How did we get all of our Neanderthal genes?

Neanderthal DNA has been very prominent in the headlines for the past couple of years. This came to a crescendo when winner of the 2022 Nobel Prize for Physiology and Medicine, Svante Paabo, got said award for sequencing the genome of the Neanderthal. We’ve learned that we share around 2% of our genome with our now extinct relatives. But how did it get there, and what does that mean for us in our day to day lives? The Francis Crick Institute’s Pontus Skogland…

Pontus - That's a great question. When people have looked at DNA and tried to sort of estimate using the known rate that we get mutations when Neaderthals and humans separated or diverged as we call it in the past, they've gotten something like half a million years ago. But I think there's really fascinating hints that there were more complex things going on. Some of it is more than hints. We know that on our mitochondrial DNA and our Y chromosomes, we have a common ancestor with Neanderthals more on the order of 400,000 years ago. Furthermore, there's some indications from people who look at fossil morphology, you know, how they look, the fossils that make it seem like sort of neanderthal traits and what is to become Homo sapiens traits. Might be diverging much earlier as well, perhaps, you know, almost 1 million years ago or maybe a bit less than that. And so I think what this is hinting at might be that it was sort of a two step process where perhaps our ancestors initially became diverged and then there was a point of contact 300,000 years ago or something like that. And that's sort of the average of that number comes out in our calculations for half a million.

Will - Ah, so this is much less of a clean split, like if some birds flew off on an island and they never saw their original counterparts ever again. This is a bit of interspecies breeding in the meantime.

Pontus - Exactly. So yeah, the equivalent would be that, you know, maybe the sea levels went down at some point and there was a bridge between the two islands, but then perhaps they became isolated again. And yet there's really been a bunch of different studies looked, have looked at this phenomenon, all publishing hints that this is what's going on.

Will - So assuming then that this 2% figure of sharing Neandertal DNA is an average, let's say. What affects the sort of exact amount from person to person or groups of people?

Pontus - The main difference is that Neanderthal ancestry is found in people that have recent non-African ancestry. So in the past few thousand years, ancestors that were from outside Africa. And that's really the line of evidence for that. This is something that happened during this expansion in our species from living only in Africa and its vicinity to expanding into far-flung areas like Europe, Asia, Oceania, and the Americas. People with strictly, for example, west African ancestry will have negligible levels of Neanderthal ancestry. People with only some sort of recent Asian or Oceanian or European ancestry will have about 2%. There's actually very little variation between people. Some of the ancestry companies kind of report information as to what your rank is among customers.

Will - And we've touched on it before in the program, but it seems the presence of Neanderthal DNA in an individual's genome does affect their susceptibility to diseases such as, for instance, covid. There's one theory that Neanderthals were exposed to certain illnesses before homo sapiens and it gave them more time to build up a resistance. So the presence of Neanderthal genes gives our immune system a bit more to play with. I was wondering if you had an opinion on that. Where do you think that's a worthy theory or if you have one of your own?

Pontus - There's the COVID question and then there's sort of the general fact that yes, since many people have up to 2% in Neandertal ancestry, that will of course affect the variation they have in their genomes and the mutations that they have. And those will inevitably affect biology in some way. There's a certain degree of variation within humans and 0.1% of that type of variation on the average trait would be explained by Neanderthal ancestry. And so of course it will impact biology. I think it's important when you see in the news of Neanderthal variants having an effect on particular physical traits or other traits, is that that's kind of the expectation. They are mutations among many others in our genome. They will influence them. Usually they do at a sort of smaller proportion of the trade. But it's really fascinating and in several examples it might indeed have been adaptive for various reasons, might have been things that were adaptive in Neanderthals that were adapted later on. COVID is of course a fascinating example. I think it could just be to chance as far as I know that Neanderthals had this variation and that it was sort of transmitted to people today. Maybe it was selected later on in Homo sapiens. That seems to be a reasonable thing to ask.

Will - If we were so genetically similar to Neanderthals to the point that we could interbred with them and they are part of our genome. Why is it that we are still here and Neanderthals seemingly are not?

Pontus - Yeah, that's another fascinating question. Neandertals mostly disappeared around 40,000 years ago. One possibility that people of course like Svante Pääbo, who's been the main researcher by far on Neanderthal DNA and awarded the Nobel Prize last year, has brought up is that it may be that they were just sort of lower in numbers and they were kind of absorbed in expanding populations. And that's sort of where this 2% number comes from. But I think it's also important to remember that this kind of ebb and flow of ancestry groups that don't contribute much to later generations. When you bring the clock forward of thousands of years, that's quite common. Neandertals disappeared 40 or so thousand years ago. The first people in Europe don't seem to have contributed much to populations just a few thousand years later. And then of course when you get even to more recent times, the last hunter gatherers didn't contribute much. You know, they lived 10,000 years ago. They didn't contribute much to later forming populations, later forming populations in turn didn't contribute much to later populations. This kind of ebb and flow I think is really quite common in our history, but that doesn't mean that human ancestry is shallow in time. In fact, our big family tree connecting all of us goes back several hundreds of thousands of years.

Will - I do like the idea that the Neanderthals aren't gone. They're just within us. Even only slightly.

Pontus - Yeah, absolutely. They're still around.