GUESTS: DR. BRIAN ARNOLD -- BIOMEDICAL DATA SCIENTIST, EVOLUTIONARY GENETICIST AT PRINCETON UNIVERSITY DR. MARIA PIA MIGLIETTA -- MARINE BIOLOGIST & ASSOCIATE PROFESSOR AT TEXAS A&M UNIVERSITY
– DR. BRIAN ARNOLD
Just like any good superhero comic, we start this episode with the science going incredibly wrong. Think: vats of toxic waste producing evil mutants that ravage the city. Or maybe not so evil. It really depends on your perspective. Just like the X-men, genetic mutations get a bad rap in the public eye. But they aren’t all nasty.
Dr. Kaylee Byers speaks with data scientist and evolutionary biologist Dr. Brian Arnold on how the genetic ‘mistakes’ known as variants occasionally encode incredible abilities. Odd elephants, immortality hiding in our ocean depths, and Rogue-ish bacteria are just a few examples. Dr. Arnold defends these genetic anomalies, and explains how they can make a huge difference to the future of humanity and life on this planet. Also joining us is marine biologist Dr. Maria Pia Miglietta, who shares an incredible ability sitting in our ocean depths. Immortality.
So strap on your capes, because we’re heading straight into the strange terrain of “heroic mutations.”
Listen to Nice Genes! wherever you get your podcasts, brought to you by Genome British Columbia.
“What’s this about tuskless elephants?”
“Wanna go to Mozambique?”
“Mutations are changing the face of the world’s largest land animal!”
“Dr. Eske Willerslev finds a bloody piece of hair”
[00:00:00] Seminar presenter: When describing the early probability of the…
[00:00:07] Dr. Kaylee Byers: Ugh, when will this seminar be over? Why did I get a PhD if I can’t even understand half the jargon in this talk? The x-axis on that graph isn’t even labelled! Also, to the person who just asked “a question”, that wasn’t a question. It was a statement. Maybe if I just…close…my eyes…for a minute…this…will go…by…faster….
[00:00:44] The Incredible Cuke: Wake up! Rat Woman can you hear me? Can you hear me? Rat woman?
[00:00:48] Rat Woman: Ooh, what’s going on?Read Transcript
[00:00:51] The Marvellous Mantis: It’s no use! It keeps shedding its tails. So many lizards!
[00:00:56] Rhino Beetle: That doesn’t make any sense. Komodo dragons can’t do that.
[00:00:59] The Marvellous Mantis: Who cares?
[00:01:02] The Incredible Cuke: Listen to me, Rat Woman, we need you to summon a swarm of furry Christmas Island rats, now! It’s the only way to defeat Komodo.
[00:01:09] Rhino Beetle: Look out!
[00:01:12] The Marvellous Mantis: Oh, no Rhino Beetle!
[00:01:16] Rhino Beetle: I can do this. All. Day.
[00:01:19] The Marvellous Mantis: Oh, thank goodness.
[00:01:21] The Incredible Cuke: Now’s the time. Call them now. Rat Woman, call them now.
[00:01:24] Rat Woman: Ah, I summon the power of CRISPR critters far and wide!
[00:01:31] The Incredible Cuke: That’s it. You’re doing it now. Now, come on, just a little further. Now, now, now…
[00:01:38] Seminar presenter: As you can see, these findings will change the future of, uh,
[00:01:42] Dr. Kaylee Byers: Oh, science!
[00:01:43] Seminar presenter: As to my slide number 2…
[00:01:50] Dr. Kaylee Byers: You’re listening to ‘Nice Genes!’, a show all about unravelling the fascinating world of genomics sponsored by Genome British Columbia. I’m your host, Dr. Kaylee Byers, and as your guide and former rat researcher, I’m reclaiming my superhero name of Rat Woman today, as we dive into the heroic world of genomics.
All right, let’s be real. You might be wondering what the heck was that all about? And let me preface this by saying it came out of the fabulous and fantastical mind of our producer, Sean, who joins me now to help explain why we’re opening with a superhero-inspired intro.
[00:02:31] Sean Holden: Hey Kaylee, how are you doing?
[00:02:31] Dr. Kaylee Byers: Oh, you know, pretty good. Uh, What was that all about?
[00:02:35] Sean Holden: Okay. To start off, I am not a biologist, if that wasn’t already clear, but while working on ‘Nice Genes!’, I’ve been pouring through really interesting papers, articles, as well as videos on genomics
[00:02:46] Dr. Kaylee Byers: Uhhuh.
