From the Vault: Mutational Meltdown

out at me. I wasn't familiar with it, and it basically gets down into and I think for our purposes here on the show, you know, it's a reason to sort of provide an overview of sort of asexual reproduction versus sexual reproduction as sort of competing ways of going about sort of the same thing for an organism, but one with more short term benefits versus long term benefits.

And I don't know, I just found it to be kind of a neat way to re examine and think about these these concepts that I imagine we've covered on the show before, and many of you out there have have encountered in varying formats.

distinguishing itself from either parent. The resulting genetic variation is highly adaptive because it provides individuals with varying traits that may prove necessary for survival in an ever changing environment. The resulting genetic diversity makes the population more resistant to disease as well.

But more specifically for our purposes here, another key benefit that comes up in the literature is looking at is that you can think of sex and genetic recombination is ultimately a means of purging deletarious mutations.

So moving on to asexual reproduction. This is a case in which you have the offspring of a single genetic parent inheriting the genes of the parent, making it a clone identical to the parent. The advantage here is that you can reproduce rapidly without all of the energy expenditure of mating. And I mean that's a pretty big statement to think about, because so many organisms we end up discussing on the podcast. You know, what is the key

thing that makes them interesting? Well, in some cases, many cases, it's how they acquire their food, But in other cases it's how do they get a mate? How do they attract a maid or pursue a mate, And it ends up taking up a whole lot of time, a whole lot of energy. And what if you didn't have to do that? What if instead you could just essentially clone yourself.

needs to go in the house. Now, there are multiple types of asexual reproduction, and we're not going to go into all of them, but you have all sorts of things like asexual budding and so forth. The sources I was looking at dealt a lot with parthenogenis, which occurs widely and invertebrates. This word stems from the Greek for virgin creation parthenos plus genesis.

of course, when an individual cannot find a mate. It's kind of there as I guess you could think of it as kind of a backup plan that or some sort of a you know, an emergency button that can be pushed. And this has been the case with some of the famous examples of say sharks or lizards such as the Komodo dragon reproducing in captivity, these so called virgin births that will suddenly occur in shock zoo keepers.

DNA sequence. I'm just recalling from memory what mister DNA tells us that some frogs are able to spontaneously change sex in a single sex environment, and thus, even though all of the dinosaurs in the park were supposed to be female, some changed into males, and thus we're sexually reproducing.

time into mating behaviors. It necessitates the existence of males, which in some cases like do little or nothing else, Like, you know, an entire division of the species just for reproduction. Mating can prove fatal in and of itself, not necessarily in a way that actually has any impact on the species. But still it's like the again, you get into these situations where the male's whole role is reproduction and then afterwards it has no purpose except maybe death. And it

can of course also can be nutrition, could be nutrition. Yeah, so it's not a complete ways. But also just mating in general creates opportunities for predators in a number of ways. You could it could be something very specific, like well, while you're mating, it's possible that something could could prey on you. But also again, just think of all the the links that creatures end up going to inmate selection

and so forth. Various examples of this, even if it's just say sexual dimorphism could mean that one member of the species is more likely to be consumed than the other.

already at a dead end. Now in asexual reproduction, there's also a potential dead end there as well, because if you don't have genetic variation occurring, if you're basically just putting out the same model after the same model, after the same model, it may well improve, it may well prove impossible for the species to adapt or to change.

So it's you know, if you're just putting out the same model after the same model, and like the market is the same for that product, then I guess you don't have anything to worry about so long as the market doesn't change. It's suddenly, if the demand for a particular you know, toy or item we were to alter in some way and you couldn't alter the product, then you'd be in trouble. And the same goes for any

kind of biological form. What happens when say, things begin to dry up, or there's warming or cooling, or whatever the case may be. Sexual reproduction is what gives you the ability to bust out these different variations on the genetic code that could prove adaptive to change. Yeah, it gives you options, diversity, Yeah, yeah, diversifies your portfolio. Now, we mentioned disease and parasites already, so that's very much the case. If you just have a whole bunch of clones,

