Did Neanderthals make us morning people?: Ancient DNA and the messiness of human evolution

Tiny Matters

In the winter of 1829, Dutch-Belgian anthropologist Philippe-Charles Schmerling discovered a fossil in a cave in Engis, Belgium — what looked like the partial skull of a small child. Schmerling is often called the father of paleontology, but even he had no idea what he had stumbled upon. Decades later, as other similar fossils came to light, the significance of Schmerling’s finding became clear: it was the skull of a child Neanderthal. It was not only the first Neanderthal fossil ever uncovered — it was the first fossil to be recognized as early human.

Although Neanderthals died out around 40,000 years ago, advances in genetic sequencing have revealed that their DNA lives on in all of us today — in our immune systems, vulnerability to certain diseases and, as more recent work has found, the likelihood of being an early riser or "morning person."

In this episode, Sam and Deboki unpack the ancient human journey and the complicated web of relationships between ancient human species. Although Homo Sapiens are the only surviving humans today, for hundreds of thousands of years we were not alone.

Transcript of this Episode

Sam Jones: In the winter of 1829, Dutch-Belgian anthropologist Philippe-Charles Schmerling discovered a fossil in a cave in Engis, Belgium — what looked like the partial skull of a small child. Schmerling is often called the father of paleontology, but even he had no idea what he had stumbled upon. The fossil was classified as a modern human and people kinda just moved on. But a few decades later, as other similar fossils came to light, the significance of Schmerling’s finding was revealed: it was the skull of a child Neanderthal.

Happy 2024 everyone, we are so excited to be kicking off the third year of Tiny Matters. I’m Sam Jones and I am joined by my co-host Deboki Chakravarti. 

Deboki Chakravarti: Hey there — I’m so glad to be back in your ears in the New Year. I think we have a great episode to kick things off. It’s about our ancient human relatives, particularly Neanderthals, and the very cool science being done to uncover our human past as well as to understand its ongoing genetic influence today.

The Neanderthal skull that Schmerling found was not only the first Neanderthal fossil ever uncovered — it was the first fossil to be recognized as an early human. But it wasn’t until 1856, when an amateur naturalist named Johann Fuhlrott identified another, similar-looking skull in the Neander Valley in Germany, that people really started paying attention. In 1864, the new human species was officially named: Homo neanderthalensis.

Sam: Today, our closest living relatives are chimpanzees and bonobos but we separated from our last common ancestor around 7 million years ago. And since then many different species who we are much more closely related to, including ancient humans, have populated the Earth. We’re just the only ones left. 

So humans are part of a group called hominins, which consists of modern humans as well as extinct human species including Neanderthals. Today’s episode will mostly focus on Neanderthals, but I feel like we should take a little trip down memory lane — evolution lane? — to get a broader sense of the hominin evolution timeline. 

Deboki: The first known hominin emerged in Africa around 7 million years ago — when, like Sam mentioned, we diverged from our common ancestor with chimps. This hominin has been named Sahelanthropus tchadensis and it looked a lot like an ape but it seemed to have different teeth, specifically shorter canines like ours. They also had a spinal cord opening underneath the skull like we have, as opposed to an opening at the back of the skull, which is what you see in animals who walk on all fours. 

What does this mean? Sahelanthropus tchadensis may have been able to walk upright, at least some, but there’s still debate there. Either way, this species was climbing trees and looked a lot like a chimp. 

The fossil record from 5 to 7 million years ago is seriously lacking, but in the fossils scientists have found, we can see things start to change. Around six million years ago, a species called Orrorin tugenensis popped up in East Africa. Based on a thigh bone from the species, there’s a general consensus that these hominins were for sure bipedal, meaning they walked upright on two legs. A fossil from another species from around that time also shows indication of bipedalism.  

Sam: And around 4 million years ago, the species Australopithecus anamensis was the first to show a loss of grasping feet. Bye, bye tree climbing! And there were actually a bunch of Australopithecus species that lived around this time throughout Africa, as well as other species like Kenyanthropus platyops and Paranthropis aethiopicus

Around 3 million years ago, the first known stone tools were used by hominins in what’s now Ethiopia. Some scientists think they were made by Homo habilis — a member of the Homo genus that we are also part of. There were a number of species living in Africa at this time, but Homo erectus was the first to venture out of Africa, migrating to Europe and Asia. Homo erectus was also the first hominin thought to have a significantly larger brain, like us. 

