The Ancient Neanderthal Traces Hidden In Your Genome

11:58 minutes

a fossilized skull on a black background
A neanderthal skull. Credit: Shutterstock

Just how much of your genome is uniquely human? It turns out the number of genetic components in the human genome that trace back only to modern humans, and not to other human lineages or ancient ancestors, are surprisingly small. In a paper published recently in the journal Science Advances, researchers estimate the uniquely human portion of the genome as being under two percent. 

Many of the genes thought to be strictly connected to modern humans appear to relate to neural processes. However, traces of genes from Denisovans and Neanderthals can be found scattered throughout the genome—including strong Neanderthal genetic signals in parts of the genome dealing with the immune system.

Ed Green, a professor of biomolecular engineering at the University of California Santa Cruz and one of the authors of that paper, joins SciFri’s Charles Bergquist to talk about the study, and what can be learned by this approach to studying our genetic code.

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Segment Guests

Richard “Ed” Green

Ed Green is a professor of biomolecular engineering at the University of California Santa Cruz.

Segment Transcript

IRA FLATOW: This is Science Friday. I’m Ira Flatow. Later in the hour it’s the intersection of beavers and wildfires. I know you’re going to want to hear that. But first, the question you might have been thinking in the lead-up to Halloween– what does it mean to be human? Yeah, SciFri’s Charles Bergquist’s is here. Hey, Charles.

CHARLES BERGQUIST: Hey, Ira. So we’re not talking vampires or werewolves here. This is a study that took a close look at the human genome and tried to map out where it intersects with the genomes of Neanderthals and Denisovans.

IRA FLATOW: So you mean other lineages of humans that are not around today, but their genetic traces are.

CHARLES BERGQUIST: Yeah, in fact, chances are that sprinkled through your genome there are plenty of genes that can be traced back to one or another of these groups.

IRA FLATOW: Now, there must be parts of my genome that are unique to modern humans, no?

CHARLES BERGQUIST: Some, not a lot. I asked Ed Green, a professor of biomolecular engineering at UC Santa Cruz, if he could put a number on it for us.

ED GREEN: It is surprisingly small the amount of our genome that you would never find in any Neanderthal. It is somewhere around a few percent. And we did this two ways. One way, just saying all of the regions of the genome that are uniquely human, genetically. And then a smaller subset of this is the regions of the genome that are uniquely human and have what we call a fix, derived allele or some genetic novelty. So it didn’t just get inherited from humans– in all humans today, but it actually has something new and different that’s specific to humans. And that fraction of the genome is less than 2%– very, very small amount of all of our DNA is just coming from human ancestors and has something that could possibly be functionally relevant because it’s actually different than what was available in other archaic human groups.

CHARLES BERGQUIST: How do you even get to that number? Walk me through that. The big question that we wanted to answer is where in individual human genomes is their ancestry from these archaic relatives, Neanderthals and Denisovans. Where in genomes do we share genes with them and where do we not?

We have in the past made maps, made estimates of how many genes. But getting a real high-resolution map of exactly where human genomes come from Neanderthals, this requires a different technique and that’s the main point of this paper, developing this technique that in its essence is just a tree. Who is more closely related to who as you go across each place of the genome? And then if you include Neanderthals and Denisovans in this giant family relationship tree, then it is easy to kind of put your finger and say here Neanderthals fall outside of all human variation. And here at this other place Neanderthals fall within human variation and it looks like that’s because humans got their genes from Neanderthals. And we can do this across the genome, across each gene, and then do cool things like make catalogs of where some humans share genes with Neanderthals, where no humans share genes with Neanderthals, et cetera.

CHARLES BERGQUIST: I’m confused on just what you mean when you say “share” a gene. You’re not saying that we have the same genetic code here?

ED GREEN: Yeah, this is a really cool thing to think about. So when we say that an individual shares a gene with a Neanderthal, what this means is that the specific DNA sequence of that gene comes from a Neanderthal closer back in time than it comes from another human.

This phrasing “share a gene with”– it conjures up this image that there are individuals that share this gene and then there are other individuals that just don’t have that gene at all. That is not the case. Sharing a gene in this context– it means that you are identical by descent, which is a crazy, jargony phrase that just means that if you go back in time– if I share a gene with a Neanderthal and I go back in time, there was an individual– a specific individual who had a name, maybe it was Frank– that individual– I can trace my copy of this gene directly to that individual and so can Neanderthals trace their copy directly to this individual, the same individual, and that individual was a Neanderthal. That would be identity by descent from a Neanderthal.