then they all have the same susceptibility to illness or parasites. Overall, the big drawback is just a lack of genetic diversity, which can also result in the accumulation of harmful mutations. And another thing about the difference between the two though, that I guess I hadn't really thought about too much, is that it being a difference between short term and long term benefits. So, asexual reproduction is great for rapidly growing a population during a time of plenty, but the

resulting population can run into problems long term. Meanwhile, sexual reproduction requires more energy and time, but generates diversity that may come in handy in the long term again when there are changes and obstacles that arise. Anyway, coming back to this idea that via asexual reproduction you can have this accumulation of harmful genetic changes. This brings us to the topic of Mueller's ratchet, which is not something I

was familiar with previously. The basic theory here is that long term reproduction, particularly a sexual reproduction, but some of the studies we're looking at they're also looking at it with sexual reproduction. Basically, you see this accumulation of harmful genetic mutations, and after thousands of generations pass by, you can eventually reach a tipping point, which we refer to as mutational meltdown. And we'll get back to mutational meltdown

in just a second. But interestingly, the namesake for Muller's ratchet is Hermann. Joseph Muller, who lived eighteen ninety through nineteen sixty seven, an American geneticis mostly known for his work on mooda genesis and for being like an outspoken critic and just sort of communicator on the dangers of radioactive fallout. He won the nineteen forty six Nobel Prize in physiology or medicine. And he was also the father of mathematician and computer scientist David E. Muller, who also

has various things named after him. So you'll find a number of things in both genetic concepts and what have you, in genetics and mathematics that have the Muller name attached to them.

as I know. But one of the things that I got really interested in here is how it violates sort of the simple assumptions that you make when you think about evolution on a surface level, because, of course it makes this reference to the idea of harmful genetic mutations accumulating over time in a species, and at a surface level, you might think, well, wait a minute, why would harmful genetic mutations accumulate? Isn't natural selection supposed to get rid

of those? And so over time, with enough enough opportunities, yes, mutations that bring more harm than benefit to an organism's ability to survive and reproduce will tend to disappear. But under certain circumstances, bad genes can accumulate. And one of the key concepts to understand here is what's known as genetic drift. So genetic drift is a change in the frequency of a particular gene variant also known as an allele, in a population due to random chance rather than to

natural selection. So random genetic drift is always happening. It's always going on in the background in the evolution of species. While you might think of natural selection as sort of acting in the foreground, amplifying or diminishing alleles because they are helpful or harmful. So you might think of, say a gene for blue feathers in some kind of bird, that gene might increase in the population, not for any reason having to do with blue feathers making the bird

survive or reproduce more. Maybe it's just you know, sheer luck one season. Or maybe there might be some kind of random thing that happens in the popular lakes, maybe a big population of blue feathered individuals come across a big cache of food or something, or there is just the the standard fluctuations in the sampling rate of the different alleles that get recombined in sexual reproduction. The smaller a population is, the more likely it is to be

irreversibly changed by random trends in genetic drift. Now you might wonder, how would that work. If the trends in genetic drift are just random, it's just chance, how would that cause irreversible changes. I think one way you might be able to compare this is if you think about gambling. Okay, imagine you're making bets on somebody flipping a coin. If you have an infinite pot of money to bet with, you could just keep doing this forever, right Like, you

might get a run of good luck. You might get a run of bad luck. You might call the coin wrong. You know, I don't know how many times it would be plausible eight times in a row and lose a lot of money. But eventually, on average, you'd have a winning streak again, and you'd win your money back as long as you can keep gambling, as long as you've got like an infinite pot to play from. But if you are gambling with a fixed amount of money, you eventually will hit a random run of bad luck and

lose it all. You will play to extinction.

drift can also do the inverse. It can take an allele and make it the only version of that gene left in the population, present in one hundred percent of individuals. And there's a term for this, The population genetics term for when an allele becomes present in the entire population is fixation. When that allele is the only version of that gene left, it is said to be fixed in

the population. Everybody's got it. And of course, once a gene variant is fixed in a population, of course, that means the individuals in that population are stuck with it, you know, unless there is new information introduced. Now that could be maybe a random mutation causes a new version of that gene to appear and then it can maybe compete, or there is inflow of new alleles of that gene, maybe by interbreeding with another population or something like that.

