Will It Sequence? 700-year-old DNA
In this episode of Naked Genetics: A mammoth discovery in ancient DNA structure; on the subject of ancient DNA, what can we sequence for a centuries old body? And, in quirks of evolution, the animal that drinks its own offspring’s blood...
In this episode
00:46 - Intact mammoth chromosomes discovered
Intact mammoth chromosomes discovered
Shivani Shukla & Aylwyn Scally
The field of sequencing extinct genomes has been rocked by a paper published in the Journal Cell, which heralds the discovery of one of, if not the, most intact specimens of mammoth DNA ever discovered. This sample, dating back 50,000 years, was found in the Siberian Permafrost, and contained genetic structures that were thought impossible to preserve over such a long period of time.
Shivani - This specimen from the mammoth was taken from a piece of the ear and it was so incredibly well preserved through the process of just dehydration and the permafrost that kind of froze it in place that it preserved the 3D structure of the DNA. And that's pretty rare because usually from ancient DNA you are scraping together different segments and trying to build a picture. But for once we've preserved the architecture of all the chromosomes and genetic material. And so we have an astoundingly accurate reading of the genome of the mammoth for the first time.
Will - How was that achieved? What were the conditions that allowed this to happen?
Shivani - The process of dehydration and just the lack of moisture in the air, and then the permafrost, it's very similar to how the Egyptians did the process of mummification. They just used hot air and drying, but in both scenarios there's just a lack of moisture and that allows biological tissue to really not decompose over time.
Will - Aylwyn, to throw over to you then, we've got this unique structure, this 3D structure. What information can be discerned from this that wasn't available previously?
Aylwyn - Well, I mean it is amazing. This is the kind of experiment that you can do with DNA from modern samples or present day samples. You could look at which bits of each chromosome are actually close to each other in the cell or even chromosomes themselves are looped up and packaged up amongst other proteins and other molecules. And that brings certain bits of the chromosome next to each other that otherwise if you just stretch the chromosome out in the line would be very far away. And it seems that those kinds of interactions, those proximity relationships are actually important for how the genome functions. It's important in determining and regulating the production of proteins in the cell and is actually part of how the DNA molecule works. So it's not just the sequence of the DNA, it's also the shape of the molecule itself and its interaction, its relationship with all of the other chromosomes, that actually are important in producing an organism's phenotype and how the cell works.
Will - Now that we have access to literally an extra dimension of mammoth DNA and we might start to be able to uncover how certain genes and how certain parts of the DNA interact with each other way better than we did before, in mammoths, aside from just knowing that and it being interesting, is there anything that it could actually be useful for?
Shivani - One of the salient findings from this was there was a specific gene, which is the EGFR and it was inactivated in these woolly mammoths and that leads to their really furry, hairy coat. But they compared this to the Asian elephant and the gene was active and they don't have this coat. So by finding interesting genes that code for different phenotypes or physical attributes, we can kind of see when temperatures change over time because of global warming. Are we able to do something about that and understand how the genes of an animal might allow it to survive these changing conditions or not?
Will - Every time a new sample of woolly mammoth appears, a biotech company, and this is no exception to this one, comes forward and goes, we would really like to be able to produce mammoths or produce elephant mammoth hybrids that resemble the extinct creature. And my question is why are people so obsessed with mammoths?
Aylwyn - I think there's a general consensus that they're pretty cool animals and it might just be about that really they're sort of iconic, prehistoric creatures. I don't know that scientifically it goes much beyond that and it's sort of a meaningless goal in my view anyway, to think about bringing back mammoths as a species. You know, even if you made a sort of elephant mammoth hybrid, a species is a lot more than just the genome of an organism. It's more than just all the molecules in it's cells, it's a whole population of organisms in an environment interacting with other species as part of an ecosystem. So unless you bring all that back, which is impossible, you haven't brought back the species. You've got this sort of chimeric creature living in a zoo. And maybe that would be a very cool zoo and maybe people would go and visit it and you might make a lot of money that way. But I don't think that's in itself an interesting scientific question. There are some very good scientists working, advocating for projects like this. And I think probably what they would say instead is that it's a sort of moonshot type project where, even if the goal itself is not achievable, in working towards it you will develop kinds of new technologies and get new scientific understandings and that those will have genuinely useful and transformative applications. I think that's what they would argue as the motive, although they may not make that explicit.