Deboki: The timeline we’ve been laying out is all on the order of millions of years ago, but now we’re going to shift to more recent times. It wasn’t until somewhere around 500,000 years ago that Neanderthals popped up in Europe and Asia. And a short 300,000 years ago Homo sapiens first emerged in Africa. It’s likely that our species left Africa in multiple waves over time, but the Homo sapiens who became the ancestors of us modern day humans left Africa around 70,000 years ago and began mingling with other hominins across the globe. 

I think we covered maybe a quarter of the species that have been found, and there are likely still so many fossils out there. But the point is: we may be alone now, but early Homo sapiens and our more ancient ancestors certainly were not. 

In the 170 or so years since the first Neanderthal fossils were discovered, hundreds more have been found. Combined with modern DNA and protein analysis, they have provided scientists with a lot of information as to what Neanderthals were like, and how they live on in us today

Sam: But before we get into that — how do you even go about collecting and sequencing DNA that is tens of thousands, hundreds of thousands, millions of years old? Typically researchers will drill into the bone a tiny bit to create a bone powder. Then they add the bone powder to a solution that breaks the powder down even further, releasing the DNA. After that, the researchers separate out the DNA and get it ready for sequencing. 

Sounds pretty simple, right? Well yes and no. Because there’s something you always have to worry about: contamination. 

Tony Capra: So these are materials that have been usually sitting in the ground for thousands and thousands of years. And so they've been covered with microbes of all kinds. 

Deboki: That’s Tony Capra, a computational biologist at the University of California San Francisco. 

Tony Capra: They've been likely handled by many different humans in the process of identifying them and finding them and transporting them to wherever they're going to be studied.

Deboki: This reminds me a lot of the episode we did at the end of last year, about forensic DNA analysis. Trace DNA contamination is a huge concern in crime investigations because you could accidentally accuse an innocent person of a crime. With ancient fossils, you want to make sure the humans you’re detecting are actually the ancient ones. 

Tony Capra: And so much of the process of studying ancient DNA involves trying to limit those sources of contamination and then extract what is truly the human DNA, and not just human DNA, but ancient human DNA. And this has been enabled by mainly advances from Svante Paabo and Mattias Meyer in Leipzig. 

Deboki: Svante Pääbo won a Nobel Prize in Physiology or Medicine in 2022 for his pioneering work in the field of paleogenomics. Pääbo sequenced the Neanderthal genome and his work also led to the discovery of a previously unknown hominin, the Denisovans.

Pääbo and others have come up with protocols that have made extracting ancient DNA possible, like building a positive air pressure clean room, pumped full of filtered air, to keep contamination out of the samples. 

Tony Capra: And then lots of really clever molecular tricks for amplifying the human DNA, and in particular, identifying the ancient human DNA by virtue of there being particular patterns of degradation that would be specific to some DNA that's 50,000 years old compared to DNA that was just shed by someone living now or living a hundred years ago. 

Sam: Human DNA is a really long molecule, and as it breaks down into smaller and smaller pieces over time, its ends get damaged. 

Tony Capra: And so that leaves certain molecular signatures on the DNA molecules that remain, that can be detected, and that then can indicate, ‘oh, because this is so short, because it has these patterns at the end, that makes it very likely that this particular piece of DNA is ancient, whereas this other piece that's much longer and doesn't have that damage profile is modern.’

Tony Capra: Twenty years ago or so when I was starting to get into this research, I never would've believed that we could have had so much and so much high quality DNA from the past. And it's really like having a time machine. It enables you to see what individuals' genomes were hundreds of thousands of years in the past. Traditionally, what we've always done in this field is sort of look at modern genomes that are available to us and build models about what likely happened in the past from some assumptions. And this has really enabled us to test a lot of those assumptions.

