Sex determined by chromosomes - exceptions?

[BonnyBo]

I’ve seen on twitter a rebuttal of sex being characterised by chromosomes and wondered if anyone scientifically literate could parse it for me?

It’s not the usual DSDs, I don’t think. I understand that with DSDs, they are disorders of development and are sex specific but this seems to be a family of XY individuals, some of whom have given birth and aren’t showing chimerism.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190741/

Does this, as a twitterer claimed, mean that sex isn’t contingent on chromosomes?

It's a discussion of an extremely rare anomoly, the family being described as "unique".

Fuck all to do with Malaga Airport fans or vulnerable autistic teen girls.

This is something that would need input from a remarkably niche forum of geneticists with hyperspecialisms.

I'd suggest that anyone who wants an understanding of this might explore that avenue if it's consonant with their comfort discussing the medical history of this unique family.

Where’s the dignity for people with DSDs in all of this, as our complex and often emotionally difficult medical conditions are trotted out and prodded by the ignorant, discussed with morbid fascination by people who have no idea about the reality of them?

https://mrkhvoice.com/index.php/2019/12/18/what-is-dignity/

The reality is that yes, when it comes to chromosomal and other rare disorders of sexual development, there are a tiny number of edge cases where the situation is unclear.

This does not have any relevance to men who claim they are women and should not be used by those men to claim that sex cannot be defined.

It's a novel DSD, and they are speculating that it is caused by a mutation in a gene on the X chromosome which, although as yet not identified or sequenced, may control an aspect of male development.

So their sex is determined by their chromosomes, but chromosomes are made of genes and sometimes genes are defective or missing.

And yes, TRAs using DSDs like this is disgusting.

Putting it in context of it being a new DSD makes sense, thank you!

It looks like an incredibly rare genetic difference being studied by very specialised scientists.
Very basically, chromosomes are made up of genes and a specific gene in a chromosome can mutate (using that word, which I know isn't perfect, as a kind of shorthand). That's why specific DSDs are linked to sex (often male rather than female) - because they'll be caused by a particular gene on a particular chromosome.
It is irrelevant to population-level sex differences between males and females.
Although I know it's really disrespectful of TRAs to use these very rare disorders to back up their faith, I think there's a (very small) positive, in that it does make me constantly reappraise my position - and conclude yet again that sex is binary and immutable.

I'm meant to be working so don't have time to read the whole paper just now. But I strongly suspect the key lies in the word 'predominantly'. Most of her ovarian (and other) tissue was XY, but some was X and a small amount was XX.

The idiots guide to sex is XX=Female and XY=Male. Delve a little deeper, and you find that it's the SRY gene that equals male.

To most involved in this area, that's where our knowledge ends. I'm sure there are cases that scientists could explain that my mind couldn't grasp.

There will also be cases in which scientists scratch their heads.

This doesn't mean that sex might not be binary. What it means is that our knowledge and understanding are not yet at a level where we can categorise the sex of every living being.

Sex by its very nature, has to binary, as the notion of sexual reproduction is binary. We have sexes because we sexually reproduce, and sexual reproduction requires two sexes.

The case posted shows, to me, that there are genes other than SRY that code a person's sex. Give it time, and humanity will have the knowledge of what each gene does. I sincerely hope I'm not around for the ethical dilemmas that will follow.

It’s the difference between ‘defined’ and ‘determined’. Sex is ‘defined’ by gamete type, where as genes ‘determine’ it. This is a better source to explain the difference.

https://www.theparadoxinstitute.com/read/defining-sex-vs-determining-sex

I feel the same way. I recently reread that Nature article, which (come to think of it) the OP will probably have tweeted at her any moment now.

https://www.nature.com/articles/518288a

The title and stand first are completely belied by the content, which describes how every element that makes up a human being (genes, chromosomes, cells, internal and external structures, hormones, developmental pathways) fits into the M/F binary. Someone with a complex DSD might have a mixture of elements, but they're all going to be M or F. None of them will be a hitherto undiscovered Quark. And it's not a spectrum 😡.

The author argues beautifully for children with complex DSDs to choose their own sex, by not operating on them as babies and letting them develop their gender identity (in the child development sense) as they grow. She only muddies the case by mentioning trans and gnc, and by hypothesising the possibility of raising a genderless child.

The final sentence "In other words, if you want to know whether someone is male or female, it may be best just to ask." often gets trotted out.

OP, if that happens to you, just point out that the advice was only intended to relate to complex DSDs.

Is this just the clownfish argument by another name?
That other species can change sex and breath underwater means that humans can change sex and breath underwater?

I completely agree that sex is binary in humans and I think all animals. Fungi on the other hand are a different story. If you say sex is obviously binary in a debate then someone will start describing sexual reproduction in fungi so you might want to google it now.

Oddly¹, they almost never bring up fungi. But if they do, it doesn't need a complex, pre-Googled counterargument because humans aren't mushrooms.

¹ Not odd at all, really, because that would require actual scientific knowledge that they generally don't have.