Shivani -There are people, private companies, or projects who run their own take on bringing mammoths back. And one of them claims that by bringing mammoths back, you can revitalise the mammoth steppe ecosystem, and that would actually slow the melting of the arctic permafrost. And I remember reading about this. So some people believe that by bringing them back you can restart an ecosystem and ancient ecosystem that slows global warming. So I think that it's very interesting, the kinds of different motives that people have for this.
Will - I feel like I know your answer to this, but for the pair of you, would you invest time and effort and resources into bringing back the mammoth?
Shivani - I think they're cute, but there are many cute animals that need saving that are alive today.
Aylwyn - Yes, exactly. I would rather invest those resources into projects that are addressing conservation today. Of course, that generally doesn't involve very complicated genome sequencing projects. So maybe that's why people don't get excited about them in the same way.
07:10 - Sequencing 700-year-old DNA
Sequencing 700-year-old DNA
Christiana Scheib, University of Cambridge & Michal Szpak, Illumina
The field of archaeology has a fantastic, relatively new, weapon in its arsenal, as gene sequencing is providing some fantastic new insights about people living a very long time ago. But just what kind of things can be discerned from bodies that have spent centuries in the ground? Well, I can’t say I’m chomping at the bit to stand next to pile of corpses. So, we will need a couple of wise sages to walk us through the world of ancient DNA...
Will - The field of archeology has had a fantastic relatively new weapon added to its arsenal as gene sequencing is providing some fantastic new insights about people living a very long time ago. But just what kinds of things can be discerned from bodies that have spent centuries in the ground? Well, I can't say I'm chomping at the bit to stand next to a pile of corpses, so we'll need a couple of wise sages to walk us through the world of ancient DNA.
Christiana - Ancient DNA is what it sounds like. It's DNA that is ancient. So a loose definition would be anything that's over a hundred years old. DNA can come from multiple sources, it can come from skeletal remains, which is what I do a lot of my work on. Or it can come from soil, it can come from pottery, it can come from lots of different sources, but as long as it's over a hundred years old, it would qualify as ancient DNA.
Will - That's the University of Cambridge's Christiana Scheib, one of the leaders of the investigation. And who is our lucky specimen this time round?
Christiana - Today, we're going to be talking about an individual from the Augustinian Friary in Cambridge. And this is somebody who probably died between the years of 1330 and 1350. Yeah, we know a little bit about the people in this cemetery based on the archaeology and some of the historical records, and now also because of the genetic work that we've been doing as part of the After the Plague project.
Will - Those of you who are quick on the draw with your maths have already noted that 1350 is just shy of 700 years old, which begs the question, where do you look for DNA on a specimen that ancient?
Christiana - If we want to look at human DNA or pathogen DNA, we'll look at at teeth and we'll look at intact tooth roots, or in this case, what we're going to talk about today, dental calculus, which is a calcified film on the teeth, which we all get, and we usually get it cleaned off when we go to the dentist. But in earlier time periods, people didn't go regularly to the dentist, and so it builds up over time and it remains on the skeleton. Dental calculus forms in layers, and so theoretically you could get different time periods in a person's life as the dental calculus builds up over time. But generally, we're more looking at sort of the bulk. So we would take some dental calculus, we would scrape it off of the tooth and then put it through our normal sort of dental calculus ancient protocols, and we can look at the entirety of what might be inside the dental calculus of that person, which will reflect what was in their mouth throughout their life. If you do proteomics on the dental calculus, you can often get some food proteins or even sometimes some proteins from if they were using their mouth as a tool or processing some sort of fibres or other materials, you might be able to find that. We can also look at microfossils, which are tiny fossils that also get embedded into the calculus, which might show indications of usage of the mouth or being around. Sometimes you find charcoal indicating that people are around fires or there's a really good paper of some nuns actually, and they had this blue ink in their dental calculus that got incorporated, which gave a picture of them actually working on manuscripts. And so yeah, from the DNA, from the proteins from the microfossils, the dental calculus can give us a nice insight into the daily life of, of somebody in the past.