[00:02:46] Sean Holden: And honestly, there have been a lot of moments that have blown my mind. And many have focused on actual genetic tricks and special abilities that exist out in our big animal and plant kingdoms.
[00:02:59] Dr. Kaylee Byers: Hmm.
[00:02:59] Sean Holden: Some of which are, what I would call, actual superpowers. Stuff that’s embedded in the genome of many living things, special characteristics that my non-biology-background looks at and says, wow, that is something I wish I could do. And at the heart of all these special abilities are: mutations.
[00:03:21] Dr. Kaylee Byers: Okay. So you naturally thought that we should take, what’s usually sitting over here in sci-fi and reel it into our actual science podcast.
[00:03:32] Sean Holden: Well, I mean, when you put it like that. Um, but yes, naturally.
So to start on this X-Men inspired journey, my fellow producers, and I hit the streets to ask one simple question. If you had a superpower, what would it be? You never know, maybe one of them is actually possible.
[00:03:50] Streeter #1: If I could have a superpower and what would it be, I would want to be invisible so that I could go and listen to what people are saying behind my back.
[00:04:02] Streeter #2: If I could have any superpower, it would be to read minds.
[00:04:05] Streeter #3: If I had a superpower, it would probably be to travel in time.
[00:04:09] Streeter #4: Probably flying because A) gas prices…And I love aerial views. So it would just be good for my wallet and for my mental health.
[00:04:20] Sean Holden: Okay. So flying is a popular power. And why not? Have you seen airplane tickets today?
[00:04:27] Dr. Kaylee Byers: Womp womp.
[00:04:28] Sean Holden: What I didn’t expect when it came to discussing mutations, is folks actually don’t always have the most favorable view of them.
[00:04:36] Streeter #1: Um, I think a genetic mutation is when you get like an extra like limb, like a, like an extra foot or an extra finger, or like an extra eye. And I don’t think they’re good.
[00:04:45] Streeter #2: I, I guess like a mutation is kind of like when something goes wrong, right? Like when something goes awry.
[00:04:51] Streeter #3: Well, it can be anything from a facial feature to something in your, like a heart valve missing.
[00:04:59] Dr. Kaylee Byers: Oh, I see where this is going.
[00:05:00] Sean Holden: Yeah. So in our mission to bust some genomic myths, I think it’s time we set the record straight.
Let’s give these genetic variations the moment in the sun they deserve and let’s think of some of them as our heroic mutations.
[00:05:16] Dr. Kaylee Byers: When it comes to genetic mutations, both Sean and I have a few things to learn about what these tiny changes in our DNA can mean for an organism.
[00:05:26] Dr. Brian Arnold: 1, 2, 3, I’m testing I’m testing.
[00:05:28] Dr. Kaylee Byers: So I spoke with Dr. Brian Arnold…
…but do you have a preference? For being called Dr. Arnold throughout?
[00:05:33] Dr. Brian Arnold: Please, Brian, Brian. Yeah,
[00:05:35] Dr. Kaylee Byers: He’s a data scientist at Princeton University, as well as an evolutionary biologist with the Shane Campbell-Staton group. And he knows a lot about genetic mutations.
Brian, thank you very much for joining me today.
[00:05:48] Dr. Brian Arnold: Uh, it’s great to be here. Uh, thanks for the invitation.
[00:05:50] Dr. Kaylee Byers: In the spirit of today’s episode, where we’re gonna be talking about genomics, mutations and superheroes. And, um, has anyone ever told you that your whole like glasses vibe is very Clark Kent?
[00:06:01] Dr. Brian Arnold: Uh, yes, actually. Uh, I think people have told me before that, uh, I resemble, uh, Clark Kent or mini Clark Kent, cuz I’m only 5’6.
[00:06:13] Dr. Kaylee Byers: So Brian, why don’t you tell us a little bit about yourself. What’s your research background? And what’s the link to genetics?
[00:06:21] Dr. Brian Arnold: My background, uh, has always revolved around evolutionary biology, genetics, and computer science.
So I did my PhD at Harvard University in the department of organismic and evolutionary biology. DNA can tell a lot of stories about a population. It can shed light on which genes or regions of the genome have recently experienced natural selection and allow that population to adapt to new environments among, among other.
