Best of NG - Sexy genes

Another interview that has stuck in my mind is the chat I had with Professor Judith Mank from UCL on her work about the genes and sex.
03 January 2016

Interview with 

Judith Mank, UCL


Kat:: Another interview that has stuck in my mind is the chat I had with Professor Judith Mank from UCL back in July 2013, on her work about the genetics of sex determination. Genetically speaking, our human species is broadly divided into male and female, determined by our sex chromosomes - XX for females and XY for men, although there are people whose chromosomes don't strictly conform to this, for various reasons. But the way that we do sex - at least on a genetic level - isn't the only way to do it. I started by asking Judith  what, biologically speaking, do we actually mean by "sex"?

Judith - So, sex can be two things. So, it's the act of actual - it's called syngamy, the combination of egg and sperm, but related to that, what we said is the evolution of sexual dimorphism so how you get separate males and females. Males and females often look different, they act different, and that's why we study it in group.

Kat - A lot of us are familiar with the idea that humans have an X and a Y chromosome if you're a man, and XX, if you're a female. Is this the only way of doing it?

Judith - No, there's a million different ways. There are a lot of fish that actually flip partly through their life. So, they start out as one sex and when there's some sort of cue, they flip to the other one. Interestingly, it seems that within a couple of hours of the cue, their brain starts changing. They start acting like the other sex and it takes about 3 days after that for the gonad to follow.

Kat - Their body completely changes as well to the other gender?

Judith - Yep, and they start reproducing within about 3 days with the other sex. There are a lot of animals that are XY like mammals are, but different sort of independent X and Y chromosomes. We study in our group, we do a lot of work on birds which are Z and W. So, in that case, the male has two Z chromosomes and the female has one Z and one W. So, the W is quite somewhere to the Y that you see in humans.

Kat - Now, this seems quite strange that there would be so many different ways of doing this in the natural kingdom. How has this arisen?

Judith - That's actually the big question at the moment to be honest. So, no one really understands how some things are fundamental as how you determine sex changes. The only thing that we do understand is this old idea of conservation - so, you've got the same sex determining system in most mammals. You've got the same system in birds. You've got the same system in fruit flies. That idea that sex should be conserved is clearly not true. So, you've got some systems like fish where within populations, you've got multiple mechanisms of sex determination and it changes very, very quickly. That seems to be much more common.

Kat - If you're going to have sexual reproduction, you need a male and female or two different things to make it work, producing eggs and sperm. Are there any inklings of maybe how these kind of mechanisms of the sex chromosomes have arisen at least in some of the animals or some of the creatures you studied?

Judith - So, there's a lot of theory. Not a lot of it is really well proved, but most people think that if you've got a gene that determines sex, say, a gene that makes you male. And there could be several different genes that might predispose you to being male, but if that gene is linked - is physically very close to another gene that confers some male benefit - so, if you have both of them, you're both a male and you're a very fit male, you're a good male then that sort of sends you along the path to having a Y chromosome. But if you have a gene that makes you female and that's close to another gene that makes you a very good female then that would sort of send you on the path to a W chromosome.

Kat - What is the advantage of actually having two sexes because you think about well, something like an amoeba where it just splits itself, it reproduces, seems to be kind of fine, bacteria seem kind fine? What is the actual advantages of having different sexes?

Judith - Well, there's two things. So one, some things have sex but don't have obligate sex. They don't always have to have sex. They can sometimes reproduce clonally.

Kat - Like a yeast?

Judith - Like a yeast, some fish, a lot of plants. So, occasional sex is useful in that it helps you adapt more to changing environments and to outpace parasites and things like that to sort of keep your immunity up.

Kat - So, you're kind of mixing your genes up, makes you a bit fitter?

Judith - Yep, exactly. Having obligate sex like we do means that you avoid any sort of inbreeding or you minimise inbreeding so if you can't mate with yourself, you avoid having two copies of a recessive deleterious alleles. In theory, the offspring are fitter, they do better, that's the idea.

