Scientific Method —

Sleeping around gave early humans immune boost from Neanderthals, Denisovans

The interbreeding our ancestors have done with other early humans may have …

The ancestry of modern humans has gotten much more interesting in recent years. Completion of the Neanderthal genome came with a bit of a surprise: they may be extinct, but many modern humans carry pieces of their genome, a sign that our ancestors had some rather significant interactions with them. About the same time, we learned that there was another group of archaic humans called the Denisovans present in Asia at the same time; nine months later, we learned that our ancestors had slept with them, too.

The evidence came in the form of DNA that was unevenly distributed within modern human populations. Modern humans had gotten their start in Africa, but Neanderthal or Denisovan DNA is rare or absent in African populations. Instead, it's more common in Asian and European populations, which suggests that interbreeding only took place after modern humans had migrated out of Africa.

What the study didn't touch on was why DNA sequences from archaic humans is still around. Was interbreeding frequent, and the DNA that remains simply present by random chance? Or did specific regions end up providing our ancestors with an evolutionary advantage? A study that will appear in today's issue of Science indicates that, for at least some sequences, the answer is the latter: they're still here because they're useful.

The DNA sequences in question encode a group of related genes called HLA. These genes serve a very specific purpose: they take pieces of proteins from inside the cell and present them on the cell's surface, where the immune system can look them over. If the immune system doesn't like what it sees, it will launch an attack against the cell. In this capacity, the HLA genes are key to determining whether tissues match well enough to allow an organ transplant with a minimal risk of rejection.

But the genes didn't evolve simply to make organ transplants difficult. Instead, they help the immune system recognize when a cell has become infected with bacteria or a virus. When a cell is infected, the HLA proteins display pieces of the proteins made by the bacteria or virus. This gets detected by the immune system, which then eliminates the infected cell. Different HLA genes provide better protection against some pathogens than others, so it's helpful to have a diverse set of them. Humans, in general, do.

The question the authors of the new paper ask is how we got them. Normally, when you look at a DNA sequence that varies among human populations, the greatest variation occurs in pygmies and Khoisan speakers in Africa. That's because these groups appear to have split off from the modern human population before it migrated out of Africa, and have had the longest time to pick up changes in their DNA. Many HLA variants, however, don't show this pattern. Instead, some forms of the genes are present only in Asian and European populations. In fact, one specific allele that is absent in the two African populations mentioned above is most closely related to some versions found in chimps and gorillas.

The simplest explanation for this, the authors argue, is that this version of the gene was lost by the ancestors of modern humans, but got reintroduced in Asia by the interbreeding that went on there. So, the authors downloaded the HLA sequences from the Denisovan and Neanderthal genomes, and examined whether they might be present in modern humans. The patterns matched what we'd expect from interbreeding exactly. The Denisovans interbred with populations that ended up in Papua New Guinea after traveling through Southern Asia. And, when looking at HLA alleles, the authors found that "All four combinations are present in Asia and Oceania, but absent from Sub-Saharan Africa, and uncommon in Europe."

In one case, the Densiovan allele is present at frequencies of over 50 percent in China and Papua New Guinea, but not present in Africa at all. In another, the allele had started to spread back along the route of migration, appearing further west in Asia.

Neanderthals show a similar pattern, except they interbred with modern humans earlier, and so had their genetic contribution carried into more of Europe and Asia. A few of their alleles have even made their way back into Africa, although they remain present at low levels compared to elsewhere.

The authors point out that the molecular data indicates that Neanderthals and Denisovans were present in Asia for roughly 250,000 years before modern humans left Africa. That would have given their immune systems plenty of time to adapt to the local hazards, which would mean that their HLA genes were likely to provide an advantage to the newly arrived humans. They suggest that it should be no surprise that, once interbreeding had provided some copies of these favorable variants, they'd end up spreading widely within this population.

Right now, however, this remains the first published case where there is strong evidence that we've retained DNA sequences from archaic humans because it was adaptive. There's no doubt, however, that others are poring through the sequence databases, looking for cases of other genes. Given time, we just might find out that the decision to interbreed with the locals was an extremely useful one for our ancestors.

Science, 2011. DOI: 10.1126/science.1209202  (About DOIs).

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