In summary they have discovered a family where there appears to be a gene or genes on the X chromosome which prevent 46,XY people from developing as male. The daughter’s Y chromosome came from her father and the disordered sexual development appeared to be in a pattern consistent with an X linked condition.

Simply put the SRY gene (sex determining region on Y) starts off a cascade that produces male development. Lots more genes are involved, hence if other genes are missing or altered then we don’t see normal development.

Interestingly males can lose Y chromosomes as they age. For example when we analyse bone marrow of older men with suspected leukaemia we often see loss of the Y chromosome in some cells. I assume this is not what they see here, but more a true mosaic.

That’s my understanding anyway, but my knowledge is from many years ago.

The genes involved in sex development haven’t all be found and understood as yet! This has nothing to do with more than two sexes though, just a family with a very unusual genetic mutation.

Ah yes the fungus argument. I have been on the receiving end of that. Also avocados apparently have some weird thing going on with their (a?)sexual characteristics. I can't remember quite what the relevance was meant to be but I didn't feel that my lack of deep knowledge about fungus was holding me back. The discussion being one about humans; and humans, as far as I am aware, being neither fungus nor avocados 😂

That's because fungi don't sexually reproduce. Sex only applies to those that reproduce sexually.

This sounds like the very rare mosaic case?

Whatever it is, it has nothing to do with the concept of an abstract, inner gender identity not supposed to be at all based on living in a sexed body.

Fungi can reproduce asexually and sexually. Sexual reproduction doesn’t necessarily mean 2 different and distinct sexes. It means 2 individuals of that species can produce offspring that share half of each of their genetic material. I think there are slugs that are always hermaphrodites and some fungi that have dozens of different sexes. Because it’s more efficient. Humans can only theoretically reproduce with 50% of other fertile humans (yes I know menopause messes with the numbers but the point stands). If you’re a fungal spore in a species with 100 different sexes you could join up with 99% of other members of your species you might encounter. Not that fungi’s (or slugs’) reproductive processes are relevant to humans.

Yes you are right. Its been a long week!

I would have been better stating that the sex binary does not apply to (most?) fungi because fungi are isogamous, meaning gametes are indistinguishable from each other. Organisms that are isogamous have mating types, not sexes.

I'd assume most organisms that now have sexes were once isogamous.

I only recently came to understand that the Differences referred to in the term DSDs are not the physical differences that result from having a DSD, but the different developmental pathways that can be travelled to arrive at the (male or female) endpoint. For example, a woman with CAIS have developed along a different genetic and endocrine pathway from the female norm, but arrive at the female phenotype (not I'm using that word quite correctly, "female form" might be better). I think this is why it's a much better term than "intersex" which makes it sound like a woman with a DSD is less of a woman that one without - further along the spectrum towards male or something equally othering. And the case described by OP is a variation in development, still arriving at one (of two) sexes in the end.
I've edited this many times and I'm still disatisfied with my lack of clarity, but I'll post as is!

And the case described by OP is a variation in development

VSD or variations in sexual development is another term in use and many prefer it to DSD because it's less prone to misunderstanding.

Or on the wrong chromosome.

But your whole body, including your sexual phenotype, is controlled by genes, located on chromosomes.

The mother in the OP has primary Chimerism with the XX part of her specifically being in the ovarian tissue.

Chimerism of this sort is obvs rare (hence the language in the study) but other types of chimerism are less rare - my DD has acquired chimerism, her blood samples and saliva samples are XY and her hair samples are XX.

This is because she had a bone marrow transplant from an anonymous donor who is a middle
aged, German, man.

My daughter’s XY chromosomes no not make her male any more than they make her German or 40 something. She’s just a 12 year old British girl with acquired chimerism.

The mother in the OP study has the extraordinary good fortune of having XX chromosomes in the exact part of the body that matters for human reproduction (and also for creating the hormones that would’ve made her grow up unambiguously female-looking)

My daughter might struggle to conceive in future due to all the late term effects of chemo, but the XY chromosomes won’t matter because she has XX gonads (and she has one cryopreserved ovary that was removed prior to chemo awaiting autotransplant if she ever decides she wants to go ahead with that).

https://www.sciencedirect.com/science/article/pii/S1875176822000579

edited to add: all the other family members with the gene mutation in the OP were infertile/had ambiguous genitalia - it’s that tiny bit of xx/lack of y in the ovary that made the mother uniquely fertile/ unambiguously female in appearance and function.

Actually from a quick skim I think her ovaries were found to be 94% XY and 6% X so there's some very complicated mosaisicm going in in this woman and her daughter (and extended family) so I THINK what they're postulating is mutations on the X chromosome as well which means that they were sent down the female path, in the womb, despite the resence of the Y chromosome.

But still, just a genetic DSD with particular mutations in the chromosomes that have all kind of downstream effects that made these people develop differently from the normal male/female patterns, like all DSD - Disorder of Sexual Development. But sex still determined by the genes on those chromosomes with mutations, as always.