Ancient interbreeding helped humans fight disease

Interbreeding between ancient humans, Neanderthals, and Denisovans influenced our ancestor’s genome. They inherited an improved immune system from them.


We are now more than a decade on from the first large-scale efforts to sequence the Neanderthal genome. In the intervening years, a lot has happened. We’ve discovered interbreeding between our species. In fact, we’ve discovered whole new species through genetics alone (which we also interbred with). We found that some from all this genetic admixture helped us, and some harmed us.

And this research is ongoing. It feels like every other month scientists discover another handy gene we actually got from the Neanderthals or the Denisovans. So as we enter the second decade of hominin genetics, let’s take a look back at how our relatives helped our ancestors survive by ramping up their immune system.

Disease and the Neanderthals

All of this admixture has produced some very sexy results (pun partially intended). Denisovan interbreeding, for example, may well help some people to survive in the Himalayas! However, some of their impacts are a bit less eye-catching. Admixture causing tweaks to our immune system probably won’t grab any headlines.  But these changes are perhaps the most significant of the lot.

Being introduced to a new environment almost always comes with some horrific diseases in tow. When Europeans imported their local diseases into native populations, the results were essentially genocidal. And when Europeans wound up in unfamiliar environments, they hardly fared better. During construction of the Panama Canal, 200 French workers a week succumbed to tropical diseases. By the time manpower and funds ran out and the project had to be abandoned, the death toll was in the tens of thousands.

From around 100,000 years ago modern humans began migrating around the world. No doubt they would have run into similar problems (although low population density may have reduced some of these effects). Fortunately for us, other hominin species had already made the journey. Neanderthals had been living in Europe for hundreds of thousands of years. Their immune system was already adapted to the weird foreign land that is Eurasia.

Some key migrations around the world, when humans would have encountered new diseases

Interbreeding and the immune system

As such, it should come as no surprise that the Eurasian immune system is built on the back of Neanderthals and Denisovans. After the interbreeding, many of the resulting genes proved harmful in humans, and were purged from our genome. However, when it comes to the immune system the story is different. Clearly, those ancient variants proved helpful to our surival and were favoured by natural selection. Now, huge swathes of modern populations have an immune system aided by ancient interbreeding.

For example, the toll-like receptors help our body recognise invading pathogens. There are 11 in humans, three of which have three unique variants. These seem to have come from other species via interbreeding. Two from Neanderthals, one from Denisovans.

The proportion of people around the world with the ancient human variants of toll-like receptors (blue) and the variants produced by interbreeding (not blue)

And that’s just the start. There’s also STAT2, which is involved in interferons. These little chums help warn other cells that something is invading the body. One unique variant of this gene likely came from Neanderthals, and is present in about 5% of Eurasians. This Neanderthal variant may also be involved in apoptosis, where a cell kills itself because it has become infected or otherwise problematic.

Or the MHC, a key component of our immune system that “tags” invading pathogens for destruction by the body. Several MHC genes from Europe and Asia have been identified with common Neanderthal and Denisovan variants.

But wait, there’s more

Of course, all of this is just scratching the surface. As my degeneration into just listing off genes towards the end may have indicated, there are dozens of more examples of other hominin species giving our immune system a boost through interbreeding.

Interbreeding between us, Neanderthals and Denisovans may have only happened a few times (perhaps); but the results are profound.  Our survival in Eurasia has been impacted by our little love triangle. Who knows where we might be without it?

Well, we’d probably still be in the region. The other species managed to survive there without the pre-adaptive help of interbreeding. But with an increased disease load we might well be living in smaller, less dense populations. And such groups bump into strangers less often, slowing down the rate knowledge spreads. Without some help from ancient horny humans, our society could be tens of thousands of years behind where it is now.

References

Dannemann, M., Andrés, A.M. and Kelso, J., 2016. Introgression of Neandertal-and Denisovan-like haplotypes contributes to adaptive variation in human Toll-like receptors. The American Journal of Human Genetics, 98(1), pp.22-33.

Grove, M., 2016. Population density, mobility, and cultural transmission. Journal of Archaeological Science, 74, pp.75-84.

Nielsen, R., Akey, J.M., Jakobsson, M., Pritchard, J.K., Tishkoff, S. and Willerslev, E., 2017. Tracing the peopling of the world through genomics. Nature, 541(7637), pp.302-310.

Racimo, F., Sankararaman, S., Nielsen, R. and Huerta-Sánchez, E., 2015. Evidence for archaic adaptive introgression in humans. Nature Reviews Genetics, 16(6), pp.359-371.

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2 thoughts on “Ancient interbreeding helped humans fight disease”

  1. clayton says:

    I have a question, that hopefully you won’t need to get too technical to answer, but it’s something I’ve been wondering about. So, we’ve gotten “good” genes and “bad” genes, from this interbreeding, and we’ve “purged” the bad ones. So, did the Neanderthals and Denisovans go through life with these “bad” genes? Or did they get “good” and “bad” genes from us? Oh, another question! Do we know if the Neanderthals and Denisovans interbred?

    1. Adam Benton says:

      Neanderthals and Densivans did interbreed. In fact, Denisovans even interbred with another, unknown species of hominin.

      As for the bad genes, they were only bad in us. Neanderthal genes were well suited to Neanderthals. But stick them in a different species and you start to have compatibility issues. Like how two horses can happily mate. But if a horse and a donkey combine you get an infertile mule. The fact that there were so many genetic issues between us and Neanderthals shows we were at the very limits of genetic compatibility, basically two different species.

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