GOING WITH THE FLOW —

Much of Neanderthal genetic diversity came from modern humans

Neanderthals' low diversity means their population was even smaller than we thought.

JOHN TIMMER - 7/12/2024, 

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The basic outline of the interactions between modern humans and Neanderthals is now well established. The two came in contact as modern humans began their major expansion out of Africa, which occurred roughly 60,000 years ago. Humans picked up some Neanderthal DNA through interbreeding, while the Neanderthal population, always fairly small, was swept away by the waves of new arrivals.

But there are some aspects of this big-picture view that don't entirely line up with the data. While it nicely explains the fact that Neanderthal sequences are far more common in non-African populations, it doesn't account for the fact that every African population we've looked at has some DNA that matches up with Neanderthal DNA.

A study published on Thursday argues that much of this match came about because an early modern human population also left Africa and interbred with Neanderthals. But in this case, the result was to introduce modern human DNA to the Neanderthal population. The study shows that this DNA accounts for a lot of Neanderthals' genetic diversity, suggesting that their population was even smaller than earlier estimates had suggested.

Out of Africa early

This study isn't the first to suggest that modern humans and their genes met Neanderthals well in advance of our major out-of-Africa expansion. The key to understanding this is the genome of a Neanderthal from the Altai region of Siberia, which dates from roughly 120,000 years ago. That's well before modern humans expanded out of Africa, yet its genome has some regions that have excellent matches to the human genome but are absent from the Denisovan lineage.

One explanation for this is that these are segments of Neanderthal DNA that were later picked up by the population that expanded out of Africa. The problem with that view is that most of these sequences also show up in African populations. So, researchers advanced the idea that an ancestral population of modern humans left Africa about 200,000 years ago, and some of its DNA was retained by Siberian Neanderthals. That's consistent with some fossil finds that place anatomically modern humans in the Mideast at roughly the same time.

There is, however, an alternative explanation: Some of the population that expanded out of Africa 60,000 years ago and picked up Neanderthal DNA migrated back to Africa, taking the Neanderthal DNA with them. That has led to a small bit of the Neanderthal DNA persisting within African populations.

To sort this all out, a research team based at Princeton University focused on the Neanderthal DNA found in Africans, taking advantage of the fact that we now have a much larger array of completed human genomes (approximately 2,000 of them).

The work was based on a simple hypothesis. All of our work on Neanderthal DNA indicates that their population was relatively small, and thus had less genetic diversity than modern humans did. If that's the case, then the addition of modern human DNA to the Neanderthal population should have boosted its genetic diversity. If so, then the stretches of "Neanderthal" DNA found in African populations should include some of the more diverse regions of the Neanderthal genome.

There and back again

In this work, non-Africans acted as a control group. The researchers identified the regions of the Neanderthal genome that they carry and checked how diverse those are within the Neanderthal genomes. They then made the same comparison with the sections of Neanderthal DNA that are found in African populations. This showed there was a clear difference: the Neanderthal DNA carried in Africans tended to come from areas of the Neanderthal genome that were much more diverse. (Meaning the six Neanderthal chromosomes we have sequences from are more likely to have differences between their DNA bases in these areas.)

A second analysis focused in on the most diverse regions of the Neanderthal genome (the top fifth percentile). Fully 60 percent of these regions were included in the Neanderthal DNA identified in African populations. By contrast, they accounted for only 23 percent of the Neanderthal DNA in non-African populations. The team also reran the analysis without the top 10 percent of diverse Neanderthal sequences and found that the matches with African genomes largely disappeared.

So, it's clear that the most diverse parts of the Neanderthal genome are largely shared with human genomes in African populations. The conclusion is that this isn't Neanderthal DNA that somehow made its way to Africans. Instead, it's modern human DNA that was picked up by Neanderthals and maintained in their population. Overall, the researchers estimate that roughly 3 to 4 percent of Neanderthal genomes consist of modern human DNA from this early interbreeding.

This doesn't explain all of the matches with Neanderthal DNA found in African populations, though—the researchers estimate that there is still somewhere between 20 and 40 percent of these matching sequences it doesn't account for. This suggests that some Neanderthal DNA did arrive in Africa through back-migration of populations that had left during the out-of-Africa expansion.


This modern human→Neanderthal shows up in the populations that left Africa, as well. But it only accounts for about 10 percent of the DNA they share with Neanderthals. All of the rest is distinctly Neanderthal→modern human DNA that was picked up during the expansion out of Africa.

A vanishing population

The converse of this finding is that the distinctly Neanderthal portions of the genome are much less diverse than the complete Neanderthal genome. And that's significant, because genetic diversity is a measure of the effective population size—small populations tend to be much less genetically diverse, in part because there are simply fewer chromosomes overall, and in part because it's more likely that individuals will mate with distant relatives.

In the case of Neanderthals, the existing estimates of genetic diversity from the genomes we had suggested that the Neanderthal population was small, far smaller than those of contemporary modern humans. The new work suggests that about 20 percent of that diversity came through interbreeding with modern humans, implying that the Neanderthal population was even smaller than those estimates.

The two other Neanderthal genomes we have date from around the time of the major out-of-Africa expansion of modern humans. And the new analysis suggests that they'd also picked up a tiny bit of additional human DNA at this time. But the researchers propose that the population was so small that this made very little difference. "The assimilation of Neanderthals into modern human populations as they spread throughout Eurasia would have effectively increased the size of modern human populations while simultaneously decreasing the size of an already at-risk Neanderthal population," the authors suggest.

Science, 2024. DOI: 10.1126/science.adi1768 (About DOIs).


JOHN TIMMERJ

ohn is Ars Technica's science editor. He has a Bachelor of Arts in Biochemistry from Columbia University, and a Ph.D. in Molecular and Cell Biology from the University of California, Berkeley. When physically separated from his keyboard, he tends to seek out a bicycle, or a scenic location for communing with his hiking boots.