Sam: Tony shared a few big results from that work. One is that there was indeed successful interbreeding between the ancestors of modern humans and Neanderthals, which has left their genetic legacy in us.

Tony Capra: It was like one of the things you'd debate at the bar, not that you would actually give a talk about at a conference, and now this is what we talk about. The second major, I think, revolution that it's caused and how we think about our recent history is just how dynamic it is and how much mixture there was between different populations over time.

And so by looking at patterns of relatedness that can be inferred from ancient DNA, both from groups like the Neanderthals that are sister groups to us, but then also ancient humans that lived 5,000 years ago or 10,000 years ago or 40,000 years ago, you can begin to infer who lived where, when, and how those individuals related to one another and to modern individuals living today. And again, that's just revealed that people move around a lot and different groups interact a lot. And so really, we can't assume that who is living somewhere 5,000 years ago necessarily contributes much, if anything, to the gene pools of individuals living there today.

Deboki: OK, now we want to get into Neanderthals more specifically. Who were they? 

Tony Capra: These are a group whose ancestors we believe split off from the lineage that became modern humans somewhere more than 500,000 years ago, some say more like 700,000 years ago, some say more like 500,000 years ago, but definitely along hundreds of thousands of years ago. And their ancestors also lived in Africa, but they moved out and lived across broad ranges in the Middle East in Europe and Asia for hundreds of thousands of years there before the groups that became the ancestors of modern humans moved into those environments. 

Deboki: That migration — of the ancestors of modern humans out of Africa, to Europe and Asia — didn’t happen until around 70,000 years ago. Neanderthals and other ancient human groups had already been living in these ranges for hundreds of thousands of years.

Tony Capra: So that's one theme of all of this ancient DNA research. It's just how dynamic these processes are. We sort of draw arrows on the map about different migrations, but it's not a march. It's a very flexible process of lots of populations moving back and forth, responding to changes in the environment, responding to other populations that are there. So it's just really, there's been a lot of change in our history and a lot of movement in our history.

Sam: To me this is so fascinating because I feel like the way we often learn about human evolution is picturing this straight trajectory — a perfect, clean diagonal line where you have one species arising at a time and they’re all their distinct, sectioned off thing but, in reality, it’s not totally clear when all of them popped up or died off and there was a lot of mixing. Evolution is messy. 

Tony Capra: The current thinking is that as these human populations were moving into ranges where Neanderthals were also present somewhere around 50,000 years ago, likely there was interbreeding. And those interbreeding events led to the fact that we now have Neanderthal DNA in the genomes of pretty much all non Sub-Saharan African individuals living today. And also those individuals also have Neanderthal ancestry, but through a variety of other processes, actually people migrating back into Africa after getting it outside of Africa, or there being other earlier events that sort of made their way into those populations. So everyone has some Neanderthal DNA, but it's about 2% of the genomes of most non-Africans living today.

Sam: Neanderthals were around for a while — longer than Homo sapiens have been around at this point. So, what happened to them? 

Tony Capra: It's a fascinating question and there are lots and lots of theories about it. So what we know is towards the end of what seems to be the time that they were around, there was this interbreeding with humans that was successful and has left this record in us of what their genomes were like. And then not too long after that, around 40,000 years ago, they went extinct. And what we do know about them is that by that point, they were living in relatively small groups and relatively inbred groups... 

Sam: We know there was a lot of inbreeding because of something called a run of homozygosity in the Neanderthal genome. Every gene has two versions or two alleles, and if you have two of the same allele for a gene then you are considered homozygous for that gene. If you have a huge stretch of homozygous genes — a run of homozygosity — it indicates that your mom and dad had very similar genomes: a sign that they were closely related. Meaning: inbreeding. Inbreeding can give rise to diseases that typically get weeded out when there’s enough genetic diversity around. That lack of genetic diversity can also make it harder for a species to adapt. 

Tony Capra: And so that means often that those individuals are sort of less robust to changing environments and environmental challenges, potentially including the humans that were moving into those environments and competing with them for resources. And so at this point, I think it's really challenging to know what actually happened, but my guess is it was a combination of factors — that populations had been declining for a while, there was then more competition with modern humans, and then also environmental changes that they were less robust to. 

