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Genetic Incompatibilities Kept Lineage Of Modern Humans And Neanderthals Apart

Our modern human ancestors had interbred with Neanderthals hundreds of thousands of years ago, passing on about 99.5 percent of the same DNA.

Despite the overlapping genes, the lineage of both modern humans and Neanderthals have been kept apart, and it's all rooted to genetic incompatibilities.

A study led by researchers from Stanford University revealed that modern humans are genetically mismatched with our ancient relatives because of a missing chromosome fragment in males: the Neanderthal Y chromosome.

The differences may have caused a "dead end" between Neanderthals and modern humans, genetically separating both groups.

Genetic Incompatibilities Discouraged Interbreeding

Neanderthal genes have been incorporated into our own, specifically on our X chromosomes.

Neanderthal DNA has been linked to people's susceptibility to allergies, as well as to the increased risks for depression and nicotine addiction.

Now, in the new study, Stanford researchers examined the Y chromosome from a 49,000-year-old male Neanderthal discovered in the El Sidrón cave in Spain. They compared it with that of chimps, and archaic and modern humans.

Turns out, the Neanderthal Y chromosome has seemingly gone extinct without leaving a trace in human DNA.

Although the missing gene could have just drifted out of the modern human gene pool, scientists say there is also another possible explanation for this distinction.

If Neanderthals and modern humans often interbred, the Neanderthal Y chromosome could have created conditions that might have often led to miscarriages, experts said. The hybrid offspring who carried the Neanderthal Y chromosome could have also been infertile.

Stanford researcher Fernando Mendez and his colleagues found mutations in four genes that could have hindered the process of passing the Y chromosome onto hybrid children. Mendez said these mutations could have played a role in the loss of Neanderthal Y chromosome.

"We should pay attention to the potential role of immune incompatibilities in population isolation," said Mendez.

Mendez and his team said male fetuses who were fathered by Neanderthal males and carried in the womb by human females would have miscarried.

One of the mutations was found in the gene KDM5D, which contributes to cancer suppression. It has been linked to higher risks of miscarriage because it can trigger an immune response in pregnant women.

Mendez said a woman's immune system may target a male fetus that carried the Neanderthal Y chromosome, specifically the H-Y genes, which are minor antigens that resemble HLA antigens. The latter is often transplanted by surgeons to ensure that recipients and organ donors have similar immune profiles.

Evolutionary biologist Mark Pagel said this could very well be the reason why the Neanderthal Y chromosome is not present in modern humans. It could be the factor that keeps both species separate from each other.

The findings of the study are featured in The American Journal of Human Genetics.

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