Instant Genius - How changes in our chromosomes could lead to the end of men

Episode Date: September 22, 2024

The Y chromosome is responsible for making people male, but according to recent research, we could see it disappear in the future. So what will happen when the Y chromosome is gone? We spoke to Jenny Graves, a geneticist at La Trobe University to find out. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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experts name audio, alongside French acoustic specialist focal, combine handcrafted tradition with cutting-edge innovation and high-end materials, delivering digital precision with analog warmth, so you can experience exceptional sound at home. Music just as the artist intended. Visit name, Hello, I'm Alex Hughes, and this is the Instant Genius podcast, a bite-sized masterclass from the BBC Science Focus magazine. Sex chromosomes, the X and Y are crucial when it comes to deciding an individual's biological sex. But there's some weirdness in the way they can act. Jenny Graves, a geneticist at La Trobe University, talks us through why the Y-chrome zone could one day disappear. leading to a change in the male species and the potential for an entirely new sex.

For those whose biology education is maybe a little bit in the past now, I think it's important to establish a point for this conversation. What are the sex chromosomes of X and Y, and what do they do? Well, you probably know that there's two copies of every chromosome, one that you get from your mum and one that you get from your dad. So chromosomes come in pairs, but the sex pair is really unusual because it's different in females and males. So females have two copies of a very large chromosome we call the X. It's got about a thousand genes on it.

Males have just got one copy of that X and this pathetic little Y chromosome, which is much smaller and has hardly any genes on it. But one of those genes is the gene that makes you male. It's called S-R-Y, and what happens is that gene kickstarts other genes that develop a testis in the embryo. The testis makes male hormones, and it's the male hormones that make the baby a boy. So without a Y chromosome, the other genes kick in, and instead you make an ovary, and the ovary makes female hormones, and the baby's born a girl. So it's a wonderful system. What it means is that the sperm carry either an X or a Y in a 50-50 ratio.

So that's why you get half boys, half girls. Very clever system. And you said just then about how it's only a very small part of the Y chromosome that makes a boy, what's the rest of it doing? It's a very good question what else on the Y, because part of the answer is not function, it's evolution. So you've got to understand that the sex chromosomes evolved from a perfectly ordinary pair of chromosomes that was identical and didn't have anything to do with sex. There's a lot of genes on the Y chromosome that are simply leftovers from the olden days when it was a pair of ordinary chromosomes.

But there are only 45 genes on the Y chromosome. One of them makes you male. A few of the others are really important to make sense. sperm, but others, we don't quite know why they're there. They simply seem to be there because they were always there and you can't get rid of them. They're just hanging around. Some of them have disappeared in, say, cats but not mice and others have disappeared in humans, but not cows. So it's all a little bit random. And in your research, you've spoken in length about this idea of rapid degeneration of the Y chromosome compared to other chromosomes.

What is it that's causing this to happen? And is there a genuine risk of it going away? People write books about this. And there seem to be a number of reasons that the poor old Y chromosome is always losing genes. And it's not just our Y chromosomes. It's Y chromosomes in general. So fruit flies, for instance, have lost pretty well all the genes on their Y chromosome too. It's the thing that happens to Y chromosomes.

And the reason seems to be, well, there's two reasons. One is that the Y chromosome, by definition, is always in a testis. It's never in an ovary. And it turns out that the testis is a very dangerous place to be, partly because there's a lot of mutation going on for making sperm needs a lot of cell divisions, and each cell division is a chance for mutation. So the poor old Y chromosome gets hit a lot. But the other thing is it's not very good at fixing itself up because there's only one in the cell,

so you can't actually swap two bad bits for one good bit of the Y chromosome as you can with an X in females or any of the other chromosomes. So that's why Y chromosomes generally degenerate really very quickly. So they tend to get deletions and mutations, the genes, active genes don't work anymore. and so they're lost by deletion, and you also get insertion of all sorts of junk, you know, bits and pieces of old viruses and things. Now, by rapidly, of course, I'm talking evolutionally here, and so rapid is 180 million years,

and we know that because we've done comparisons of very distantly related animals. So, for instance, we've done a lot of work with kangaroos and even platypices, and kangaroos have much the same exercise. and why a chromosome as humans, but platypuses don't. They have a completely different system that's more like a bird. So we know that that's time zero.

At that time, our sex chromosomes were just plain old chromosomes that didn't have anything to do with sex. So that means we know that things started about 180 million years ago, that most of those thousand genes have been lost, and that means we can calculate the rate of loss. So by the time this is any real issue,

podcast episode will be long, long back into history. Well, it's rather funny that people get so upset about losing the Y-Kromism, and my back of the envelope calculations are, well, if you're losing eight or nine genes per million years, there's only 45 left, it's all going to be gone in six or seven million years. And people get upset about that, I'm thinking six or seven million years is a long time to, I think we have more urgent things to worry about. We've only been human for 100,000 years after all. Do we really think we're going to be around in six or seven million years?