Ancient DNA has been really revolutionary in our understanding of who lived where, when, and how they related and who interacted with whom. But in my view, it's taught us a lot less about what those individuals were like. And that's something I'm really fascinated to try to understand because, before this, all we had to study our ancestors was just the few bones and artifacts that remain from them. And now we have this whole new way of trying to understand what they were like from their genomes. And with that in mind, my group has for a long time been really interested in trying to understand both what can we infer about Neanderthals from their genome sequences and what can we infer about them based on how the DNA that remains in us — and that doesn't remain in us — has influences or could have had influences.

Deboki: Tony told us that there have been a few big themes that have come out of research from his and other labs. The first is that for most of our traits, it was likely at best neutral and in many cases bad to have Neanderthal DNA. How do we know this? Well, scientists can reconstruct about 40% of the Neanderthal genome from looking at Neanderthal DNA in modern humans. But there are a lot of places in our genomes where we don't have Neanderthal DNA, suggesting that it was better to not have their DNA in those positions. 

Conversely, Tony’s and other labs have found a few traits in the modern human genome that seem to be more connected to Neanderthal DNA than you’d expect. 

Tony Capra: And the biggest theme that we've found in terms of what those traits are, is that they're traits that are involved in direct interactions with the environment. So this makes actually a lot of sense to us because the idea is that Neanderthals had lived in these environments outside of Africa with all their unique pathogens, their unique climates, their unique diets, for hundreds of thousands of years, and had adapted to those unique environments. 

Deboki: So when modern humans moved into those environments tens of thousands of years ago, breeding with the Neanderthal populations may have provided our species with genes that helped us adapt to that new environment and the new climate or diseases that came with it. 

Tony Capra: And so if that were true, we would think that the remnants of that process would be involved in the parts of our body that are most strongly and immediately affected by natural selection when you move into a new environment. And so these are things like the immune system, which is constantly engaged in this arms race with the pathogens in an environment to prevent them from infecting us and making us sick. And so that's sort of an exciting piece of evidence that suggests that maybe some of these genetic variants that remain in us today are the remnants of that process of adaptation … that was facilitated or helped a little bit by interbreeding with the Neanderthals.

Tony Capra: Another group had observed a particularly strong effect of a Neanderthal genetic variant in modern populations in the UK Biobank on chronotype, or on a person's preference for waking up early versus late.

Sam: So Tony and his lab, including graduate student Keila Velazquez-Arcelay who led the work, decided to try to understand if the Neanderthal DNA in modern human genomes could influence our circadian clock — ​​the 24 hour cycle that our bodies undergo.

Tony Capra: Almost all the cells in our body have a circadian clock. And basically this is a little molecular machine that cycles throughout the day and keeps track based on incoming input from light sensing cells and temperature and all sorts of other cues, what that light dark cycle that you're experiencing looks like, because it's really important to regulate all sorts of processes in our body to those external cues. So it's not just when we get sleepy and when we wake up. It's our metabolism. It's our immune system. Essentially every part of our body has some input in terms of modulating its activity based on the time of day.

Deboki: In the study, the researchers identified 246 circadian clock-related genes in modern humans and then used an artificial intelligence technique called machine learning to understand how variation between modern human and Neanderthal DNA — specifically in those circadian genes — could affect their function. 

The researchers then homed in on the variants likely to have an effect — that were also of Neanderthal origin — in the genomes of hundreds of thousands of people in the UK. They found a striking impact on morningness, or increased likelihood of someone being an early riser or ‘morning person.’

Tony Capra: So we don't actually think that the benefit comes from waking up early in the morning. We think that this is actually a signal of having a clock that is more able to adapt to that variation and light dark levels over the course of the year so that your clock is sort of properly timed. You get less jet lag if you've got a clock that's running like this than if you have one that is not.

Sam: This kind of work could help us understand why we have the sleep patterns we do and maybe alter them. Other Neanderthal genetic findings are helping us better understand our immune systems. For instance, a genetic variant from Neanderthals has been linked to a much higher likelihood of having Crohn’s — an inflammatory bowel disease. And, in September, 2020, researchers reported that a major genetic risk factor for severe COVID-19 is inherited from Neanderthals. 

