In this episode of Naked Genetics: What new DNA techniques are revealing about human sacrifices in Mayan culture; we debunk the 'junk', in junk DNA; and, the upside down sea snail that makes rafts of its own snot...
In this episode
00:34 - What ancient DNA reveals about Mayan sacrifice culture
What ancient DNA reveals about Mayan sacrifice culture
Shivani Shukla & Aylwyn Scally
A genetic study has uncovered some fascinating details about the life and death of those put to ritual sacrifice in the ancient Mayan city of Chichen Itza. Modern day Chichen Itza is located in the Yucatan peninsula in Mexico, and in its heyday, around 1300 years ago, was a site of major significance for the Mayan people. At that time, ritual sacrifice was a somewhat common means of providing nourishment for their gods and goddesses. And now, a new study of ancient DNA remains found at the site have revealed more about the demographics of those selected for sacrifice, but also what happened to the genetic composition of the indigenous population in the millennium since.
Aylwyn - My understanding is they were extracted in the usual way for ancient DNA, which is from the Petrus bone, which is a bone in the inner ear which has a high concentration of DNA. It's quite a dense bone and therefore more resistant to sort of the leaching out of DNA into the environment. And I think that was what they did, because they did mention that for some of the samples, that bone wasn't found and therefore they weren't able to get DNA and
Will - Shivani, I feel like this might be a bit of a study into the bleeding obvious, but how can we be sure that these are sacrificial remains?
Shivani - The site in which these burial remains were found is just one of many Mayan sites where these human sacrifices are made. As studies progress and we understand more about the Mayan culture, we know that human sacrifices, whilst not as common as we believe, were part of their kind of giving back to the gods, and they believed in the importance of nourishment. So we do see other very similar kinds of mass burial sites in South America at least.
Aylwyn - I don't know if it's true for all of them, but I guess the fact is that you find a large number of children all in one place, which is suggestive of that not being just a normal burial site. So I think that some of it is inferred due to the religious nature, and we know that ritual sacrifice was an important part of Mayan culture.
Will - And I suppose being found in a cenote, it's unlikely that they all went down there and just died by accident.
Shivani - Yeah, these were all found in underground caverns. So we know, I think, that the Mayas believed there was a connection with Gods in these caverns. And also like Aylwyn said, there were many similarities between the remains. So there seemed to be a preference for twins and a preference for children. And I think they were all male. That can not be by coincidence. They're clearly selected. And, you know, twins play a really important role in Mayan culture, and one of their main religious texts has this concept of hero twins who sacrifice themselves for the betterment of the world. So twins are a recurrent theme we see in many burial or sacrifice sites for the Mayans.
Aylwyn - You do raise a good point though, Will, in that one of the opportunities that arises when you have a new source of evidence, like genetic evidence is, is to keep an open mind with regard to some of the interpretations that have been made based on other evidence and to say, 'well, you know, is this also consistent with those stories?' But it is also true, maybe not here, but certainly in other sites around the world, that we have discovered things through genetics that maybe don't necessarily agree with every aspect of the story that people had proposed before. So it's worth asking those basic questions.
Will - So much like the Rapa Nui study of last month, this is a good bit of DNA confirmation of a previously posited archaeological theory.
Aylwyn - I think in this case. Yes.
Will - As you said, it revealed that the preference was for young males and even twins due to the ideological preference of that being a more potent sacrifice. Did it reveal anything about how they lived before they died, though?
Aylwyn - A lot of their diets had been quite similar too, and I think the interpretation of that was that they had been eating a diet as part of a ritual in preparation for sacrifice of something. I mean, one wants to watch out with interpretations like that because that's something where it would seem there's a number of possible explanations.
Shivani - I mean, it would also make sense if children were to be living in the same area where a certain type of crop is grown, that everyone's diets would be similar. So I suppose it's hard to make the distinction of whether the diets are preselected for ritualistic purposes or everyone's just eating the same thing, because that's what there is.