But for a closed population, once a gene variant is fixed, they're stuck with it. Now, the important thing to realize is that alleles don't have to be the best version of that gene. They don't have to be helpful to survival or reproduction in order to become fixed in a population. In big populations, harmful versions of genes will not tend to dominate over time. They will tend to get removed

or remain in the background. But in small populations, because you're essentially gambling with a small purse, those deleterious alleles can become fixed just through bad luck. So you imagine, maybe every season within a population, you pick a randomly assorted number of the individuals in that population, You say, whichever allele they've got, make another copy of that one, and then you just keep doing that over and over.

You can get random results where suddenly a gene that's not very good for the population is suddenly the only one left. So that's how genetic drift can cause deleterious, harmful genes to become fixed in a population. But I was wondering, Okay, so what's the deal with this idea of mutational meltdown. What's happening there? Well, I was reading about this in a in a biology textbook I found called Practical Conservation Biology edited by David Lindenmeyer and Mark Bergmann.

And you know, one of the things that the authors mention is that every population carries some load in the background of deleterious recessive genes. But the core theory of mutational meltdown again, it's something that really applies in particular to small populations. That's where it's really dangerous. The author's write quote. In small populations, the dominant genetic process is drift.

If the size of the breeding population is very small, then random drift can overwhelm natural selection and a population can accumulate and become fixed for quite deleterious mutations. If the decline in fitness that results from the accumulation of new mutations reduces fecundity, so it reduces birth rates and reduces survival to the extent that the population declines, feedback between random genetic drift and mutation is set in motion.

As the population size decreases, random genetic drift becomes a more significant force, and the rate of fixation of deleterious mutations increases, further reducing population size. So it is this feedback loop between the harmful mutations making the population smaller and thus increasing the effects of genetic drift compared to the effects of selection forces.

this applies in captive populations in a conservation context. So because captive populations of animals where you know there's concern for the species level survival, because those might those animals are not really competing in the wild to survive, It is very easy, in fact, for them to accumulate deleterious mutations in their genome because you have this genetic drift factor.

But then also the normal selection pressures are not really applying at all, so once the population is reintroduced into the wild, the build up of all these deleterious mutations acquired through genetic drift can be quite harsh, and they say that this could explain some examples of basically poor performance of captive bread individuals of endangered species after being released into the wild.

mutations in small fruit fly populations. This was cited to Gilligan at all in two thousand and five, and they didn't find it. They didn't find evidence of these of these loads they expected. So I guess some questions about how the theory of mutational meltdown actually applies to populations in the wild.

or seemingly more beneficial? Like why sexual reproduction at all? But anyway, as I understand it, based on what we're looking at here, yeah, we have Mueller's which is the theoretical process that then could bring us to this end game of mutational meltdown. Mutational meltdown in this regard would be considered a subclass of an extinction vortex. Extinction vortex is a larger classification entailing different environmental, genetic, and demographic factors.

It's also worth noting and perhaps inflating the obvious here, and that is that extinction is in the long term inevitable. All species eventually face extinction, and I've read that something like more than ninety nine percent of all species to ever exist have gone extinct. Again, this is stuff that makes perfect sense when you spell it out, but also it can sort of mess with your short term, short, short lived human brain when you start again thinking about

the really long term history of life on Earth. So, of course, one of the big obvious challenges to exploring all of this is that humans have only been around on Earth and in a position to look for examples of things like mutational meltdown for a very short period

of time. And if most asexual species or populations don't last very long, do you know, theoretically to Muller's ratchet or to the stability of sexual reproduction outlined and things like the red queen hypothesis, then the various examples of ancient asexual species that we have that are more easy, you know, to look to, those are going to be

exceptions to the rule. And then this creates additional additional questions arise, well, how has this asexual species been able to survive these challenges, these rigors that we're identifying in the data here. And you know, one of the sources I was looking at two thousand and eights quantifying the threat of extinction from Mueller's ratchet in the diploid Amazon

molly This is from Low and Lamach. They point out that, yeah, these species are of considerable interest to researchers for these very reasons.