On the flip side, there are researchers using AI to try to identify different antimicrobial compounds that Neanderthals may have produced that we don’t, that could be used to fight antibiotic resistant bacteria, which, in just the United States, cause millions of infections and tens of thousands of death each year. But aside from any medical applications, learning about Neanderthals tells us about modern humans on a much bigger evolutionary scale. 

Tony Capra: You can possibly ask, where did we come from? How do our genomes work? Each one of us is walking around with a genome, and that genome somehow encodes all that is needed to make a human, and all the amazing variation we see in humans living today. And that process is just miraculous to me, and I really want to understand it as well as I possibly can. And by looking at these ancient individuals that lived 10,000 years ago, 30,000 years ago, 40,000 years ago, a hundred thousand years ago, we get an incredible reference point to looking at what's similar and what's different, what has changed, what hasn't changed.

And until recently, all we had been able to do was compare our genomes to those of our closest living relatives, the chimpanzees. And while they're very similar to us in many ways, they're also very different. And we have all sorts of amazing characteristics that at least we feel are essential to the nature of being human and being able to study these individuals that lived in the past and are much closer to us is just, I think, an incredible opportunity to understand the nature of what it is to be human, at least at the biological level.

Sam: It's time.

Deboki: First of the year.

Sam: I know. Do you want to go? Do you want me to go?

Deboki: I can go.

Sam: Okay. Cool. Go for it.

Deboki: Mine becomes related. It doesn't start related, but it sort of eventually is kind of related.

Sam: Okay. Cool.

Deboki: Okay. My tiny show and tell, my first one for the year, is based on this article in the New York Times by Carl Zimmer called Flowers are Evolving to Have Less Sex, which is like inherently I saw that title and I was like, great. I want to know more.

Sam: It's a great title. Yeah.

Deboki: Yeah. So this is based on a new study looking at the relationship between flowers and pollinators. And particularly the study found that some flowers are preferring to fertilize their own seeds instead of relying on pollinators to help them reproduce with other flowers. So the reason why scientists have been curious about this relationship is because they want to know what is the effect of pesticides and what is the effect of habitat loss on this dynamic that we know of between pollinators and flowers.

And so in this study in particular, they were looking at the field pansy, which usually relies on bumblebees to do their pollination. But what they have found is that increasingly it looks like field pansies are turning to something called selfing, where they fertilize their own seeds with their own pollen. They've also found that this seems to be happening pretty quickly in the grand scheme of evolution. They've seen the switch happening within 20 generations. And so in general, when we think about how organisms reproduce, selfing is sort of on the lines of reproduction methods that are easier, but they're also less likely to give you that genetic variation that you want.

So related to some of what we were talking about today, sexual reproduction is great because it gives you all of this genetic variation that lets you adapt and evolve, but it is also potentially costly. It takes a lot of energy. It takes a lot of effort. In this case, you got to wait for a pollinator to come by. So there are times where for some organisms, it's better to do something like selfing, where even if you're not going to get that variation that helps your species survive in the long term, you'll at least be able to reproduce in an easier way that just lets it happen.

Specifically, they were comparing field pansies from this cache of seeds that were stored in the '90s and early 2000s to newer seeds basically and they found that when they compare the newer seeds to the older seeds, the newer ones were doing selfing a lot more. And also while the size of the overall plant stayed the same, the flowers themselves had gotten smaller and were making less nectar. And they also found that bumblebees seemed to prefer the older ones to the newer ones.

So they think that this is a sign that field pansies are putting less effort into sexual reproduction and maybe putting that energy towards other processes like maybe dealing with diseases. And obviously this then becomes an issue for bumblebees too. Like if flowers are making less nectar, if they're investing less in that relationship, maybe that's going to be a problem for pollinators as well. Though, as a caveat to that, there was another scientist interviewed for this article who did work with morning glories where it turns out they're actually developing larger flowers, which they think might be a strategy to attract more pollinators.