[00:06:53] Dr. Kaylee Byers: So there are a couple of stories I wanna cover with you regarding mutations and sort of the stories that our DNA tells. So from the perspective of an evolutionary biologist, what are mutations in our DNA?
[00:07:06] Dr. Brian Arnold: So all life consists of cells. Bacteria consists of a single cell. Eucaryotes, like humans, consist of multiple cells that are this, like, beautiful collaboration that allows the emergence of other traits, like intelligence. Cells need to divide. Every time they divide, they basically have to copy their genome and bring it to different sides of the cell, and then the cell splits. The proteins that are involved in copying the genome are not perfectionists. They have some low rate of committing an error. And so when a cell divides, the daughter cell that it gives rise to, might have a perfect copy, but more often than not, there are a few differences. And I think, you know, for instance, in humans, we have on average 70 mutations that distinguish us from our parents.
You, you might think that these mutations are, are bad, but in, in rare circumstances they are beneficial.
[00:08:12] Dr. Kaylee Byers: Is it possible that they also don’t do anything? Can they also be neutral?
[00:08:15] Dr. Brian Arnold: A vast majority are either, neutral, slightly deleterious, and some are highly deleterious. And then an even smaller amount are beneficial.
But again, it’s almost like going into your computer and switching around some of the components and expecting it to, you know, suddenly function more optimally. One of them might be beneficial, and then evolution is kind of the ‘engineer’ that selects for these beneficial mutations.
[00:08:44] Dr. Kaylee Byers: If we have all these cells in our body that are splitting constantly, and we have these errors, you know, how do these mutations become heritable? How is it that I then pass mutations on to, say my offspring or, or an organism does that, what’s the difference there?
[00:08:58] Dr. Brian Arnold: So heritable, in, in humans, heritable changes involve mutations that occur in our germline cells. We have a bunch of cells in our body, some of them I’ll refer to as somatic, like the, the cells in my hand. And some of them are in, uh, my, my germline. So in humans, these would correspond to mutations in the organs that produce egg and sperm. So if I acquire a mutation in, you know, my hand or in a hair follicle, that mutation won’t necessarily be passed on. But if it’s in one of my, uh, germline cells, then I will absolutely pass those on to my offspring.
[00:09:38] Dr. Kaylee Byers: Brian’s understanding of mutations took him to a truly fascinating area of research and to another continent. A buddy from his days back at Harvard, came to him with a question. One that would set him on quite the little adventure.
[00:09:54] Dr. Brian Arnold: And I’ll never forget this. I was in a climbing gym. Uh, climbing is quite popular in Cambridge, Massachusetts, and I got this text message from Shane.
[00:10:02] Dr. Kaylee Byers: Shane Campbell-Staton, his friend.
[00:10:04] Dr. Brian Arnold: He’s just like, ‘Hey, do you want to come to Mozambique with me and study elephants?’
[00:10:09] Dr. Kaylee Byers: A hundred percent yes.
[00:10:10] Dr. Brian Arnold: Hundred percent yes. And when I followed up with him about, you know, what the particular question was, he had recently saw on YouTube, a video of tuskless elephants and how this phenomenon of tusklessness has been present in African elephants for a long period of time, but in some regions, uh, it has increased dramatically in frequency. And so he was thinking, I wonder if we could find which mutations are causing this feature in elephants, that’s literally changing the face of the world’s largest land animal.
Neither of us had worked on elephants before. We need to work with elephants now, we need to get genetic material, how do we do this? Uh, it was not easy. Especially in Gorongosa National Park in Mozambique, which is where, uh, we decided our study population would be. The elephants are sometimes – they’re tricky to find, but even when you do find them, they can be a little aggressive towards humans because there was this Mozambican Civil War and survivors of that war kind of have passed on culturally to their offspring, to kind of fear humans.
So, our original plan was to drive around the park and find elephants, and kind of hang out at a safe distance with binoculars and just observe them. And wait for them to defecate and then keep track of who defecated, where, such that we knew where a tusked elephant pooped and were a tuskless elephant pooped. So that was our original plan to get elephant DNA.
And, you know, we spun this idea by some of the other scientists there who had much more experience than us and the looks on their faces weren’t promising.
After a week and a half of driving around the park for six to eight hours a day, we could not find even a single elephant. We found tons of poop, everywhere. Um, but never did we see a live elephant that we could observe pooping so that we know the DNA sample came from a tuskless or tusked elephant. So, yeah, after about a week and a half, you know, we were kind of driving around and we weren’t really saying much to each other.
