure — New research suggests a genetic dynamic that may have contributed to Neanderthals' extinction. Neanderthal-Museum, Mettmann CC BY-SA 4.0 via Wikimedia Commons

Did interbreeding between humans and Neanderthals cause the latter’s extinction? New research suggests a genetic incompatibility between the two species may have contributed to the Neanderthals’ demise.

The study, posted on the preprint server bioRxiv earlier this month, has not undergone peer review. But it could help explain why Neanderthals went extinct about 40,000 years ago.

Key takeaway: What's a paleogeneticist?

Paleogenetics analyzes the genes of now-extinct species with the help of preserved genetic material. Though scientists had long wanted to study the genes of long-gone species, the field kicked off in earnest in the early 1980s thanks to advances in technology and the first successful sequencing of a strand of ancient DNA.

Researchers investigated the gene PIEZO1 and its variants in both modern humans and Neanderthals. The gene impacts red blood cells in both species. The analysis suggests the Neanderthal variant likely allowed their red blood cells’ hemoglobin (the protein that delivers oxygen to tissues) to hold on tightly to oxygen molecules.

Known as red blood cell oxygen affinity, that trait could have been beneficial for Neanderthals that mated with humans. But once Neanderthal-human hybrids began mating with one another, the variant could have turned into a disadvantage, the researchers write.

“While potentially advantageous in Neanderthals, this trait became detrimental in hybrids,” they conclude. Pregnant hybrid mothers who carried just one Neanderthal allele would not have been able to deliver enough oxygen to offspring with two of the alleles, an incompatibility that would have endangered pregnancies, increased the likelihood of severe developmental problems, and reduced the fetus’ chances of surviving.

In other words, a hybrid mother with a human variant and a dominant Neanderthal variant of PIEZO1 carrying a fetus with two modern human variants—from a modern human father or hybrid father—could have led to a failed pregnancy.

Queensland University of Technology paleogeneticist Sally Wasef, who was not involved in the study, tells NewScientist’s James Woodford that the study provides “good insight.”

Humans and Neanderthals interbred for thousands of years. But the current research suggests it wouldn’t have taken much to topple Neanderthals, genetically speaking—just a single gene mutation and ongoing hybrid mating between Neanderthals and Homo sapiens.

“Even a minor hit to reproduction can push small groups below replacement, which can start a slide in numbers and, in fragile settings, an extinction spiral," Wasef tells NewScientist. Replacement-level fertility rate is the fertility rate necessary to keep a population’s size stable without migration.

Though about 2 percent of the genome of modern humans with Asian or European ancestry comes from Neanderthals, modern humans’ mitochondrial DNA—inherited from mothers—lacks any sign of Neanderthal influence. The study offers an explanation for that, too: As gene flow progressed, the researchers suggest, modern humans likely inherited Neanderthal DNA mostly from Neanderthal fathers.

“This is one of many potential cases where the gene variant coming from an archaic population had some bad effects, causing it to decline in frequency over time in modern people," John Hawks, a biological anthropologist at the University of Wisconsin-Madison who did not participate in the study, tells LiveScience’s Kristina Killgrove.

The same genetic mechanism may play a role in some pregnancy complications today, the researchers suggest. Wasef expresses some caution treating the study as conclusive, however, I would treat this finding as one piece of the puzzle rather than the whole story,” she tells New Scientist. “The effect is likely to be modest and to add to other ecological and social pressures.”

More broadly, though, the study sheds light on how ancient humans interacted with other species back when Homo sapiens weren’t the only humans walking the Earth.

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