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Welcome to this podcast about human sex chromosomes X and Y. Everyone gets taught at some point about sex determination in humans, and I say specifically humans, because there are many different types of sex determination, such as the ZW system, where the males are the simpler genetic default, and the females require that extra something to develop, as with the Y chromosome for males in the XY system. There’s also the X0 system where the absence of a second sex chromosome creates males, and the double sex chromosome X creates females. However, this isn’t the same X chromosome behaviour in humans and the XY system, because in humans, lacking the Y chromosome doesn’t create males, quite the opposite, it creates female-presenting people with what is known as Turner’s syndrome.

Timestamps

 

A lot of people might be forgiven for ending up believing that sex itself and in its entirety is contained in chromosomes X and Y… 0:51

ZW sex-determination system https://en.wikipedia.org/wiki/ZW_sex-determination_system

X0 sex-determination system https://en.wikipedia.org/wiki/X0_sex-determination_system

 

Was there a need to evolve two new kinds of organism, a male and a female, or was it far easier to evolve a counterpart to a default organism… 2:46

Evolution of sexual reproduction https://en.wikipedia.org/wiki/Evolution_of_sexual_reproduction

 

Is there a similar toggle on the X chromosome? No, there doesn’t need to be, because once you have a sex trigger, the other sex is simply the standard development… 4:47

Diagrams of genes on human chromosomes including X and Y https://public.ornl.gov/site/gallery/gallery.cfm?topic=47&restsection=HGPArchive

Androgen insensitivity syndrome https://en.wikipedia.org/wiki/Androgen_insensitivity_syndrome

 

A father will contribute breast size genetic predisposition to his daughter just as a mother will contribute penis size predisposition to her son… 9:08

Hormone therapy (overview) https://en.wikipedia.org/wiki/Hormone_therapy

 

More basic genetic qualities can be far more significant in determining people’s overall appearance, such as height, hairiness, body type, and extent of sexual characteristics like breast size or muscle mass, than whether they are the female or male version of themselves… 11:55

 

If the Y chromosome is shrinking, it’s because it doesn’t need to be bigger… 16:34

If crucial Y chromosome genes move to an autosome, it doesn’t matter if the Y chromosome genes “disappear” (Sex chromosome-to-autosome transposition events counter Y-chromosome gene loss in mammals, Hughes et al., 2015) https://www.ncbi.nlm.nih.gov/pubmed/26017895

Evolution: Have Wings Come, Gone and Come Again?, Stone and French, 2003 https://www.sciencedirect.com/science/article/pii/S0960982203003646

The ethics of changing genes in the embryo, Sarah Chan https://www.eurostemcell.org/ethics-changing-genes-embryo

 

Script

 

Intro

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Intro Hi guys, how’s it going?
The cell receptor for testosterone is encoded on the X chromosome. Didn’t see that coming, did ya? ♪ tune

 

Sex Determination Options

Welcome to this podcast about human sex chromosomes X and Y. Everyone gets taught at some point about sex determination in humans, and I say specifically humans, because there are many different types of sex determination, such as the ZW system, where the males are the simpler genetic default, and the females require that extra something to develop, as with the Y chromosome for males in the XY system. There’s also the X0 system where the absence of a second sex chromosome creates males, and the double sex chromosome X creates females. However, this isn’t the same X chromosome behaviour in humans and the XY system, because in humans, lacking the Y chromosome doesn’t create males, quite the opposite, it creates female-presenting people with what is known as Turner’s syndrome.

Now, back to the topic of this podcast, which is specifically the understanding around XY sex determination in humans, and the impression chromosomal behaviour gives. A lot of people might be forgiven for ending up believing that sex itself and in its entirety, is contained in chromosomes X and Y. Quite literally, that somehow all that it means to be a man is on the Y chromosome, and all that it means to be a woman is on the X chromosome… For people who think sex is everything, it does beg the question… what are all those other 22 chromosomes even doing anyway? What if I told you that all that it means to develop as a sex is not on chromosomes X and Y? Could it be that only one of them is actually a sex chromosome? Coming up next… ♪ tune

 

Birthing Sex

To understand the evolution of sex determination, let’s delve into the meaning of sex to begin with. The requirement of mixing different genomes together, rather than cloning individuals with very similar DNA for reproductive purposes evolved because it could produce more adaptive iterations of an organism, quicker than its counterpart asexual version. So, the sexually-reproducing mode evolved out of the asexually reproducing mode, and for humans, this would have been a very, very, very long time ago. But when it did happen, think about it. Was there a need to evolve two new kinds of organism, a male and a female?