I kind of felt like we both knew that things weren’t going well, but we weren’t quite ready to admit that because we had invested so much into the project at this point. In Gorongosa, that had been an unexpectedly wet summer. And so, you know, water was everywhere. And so the animals were quite dispersed. The grass was really high, we could really only see 15 feet to either side because there’s, what’s called elephant grass, which was literally 20 feet high. It can, it completely obscures all wildlife, even elephants.
So reality slowly started setting in that this wasn’t gonna work out. So we were brainstorming ideas about kind of what we could do moving forward.
And there were some behavioral ecologists working at the park. They were putting, um, tracking collars on elephants to monitor their movement throughout the park. And also trying to study how elephants might interact with the neighboring communities, kind of like elephant human conflict. So, you know, at dinner one night with, with these scientists, we were asking them — So, you know, when you are in your helicopters, tranquilizing, elephants to put collars on, would it be possible to only target females? Because this phenomenon of tusklessness is only present in females. Male elephants always have tusks. And they were like, yeah, sure. Beautiful, cool. Uh, could you get a blood sample for us?
And they were like, absolutely. We have a veterinarian on staff at the site when the collar is being put on. So we’ll just take a blood sample. Cool. Uh, also, could you target equal numbers of tuskless and tusked elephants? Totally fine with it.
And so that’s when the study kind of actually began. So when you put a collar on an elephant, uh, you know, typically there’s someone in a helicopter with a tranquilizer gun and they try to shoot the elephants in the, in the hip, in the upper part of the leg.
And then it goes to sleep and there’s a ground team that quickly drives in. I was on the ground and, and there are also, you know, Mozambican scientists there who are working at the park. They can identify individual elephants based on their marks and scars, various traits. And, you know, we try to quickly collect as much data as we can as quickly as possible.
And then the veterinarian injects some kind of reversal that reverses the effect of the tranquilizer so that the elephant can immediately wake up.
[00:15:00] Dr. Kaylee Byers: What was the feeling you and Shane had in this moment in front of this elephant, besties studying this animal together?
[00:15:07] Dr. Brian Arnold: Just kind of surreal, to be honest, like it happens so fast. I mean, you’re in and out and you’re trying to move as quickly as possible. These animals are just incomprehensibly big. I mean, I knew they were big, but when you see them, you know, up close and personal, uh, at least that close, it was truly humbling to kind of have any part in studying their, their history. They’re absolutely marvelous creatures.
[00:15:39] Dr. Kaylee Byers: Ultimately, you gather the samples from these elephants. And what did you discover when you took those blood samples back to the lab? What was the finding? What was the answer to the text message question?
[00:15:50] Dr. Brian Arnold: So, when we got back from, um, Gorongosa National Park, we had a variety of data. We observed that in the, the Civil War in Mozambique caused the elephant population there to decline by about tenfold.
And we observed that the frequency of tusklessness, more than doubled throughout the war and can only be explained by differential survival or natural selection, in which elephants with tusks were less likely to survive the war because they were more likely to be targeted by poachers. So for every tusked elephant that was killed or poached, five tusked elephants died. And so, you know, from an evolutionary perspective, that’s a huge advantage.
So one day Shane and I were reading the literature about dental abnormalities in humans. And we came across these examples that were only present in females and this piqued our curiosity. So anatomically elephant tusks are teeth. They’re basically lateral incisors that just keep on growing. And in these examples of humans that we found, that the reason that the dental abnormalities were only present in females is because it involved a mutation on the X chromosome that was lethal to males. So you never observe males harboring the abnormality because they just, you know, die super early in development, such that you never get the chance to observe them.
You know, for instance, it would be a, a miscarriage.
[00:17:24] Dr. Kaylee Byers: Okay. So they’re not even born. It’s fatal.
[00:17:25] Dr. Brian Arnold: That that’s one example of a male lethal mutation. Absolutely.
So, boom, we got this idea. If this were the case in elephants, then the tuskless moms should give rise to significantly more female offspring than male offspring and when we analyzed these data, our jaws dropped. We could not believe when we observed that tuskless mothers gave rise to significantly more female offspring, to a degree that we would expect if they were harboring a male lethal mutation on the X chromosome.
The way I think about it is this mutation is on the X chromosome and it has two effects.
