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The Evolution of Sex

Jenny GravesJenny Graves

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Matt Smith:

Welcome to the La Trobe University podcast. I'm your host, Matt Smith, and I'm here today with Professor Jenny Graves. She's from the Research School of Biology at the Australian National University. Thank you for joining me, Jenny.

Jenny Graves:

You're very welcome, Matt.

Matt Smith:

You're here today to talk to me about your own unique take on Darwin's Theory of Evolution, which is the evolution of sex. How did you get into that sort of topic?

Jenny Graves:

Well, through chromosomes and cells, why we had always been interested in sex chromosomes, because they're extremely weird. But we're interested in the X chromosome because there's a mechanism to switching the whole chromosome off to make females the same as males, because females have two X's. The males have only one, and of course that's not fair.

There's an epigenetic mechanism that switches off a whole X chromosome, and that's what I was working on. So I really had nothing to do with sex at all until one day, when the gene from the sex determination gene on the Y chromosome had been - you know, lots of people are looking for it, not including us, and I saw a wonderful paper coming out from America claiming that they had found this gene. So I thought, 'Well, that's right. Nothing to do with us. But isn't that terrific?'

And I got a phone call from this guy that night to say, "Would you have a look at this gene in kangaroos? Because it should be on the Y chromosome if it's the right gene." So we had a look at it and it was the wrong gene. Of course, it wasn't on the Y chromosome. It was somewhere else that was clearly the wrong gene. It was actually my student, Andrew Sinclair, who went to London and cloned the right gene.

So that sort of got us off on a totally different trajectory, looking at sex chromosomes, looking at the Y chromosome, looking at the gene that makes you male. So that's really how we got into it.

Matt Smith:

What does this gene do? I mean, if you turn it off, what would that mean for us species?

Jenny Graves:

Well, it's interesting. This was in 1990. So that was, like, 19 years ago. And we all assumed that once you got this magic gene, all the other genes on the pathway kind of fold over like dominoes and we'd know all about how to make a testes.

And that really has proved much more difficult than anybody thought, because it turns out that this gene doesn't really seem to work directly. It turns on another gene that we know about, but there seemed to be genes that turn it off and other genes that it turns off, that in turn off something to do with the testes, so it may actually turn off something that's turning off a testes. And we still don't really know the details, but a lot of our work has been to look at this gene and the protein that makes and figure out how it might work to make you male.

Matt Smith:

Does that mean that without that gene, well, there would be no males?

Jenny Graves:

Yes. Without that gene, all the embryos would turn into females because it's that gene that kick starts the development of a testes in an embryo, and it's the testes that churns out hormones, and it's the hormones that make you male.

Matt Smith:

And is that gene as a result - well, I suppose I might sound a bit worried when I say this, but is that gene nice and safe then? Is it going anywhere?

Jenny Graves:

No, it's actually in a terrible shape because it's on the Y chromosome, and the Y chromosome is degrading and degrading. Y chromosomes do that for all sorts of complex reasons. Once a chromosome acquires a gene that makes you male, that's kind of a kiss of death because that means that the chromosome is always in a testes and never in an ovary, by definition, because it makes the testes, and it turns out a testes is a very dangerous place to be.

There's a lot of variation that happens because making sperm, you have to go through many, many, many cell divisions. So, the whole chromosome is subject to a lot of mutation. And repair is not very good in a testes. It's a very oxidative environment. And so the plural Y chromosome is being buffeted the whole time, and so it's losing genes at a terrific rate and there will be nothing left of it in five or six million years.

Matt Smith:

In five or six million years? I'm now saying this as a concerned male and as a guy who's got four sisters and no brothers - what sort of situation will we potentially be in if we're around as a race in five million years?

Jenny Graves:

Of course, there's a big 'if' here. I mean, sometimes I think we'll do very well to last the next 5.8 years, let alone millions of years. That's a really interesting question, though, because this has happened in other species, that the Y chromosome is completely degraded and something else has taken over.

Matt Smith:

Is this where females can change into males as needed?

Jenny Graves:

No, although there's some fish that will do that.

Matt Smith:

I think frogs do that as well.

Jenny Graves:

No, I don't believe so. Frogs have got very genetic sex determination usually. But there's some fish that, if you take the male away, the biggest female will become male. But that seems a bit - there's two kinds of sex determination.

One is determination by something in the environment, and it's usually temperature. So, for instance, in crocodiles, if the eggs are incubated where it's hot, they'll all be male. But if you take the same eggs and you incubate them where it's cooler, they'll all be female. So there are no genes that tell you to go this way. It's all temperature that's directing the testes formation.

On the other side, there's a genetic sex determination, which means that there's a particular male-determining gene or a female-determining gene in some species. This is what we're interested in. It's how chromosomes become sex chromosomes and what ultimately happens to them.

So it seems that everywhere you look in the insects or mammals, what happens is that if there's a male-determining gene that defines a Y chromosome, and that means it's always in the testes so it degrades really fast, that means that you have to ask, well, "What next?" And either you become extinct, or you can go the path in the genesis which is a female only.

And there are actually some lizards that do that. I don't think that's very likely because there's a whole lot of genes that aren't active in their sperm. They're called imprinted genes, and we've got 30 of those. So I think we need sperm and we need males. So, without males, we would become extinct.

