By now, it’s firmly established that modern humans and their Neanderthal relatives met and mated as our ancestors expanded out of Africa, resulting in a substantial amount of Neanderthal DNA scattered throughout our genome. Less widely recognized is that some of the Neanderthal genomes we’ve seen have pieces of modern human DNA as well.
Not every modern human has the same set of Neanderthal DNA, however; different people will, by chance, have inherited different fragments. But there are also some areas, termed “Neanderthal deserts,” where none of the Neanderthal DNA seems to have persisted. Notably, the largest Neanderthal desert is the entire X chromosome, raising questions about whether this reflects the evolutionary fitness of genes there or mating preferences.
Now, three researchers at the University of Pennsylvania, Alexander Platt, Daniel N. Harris, and Sarah Tishkoff, have done the converse analysis: examining the X chromosomes of the handful of completed genomes we have. It turns out there’s also a strong bias toward modern human sequences there, as well, and the authors interpret that as selective mating, with Neanderthal males showing a strong preference for modern human females and their descendants.
What type of selection are we looking at?
Given how long modern humans and Neanderthals had been evolving as separate populations, some degree of genetic incompatibility is definitely possible. Lots of proteins interact in various ways, and the genes behind these interaction networks will evolve together—a change in one gene will often lead to compensatory changes in other genes in the network. Over time, those changes may mean re-introducing the original gene will actually disrupt the network, with a negative impact on fitness.
That means the introduction of some Neanderthal genes into the modern human genome (or vice versa) would be disruptive and make carriers of them less fit. So they’d be selected against and lost over the ensuing generations. Of course, some segments would likely be lost at random—the genome’s pretty big, and the modern human population was likely large and growing, allowing its DNA to dilute out the influence of other human populations. Figuring out which influence is dominant can be challenging.
One way to sort this out is to make the same comparison with Neanderthal genomes. If a Neanderthal gene is disruptive in a modern human context, then it’s likely that the modern human version will be disruptive in Neanderthals. And, in fact, that’s what we seem to see: A look at one Neanderthal genome found that there’s some correlation between the Neanderthal deserts in the human genome and the human deserts in that Neanderthal.
All of that, however, doesn’t go far to explain the fact that the X chromosome looks like a giant Neanderthal desert, with long stretches of nothing but modern human DNA. The genetics of the X is complicated by the fact that males inherit a single copy from their mothers, so they have only a single copy of almost every gene on it. If any of those genes are causing problems, they will be quickly selected against in males.
Thus, evolutionary selection against the Neanderthal X is definitely an option. The alternative they consider is that it’s the product of biased matings. If most mating between the two groups was biased in some way, it could skew the frequency with which the X chromosome was inherited. For example, if most of the matings involved Neanderthal males and modern human females, then you would have fewer Neanderthal X’s around as a result, since only half of a male’s offspring will inherit an X chromosome from them.
A strong preference
To figure out which result might be the case, the researchers again turned to the three Neanderthal genomes we have available, looking at the pattern of inheritance along the X chromosome. That was compared to X chromosomes from African populations that have very little Neanderthal DNA.
The results contrasted sharply with what was seen elsewhere in the genome, where Neanderthal deserts in modern humans correspond to human deserts in the Neanderthal genome. Instead, the X chromosome in Neanderthals tended to have an excess of modern human sequences—exactly as you see in modern humans. It appears that the modern human X ended up more common in both human and Neanderthal populations.
Could this be from evolutionary selection for something favorable about it? The researchers found that modern human DNA found on the Neanderthal X had a lower than average frequency of important sequences like those that regulate nearby genes or code for proteins. While that doesn’t rule out evolutionary selection as a factor, it does make it seem a bit less likely, since there’s less indication that the DNA being kept around is functional.
That leaves preferential mating as a more probable explanation. But the modern human DNA was present at such a high frequency on the X that it’s difficult to explain by a simple preference of Neanderthal males for modern human females. Instead, you’d have to have a continued preference for the offspring of these matches as well. “We did not rule out more complicated scenarios combining selection and sex biases, such as natural selection acting as a modifying force on top of the strong signature left by sex bias,” the authors also note.
Overall, we’re left with a picture of a relatively large number of matings between male Neanderthals and modern human females. The offspring of these matings ended up in both the modern human and Neanderthal populations; in the latter, their offspring were favored enough to have led to an excess contribution to the X chromosome.
Science, 2026. DOI: 10.1126/science.aea6774 (About DOIs).