I love to think so, but sometimes I wonder if we're going to be around in six or seven years, or alone millions of years. So if we did flash forward six, seven million years, if we go to this sort of endpoint, what does this idea look like if you do find a world of humans without a Y chromosome? Well, that's a terribly interesting question. and people, again, have written books about it. The really neat thing is that there's some groups of rodents that have actually done this. They have lost the Y chromosome.

They have lost the S-R-Y gene. And they do sex in a different way now. So we know that you can't just lose the Y and become pathogenic species like some lizards are. That won't work with humans because we have a number of genes that have to come through sperm in order to be active. These are called genomically imprinted genes, and that means we can't become pathogenotes like lizards are. So we do need men and we do need sperm.

But, of course, the alternative to just becoming extinct is we might be able to evolve a new sex-determining gene. And that's just what these rather odd-ball rodents have done, developed a new sex-determining gene. And you've talked in the past about being this idea of a potential war of the sex genes. Could you expand on that a little bit? It's not quite as dramatic as I make it sound there. Well, there's no problem about making new sex genes.

It's actually quite simple to make a sex gene. We've looked at the evolution of the SIY gene. It evolved just by taking another very ancient gene that's active in the brain and the nervous system and making it active in the gonad before it differentiates, and that becomes sex determining. So there's no problem making a new sex determining gene. The problem is what you do when you've got an old one and a new one coming in, you have sort of a battle of the sex genes.

You might have one male determining gene on a Y chromosome, and maybe you'll have a female determining gene on a W chromosome as well, and so you'll get a lot of infertility, and that's obviously a very bad thing. But we'd like to know more about how you swap over from one system to another system without a trough of infertility. And so it's terribly interesting to look at these rodents that have actually done it.

So there must have gone through the slew of despair and come out the other side with a new sex-determining gene. We'd love to know how that process eventuates. And you touched on something that I want to talk about, that there's across the world a rise in infertility rates. Is there any connection between this issue that's happening and the potential loss of the chromosome? Almost certainly not.

I think there's lots of other things that are going on, particularly in our environment, which is full of pollution and hormone mimics and all sorts of things. I'd have my money on those rather than the disappearing Y chromosome. I think the Y chromosome works pretty well. I mean, it's one of these things that I call it dumb design, as opposed to intelligent design. Sex chromosomes are really a dumb way of doing things because they have so many problems.

One problem being the disappearance, but another problem being the fact that there's only one ex-chromosome in males and there's two in females and that's obviously not fair as well. So there's all kinds of problems that are introduced by sex chromosomes and that's the same for fruit flies. Their sex chromosomes are a problem to them as well. So it's sort of inherent in the business of being a sex chromosome that you're going to extinct yourself in enough time. And as you've sort of mentioned throughout this, there's been pushed back to this idea of a disappearing gene, even when you look at the long length of the timeline, some people say that, you know, it's just not going to happen, it can outsmart genetic decay. Is there an argument to that?

Yes, there are lots of arguments to it. And my back of the envelope calculation is very simplistic. It's just assuming a linear decline, but almost certainly it's not linear. What I would predict is it happens very, very rapidly and then it slows down. And so probably we're looking at the slow part of it now. It looks like nothing much has happened to the Y chromosome. If you compare our Y chromosome with gorillas and chimpanzees, chimps and gorillas have lost extra genes from their Y chromosome, probably because they have a much smaller population than human population.

So I think it's probably true that it's slowing down, but that doesn't mean it's not going to happen. I mean, it could happen tomorrow. I sometimes wonder whether it's actually having. happened in a human population somewhere in the world, there may well be a human population in which the Y has disappeared and we now are working on a different sex gene and a different sex chromosome. How would we know without taking swabs from everybody and looking at their genomes? You know, we still have boys, we still have girls. So it's more in a way that it's just

the likelihoods spreads over millions of years, but we could be. seeing this in a much shorter time frame. Yes. I think, you know, they're very wide margins of error from next week till never. Yeah, that's quite a big gap, actually. It's a big gap, but it has happened. It's happened in two groups of rodents, and so there's no reason it can't happen in humans. We have a lot of humans on this planet, so that's probably means that it's more robust than it would be in a gorilla, but it also means there's possibilities, particularly in small populations with a lot of inbreeding, of doing this swappy to a new sex gene on a new chromosome. We now understand how it happened in spiny rats, and it's a beautiful story. It's very, very simple. What happened

was the SIY gene on the Y chromosome got completely lost, and instead, the gene that SRY usually kickstarts, which is called SOX-9, is developed a sex-specific switch on one end of the gene, which turns it on double in males. So it's a very, very simple little switch, and it could happen any time. And obviously, that's what's funny rats thought, oh, well, this works just as well. get rid of the Y, get rid of SRIY. We've now got a new sex chromosome. I think Sox 9 is on chromosome too. That becomes our new sex chromosome. I mean, the more you talk about the Y chromosome, the more I'm surprised it hasn't already died out on its own. It seems to make lots of very bizarre decisions. Yes, well that's why I love sex chromosomes. They break all the