One is that it’s dominant for tusklessness meaning you only need one copy to be tuskless, but it’s recessive for lethality, meaning you need to have both copies mutated in order for the recessive lethal feature of the mutation to be expressed. But males only have one X chromosome. So if they have one copy, this recessive lethal feature of the mutation gets expressed, they die.
But females, on the other hand, they had two copies of the X chromosome. So when they inherit one of these mutations, they express the dominant tuskless phenotype but they do not express this recessive lethality aspect of the mutation because they have another copy of the X chromosome that does not have this mutation.
[00:18:58] Dr. Kaylee Byers: This is so interesting. So I mean, females then can really never have that, that lethality because the males can’t have one copy. So they never get the copy from, from the male parent.
[00:19:11] Dr. Brian Arnold: So smart. Absolutely. It took me a while to figure that out and yeah, you got it immediately. Yeah, that’s great.
[00:19:15] Dr. Kaylee Byers: I mean, I didn’t do the research. You did just kind of spoon feed that to me. So thanks though, that’s why I got a PhD!
This is a story where humans have put a pressure on elephants. One where being an elephant without tusks was an evolutionary advantage, which meant that you were more likely to survive and have adorable little female tuskless babies. So in this case, sometimes mutations are a bit like superpowers. They’re kind of like an invisibility cloak. So we can see how mutations can improve things like survival. Brian, are there other examples of mutations that are literally a lifesaver or had a quote unquote heroic result?
[00:20:03] Dr. Brian Arnold: So in terms of life-saving mutations, I guess a lot of examples that I think of are related to humans. They have allowed humans to adapt to environments that have lower concentrations of oxygen.
So, uh, the scientific term for this would be, uh, hypoxia, which is a condition where there’s not enough oxygen in your system for your tissues to properly function. And so there are two such environments that I can think of that humans have adapted to.
There’s this community in Indonesia called the Bajau and they have been engaging in breath-hold diving for thousands of years. And genetic analyses of their genomes have shown that they’ve adapted to acute hypoxia from diving and hunting for food underwater, by having enlarged spleens, which is an organ that contracts in response to the dive stimulus, to provide kind of an oxygen boost through releasing red blood cells.
And another example is adaptation to high altitude in which there’s also lower oxygen. And in this case, sequencing, the genomes of Tibetans has shown, even though they’re living at such a high altitude, they have no such increase in red blood cell count. And it’s, it’s not ideal to have a higher red blood cell count because that makes your blood a little more viscous and it kind of can put strain on your circulatory system and can even, you know, complicate pregnancies. So the fact that Tibetans are able to live with ease at this altitude with a normal blood cell count is kind of evidence that they’ve adapted to this new environment.
[00:21:53] Dr. Kaylee Byers: But, what are the genomic wonders and villains of mutations?
You’re listening to ‘Nice Genes!’, a podcast, all about the fascinating world of genomics and the evolving science behind it. Brought to you by Genome British Columbia. I’m Dr. Kaylee Byers, your host, and I have a quick favor to ask if you’re liking the show. Hit follow on Apple Podcasts or wherever you get your shows and continue the fight for genomic myth busting by taking yourself off mute-ation and telling a friend about us. We thank you, and so do the tuskless elephants. They’re really into podcasts.
For this next segment, I wanna dive into another fascinating, real-life superpower.
[00:23:54] Dr. Maria Pia Miglietta: I jump in the water and the water is warm because it’s the tropics and the water is clear.
[00:23:00] Dr. Kaylee Byers: That’s Dr. Maria Pia Miglietta, she’s a Marine and evolutionary biologist based at Texas A&M University. And she’s taking us down into the warm ocean depths of Bocas del Toro in Panama.
[00:23:15] Dr. Maria Pia Miglietta: And there’s silence and there’s just the noise of your bubbles, as you breathe in and breathe out. It’s peaceful. Above all it’s extremely peaceful and you can really focus. You have one task and, you know, there can be a big fish, there can be a beautiful animal swimming by. I don’t even look at them. I’m focused on the tiny, tiny things on the rocks.
[00:23:43] Dr. Kaylee Byers: Dr. Miglietta needs to have a keen eye because she’s searching for one tiny little fella about the size of your pinky nail.
[00:23:52] Dr. Maria Pia Miglietta: Right. You’re in the ocean looking for that single species of interest, which is rare, which is tiny, which is hard to see. And the ocean is immense and we keep searching. We are on the bottom slowly screening the bottom of the ocean, trying to find jellyfish, uh, the colony that resembles Turritopsis dohrnii.