Matt Smith:

It would be up to artificial means simply to propagate at that point.

Jenny Graves:

Well, we'd have to clone ourselves, which sounds like a great bore. But the good news is that there's actually some rodents who have done this. This is a little creature that lives in Iran and Azerbaijan. That's not the easiest thing to study. But it's actually lost its Y chromosome, lost its male-determining gene, and must have a new one somewhere. We don't know where or what, but we'd really like to find out. So it's actually done a flip-flop. It got rid of the its old Y and it's now working on a new one.

Matt Smith:

So this seems to be a common thing in the animal kingdom?

Jenny Graves:

Yeah. We know that, for instance, in fruit flies, they've actually gone through three different Y chromosomes. So one completely degrades, but it's good to have a Y chromosome because otherwise the poor X doesn't quite know what to do at mitosis, the cell division that make sperm, so it looks like some passing chunk of DNA got captured and made into a Y chromosome, and that's been endowed with fertility genes.

So sex determination is different in fruit flies. It's not a gene on the Y chromosome that makes them males. It's actually the number of X chromosomes they have. So there's all sorts of ways of doing it and all sorts of genes that can be a trigger factor.

And you think, 'Well, that's kind of strange. You would think something as important as sex would actually be very conserved, and you wouldn't want to mess with sex.' But in fact, it's quite the other way around. Although the pathway of making a testes is very conserved, the trigger that pathway is extremely different in all sorts of different animals.

Matt Smith:

How does that theory tie in with evolution now? As you say, you think that would be something that would be preserved. But it clearly isn't, and humans aren't the only species that that is happening.

Jenny Graves:

No, that's right.

Matt Smith:

So, isn't the whole point of the Theory of Evolution is to keep the things that are useful to a race?

Jenny Graves:

I think this is what makes sex uniquely interesting. I mean, Darwin was extremely interested in sex, and so were the first great geneticists. Harry Fisher was extremely interested in sex, JB used to hold that in because it seems to break the rules. Things barreling along very fast, it seems to be suddenly crazy, but of course - I mean, really what Darwin was saying is it's all a big accident, you know? It's a random change, it's sort of being seized on a selected. And sex is a wonderful example because things happen so fast, so sometimes very crazy things are accidentally put in place and those are selected for.

And we see lots and lots of examples of genes that are there essentially by accident, but evolution has fashioned them into genes that make you male or genes that help you make sperm.

Matt Smith:

So if I've got my heart set particularly on having a son, I should maybe wear some protective padding before I get to that point?

Jenny Graves:

Well, Y chromosomes are at risk, and of course there are numbers of men who are infertile, and that's very often because they've lost a chunk of the Y chromosome which has got one or other of these fertility genes on it.

Matt Smith:

So how do reptiles deal with the problem because they're a throwback on the evolutionary stage before mammals evolved?

Jenny Graves:

Well, what we're doing now, which might interest you, is we're very interested in how they get from being a temperatures-determining sex to genes and chromosomes, because we thought they were completely different. But that's not true.

We've been looking at the dragon. We have a lovely grant called "Sex in Dragons". It's the little game with lizards. It's really great. It's got green horns and frills. It's very, very fetching. They're pets and you can buy them in pet stores.

And they're amazing! They sort of sit on your shoulder like a statue. They just don't move a muscle until you put some prey, some cockroaches or something, and then they'll go mad until they've eaten every one of them, and then they totally freeze again. So they don't waste a lot of energy, these guys.

But we thought they'd be interesting because they have a gene, they have sex chromosomes and genetic sex determination, we've explored that. But if you raise the X at a high temperature, they're all girls. And so that gave us a completely new idea about how sex could flip-flop between being temperature-determinant, being genetic-determinant, and now we think that probably there's some underlying genes that determining sex in probably all reptiles, maybe even crocodiles.

Matt Smith:

Is there any way in the future to kind of encourage humans to go to that sort of thing as well?

Jenny Graves:

Well, it could have few problems in the warming world. I mean, do we do one where are we going to end up with all male alligators? And curiously enough, turtles are the other way around, so when it's hot they're all girls and when it's cold they're all boys, so we'll end up with girl turtles and boy alligators, and that's not going to work very well.

Matt Smith:

Is that coming up in their populations?

Jenny Graves:

People have said they're very concerned about temperature-sensitive sex because it will be messed up if the world gets two degrees warmer. Because it's very, very sensitive, you know? Two degrees and you go from all boys to all girls.

I'm not too worried because the work that we did a few years ago in America showed that there's actually quite a lot of variation. So if you take the eggs out of an alligator nest and you incubate them at the same temperature, and then you take them out of another nest and incubate them at the same temperature, you don't actually get the same ratio.

So I think probably there's some sort of a genetic predisposition to hotter females or colder females. And so I think that if there's enough variation, you'll get very rapid selection to raise the what do you call the 'pivotal temperature' between being a boy and being a girl. So I'm not too worried about alligators and turtles. I'm more worried about people.

Matt Smith:

Professor Jenny Graves, thank you for your time.

Jenny Graves:

You are very welcome, Matt!