Will - So not only can they learn about the person themselves, but also even the microorganisms and other compounds that were present in their mouths. But if you are looking at skeletal remains, some of which were buried in so-called 'plague pits', do you have to be wary of any dormant illnesses being brought up with the samples?
Christiana - Ancient DNA is physically different from modern DNA in a few ways. Essentially over time, DNA chemically breaks down, and so as all organisms die, they start to break down. And so ancient DNA is characterised by short fragments, low amounts of DNA and also certain degradation changes in the actual bases in the DNA. And so even if we're looking at a plague pit or something where we know there's been disease, it's very unlikely that that disease would be still viable. It's not like the mummy or the most recent sort of Tomb Raider movie where they open up the tomb and everybody gets this disease. It doesn't really work like that.
Will - So the nature of DNA decay is somewhat of a blessing when it comes to reducing the risk of disease, but it's a double-edged sword, of course. As this breakdown means, sample sizes are absolutely tiny. So with the odds not really in their favour, what was discovered when they got their teeth into the ancient DNA? Illumina's Michal Szpak, who worked on the sequencing samples, is here to take us through it.
Michal - So what did we find? Well, we found the presence of the Y chromosome so we could confirm it was a male individual. Actually 80% of the data couldn't be matched, but that's not unusual. And you know, it's for various reasons. So partially due to gaps in the reference database, but also naturally occurring variation. But also the, ancient nature of the ancient DNA, so you know, the damage and chemical modifications that Christiana was talking about. And then, from those reads that could be assigned to a species, 99% were bacteria. And of that, around 85 to 90% were oral bacteria commonly found in the human mouth, which is consistent with the sample origin. So we are happy about that and almost 50% were sulphate reducing bacteria involved in gum disease. But we also found a number of less common but nastier bacteria also causing gum disease and dental infections such as Tannerella forsythia for example, but also Streptococcus pyogenes, which is infrequent, but usually pathogenic. It infects human throat and mouth and skin often causing scarlet fever and skin rashes. But also dental abscess.
Will - So a lot of common mouth bacteria, some uncommon a bit nastier bacteria, but little to no presence of the real nasties at the time, smallpox, typhoid, leprosy, what have you. So first of all, well done to this individual for potentially avoiding all of those horrible diseases, but it does mean that the cause of death remains a mystery.
Michal - Yes, you know, the cause of death could be natural. We didn't find anything obvious. You know, none of the bacteria that we found are likely to cause death. It kind of looks like a pretty normal oral microbiota. It's not unheard of for commensal bacteria to cause infections. They're part of normal microbiota, meaning many people carry them without any symptoms, but in some cases they can lead to serious illness or in extreme cases even death. You know, as, for example, as seen in some forms of streptococcal infections. We found some streptococcus, but it's rather unclear which strain. So it is very, very unlikely that any of those would cause death.
Christiana - We normally wouldn't look for cause of death in oral dental calculus. Normally if you're looking at ancient pathogen DNA, you're looking at something septic, so something that would've been in the bloodstream. So if we're gonna find Yersinia pestis, that's going to be inside the dental pulp chamber or inside of a bone somewhere where you're actually getting the remains of what was in the bloodstream at the time of death. And so even if we found a streptococcal strain inside the dental pulp cavity, instead of say in the dental calculus, you still wouldn't be able to say for sure that 'oh, it was some sort of infection.'
Will - Even so, it is a treasure trove of information, and this field of sequencing has the potential to uncover a whole lot more going forward.
Michal - There's been a lot of buzz around ancient environmental DNA found in the soil dirt and sentiments, which can preserve very well, under right conditions, and serve as a great source of DNA in the absence of skeletal remains especially. Well, in fact the oldest DNA ever sequenced was from 2 million years old sediments in Greenland. So I think more sampling and sequencing around the world would give us a better picture of past ecological turnovers, and I think that would be quite exciting.