Aylwyn - Yeah. We should maybe clarify also what we mean by isotope data. That's another kind of molecular data that one can get from ancient remains, not genetic data. Essentially you're looking at the particular types of molecules that you find, and there are different versions of molecules that are often characteristic of different origins in the ecosystem or in diet. And so that actually does give you an insight into what people have been eating and into their environment that they've been living in. So that's been a part of archaeological science for a few decades. And so it's quite nice now we get these studies that really combine sources of evidence of various different types, including genetic evidence to really build up a picture.
Will - I suppose a good secondary side effect of this study is that you get a genetic map of the individuals, the indigenous people that lived in that area kind of pre and post colonization as well. Do these remains show that the modern day populations have had any significant alterations to their genomes in the time since?
Aylwyn - Well, I think the first thing to note is actually there's quite a lot of similarity between the nearby modern population and the ancient population of this ancient city. And we're talking about going back well over a thousand years, I think about 1200 years or something. And so there are quite a lot of similarities. So that suggests there's a lot of shared ancestry that a lot of the ancestors of present day people are similar to the ancestors of these people in the ancient city. There were a few changes. One for example being that these ancient individuals seem to have a little bit more genetic similarity to present day and ancient samples from the Caribbean. So there was obviously some shared component of ancestry there, which has since been either diluted or lost in the present day in the modern population.
Shivani - I think it's interesting to note that during colonisation, the Mayans were, well, not only persecuted, but underwent a lot of natural selection because they were exposed to pathogens such as smallpox. So, by comparing the kind of the alleles with the remains in the present day population, it does actually support that the present day Maya have undergone a large degree of pathogen selection. You can tell by the overlapping of these particular alleles. So it's another incident of what we think to be true versus what is represented genetically. I think it's just interesting that, you know, things have advanced so much to the point they know which alleles correspond to which diseases. So there's a specific one quoted here, which is a binder for salmonella peptides. So I think as things become more sophisticated, not only can we say, oh yes, there's been natural selection and pathogen resistance, we can even say what to, and I think that's really interesting.
A study published in Nature has appraised the genetic impact that an extinct species of cattle has on our modern populations. The Auroch was a wild bovine that appeared in Europe about 650,000 years ago. It grew to a height of 1.8 metres and lived throughout much of the continent, before being driven to extinction due to hunting and habitat loss in the 1700s. But their genetic legacy lives on. The analysis of ancient auroch DNA has revealed when and how these wild beasts were slowly coveted into our more docile domesticated cattle.
Aylwyn - In a very straightforward sense, it's just a direct comparison. We know that modern cattle derive, and there are various versions of modern cattle too, but they all derive from domestication of ancient aurochs populations. And so you're right that we can do, and there were people, people did initially do studies of just looking at modern cattle and trying to tease out. Can we work out what the ancestral relationships between these present organisms are? But it's now we've got a thing to compare with, it just makes it a lot easier. You know, you're trying to do a jigsaw puzzle without looking at the box. It's a lot harder than when someone shows you what the picture's supposed to be. And to some extent seeing the ancient genomes from which the present day domesticated cattle derive that helps us solve that puzzle.
Will - What do we now know then, when we compare the two DNAs and what insight does it give us as to when humans started to domesticate them?
Aylwyn - Well it's quite an interesting picture actually, because today we have, broadly speaking, there are two groups. There's the Bos taurus, which European cattle are derived from and which are familiar to all of us in the fields around us in Europe. And then there are also Bos indicus, which is the cattle domesticated in South Asia. And all, or nearly all, Asian cattle are derived from that domestication. And it's believed, I think, still that those are the two main domestication events. And both of those derived from ancient wild aurochs. There were different, or populations around the world, just like other animals. And we can see ancient European aurochs and ancient Asian and north Asian aurochs. And this study was able to sequence DNA from various samples of all of these different aurochs species. And it seems that the aurochs, their common ancestor goes back kind of a hundred, few, couple of hundred thousand years that there's a sort of divergence of the aurochs into different groups in Asia and Europe, and then subsequently the European cattle. Those emerged from the domestication of some wild aurochs population, aurochs population in sort of the Middle East, western southwest Asia, that part of the world. And then spread from there. As Europeans moved out to the Middle East and brought farming techniques into the rest of the world, into Europe, et cetera, they brought their cattle with them.