rules of evolution. They're rule breakers. I love that. Absolutely. Ambition comes in all shapes and sizes. At First Citizens Bank, we roll with your goals because we're built for what you're building. Fit for your ambition for Citizens Bank. In a place like Los Angeles, people don't stop being who they are. Writers, thinkers, creators, people with stories still unfolding. That spirit lives on at Kingsley Manor, a community shaped by individuality, creativity, and lives well-lived. So when the conversation turns to what's next, it isn't about step. away. It's about continuing the story. Explore your options at kingsley manor.org, a non-profit month-to-month senior community within the Front Porch family. This podcast is sponsored by name, audio,

and focal. With over 100 years of combined expertise, name and focal have been bringing music to listeners just as the artist intended. Since day one, this mantra has shaped every innovation in high-fi design, technology and acoustic engineering, balancing craftsmanship and tradition with pioneering thinking. Name Audio pushes cutting-edge technology to ensure digital precision whilst sustaining Pratt, pace, rhythm and timing, the elusive quality that makes music feel alive and gives it emotional texture. Today, in partnership with French acoustic specialist's focal, name audio creates systems that deliver exceptional sound, an unforgettable listening experiences at home.

Try it for yourself at a focal-powered-by-name boutique. Visit focal-powered by-name.com for more information. We've spoken a little bit about other animals and other kinds of sex chromosomes. Is it X, Y, and everything, or is that just found in humans and certain animals? It's X-Y in all mammals. The theory in mammals, that is, the central mammals and the marsupials, have essentially the same X and Y. Monotremes are really bizarre. That's platypuses and the kidneys are very, very bizarre.

They have 10 sex chromosomes, not just two. They have five X's and five Y, which is really very strange. But the really weird thing is they're not related to our sex chromosomes at all, but they're strongly related to bird sex chromosomes, which are completely different. In the case of birds, it's a male that has two copies of a large, gene-rich-z chromosome. And the females only had got one copy and this pathetic little W chromosome that doesn't really seem to do anything. And one of the other things I wanted to ask

you about is obviously gene editing is seeing a rise across the world, especially through programs like CRISPR. Is there a possibility of editing these kind of sex chromosomes looking forward if there was to be a weakness in the wide that comes up earlier than expected? Well, we now know thanks to the spiny rat, that all you have to do is insert a little switch right by Sox9 and you can get rid of SIY and the Y chromosome any old time. It's not quite as simple as that because, as I said before, there are other genes on the Y chromosome that you need to make sperm.

So you can make a male, but you can't make a fertile male without introducing these as well. But you wouldn't really have to CRISPR those. You could simply stick them on another chromosome and they work perfectly well. We can do that with genetically engineered mice. I don't see any reason to do it with humans. I don't think we're that desperate.

Maybe in seven million years, I'll think differently. We'll come back to you in seven million years. Yeah. And obviously you've spent years studying these sex chromosomes, both in humans and animals. What do you think is the most bizarre thing you've come across in that time? I mean, we've spoken about some truly bizarre combinations. Oh, gee.

I think it would be hard to beat the platypus. That is an impressive one. Yeah, that's very impressive to have five different chromosomes all involved. They're not all required for making sex. There's one very small chromosome, which is probably the real white chromosome. But other chromosomes have sort of jumped into the act as well, and they form a big long chain. And so you'd say, well, that is the dumbest thing I've ever heard. But, you know, it works and evolution doesn't care whether it looks dumb or not,

as long as it works and as long as it can't unhappen, you kind of stuck with it. Yeah. If it's not broke, you know, it's working. It's not broke. Don't fix it. Exactly. So say, you know, we've spoken about this timeline that stretches across millions of years. Obviously, none of us are going to be able to quite experience that unless something truly

remarkable happens, is there anything that we will notice any noticeable changes in sex chromosomes within our lifetime? Well, of course, we see changes in sex chromosomes all the time. There's babies who are born with sex chromosomes that have rearranged or deleted or mutated. So we have a big store of, well, what happens if you mutate this gene or this gene or this gene? That's how we've found out pretty much how SRY works because it kickstarts its other genes, Ox 9, but it interacts with other genes that actually turn on other genes and turn off ovary-depending genes. So there's actually 60 genes that you need to become either male or female. And it's sort of a more of a balancing act than anything else.

It's a real push-me-pull-you kind of system. And so I think that explains why there's so much. variability, not just in sex determination, but also in mate choice and in gender affirmation. So the whole system is really a lot of genes all working together. And if some of them are a little bit more active than usual or a little bit less active than usual, you'll get variations, either in sex determination or in behavior. There's all kinds of variation there. Thank you for listening to this episode of Instant Genius.

That was Jenny Graves talking about the disappearing wide chromosome. The Instant Genius podcast is brought to you by the team behind BBC Science Focus magazine, which you can find on sale now in supermarkets and newsagents, as well as on your preferred app store. Alternatively, you can come and find us online at sciencefocus.com. This podcast is sponsored by name, audio and focal. The texture and emotional depth of music can be lost through digital sources or poor signal. Name Audio believes you can have digital precision with analogue warmth.

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