Will - And one last question to ponder. With increased oral hygiene around the globe, are future archeologists going to find dental calculus less useful?
Christiana - I would say it depends. You know, there are still people who don't brush their teeth as much and also if you have some other condition. For example, we see this in the skeletal records, individuals who've had some sort of paralysis and are not able to scrape that off or who don't have good care at the end of their life. Not everybody ruthlessly cleans off all of their dental calculus and their plaque every single day. So it doesn't rule it out. It probably makes it a bit less likely but it's not going to make it impossible to find these sorts of things in the future.
Michal - I definitely, personally know quite a few people who have very obvious dental calculus in plaque, so I think it's going to be with us for quite some time.
Will - So, is our take home message, please go and brush your teeth to confuse future archeologists and I guess also help your health out too.
Michal - Please make it harder for future archeologists. Indeed.
16:51 - The ant that drinks its childrens' blood
The ant that drinks its childrens' blood
And now, to round off this month’s Naked Genetics, it’s time to explore another quirk of evolution...
You join me in the humid forests of Madagascar. When you think of madagascar, what springs to mind? Lemurs? Unnecessarily long names for capital cities? Both answers are absolutely valid. But, move over Romania, for here there are real life vampires. Vampires that drink their own children’s blood. Kind of.
Our search for such a horrifying creature leads us to the forest floor at dusk. And, whilst the scene looks like a fairly standard one found in a tropical forest, take a closer look at that seemingly innocuous ant that is passing by. Notice anything unusual? What’s that? You don’t spend time comparing the mouthparts of ants? Well, don’t you look foolish. Fine, let me introduce you to Adetomyrma venatrix, also known as… the dracula ant.
Ok lets be real for a moment, for how shocking the concept of vampires drinking blood is, its an act that is really not all that uncommon in the animal kingdom. Mosquitos, the world’s worst thing, are perhaps the most common instance of sanguinivory. I’m sure a few of us may well have fallen victim to a leech, maybe even a tick, maybe even a vampire bat. And like, I get it. Blood is full of nutritious delicious proteins and what have you. I’m not here to judge, we all have to survive somehow. But there is definitely a difference between having a snack on a nearby organism, and deeming your own offspring to be fair game. What is the evolutionary advantage of keeping it in the family?
If you were to follow one of these ants back to its nest, you’d find a humble abode of about 500 other ants going about their daily business. Finding food, protecting the queen, and raising their young. And unbelievably, drinking their young's blood is part of that protective process. This is a mutually beneficial act.
I also just want to sidenote here for the two people yelling at me for calling it blood. I know ants don’t have blood. It’s called haemolymph, I know there’s a difference. It’s the invertebrate version of blood. I’m sorry I lied to you, I hope one day you can come to forgive me. Anyway.,,
This is a mutually beneficial act. Not only do the adults get a refreshing glass of… insect juice. Look it’s grim but it’s full of nutrients. The offspring benefit because excess haemolymph can cause infections to build up and make the larval ants ill. By draining it, it lowers the risk of the ants getting ill.
The act of drinking is pretty much as you'd imagine. The adult pierces the larva's skin and laps up the haemolymph that drains out. It sounds fairly grim, but the wounds heal quickly enough and the larva grows up big and strong. Isn’t nature wonderful.
And that’s it for the vampirism side of things, which is not a sentence I ever anticipated saying. But I also couldn’t move on from these bizarre creatures because there is just so much going on that is worth talking about. For instance, did you know that dracula ants are the fastest animal on Earth? Again, kind of. If we’re being pedantic, they hold thew record for the fastest animal action currently known. Those jaws that I told you to look out for, can swing shut at an extraordinary 90 metres per second. That’s 201 miles an hour. That’s probably overkill for an ant, but here we are. How do they do it? Well, push your thumb and index finger together really hard. Then let one slide over the over. They fly past each other at some lick, don’t they? The ants do the same with their mandibles.
So, two quirks of evolution for the price of one. No news yet on whether they are related to one another, so, and I cannot stress this enough to any athletes out there, do notary and harvest your children in an attempt to become faster. I’ve heard of blood doping, but that is just a step too far.
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