So I think that's interesting too because kind of what that's pointing to is this idea that there are different evolutionary strategies. So some are just trying to more aggressively pursue sexual reproduction and some are more pursuing this selfing approach. And so I think it's interesting that you get these different strategies and we'll see long-term how that shapes the relationship.

Sam: That's so fascinating. I think it is really cool to also that reminder that what are the circumstances at that time? What is the best thing? And it's not necessarily a super long-term strategy all the time. That's not how evolution works, right? The idea is really survival. So maybe that just means selfing versus sexual reproduction for some species and others are, like you said, going all in on trying to attract pollinators and keep that going, and who knows what else can happen before long-term happens. So sometimes just the fastest, quickest, easiest thing might be ideal.

Deboki: Yeah. It was interesting because in this article one of the scientists mentioned that potentially one of the things they're concerned about is that these flowers could forget how to do sexual reproduction essentially and not easily relearn it. One of my favorite papers is this paper about the evolution of amoeba sex because in amoebas there's actually been this long, weird, complicated history of them losing and gaining sexual reproduction-

Sam: Oh, weird.

Deboki:... Because it's just the trade-offs for them I guess change a lot. And so it's really fascinating that they gain it back, but that might be a lot easier for an amoeba than a plan. And so yeah, it's kind of fascinating to think about.

Sam: So my tiny show and tell is about the solar eclipse that we are expecting in the spring and why it's going to be so cool. So we're expecting it on April 8th. For people who don't know, a solar eclipse, it's when the moon blocks out the sun. And if you are in something called the path of totality, then it fully blocks out the sun. We had a solar eclipse back in 2017, and of course some parts of the United States did experience totality, but apparently this one is going to be so much cooler.

First off, it's going to last longer and be darker, and that is because the moon will be at a point in its orbit where it's quite close to earth, which will make it appear quite large. And so then as a result for anyone who's able to make it to the path of totality where the moon completely blocks out the sun's disc, it's going to be especially dark and it's supposed to last for nearly four and a half minutes, which is almost two full minutes longer than the eclipse that we had in 2017. So when the eclipse happens this year, the sun is also going to be more active, which I guess will make the eclipse appear even more intense.

I did not know this, but apparently the sun goes through this 11-year activity cycle. I should know this, but I didn't know this. And we're going to be closer to what's called solar maximum, where you get all these bright pedal streamers of plasma that come off the sun and a few other things. And so I guess that's going to kick up the intensity a notch. And this is going to be the last major eclipse that's going to cross North America for 20 years. So I don't know. If you can see it, definitely go see it. I'm actually going to head up to Vermont to try to get in the path of totality, and I just bought glasses for it.

And I will also say that part of this also, I guess, is to tell people that they should check NASA's website. And I'll leave a link in the episode description to see which ones are legit, because I guess this is a big issue where if you just go on Amazon or something, there are a lot of sellers who are selling stuff that actually is not legit and could then be damaging to your eyes. So I'll put a link so that you can find real NASA vetted sellers.

Deboki: That was a very useful PSA, because I keep forgetting about this. I only remember because my in-laws live in Austin, and so I think they're pretty directly in the path, and so they've been really, really excited for it. And so they're like, yes, we're getting the glasses. They're prepared. They're ready. I think they're also ready for people to be coming to Austin to go see it. But yeah, that's a very useful PSA on multiple levels. Also, the thing about making sure to get the legit solar viewing glasses, because that would be really upsetting.

Sam: Yeah, let's not burn our eyeballs, people.

Deboki: Thanks for tuning in to this week’s episode of Tiny Matters, a production of the American Chemical Society. This week’s script was written by Sam, who is also our executive producer, and was edited by me and by Michael David. It was fact-checked by Michelle Boucher. The Tiny Matters theme and episode sound design are by Michael Simonelli and the Charts & Leisure team. 

Sam: Thanks so much to Tony Capra. If you have not rated and reviewed Tiny Matters, please do! Let’s start off 2024 strong. If you want another way to support the show, buy one of our coffee mugs! We’ve left a link in the episode description. You can find me on social at samjscience.

Deboki: And you can find me at okidokiboki. See you next time.