Or was it far easier to simply evolve a counterpart to a default organism, which would then become sexed by virtue of two versions existing together? While the sex determining element, be it a gene, a chromosome or even an environmental trigger, evolved to toggle a sex, such a male in humans by way of the XY system, a similar toggle was not required to have a second, female sex development because that one could just remain a developmental so-called default, for lack of an input, or the toggle, required for it to exist. In some species of fruit fly which have the X0 system, the simple default is male, while the toggle-dependent sex is female; for these purposes, the concept of simple, or default is used just to convey the concept that a state is more basic, and requires less input to exist. So, what is the role of chromosomes X and Y in human development alongside the other 22 chromosomes, called autosomes? Find out in a second… ♪ tune

 

Nothing Female about X

All chromosomes carry the genetic information pertinent to that kind of organism. For sexual species, that information includes everything required to develop different sexes, but of course, contrary to hopefully very old popular beliefs, different sexes are not different species. Therefore, that information must be carried by everyone – except, of course, the toggle switch itself. In humans, the sex toggle switch is found on the Y chromosome. Think of it as a key to a house. You carry it with you to be able to access it, but you don’t carry the house on the key.. that would be ridiculous. Is there a similar toggle on the X chromosome? No, there doesn’t need to be, because once you have a sex trigger, the other sex is simply the standard development.

Female development doesn’t need a key, it just walks straight in. Inside, you still have the cupboards that contain alphabet soup, but as it happens, the aforementioned male key also doubled as a secret key to the special hob function required to boil the alphabet soup to the correct temperature… Alphabet soup being whatever male characteristic at whatever point of development you want to think about. Alphabet soup could be a hipster beard, and yet loads of key owners grow up to open their cupboards and find that there’s still no alphabet soup there! More on that later. So, in terms of so-called sex chromosomes X and Y, I will argue that only Y is actually a sex chromosome in a true sense. Human chromosomes are arranged and named based on their size.

Chromosome 1 is the largest, and chromosome 22 is the smallest. If X and Y were lined up accordingly and numbered, X would correspond to chromosome number 8, while Y would correspond to chromosome number 20. There’s a lot going on in chromosome X, and it’s not to do with sex – but hilariously, it would be more to do with the male sex rather than female, based on its actual component genes. If you got this far, you probably know that genes don’t code for body parts, like oh, here is the boob gene, and here is the dick gene. Genes are very basic building blocks. For example, some stuff on the X chromosome includes magnesium transporter 1, cytochrome c oxidase subunit 7B (this is not made up by the way!), phosphoglycerate kinase 1, fibroblast growth factor 16, and of course, the androgen receptor gene. Androgen receptors being what enables testosterone to activate male specific functions… yep, encoded on the X chromosome.

The irony is beautiful… If you wanna know where I found these gene location details, go back to episode 1 where I teach you how to research anything in life science! The X chromosome is quite large, and has nothing to do with femaleness, it’s simply yet another indispensable human development chromosome, like the other 22. The Y chromosome is specifically evolved to govern sex development. It toggles it, but the many materials required to make a human, male or female, are still encoded on all those other chromosomes. Where the androgen receptor gene is mutated in people with androgen insensitivity syndrome, the lack of processing of testosterone results in a more female developed body.

So in a way, the Y chromosome is required to develop testes which then produce testosterone, but the androgen receptor gene on the X chromosome is required to actually ensure this is processed and the body develops fully on the male pathway. How do the different stages of sexual development, before birth, during puberty and beyond, interact with factors such as external administration of cross-sex hormones like hormone replacement therapy? Find out next… ♪ tune

 

Developmental Timelines

The understanding that certain genetic products are activated over an individual’s developmental lifespan at different points is crucial to knowing how the different components of sex determination and later expression work. As previously mentioned, the interruption of male development in a foetus with androgen insensitivity syndrome means that their Y chromosome genes begin testicular development, but the insensitivity to testosterone halts masculinisation there. Once a baby is born, certain characteristics cannot easily or at all, be reversed, as many critical tissues and organs have already been formed.

Female gametes, which are precursor egg cells, are not even made during adulthood, as they’re all set before birth, to be potentially used decades later. A further key developmental point is puberty, when sex hormones finally activate other features. At this point, a lack of those hormones can prevent those developments, while external administration of cross-sex hormones, as is done for people who are transgender for example, can activate development of features that would not develop with their endogenous sex hormones.

People who developed as female before birth can go on to have a male puberty, and vice-versa. Some features are newly developed and are the same regardless of birth sex, such as voice depth, hair growth, breast development, while others, which were more reliant on pre-birth development, such as sex organs with their associated fertility, would shift to a much lesser degree, or not at all, based on birth sex. This is to further emphasise the previous point about these sex characteristics being carried by everyone genetically, apart from the actual male sex trigger on the Y chromosome.