[00:24:20] Dr. Kaylee Byers: Now, despite this jellyfish’s small size, it has an ability that has huge consequences. And I mean, huge.
[00:24:30] Dr. Maria Pia Miglietta: The common name is the “immortal jellyfish”.
[00:24:36] Dr. Kaylee Byers: The immortal jellyfish is the only animal on this planet, that we know of, that has this particular incredible power.
[00:24:45] Dr. Maria Pia Miglietta: They are hydrozoans, first of all. And so hydrozoans, so all of them have a complex lifecycle. When the season is right, the colony produces the jellyfish as a little bud of the polyp. The jellyfish grows to a decent size, and then it detaches from the mother colony.
That is the sexual stage. So it produces the eggs or the sperms, the gametes, sets them free in the water. And then they, they fuse there in the water and they form the larva, the planula. And so you close the lifecycle, polyp, jellyfish, larva, polyp, and you keep going. What happens to the jellyfish after it releases the gametes, it dies. Now Turritopsis escapes this fate.
And so if you try to kill the jellyfish of Turritopsis you starve it. You cut it, you stress it in many different ways. It doesn’t die. It forms a ball, and it settles on the bottom and the ball will stay as such for 24 hours. And there is some reorganization there that goes on and the ball then transforms itself into the polyp instead of dying, going in one direction where all the jellyfish go, to revert and rejuvenate in the polyp.
And the colony when the season is right, can produce hundreds of new jellyfish. So you can see how from one jellyfish that doesn’t die, then you can get hundreds new from this reverse development.
[00:26:23] Dr. Kaylee Byers: But, with great power…
[00:26:27] Dr. Maria Pia Miglietta: Turritopsis dohrnni, we showed it’s an invasive species. Uh, we call it a silent invader cause it’s everywhere.
[00:26:35] Dr. Kaylee Byers: These tiny looming medusae though, originally residents of Caribbean waters have had more than a lifetime to get around. They’re infamous ship hoppers floating from Panama to Spain and Florida to Japan.
[00:26:50] Dr. Maria Pia Miglietta: It’s very successful in spreading around the world.
[00:26:54] Dr. Kaylee Byers: A handful of specialized researchers like Dr. Miglietta have spent decades trying to understand the genomic mystery behind the immortal jellyfish.
[00:27:03] Dr. Maria Pia Miglietta: And so the first step where we wanted to start was okay, let’s have a look at the cyst. The cyst is this unique life cycle stage. And so what’s happening in the cyst at the genomic level? And so we followed the gene expression patterns of the entire lifecycle. And, uh, we identified a cluster of genes, they’re turned on in the cyst, but there is also the process of cellular transdifferentiation that is occurring in the cyst.
It is the ability of an adult cell, uh, to become something else. And the other thing that makes cellular transdifferentiation hard to study is that in those animal where, that occurs, it happens in weeks. Now in Turritopsis, you have cellular transdifferentiation that happens in 24 hours.
And so, are they using the same genes as other Turritopsis in different ways? Or is a mutation probably multiple mutations, or there is a difference in the genome that allows Turritopsis to gain this new function, to evolve this new trait of immortality?
And so that is our next step. What Turritopsis can give us is a system where we can understand those processes, transdifferentiation, aging, uh, our DNA repair, and that can help us focus on some aspects of, of genetics. And so my idea is that we should dive in.
[00:28:41] Dr. Kaylee Byers: Even though humanity’s footprint on the planet is considerable, we continue to uncover new species adaptations and ecologies in the deep abysses of our planet’s oceans, the dense foliage of its jungles and the brisk expanses of its Tundras. But don’t take my word for it. Let’s bring biologist, Dr. Brian Arnold, back to see what he thinks.
Brian, as an evolutionary biologist, what are some examples of mutations and adaptations that have fascinated you and have any of them been things that we as humans might try to tap into?
[00:29:16] Dr. Brian Arnold: Personally? I Am most impressed by bacteria. They have been around for 3.5 billions of years. They were some of the first organisms on this planet.
I think they’re gonna be the last before the sun explodes and engulfed us all. So yeah, I mean, you know, mutations are great, but bacteria are able to pick up entire genes from their environment. It’s this phenomenon called “horizontal gene transfer”. It happens amongst all species across the bacterial kingdom.