Will - We've got the timeline then. Do we have any idea about the process itself? Because it's kind of fairly widely accepted now in the case of wolves that we managed to pick the most docile ones and kind of inadvertently, selectively breed from there. Was this a similar situation?
Aylwyn - I don't know that we know anything about how docile they were, and I suspect it's conjecture that they probably weren't. A wild oryx would've been quite a formidable beast. And so therefore there is some evidence from this study that actually the initial domestication event didn't involve that many animals, probably because it was somewhat risky business to try and go and capture one. And also, if you think about it, suppose I want to start domesticating some animal or group of cattle, maybe the thing I do is I somehow kind of put a fence around a whole herd, and thereafter that's my herd. And I start kind of trying to domesticate the offspring and so on. Actually, it seems like an easier approach, which is what was taken, was you just capture one female animal and you somehow tether that or keep it within your control, and then you allow that animal to breed freely, relatively freely with the wild population, with wild males. But then you've got control over that female and her offspring, and therefore you can build up your stock that way. And it seems that's what's happened. And therefore we can see evidence that the domestication is somewhat female dominated at the earliest stages. And that there's lots of ongoing interbreeding with the wild population. And that carries on throughout the early domestication period. There's a number of these similar domestication stories where we're trying to put it together and it's surprisingly hard. And one of the reasons why it was hard actually is that this pattern of ongoing with the wild population, you know, it's not like we take the whole wild population, domesticate that, and then there are no more wild animals. The wild animal continues to exist. And this pattern seems to be something that's actually the nature of domestication. I'm not sure that we've found any examples where there was this sudden domestication and a complete isolation of the domesticated crop or animal.
13:30 - Mutated 'junk' DNA could lead to rare health problems
Mutated 'junk' DNA could lead to rare health problems
Ernest Turro, Icahn School of Medicine at Mount Sinai
For the most part on this programme, we look at the DNA that codes for stuff, the bit of our genome that creates real tangible proteins or what have you, that go on to change our body in some way. But do you know what percentage of our entire genome, everything stored in our DNA, actually directly codes for stuff? It’s about 1%. So what on Earth is the other 99% doing? Well, for a long time, we had a simple answer: nothing. It was ‘junk DNA’, remnants of bygone protein recipes that we no longer have any need for, or stuff that came in via disease or other means that we have nothing to do with. And for many decades, this opinion persisted. Now however, we realise that a lot of what goes on behind the scenes in our DNA is heavily controlled and moderated by these non-coding proteins. So today, let's have a peek behind that curtain, and debunk the junk.
Starting with the idea that certain non-coding DNA is responsible for part of the splicing process of specific genes. Say you want to take one recipe out of a cookbook, you need to know where to start and where to end looking at the recipe, so you don’t accidentally add cake ingredients to a pasta. The presence of this non-coding dna as a means of selecting the right bit of genome to make into a protein can mean very rare health problems present themselves if this process goes wrong. I’ve been speaking to Mount Sinai’s Ernest Turro, author of a new publication on just such a disease, and he began by giving me a rundown on how attitudes towards junk DNA have had such a pivot in recent years…
Ernest - The term 'junk DNA' was coined over 50 years ago by an evolutionary biologist, the same year that the term junk food was popularised by nutritionists. And just as junk food had no known nutritional value, junk DNA was used to refer to regions of the genome without a known function. At the time, that would've encompassed almost the entire genome. But over the years, it's become apparent that actually quite a lot of the genome is functional. About 10 years ago, colleagues in Cambridge published a paper pointing to a very large proportion of the genome being biochemically active. I think the figure was 80%, and that that statement actually stirred up a bit of controversy at the time. And I think there's no real consensus on what exactly should be considered junk DNA. So I think the term has fallen considerably out of favor in recent years. I think it might be more useful to think of the genome as containing a vast array of elements of different kinds. So some of those elements are genes. My old Cambridge boss, Willem Ouwehand, would liken them to lights in a room. And other elements are more akin to regulators or, or dimmers, uh, for those lights. And I think genes are certainly the most important of the elements. And they come in two broad flavours. So you have coding genes and non-coding genes. And there are about 20,000 coding genes, which are the stretch of genome that is transcribed into RNA molecules, which are then translated into proteins. So in the case of coding genes, the RNA's purpose is really only to mediate the production of proteins from that gene. But there are also tens of thousands of non-coding genes. And these are transcribed into RNA, but it stops there. The RNA is not translated into a protein. My research group specialises in the development and the application of statistical methods to discover the genetic changes or variants in human genomes that are responsible for rare diseases. And these disease causing changes, they might happen in regions of the genome that previously would've been considered to be junk DNA.
