Sex determined by chromosomes - exceptions?

I doubt the article about determining sex will be quoted by TRAs. It says

determining sex does not mean “observing” or “identifying sex” in the colloquial sense. Instead, determining sex is a technical term for the process by which genes trigger and regulate differentiation down the male or female path in the womb. This determines the structures that can support the production and release of either gamete type, and thus, the individual’s sex.

and

an individual’s sex is defined with respect to gamete type and identified by the structures that support the production and release of either gamete.
Thus, while there are various mechanisms that control male and female development, there are still only two endpoints: male and female.

As the saying goes..'science - it's like magic, but real.'

We have had this paper posted here on MN previously as a 'gotcha'. However, just as AIstolemylunch says, this paper doesn't do what most people who use it as a 'gotcha' think it says. I don't believe this woman or her mother produced both sperm and ova. Only one. Their bodies are formed to produce one gamete whether successfully or not.

The supposed 'gotcha' is all about Chromosomes and those only. But many of the posters on MN are fully aware that Chromosomes are just one aspect of the categorisation of human sex.

That's funny. Just read the thread and saw all the scientists using the word fascinating. Now I have a mental picture of peering at a tra like a specimen whilst murmuring the word fascinating to myself.

Fascinating. There is brief mention of mosaicism , not all cells in the body will share the same genetic material I understand.
Was there mention of any consanguinity?

Sorry, will read whole thread to check for experts.

The more I read, the more I realise what miracles we are.

@AIstolemylunch thank you for all your explanations

Humanity used to aspire to be ‘only a little less than the angels’. Now some of them aspire to be mushrooms. Oh well…..🍤🧌

Not even hypothetically possible. There are millions of possible arrangements of the atoms within the molecule that we call DNA and millions of possible combinations of genes on chromosomes and lots of different arrangements of chromosomes in cells with movement of bits of DNA between them, but there are only 2 possible outcomes of sexual differentiation in mammals - set up for having large gametes/eggs - female, or small gametes/sperm - male, whether or not a particular individual actually does have/produce them.

There is no third sex possible from all that diversity and nobody is intersex, even if they have tissues with different chromosomal arrangement (mosaicism). There is no other possibility than egg or sperm resulting from meiosis (the specialised type of cell division that create sperm or eggs). There's no Spegg or Esperm and hence there's only ever 2 sexes possible. Sex is the outcome of all that genetics. It doesn't mean that someone with a Y chromosome can't end up female, or vice versa, the other way round from 'the norm'. But still, binary, and only 2 possible oucomes. Which is pretty remarkable really given all the background genetic diversity and shows how sexual reproduction has been honed by evolution over millions of years.

Hypothetically speaking, if there were some arrangement of chromosomes that made a "3rd sex" possible, it still wouldn't change the fact that Málaga airport personnel all have the standard male chromosome arrangements.

Not that I'm saying people shouldn't try to understand it btw, I know eff all about astrophysics but I still like reading about it, just that it's hard because the people who do understand it, at the molecular level, haven't traditionally been very good at explaining it in terms that people that haven't studied it at depth can digest it. I do think that is changing now though, which might be one positive thing to come out of the trans delusion, and there are people on twitter etc doing sterling work explaining the genetics of sex determination such as Zachary Elliot. Plus these threads of course where I have learnt as much about feminism over the years as I learnt about DNA at university.

Fascinating case though now I've read through it all. Nothing revolutionary here though, just confirms that there are many, many different genes involved in the pathway of sexual differentiation in humans/mammals and that you can get very unexpected outcomes from 'the norm' with unusual mutations, which may or may not be on the sex chromosomes. And that's what's happened to this family, unusual mutation(s) has been propagated through it and given odd results. Still only 2 possible sexes though and still the body you end up with is determined by the particular gene variants you have encoded by the DNA that makes up the chromosomes in your cells, and the hugely complex interplay between them all.

This is the trouble really, it's massively, massively complex and the interplay between 100s of thousands of genes encoded on the 46 chromosomes (ish, some can get added or lost) that everyone has in every cell of their body, can lead to millions of slightly different outcomes. The underlying mechanism of sex determination remains the same though and you end up either male or female, whether you look like that from the outside or not and whether you're fertile or not. I spent 4 years studying molecular biology and genetics at university so can get the gist of this paper, as can other people on these threads with scientific training. But people on twitter who didn't even pass Biology GCSE (that barely touches on inheritance of genes) are now trying to understand how it works to prop up ideological causes without doing the work - which in this country is science GCSEs, A levels and Science/Medicine university degrees.

Fascinating. Thank you.

Yeah but elsewhere in the paper they don't even mention the <1% 46 XX and suggest the 5.9% 45 X may be artifactual so they're not saying that it's the <1% 46 XX cells that have made this woman uniquely fertile (though her XY daughter is not), and such a tiny proportion of cells even if real wouldnt be enough, they're saying, or speculating, that there's some other mutations in genes going on in the 93% cells with XY chromosomes on the X chromosome which have 'sex reversed' her ie sent her down the female development path to develop functional ovaries and a uterus instead of testicles, as would normally happen if you had predominantly XY cells in the tissues that turn into gonads - testicles or ovaries.

Here’s the bit where it says the ovarian tissue has a tiny bit of XX.

Genetic mosaicism is when you have different chromosome combinations in different cells in different tissues in different parts of the body, as oposed to all your cells in your whole body being having the same chromosome tally (apart from the sex cells, sperm and eggs). It causes all sorts of odd and unexpected results.

For example, my friend was initially told that her baby had Down Syndrome when pregnant after initial testing because they picked up male cells with trisomy 21 - an extra copy of chromosome 21, which is the cause of downs syndrome. However, her child does not have Downs Syndrome because it was a case of moascicism and that happened after the cell lines split shortly after conception so the cell that went on to form the placenta had the extra copy but the cell that went on to form the embryo and baby did not.

All genes on chromosomes and the myriad possibilities for things to happen differently from how they usually happen. And even mutations are 'normal' because that is the basis for evolution as some will have been beneficial/positive over the years that humans have evolved.

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.

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.

Or on the wrong chromosome.

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

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.

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!

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.

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.

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.

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

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 😂