One particular example I love? There was this group that was studying the gut microbiome in mice. And what they observed was when they introduced a new [bacterial] strain to this gut, which is before any mutations occurred in this new bacterial strain, they were introducing to the gut, the bacteria would pick up this gene or set of genes from the environment, from the bacteria that are already present there. That allows it to better survive and reproduce in this environment by utilizing unique carbon resources in the mouse gut that wasn’t present in the previous environment that this bacterium came from. So, but bacteria are able to get, you know, wholesale, entire genes or sets of genes and genetic pathways and quickly evolve new traits, again on a time scale that is shorter than waiting for a mutation to arise.
[00:30:58] Dr. Kaylee Byers: So, if we’re thinking about the “X-Person” equivalent of this, is it sort of like Rogue who can reach into other superheroes and grab their powers? Only in this case, Rogue is also then taking that and putting it into her genome.
[00:31:11] Dr. Brian Arnold: That’s a fascinating analogy. Yes, it is absolutely like that. and I, I wish I wish we had this.
[00:31:16] Dr. Kaylee Byers: You called that fascinating, but not good.
[00:31:18] Dr. Brian Arnold: Well, I mean, just the ability to kind of have big dramatic changes immediately. I mean, these are the kind of changes that are great if the environment changes very dramatically and it allows bacteria to colonize kind of every nook and cranny of this planet
[00:31:37] Dr. Kaylee Byers: How could people use this? How might these kinds of mutations relate to us?
[00:31:42] Dr. Brian Arnold: So, uh, there are a variety of ways horizontal gene transfer might occur. One involves the bacteria running into the DNA and taking it up. But another version of gene transfer is mediated by what are called “bacteriophage”. These are, these are bacterial viruses.
And so what bacteriophage do is they look like little spaceships. They’re terrifying. They land on the surface of a bacterial cell and they inject their genome. And then they use the molecular machinery present in the bacterial cell to basically replicate its own genome. Package those into new virus particles, and then the bacteria explodes releasing hundreds of new bacteriophage.
And so what happens is occasionally when, uh, a bacteriophage infects, a bacterial genome it’s genome gets integrated into the bacterial genome, such that the bacteria can now use the genes present from the phage.
So to get back to your question, how can this horizontal gene transfer impact human society? Well, you know, there’s this problem of antibiotic resistance among bacteria, and if someone has a surgery and they get an infection with a bacteria that’s resistant to many of the first line antibiotics. That can be a very dire situation. This kind of field that’s been emerging is called “phage therapy”.
So in theory, if antibiotics aren’t working, you could engineer a phage to go in there, uh, a kind of, uh, weapon of sorts that we might use to infect the bacteria and kill them that way.
[00:33:26] Dr. Kaylee Byers: I wanna come back to the tiny, but mighty immortal jellyfish. What thoughts cross your mind when you think about them and, and what do they have to teach us?
[00:33:38] Dr. Brian Arnold: Yeah, uh, absolutely fascinating. On the organism level, it’s immortal, but on a cellular level, there’s a lot of turnover. Do they kind of accumulate mutations? I mean, even though they’re able to go through these what seemed like birth-death cycles, you know, how, how many can they go through?
[00:33:55] Dr. Kaylee Byers: I’m also curious about that, I was reading and it does sound like they can accumulate mutations. And I was wondering at what point is that a problem? Our immortal jellyfish has me thinking about this, uh, one thought experiment, which is called the “Ship of Theseus” dilemma, that goes a little, something like this…
The Ship of Theseus takes us back to a story from Greek mythology. The ship’s wood rotted over time. So, to keep it in standing order builders would replace the old planks with newer and stronger timber. But the question is, if centuries proceed and piece by piece, the ship’s wood is replaced is it even the original ship of Theseus, or is it something different entirely?
Over to you, Brian. Uh, when it comes to our immortal jellyfish, it replaces cells regularly to undergo its transition from adult medusae to polyp, then back again. So, is our jellyfish a Ship of Theseus?
[00:35:01] Dr. Brian Arnold: Well, I guess, you know, with the caveat that there may not be a right answer, it’s totally a different jellyfish. I mean, if it’s composed of completely different cells that were never there. You know, I guess from, from a cellular perspective, it’s a very different organism consisting of cells that were not present when it was originally born.
[00:35:20] Dr. Kaylee Byers: Right. But doesn’t that happen for us too? Right? Our cells are sort of constantly changing. Right? Like we’re, we’re getting new cells and, and they’re moving. Are we… #WeAreAllTheseus?