Will - Given that your area of research is based around rare diseases, what do you think these areas of non-coding genes, that's what we should probably refer to them as, that you looked at are actually responsible for?
Ernest - So our publication in May in Nature Medicine concerns a non-coding gene called RNU4-2. We found that genetic variants in this gene were responsible for a neurodevelopmental disorder that we estimate affect tens of thousands of people around the world. In 2021, Daniel Green and my group completed an initial genetic association study of all the genes, so both coding and non-coding, across all the rare diseases, in this very impressive genomics England dataset. We identified hundreds of associations with coding genes and also a few very promising associations with non-coding genes. And so we decided to write up a paper on the coding genes first, which appeared in Nature Medicine last year before moving to the non-coding genes. And when we returned to our analysis of non-coding genes, we immediately focused on this really small non-coding gene called RNU4-2. This very small non-coding gene, its only 141 bases long contains variants which are responsible for this neurodevelopmental disorder, which is now called RNU4-2 syndrome or ReNU syndrome. The syndrome features, you know, intellectual disability and other traits such as short stature, small heads, seizures. And what's really striking about this is that we estimate it affects about 1 in 25,000 young people. And this would make it amongst the most common monogenic causes of neurodevelopmental disorders known to date.
Will - How could, though, the mutation of a non-coding gene lead to the formation of a neurodevelopmental disorder?
Ernest - That's a really good question. The RNA that this gene encodes is called U4 and it is one of the five small RNA components of a molecular complex called a spliceosome. So spliceosomes, as their name suggests, play a crucial role in splicing exons together within the nucleus. So exons are like linear islands in an archipelago. They are separated regions of the genome, which are transcribed into RNA and then they're spliced together to form a mature RNA molecule, which can then be translated into a protein. So there are two types of spliceosome in humans, there's the major spliceosome and there's a minor spliceosome. And in fact, defects in two small non-coding RNAs, which are in the minor spliceosome, have been previously tied to a rare disease. Now, these RNU4-2 mutations that we published earlier this year represent the first reported non-coding defect in the major spliceosome.
Will - So just so I've got this straight, the idea that these non-coding genes are responsible for splicing coding genes, but they may cut it at the wrong place and therefore the recombination leads to, say, an incorrect protein which could lead to a neurodevelopmental disorder.
Ernest - That's exactly it, that's the running hypothesis. We just haven't really been able to find a large-scale defect in this slicing process in mature cells that we've studied from patients. And that's why this kind of lab work where you take cells and differentiate them into different types of cells that we can't study from patients and look at the splicing and those cells could shed some light into where the splicing problems occur and which cell types this variant splicing occurs.
Will - It seems extraordinary that we've spent so long ignoring this huge other part of our genome. And I guess the mind boggles at how many other neurodevelopmental but also physical disorders could be down to errors going on in non-coding DNA that we've previously ignored.