So in most of the models they ran, the expected time to extinction for this species was less than previous estimates on the age of the species, So it would seem that the species has outlived its genomic expiration date.

If Mueller's ratchet and mutational meltdown is indeed a factor the author's right quote, several biological processes can individually or in combination solve this genomic decay paradox, including paternal leakage of undamaged DNA from sexual sister species, compensatory mutations, and many others, and they, of course conclude that more research

is ultimately required. Another paper that looks into all this that I found quite interesting was Deleterious mutation Accumulation in Asexual Tymema stick Insects by Henry at All, published in twenty twelve in Molecular Biology and Evolution. In this paper, the researchers look at six independently derived asexual lineages and related sexual species of the temma stick insects. So we're talking about closely related species, some that reproduce sexually and

others that reproduce asexually. The idea here, of course, is the closeness. They're the related closely related to each other, so this would make the accumulation of deletarious mutations stand out more in the asexual species versus the sexual species, and that seems to be what they found. Quote. We found signatures of increased coding mutation accumulation in all six asexual tymema and for each of the three analyzed genes, with three point six to thirteen point four fold higher

rates in the asexuals as compared with the sexuals. They also point out that the coding mutations and the asexuals are likely associated with more strongly deletarious effects than the sexuals due to some specific molecular reasons that they outline

in the article. They conclude that quote deletarious mutation accumulation can differentially affect sexual and asexual lineages and support the idea that deletarious mutation accumulation plays an important role in limiting the long term persistence of all female lineages.

enhances the efficiency of purifying selection. This is fascinating, It's not I mean, certainly the authors are not arguing that this is the case, but it's obviously this is not like a smoking gun for the whole idea here, but it does seem to give us some interesting evidence to back up some of these ideas, though of course also raising additional questions about you know, what exactly going on. Now.

There's a I've mentioned ted Ad before. There's a great ted ad video titled no Sex, No Problem, and I highly recommend checking that out. It has a nice overview of sort of the different the different strategies of asexual versus sexual reproduction, and and and briefly mentioned some of the concepts we're talking about here. Uh. One thing that I thought was interesting in this videos it points out that pa fits are a great example of an organism

that utilizes both sexual reproduction and asexual reproduction. Uh Uh. But but depending on what the circumstances are, So with these particular a fits, when it's springtime, they are asexual reproducers. So it's like it's this is the these are the fat times, Like it's it's time to feed, it's time to red it's not time to worry too much about, you know, differentiating your product. It's about just getting product

on the shelves, and so that's what they do. But then when autumn rolls around, then it's time for sexual reproduction. So it's like, Okay, this is our time to think about the product. This is our time to get experimental and see what we can do to change up our

offering for the next season. So I thought that was just a really really interesting, like single species example that kind of sums up some of the benefits and some of the costs involved with asexual versus sexual reproduction, Like this is not the It's kind of like when you think about films in a series, for example, when it's time to make Wrong Turn two, you're not necessarily thinking about, well, how am I going to recreate? No, you don't recreate.

You just do what worked the first time, accept more of it. This is the springtime of the wrong term franchise. Much later, when it's run out of gas, that's when you can you can sit down and think, yeah, that's when you can be like, how do we reanalyze this, how do we reconceptualize Wrong Turn for a new audience? And maybe we can hire Matthew Modine to be in it too, and.

with the Purge this time? And then it's like cut that we're doing a TV series, so just like ten the Purges, and then we'll work about innovating after that.

That's usually where our discussions of films about mutants would wind up, but sometimes those mutations accumulate in the core episodes as well.