[00:35:33] Dr. Brian Arnold: Uh, great question. But, but if, if that were the case then yeah, but like psychologically, I feel like I’m a completely different person every five years, so….
[00:35:42] Dr. Kaylee Byers: Or every minute. But what about the jellyfish? What about them psychologically? That’s what I wanna know. I wanna interview the jellyfish.
[00:35:48] Dr. Brian Arnold: That would be great to know what they’re thinking, if anything.
[00:35:51] Dr. Kaylee Byers: We asked the same question to Dr. Maria Pia Miglietta as well.
[00:35:56] Dr. Maria Pia Miglietta: I, I think still the same jellyfish in the sense that the DNA duplicates… genetically its the same animal; it’s duplicating its genome and it’s the same identical animal, except for the mutations that will occur, um, that will accumulate with, with the, the changes, how many mutations occur?
What we’re seeing is one of the, of the elements are active in the cyst is DNA repair. In the cyst there is a lot of effort going to clean up the mutations. Okay. And so, to me, doesn’t matter, many regeneration cycles the jellyfish will go on, it’s still the same
[00:36:39] Dr. Kaylee Byers: The reason I brought up some random Greek philosophy is for one important point on our theme around mutations. And that is to round us out on this idea of adaptation and change from elephants to jellies, antibodies, and bacteria. How do we need to view mutations going forward as part of our biology? Our cells and DNA, they change and grow, but we are the same person… or are we? So, what’s your perspective as an evolutionary biologist?
[00:37:10] Dr. Brian Arnold: Personally, I think about life from the cellular perspective. Bacteria are single cells. Higher organisms like humans are kind of this beautiful collaboration of, of single cells. So, you know, as DNA replicates, it makes errors. These give rise to mutations. I mean, if, if we perfected DNA replication, such that all of our cells were clones, all of our children were clones, then there would be no genetic variability to kind of adapt to new environments, to adapt to any kind of like global climate change, et cetera. So having these enzymes as imperfect is kind of a very good thing. So, this imperfection is in some sense, a perfection. I mean, that sounds kind of cheesy, but in some sense, you know, it allows organisms to persist over time by changing their genetic content.
[00:38:10] Dr. Kaylee Byers: Dr. Brian Arnold. Thank you so much for taking the time and joining us today. It’s been a real pleasure.
[00:38:15] Dr. Brian Arnold: It was very fun. Uh, thank you so much for having me.
[00:38:52] Dr. Kaylee Byers: My guest today has been data scientist and evolutionary biologist, Dr. Brian Arnold from the University of Princeton. You can also check out some of the really cool work he’s doing with the Shane Campbell-Staton group by going to campbellstaton.com to learn more.
[00:39:07] Rhino Beetle: You can get the hit new genomics-inspired superhero action figures today! Rat Woman and a hoard of CRISPR Christmas Island critters. The Marvellous Mantis and her punching speed and The Incredible Cuke as he shifts from solid to liquid, and of course….
[00:39:27] Rhino Beetle: wait, what do you mean we’re holding production? What am I supposed to do with 600 boxes of action figures? Now you listen to me, buddy.
[00:39:38] Dr. Kaylee Byers: You’ve been listening to ‘Nice Genes!’ a podcast brought to you by Genome British Columbia. If you like this episode, go check out some of the previous ones and follow the show to catch new ones coming up.
And the education team at Genome BC has compiled resources as well as a Learn-A-Long activity sheet for each episode, check them out in our show description and on genome bc.ca. Message us on Twitter @GenomeBC. Let us know what you think.
[00:40:13] Dr. Kaylee Byers: Join us on our season finale of Nice Genes.
[00:40:18] CeCe Moore: I think this case in many others that followed, showed that we are identifying a, perhaps a new type of criminal, one who perpetrates a very violent crime one time and then appears to have never done it again. Fades right back into society, seems to be this normal person, with a relatively normal life, is capable of this type of violent crime.
[00:40:42] Dr. Kaylee Byers: I investigate one of North America’s longest-standing cold case mysteries that’s finally found some answers through, you guessed it, genomics. Follow us on Apple Podcasts or wherever you get your shows. Until then, medusae-e you later!
DID YOU LIKE THIS EPISODE? THEN YOU SHOULD LISTEN TO…
GUEST: CECE MOORE - GENETIC GENEALOGIST, EVE LAZARUS - TRUE CRIME AUTHOR AND PODCASTER FROM COLD CASE CANADA.LISTEN NOW