Ernest - That's right. I mean, the cost of sequencing was such that there was a case to be made for only sequencing the protein coding genes initially. If you can sequence fifty patients instead of one by restricting the regions of the genome that you sequence to the protein coding genes, then that might initially lead to more scientific findings than if you sequence the entire genome. Because it's reasonable to suspect that many, if not most, of the variants that cause diseases are located in protein coding genes. But by the late 2010s, the cost of sequencing a whole genome had gone down quite drastically. And so that made it much more attractive to sequence entire genomes in large numbers of patients. And that is what's allowed us to discover that indeed some non-coding genes can cause mutations that can cause really quite severe diseases in humans.
Will - I'm envisaging a future where this sort of research looking more and more into non-coding DNA could go hand in hand with better earlier diagnoses of neurodevelopmental disorders, such as the ones you found, perhaps autism. Do you see that as being a potential future?
Ernest - Absolutely. One of the things that has happened as a consequence of this discovery is that all the big clinical genetic testing labs are scrambling to adapt their tests so that they can pick up sequence variants in this small gene. And one of the issues with testing that restricts to specific regions of the genome is that they need to be adapted regularly every time that there's a new discovery. If it's in the non-coding parts of the genome, then the test will probably need to be adapted.
22:55 - How 'junk' DNA could control how species evolve
How 'junk' DNA could control how species evolve
Yukiko Yamashita, MIT
Our non-coding DNA could dictate an organism's ability to speciate. Speciation is the term that described the ability to evolve into a new species, and it could be heavily influenced by so-called ‘satellite dna’. This is DNA that encompasses our coding DNA, and gives it structure. The 3 dimensional structure of a gene can heavily influence how it expresses itself, so how the satellite DNA acts around it surely has some say in how those genes behave, and even the rate at which they mutate, the backbone of speciation. MIT's Yukiko Yamashita explains more...
Yukiko - So if you think about coding DNA, you can imagine the contents information of a book. Those words that you enjoy in the book, that is a coding part. On the contrary, we barely pay attention to the binding margin of the book, because it doesn't give us any information. However, the binding margins are critically important because if we don't have it, all those pages are completely jumbled up. After you read page one, you don't know where page two is and then you end up jumping to page 527 and then you know, the next thing you see might be page 18, that kind of thing. So one function the satellite DNA might be playing is to function as a glue or a binding margin of the pages of the book to bring all pages or in another's chromosome in this case together into one place so that you know, it doesn't get separated from each other.
Will - So if you had two organisms with different satellite DNA, how could that affect their speciation?
Yukiko - So you could imagine, the exact same story. Two publishers can publish those two stories and then one publisher might decide to bundle those pages on the side. And then on the other hand, the other publisher might decide to print a book in a way that everything is bundled on the top of the pages. The story is exactly the same, but if you mix up those pages before bundling and then how can you decide how to bundle them into pages in the right kind of order. But then just because formatting the information is not the same, you cannot just form the correct functional book. That might contribute to some sort of dysfunctionality of the hybrid cells.
Will - Yes. I suppose if you had half of the pages from one book, which had binding on the side and half the pages was binding on the top, they wouldn't be able to fit together. There'd be basically two different books.
Yukiko - Exactly. Yeah. So that could actually explain that even when protein coding genes are extremely similar to each other, the two kinds of chromosome from two species might not necessarily function very well.
Will - So do we think the changes in satellite DNA could come about due to random mutation, same as regular speciation?
Yukiko - I think probably satellite DNA mutates even faster because coding sequences are so much of a constraint so that there's a selection against the changes, right? So that means if you are talking about the book, if you change just one character in the word, the whole meaning could change. Zoom versus zoo would be very different. And then also probably Zoom would be very different from boom and then the next change like bloom is going to be completely different. But then if it's just formatting information, the satellite DNA is just formatting information. And then for example, satellite DNA can be just A-A-T-A-T repeating so many times only to signal out 'put the glue here' or that kind of thing. Let's say you have 10,000 copies of A-A-T-A-T still probably it's going to work completely okay, but 1000 copies mutated to A-A-T-A-C. I think that there is minimal impact to the species. So that allows satellite DNA to change much more than individual words as a content information. So I think that's why the satellite DNA or those kinds of non-coding junk DNA tend to change a lot. And then by the time you realise your formatting information, like binding margin information, might be very different from your cousin species or cousin populations.
