Neanderthal males preferred human females, genetic study finds

Thin stretches of the human X chromosome look oddly empty when you scan for Neanderthal DNA. Geneticists even have a name for the gaps: “Neanderthal deserts.” They sit there like blank tape in an otherwise crowded recording.

For years, the standard story went like this: Neanderthal DNA landed in our ancestors’ genomes. However, some of it was harmful, especially on the X chromosome. Natural selection, the thinking said, gradually stripped those “toxic” variants away.

A new analysis from Sarah Tishkoff’s lab at the University of Pennsylvania argues that the emptiness may say more about who paired with whom than which genes were dangerous. In Science, the team reports a mirror-image pattern inside Neanderthal genomes. Neanderthals carried unusually high levels of modern human DNA on their X chromosomes compared with the rest of their genome. That reversal, they say, makes simple “toxicity” a much harder explanation to defend.

“Along our X chromosomes, we have these missing swaths of Neanderthal DNA we call ‘Neanderthal deserts,’” says Alexander Platt, a senior research scientist in the Tishkoff Lab. “For years, we just assumed these deserts existed because certain Neanderthal genes were biologically ‘toxic’ to humans, as tends to be the case when species diverge, so we thought the genes may have caused health problems and were likely purged by natural selection.”

The new work does not deny that selection mattered. It does challenge the idea that selection alone can explain why the X chromosome looks so different from the rest of the genome in people with non-African ancestry. These individuals typically carry small amounts of Neanderthal DNA elsewhere.

Tishkoff, the David and Lyn Silfen University Professor in Genetics and Biology in Penn’s Perelman School of Medicine and School of Arts & Sciences, frames the question against a long history of separation and reunion. Roughly 600,000 years ago, she says, the ancestors of anatomically modern humans and Neanderthals split into distinct groups. Modern humans evolved in Africa. Meanwhile, Neanderthals evolved in Eurasia. Over hundreds of millennia, populations moved, met, and mated. They also traded DNA segments in the process.

To test what might be driving the deserts, the Penn team flipped the usual comparison. Instead of only asking what Neanderthal DNA remains in modern humans, they asked what modern human DNA remains in Neanderthals.

They examined modern human DNA preserved in three Neanderthal genomes: Altai, Chagyrskaya, and Vindija. As a reference, they used genomes from diverse sub-Saharan African populations described as having historically never encountered Neanderthals.

The study relied on a panel of 73 women from three sub-Saharan African populations: the !Xoo and Ju|’hoansi, Khoesan forager groups from Botswana, and the Chabu, foragers from southwest Ethiopia who speak an unclassified language related to Nilo-Saharan. These populations were described as containing less than 0.1% Neanderthal ancestry. The team used a local introgression identification tool called IBDmix to detect older gene flow patterns.

The Altai individual, a female specimen, anchored much of the analysis. The paper describes it as the oldest high-quality Neanderthal genome sequence, dated to 122,000 years ago, and likely to have the simplest admixture history. The team also looked at female specimens from Chagyrskaya, dated to 80,000 years ago. Separately, they examined Vindija, dated to 52,000 years ago.

“What we found was a striking imbalance,” says Daniel Harris, a research associate in the Tishkoff lab and co-first author. “While modern humans lack Neanderthal X chromosomes, Neanderthals had a 62% excess of modern human DNA on their X chromosomes compared to their other chromosomes.”

In the Altai genome, the paper reports that the proportion of modern human ancestry on the X chromosome was 1.62-fold higher than on the autosomes, with a positional resampling P value of 0.0046. Chagyrskaya and Vindija also showed X-to-autosome introgression ratios above 1. The positional resampling P values were 0.0001 and less than 0.0001, respectively.

That “mirror” result pushes against the simplest version of the toxicity story. If Neanderthal and modern human X chromosomes were broadly incompatible, the team argues, you would expect modern human DNA to be scarce on Neanderthal X chromosomes too. Instead, it was enriched.

So what else could create deserts on one side and an excess on the other?

The answer, the authors argue, lies in sex-biased interbreeding. Platt says the pattern indicates gene flow occurred predominantly between Neanderthal males and anatomically modern human females. This would reduce the number of Neanderthal X chromosomes entering the modern human gene pool.

Because males and females inherit and pass on X chromosomes differently, the direction of mating matters. Females carry two X chromosomes. Males carry one X chromosome. If Neanderthal males paired more often with modern human females, fewer Neanderthal X chromosomes would move into humans. Additionally, more modern human X chromosomes could move into Neanderthals.

The team ran mathematical models and reports that mate preference is a parsimonious way to reproduce the observed ratios. The paper also lays out alternative demographic possibilities, including sex-biased migration. But those models, the authors say, require more complex, shifting scenarios across time and geography to reach the same patterns.

The researchers stop short of claiming one force did everything. They write that demographic sex biases could still matter and cannot be excluded. They also point to evidence consistent with selection acting as a modifier on top of sex bias. For example, in the Altai Neanderthal, introgressed regions on the X chromosome were depleted in putatively functional elements. The combined depletion showed a resampling P value below 1 × 10−5.

There is another hard limit, too: the study notes that researchers do not have Neanderthal genomes that postdate the 45,000 to 49,000 years ago admixture event that introduced Neanderthal ancestry to the modern human gene pool. The “natural experiment” they used instead comes from an earlier introgression event around 250,000 years ago. This left modern human ancestry in the Altai Neanderthal genome.

Even so, the authors argue the signal looks consistent across admixture events separated by about 200,000 years.

If sex-biased mating shaped which Neanderthal DNA persisted, then parts of the human genome may reflect social behavior as much as biological filtering. That matters for how you read genetic patterns in general. A dip in ancestry on a chromosome does not automatically mean “bad genes got removed.” It might mean fewer genes arrived there in the first place.

The approach also offers a template for studying other ancient encounters. By comparing X chromosomes with autosomes, and tracking which ancestry shows up where, researchers may be able to infer the direction of mating and movement even when the archaeological record stays quiet.

Research findings are available online in the journal Science.

The original story "Neanderthal males preferred human females, genetic study finds" is published in The Brighter Side of News.

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