Neanderthal-Human Hybrids Likely Experienced Genetic Incompatibilities

Although modern humans are thought to have driven Neanderthals extinct, it was not simply through conflict or violence. New research indicates that the genetic incompatibility from interbreeding between the two species may have led to increased chances of pregnancy failure in hybrid mothers. This genetic mismatch could also provide insights into some contemporary pregnancy failures.

Studies in genetics reveal that there was ongoing interbreeding between Homo sapiens and Neanderthals around 50,000 to 45,000 years ago. While Neanderthals became extinct approximately 41,000 years ago, remnants of their DNA endure in modern humans of non-African ancestry, accounting for about 1 to 2 percent of their genetic makeup.

Interestingly, no mitochondrial DNA from Neanderthals is found in modern humans. Mitochondrial DNA is inherited exclusively from the mother, as it is carried only in the egg cell, not in sperm.

Patrick Eppenberger and his team at the University of Zurich in Switzerland propose a possible reason for this phenomenon. They suggest that mothers with Neanderthal and Homo sapiens ancestry faced a higher probability of pregnancy loss due to genetic mismatches between their genes and those of the developing fetus.

Variations of the gene Piezo 1, crucial for oxygen transport in the bloodstream, existed among Neanderthals and Homo sapiens. The researchers conducted analyses on DNA from both groups and constructed models of how the PIEZO1 protein interacted based on these differences. They also experimented with human red blood cells in laboratory settings, simulating effects caused by Neanderthal genes.

The findings revealed that the Neanderthal variant V1 of red blood cells exhibited a stronger binding affinity for oxygen compared to the V2 variant of Homo sapiens. The dominance of V1 implies that individuals inheriting both V1 and V2 would have red blood cells highly efficient at oxygen transport.

This suggests that a fetus conceived from a Neanderthal and a Homo sapiens mother could have been healthy, but complications might have arisen in the subsequent generations. A hybrid mother carrying a fetus with two copies of V2 would struggle to deliver sufficient oxygen through the placenta, potentially stunting fetal development and heightening miscarriage risks.

In their study, Eppenberger and colleagues assert that such incompatibilities could have led to lower fertility rates among Neanderthals. They wrote, “Over thousands of years of cohabitation, even minimal gene flow from modern humans into Neanderthal populations may have gradually introduced reproductive disadvantages that intensified over generations.”

This situation was likely less problematic for Homo sapiens, as their population numbers were significantly greater. Even though Neanderthal DNA could likely integrate through paternal lines, V1 variants would be swiftly purged by natural selection. This could clarify why Neanderthal nuclear DNA has persisted in some humans, while their mitochondrial DNA has not.

Researchers also pointed out that, while modern human mitochondrial DNA does not come from Neanderthals, instances of similar mutations in the Piezo 1 gene can still result in unexplained miscarriages today due to gene incompatibilities between mothers and fetuses.

Sally Wassef from the Queensland University of Technology in Brisbane, Australia, remarked that the newfound understanding of second-generation incompatibilities offers valuable insights. “Even minor reproductive disadvantages can lead small populations below their replacement levels, triggering declines and potentially leading to extinction in vulnerable environments,” she notes.

“However, I view this finding as merely one piece of a larger puzzle,” she adds. “While its impacts are subtle, there are likely other ecological and social factors at play.”

Laurits Skov at the University of Copenhagen in Denmark shared that multiple elements likely contributed to the extinction of Neanderthals, including climate change, the emergence of modern humans, small Neanderthal populations, new disease introductions, and genetic incompatibility.

Skov further expressed skepticism about the notion that this disparity in oxygen affinity stems from a singular mutation within the Piezo 1 gene, as proposed by the researchers.

“Further research is essential to accurately evaluate the implications of this mutation and the effects of differing maternal and fetal gene profiles,” he emphasizes, “as well as to determine its potential role in Neanderthal extinction.”

Neanderthals, Ancient Humans, and Cave Art: France

Join New Scientist’s Kate Douglas on a captivating journey through time, exploring significant Neanderthal and Upper Paleolithic sites in Southern France, from Bordeaux to Montpellier.