And if that is the case, then this must have happened by admixture from a Neanderthal. My relative long ago was a Neanderthal named Frank and I got this DNA– that’s what I mean by sharing a gene with Neanderthal. Now that gene, whatever that gene is– almost certainly every other human and every other Neanderthal on the planet has that gene, they just have a different version that they inherited from a different ancestor who may or may not have been a Neanderthal. And not only does every other human and every Neanderthal have that gene, probably every mammal has that gene. But it’s just a different version that they didn’t inherit from, even a primate– for whatever species they are. So genes– this kind of gene set, 20,000 genes or so, is pretty uniform across all of mammals and even wider, with some variation. But when we talk about sharing a gene with a Neanderthal versus somebody else, we’re talking about identical by descent.

CHARLES BERGQUIST: Would it be fair to say like we all share genes for eyes, but some of us have genes that say blue eyes, versus green eyes, versus brown eyes.

ED GREEN: Exactly. There’s about eight genes actually that influence eye color, but whatever. This gene that has to do with eye color, and there are genetic variants in that gene, and you can ask how similar or different is my DNA sequence in that gene, and that may be more or less, depending what version you have.

CHARLES BERGQUIST: If you’re looking back through the genome here, can you trace any specific traits to specific origins?

ED GREEN: Well, when we were able to make this map and see what genes are shared with Neanderthals? What did we get from Neanderthals? What did we not like from Neanderthals? We could start to ask broad questions and specific questions. And one of the most interesting results was in this broad question.

If we just look across all humans and say where does nobody have Neanderthal genes either by long ago, the common ancestor of humans and Neanderthals, that version of gene bopping around in Neanderthals and humans not really caring to do anything different with it or don’t have Neanderthal version of a gene by admixture. Where are the genes where neither one of those things happen, where humans, currently living modern humans, made some genetic change to a gene? And when Neanderthal genes came in, we didn’t like it. We got rid of all of those genes where we just don’t like what Neanderthals had on offer, we don’t like the old version, didn’t keep it around, and didn’t accept the Neanderthal version when it was reintroduced to us.

And what’s interesting is these regions of the genome are highly enriched for, first of all, genes, in general, and, second of all, genes that are expressed or have some indication that they have something to do with neural function. So neural-related genes were extremely overexpressed in this map of not Neanderthal. We don’t want the Neanderthal version of the genes. Our ancestors got rid of it somehow. And that map– that kind of map where we’re not Neanderthal is highly enriched for neural-related genes.

CHARLES BERGQUIST: Are there places in the genome that there really is a lot of Neanderthal influence, that their version of that specific gene was just way better than whatever was standard issue at the time?

ED GREEN: Perhaps. And there have been some descriptions of Neanderthal admixture variants that have gone to high frequency in human populations today. Some of these our immune system-related genes, which, on their surface, are easy to understand what they’re doing. They help us interact with pathogens in the environment. But beyond that, it becomes very difficult to say exactly what they’re doing– what pathogen and when this advantage take place.

There is the outline of a interesting story there. Historically, there must have been something that happened that caused these variants to go to high frequency. Whenever you see Neanderthal genes or any genes go to high frequency very fast and it’s due to selection, this means that people died. That’s the only way that you get something to go to high frequency selection. It sounds like such a clean, clinical word. Selection means people died. And these immune system genes going to high frequency, it means that if you didn’t have it that you died. But what exactly was killing individuals, that’s really hard to know. And that’s most of the story of the– or a lot of the story, anyway, of Neanderthal admixture genes that went to high frequency.

We honestly, because of this map, having this for the first time, being able to see where we don’t have Neanderthal genes, we were focused on that. What are the things that are unique to all humans? Everyone who is alive today in the world, all humans, that Neanderthals just didn’t have figured out? What is it that makes humans unique, even compared to Neanderthals and Denisovans, our closest extinct relatives. What are the things that we brought to the table that made us the awesome things that we are today.

CHARLES BERGQUIST: So does that change how I should think about myself as a species?

ED GREEN: I guess it depends how you thought of yourself before. But you should be proud. We should all be proud of this genetic uniqueness that we have. And it’s a bit telling that what genes are involved here. We would love to know more about the functional consequences of this human uniqueness. And 2% doesn’t sound like a lot, but the genome is a big place– three billion base pairs long. And 2% of three billion is quite a bit. We’ll be busy for some time trying to figure out what were the functional consequences of this 2% human uniqueness.

CHARLES BERGQUIST: Ed Green is a professor of biomolecular engineering at the University of California Santa Cruz. Thanks so much for taking the time to talk with me today.

ED GREEN: Well, you’re welcome. Pleasure to be here.

CHARLES BERGQUIST: So, Ira, be proud of those 2% of genes.

IRA FLATOW: Thanks, Charles. 2%, two degrees of separation– I will keep that in mind.

Meet the Producer

About Charles Bergquist

As Science Friday’s director, Charles Bergquist channels the chaos of a live production studio into something sounding like a radio program. Favorite topics include planetary sciences, chemistry, materials, and shiny things with blinking lights.

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