Will - If that is the case then, albeit completely inadvertently, perhaps unfairly, do we think then that certain organisms with certain structures of satellite DNA may be able to adapt quicker than others?
Yukiko - Oh, that's an interesting possibility <laugh>. it's possible. I feel some species might get lucky to get an adaptable kind of satellite DNA. I don't know if species or any organisms would have that foresight <laugh>. So let's go that direction because that is going to make us better and then more adaptable in the face of changes. For that, you know, I want to be very neutral. But with that said, yes, you know, in hindsight the sudden changes that happen to your satellite DNA structure, junk DNA structure, might make a particular species a little more faster evolving. That's possible.
28:44 - The sea snail that makes rafts with its snot
The sea snail that makes rafts with its snot
To round off this month's Naked Genetics is another edition of Quirks of Evolution...
You join me in the tropical near coastal waters of the Pacific ocean. More specifically, right at the surface. The pelagic zone of the ocean is one that sees immense turnover on a daily basis, as the abundance of sunlight and tidal currents cause an unimaginable number of microorganisms to float through. Staying on the surface is a banquet in a very open ocean, providing you can do two things. One, you can be sustained by jellyfish and hydrozoa. Secondly, you have some means of staying at the surface. This group of unrelated organisms that occupy the niche of surface water, or just below it, are called neustons, and they employ a range of tactics and adaptations. Most things can just inherently float, like the Portuguese man o’ war. Pond skaters do so by not breaking water surface tension. And then we come to the curious case of Janthina janthina - the violet sea snail.
The violet sea snail is a beautiful organism, as snails go. A shell consisting of light purple shading on the spire, down to even deeper purple on the ventral side. It measures about 4cm by 4cm, a colossus in the neuston world. But looks only get you so far in the animal kingdom. It’s still a snail so it isn't exactly fleet of foot (singular). And it can’t swim, which is sub optimal for an ocean dweller. So if you can’t float naturally, you’re going to have to make your own raft…
At the surface of the ocean, alongside all that food and also a trillion billions bits of microplastic, are air bubbles, pockets of O2 that haven’t yet burst and joined the wider atmosphere. And the violet sea snail makes use of these in a truly extraordinary way. By wiggling its foot to and fro, the snail produces mucins, slime-esque proteins that come out of epithelial tissues. These mucins are amphiphilic, they love water and fat, so they’ll stick to the snail and water. But they will also trap air. So, by lassoing air bubbles with its own goop, this snail can hang upside down on the surface of the sea, and catch a meal as it floats on by. It takes an hour to create a raft of bubbles which can keep the snail at the surface buffet for quite some time.
But what if someone were to find it? Surely hanging out at the surface whilst being unable to escape is just asking to be snatched up by a hungry mouth? Well, did you think those purple shadings were just for vanity’s sake? This snail is not just a pretty face. No, this is a remarkable case of reverse countershading, which I guess could just be called shading?
For those out of the loop, many marine organisms, ranging from great white sharks to penguins, have a white tummy and a dark back. The deep sea is dark, and the surface is bright. Therefore, anyone looking at your white tummy from below won’t see you against the surface, and anyone looking at you from above won’t see you against the dark of the sea floor. This is countershading, simple but brilliant. So why does the snail have a dark ‘tummy’ and a lighter ‘back’? Because it feeds upside down, meaning the colours are flipped.
I could go on about this wild seafaring snail. How it changes sex halfway through its life, how it can raft in groups to make even bigger flotation platforms. But if anyone ever says you aren’t suited for a role, kindly let them know that a humble snail is thriving perfectly well at the surface of the big blue sea...
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