Kat - One of the things I'm very interested in your work is the idea of conflict within the sexes. This isn't sort of the battle of the sexes - men versus women. This is kind of conflict between genes at this kind of level. Tell me more about that.

Judith - If you think about it in humans, men and women have - they only differ on the Y chromosome and the Y only has a few dozen genes at most. And so, for 99.99% of genes, they both have them. But yet, men and women look different, they act different, they have different interests, sort of as a sex and so, that means that the optimal function of any gene can differ between men and women. So, it's this idea of conflict over the optimal usage of a given gene.

Kat - So that the genes that you have on your sex chromosomes maybe kind of determine how the other genes get used?

Judith - Well, you can have conflict without sex chromosomes. So, there are lots of animals that have lots of conflict and don't have sex chromosomes at all. Conflict can be in any part of the genome. Any gene that codes a phenotype, some sort of form that differs between males and females. So, if you think about behaviour - so we work on birds a lot, males often find the highest point they can to scream their heads off, so the females notice them. And that's not great if a female does that because she doesn't get any benefit from it. Males don't really take any notice of it and it makes her much more conspicuous to predators. So, the gene that encodes that behaviour is under conflict. So, males want that behaviour, females don't. Males benefit from it, females don't. So, there's this conflict over what it causes.

Kat - Do we know anything about what helps to kind of establish which way you go with it? Is there a role of hormones? Is there a role of the environment, anything?

Judith - Hormones can kind of resolve this conflict in a way. So, if you get one of those genes under the control of a sex hormone, that means that it's only going to be expressed in one sex and that results all the conflicts. So, if they both got the gene, but only one of them uses it.

Kat - What for you is the thing that when you discovered it was like, wow, that's weird!

Judith - That changes by the moment, but I think the thing that I'm most obsessed with currently is the study we just did in turkeys. So, I didn't know about this until I went up and talked to a breeder. So, turkeys actually come in two male phenotypes, two male forms. So, there's this dominant male and then there's this subordinate male, and the dominant male and the subordinate males, they're actually brothers. All the brothers in a given clutch, the winter before they mature get together and they battle it out for who's going to become dominant. The dominant male has the sexually selected traits. It's got this big tail. It's got this iridescent plumage. He makes that really goofy gobbling sound. He has a snood and a wattle and a couple of other things. The subordinate male has most of those, but a little bit less. The subordinate males actually advertise for females with their dominant brother and there's some evidence of having a lot of very attractive subordinate males actually pulls more females in, but they never mate. All the matings go to their dominant brother. They never try and buck the system, so they never and put off their dominant brother. We were interested in the gene expression patterns underlying this.

Kat - Because this is like a wingman basically - well, literally.

Judith - Wingmen, exactly yeah. It's this really bizarre system and I had no idea this was going on. And so, I went up to this breeder and Yorkshire and she showed me the way it works and then I started reading about it and it's amazing. It's also the least tractable system in the world. These things take two years to mature. They're big. They're mean. They're expensive. They don't want people. They're not ideal in that sense, but it's just fantastic. So, we were interested in sort of the gene expression differences between the dominant and subordinate male because both are male. But in some senses, the dominant male is a bit more male in terms of all these traits he's got. It was really amazing for thousands of genes. The subordinate male was a little bit less male in expression and a little bit more female. They only differed from the dominant brothers by a few genes, you know, very much. They're only like 4 or 5 genes that differed a lot, but across the spectrum of all 7,000 expressed genes, they showed these very subtle differences that affect the phenotype, sort of as an aggregate.

Kat - Almost like it's like kind of a third sex for turkeys?

Judith - Not quite, but if you think about sort of sex along an axis, they're clearly on the male side, but they're just a little bit less male. They're not intersex by any means. They can reproduce if they wish.

Kat - If they got the chance.

Judith - Yeah, exactly.



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