The Neanderthal Y chromosome is much more closely related to the Y of modern humans than to the Y of Denisovans, another archaic hominin that lived in Eurasia at the same time as Neanderthals, according to a study published today (September 24) in Science. This stands in stark contrast to the rest of the nuclear genome, which has clearly placed Neanderthals and Denisovans as sister groups in a lineage that split from the ancestors of modern humans. The Y chromosome data—the first from Denisovans and the first high-coverage from Neanderthals—suggest that earlier Neanderthals had a Denisovan-like Y chromosome, but that this was replaced by the Y chromosome of modern humans after Neanderthals interbred with them between 370,000 and 100,000 years ago.
“It’s a really a great surprise,” says Mikkel Heide Schierup, an evolutionary biologist at Aarhus University who did not participate in the study but wrote an accompanying commentary. Only a few percent of the rest of the Neanderthal genome appears to be made up of modern human DNA, yet this study found that three different Neanderthal individuals, unearthed at sites spread across Eurasia and dating to periods tens of thousands of years apart, all carried modern human–like Y chromosomes. This suggests the widespread replacement of the Y across the Neanderthal population, he explains. “It’s a pretty dramatic event.”
Recent years have seen the publication of a handful of high-coverage Neanderthal and Denisovan genomes, but because they were female, there was very little, if any, sequence data on the archaic hominins’ Y chromosomes. To get a better understanding of Y chromosome makeup, computational biologist Janet Kelso of the Max Planck Institute for Evolutionary Anthropology and her colleagues dug deeper into samples from archaic male hominins that had been found over the years.
From samples of three relatively recent Neanderthal remains, all dating to less than 53,000 years ago, and two older Denisovans, the researchers used various techniques to enrich for hominin DNA, and Kelso’s PhD student Martin Petr designed probes to specifically fish out Y chromosome sequences. The researchers then compiled about 7 million base pairs of sequence data for each archaic individual’s Y and compared the sequences with those from modern humans of African and non-African descent.
“The most striking thing that immediately popped up is that all three Neanderthal Y chromosomes are more closely related to the modern human or present-day human Y chromosomes than the Denisovan Y chromosomes,” says Petr. While this wasn’t what the researchers were expecting, he notes that this is not the first time researchers have seen this pattern; the mitochondrial genome of Neanderthals is also more similar to the mitochondrial sequences of modern humans than to those of their sister group.
“It is remarkable to see that both uniparental markers, so both [the] Y chromosome and mitochondrial DNA, they show the same story,” says Cosimo Posth, a paleogeneticist at University of Tübingen in Germany. In 2017, he and colleagues analyzed material from a very early group of Neanderthals and revealed their mitochondrial DNA (mtDNA) to be more similar to the Denisovan mitochondrial genome. This finding led to what Petr says is “currently the most widely accepted model” for the patterns of mtDNA similarity: Neanderthals originally carried a Denisovan-like mitochondrial genome, but it was replaced by gene flow by mtDNA from an early lineage of modern humans that had left Africa and migrated to Eurasia, where they interbred with Neanderthals.
Petr, Kelso, and their colleagues suspect the Y chromosome followed a parallel fate. “I think it’s highly plausible that it could have happened at the same time . . . maybe not one breeding event, but one period of time,” Kelso says.
Tony Capra, an evolutionary geneticist at the University of California, San Francisco, who was not involved in the study, agrees. “I think that that definitely adds support to this hypothesis [of replacement]—that we see that same pattern with the Denisovan being the outgroup to the modern humans and Neanderthals for both the mitochondria and the Y chromosome.”
Researchers agree that it’s very unlikely that both the mitochondrial genome and the Y chromosome spread through the Neanderthal population due to chance. More probable is that the modern human DNA provided a selective advantage to those Neanderthals who carried it. “We don’t know what was the selective agent but it seems like you need one,” Schierup tells The Scientist, “because it’s a relatively short time” to see a chromosome sweep through a population, with interbreeding with modern humans estimated to have taken place at most only a few hundred thousand years ago and the modern Y chromosome becoming widespread by about 50,000 years ago. Exactly when the replacement started is impossible to pin down at this point, however, notes Posth.
Petr ran several simulations that showed even a slight fitness advantage of the modern human Y would strongly favor its spread after introgression. He explains that Neanderthals experienced long periods of very small population sizes, which makes natural selection less efficient at weeding out deleterious mutations. Combined with the Y chromosome’s inability to recombine, it’s possible that the Neanderthal Y had accumulated deleterious mutations that the modern human Y was free of.
Going forward, Petr, Kelso, and others say they hope that Y chromosome sequence data from older Neanderthal individuals will reveal if they carry the original Y chromosome before it was replaced by the modern human variety. “If we have good enough Y chromosomes, we could even compare the deleterious mutations,” Kelso says, and see if the older Neanderthal Y chromosome did indeed have more.
“That’s what I really like about this result,” says Capra, “it makes a very specific prediction about what the Y chromosomes from the older Neanderthals should look like.” He adds that he’d also like to see more functional analyses of the Y chromosome sequences we do have, for example, by looking at genetic differences between the Denisovan Y chromosome and the Y chromosomes of Neanderthals and modern humans. “I’m really curious to know what did these variants on these Y chromosomes do.”
The new findings highlight the dynamic nature of hominin history, says Posth. “We need to stop thinking of continents as isolated entities. . . . Through time, there’s been multiple contact between Africa and Eurasia, and this is leaving a trace, a detectable trace, in the genome of Neanderthals” and of modern humans.
M. Petr et al., “The evolutionary history of Neanderthal and Denisovan Y chromosomes,” Science, 369:1653–56, 2020.