A father will contribute breast size genetic predisposition to his daughter just as a mother will contribute penis size predisposition to her son – they would just be more masked, because those parents did not fulfil those genetic predispositions in the absence of the other sex hormone that would have let it happen. Beyond sex, many other features are subject to genetic predispositions, which can be quite hidden, and very variable in different human populations. Is hairiness a matter of sex more so than of more basic genetics? Find out in a tick… ♪ tune

 

Traits and Sex

Some people, such as the aforementioned people who are trans, are uniquely positioned to cross the sex boundary that is held in almost a holy-like regard by others. The widely-held expectation that sex, and the effects of sex hormones, should be a major, earth shattering thing, is still very strongly present in people’s attitudes to viewing themselves as a sex first, and everything else second. However, more basic genetic qualities can be far more significant in determining people’s overall appearance such as height, hairiness, body type and extent of sexual characteristics like breast size or muscle mass, than whether they are the female or the male version of themselves.

As such, many men who are trans and await their long term masculinisation effects, such as growing a beard, try to gauge how long it should take, as if it’s a function of the amount of testosterone they have, rather than their basic genetics. By comparing different populations, this can be seen very easily, where certain populations of women can be far hairier, taller or more muscular than the men of other populations altogether. These features associated with maleness can exist in females just as fine, as they can be lacking in males, just as fine. By just as fine, I mean without impeding their fertility in any way, which would be relevant to their sexual function. To highlight the extent of this misperception of general features across different populations as assigned to sex, I have a couple of anecdotes.

I was in Cambridge once getting a fantastic falafel from this falafel van in the city, that was very popular, and it was lunch time, so there were a good ten or more people waiting around, when this grandma-like person joined us, with her young granddaughter-like child, who must’ve been pre-pubescent, maybe 10 years old or something like that. It was summer, so she was wearing a dress and was sort of oblivious to our judgements, like she was still in that innocent kid phase when you haven’t formed the ability to be self-conscious or anxious in public. As I noticed her, her legs caught my attention as they were very hairy, the amount of which any properly conditioned grown female child would recognise as unacceptable in public, punishable with judgement and derision. I know, because I lived 24 years as a woman, if you recall the intro for episode 1! Anyway, the kid was hairy and wearing that dress, they stood out, and her grandma person was clearly ok with the situation, because there was nothing wrong with the situation,

But myself, alongside everyone else there waiting for their falafel, had already noticed and become quite unsettled, first by the sight of something entirely normal that we were raised to treat as abnormal, and second by the realisation of this thought and how utterly ridiculous it was that we collectively reacted to a normal child as if it was something insane. The second anecdote is funnily enough, also hair related. I was quite young when I noticed that among the puberty induced hair growth, my nipples had also acquired some hairs of their own. I thought it might be quite strange so asked my mother and she said I got them from my grandma who also had them.

She said it as if it was a very rare occurrence, that my grandma unfortunately passed down to me, almost as a curse. I genuinely thought it was a crappy genetic failure, almost, when it was actually beyond normal. Well, at least I’m a man now, so that genetic failure is now a genetic success by way of me being a sexy beast. If you like your women hairless, you’ll have your men hairless, and if you like your men tall, but the men like their women shorter than them, the kids will not be getting any taller…. Within the same population, those sex differences will be significant, but between different populations, those differences may well pale in comparison. For the last bit, let’s talk a bit about the latest sensationalist coverage of the Y chromosome getting smaller, and maybe even disappearing altogether… Stay tuned… ♪ tune

 

Sex Extinction

Having already covered other sex determination systems, such as ZW and X0, it seems odd to act as though there’s only one way to have sex or to be male.. Having further covered the possibilities around later stage sexual characteristic development with exogenous hormones, that seems further unlikely. Now if we also take into account the ever-expanding set of genetic engineering tools whereby whatever is undone can just as easily be redone, whether that’s removing a gene or setting a certain sexual development in a foetus, it is clear that we are not facing a dead end of human evolutionary potential, but rather a very, very open end.

If the Y chromosome is shrinking, it’s because it doesn’t need to be bigger. If sex determination is quite happy without a particular gene or chromosome, then that’s alright too. In the X0 system, the counterpart sex chromosome disappeared because that enabled sex determination by just toggling the X chromosome as a single or as a pair. Like wings, things can evolve, de-evolve, and re-evolve many times in history, and with increasing genetic and environmental biotechnological manipulations that we as humans are developing, it’s hard to imagine an irreversible future of any kind. I don’t have a Y chromosome after all, and here I am.

 

Outro

Thanks for listening, and remember… The knowledge we have is the result of what we choose to look for. Byeeee ♪ tune