Why is Y (the chromosome)
I was listening to Sabrina Carpenter, as you do, and a some of the lyrics caught my brain. In Juno she sings
Whole package, babe, I like the way you fit
God bless your dad’s genetics
and then I read an article which isn’t worth referencing here, but it said (paraphrased)
You have 23 chromosomes, 22 pairs plus X and Y which aren’t a pair, but act like it in some specific circumstances
which jumped out to me because of the common viewpoint that “the Y chromosome contains all the ‘male’ genes”, which is just plain wrong.
A quick note on terminology
In this post I’m using male and female as they’re used in biology - that is to describe the external genitalia as seen at birth.
So the Y chromosome doesn’t contain “male genes”?
To understand this we need to jump back a bit into basic genetics so we can step forward.
How you get your DNA
Humans have 23 chromosome pairs, 22 autosomes and either a pair of Xs or an X and a Y. In school biology we learn that you get one of each pair from each of your parents and when you have children they get one of these pairs. Then if you stay on for the next class you’ll learn that in meiosis the DNA of each chromosome pair gets mixed around, which means the chromosome passed on to children contains a blend of both of your parents. Except, of course, for X and Y. If you have two X chromosomes they’ll swap genes, but if you have an X and a Y they won’t because they’re not a “real pair”.
Except that’s not quite true.
The Y chromosome has a small section known as the pseudoautosomal section. This contains genes common with the X chromosome and is subject to the normal gene swapping.
Ah! Then the rest of the Y contains all the “male genes”!
Not so fast!
Lets look the size of the chromosomes. Chromosome length is measures in base pairs. If you recall DNA is made of a sequence of four nucleotides, cytosine, guanine, adenine, and thymine. Each nucleotide is in a pair in the DNA strand, and base pairs is a count of these. Normally you’ll see mega base pairs, or Mbp, as all chromosomes have millions of base pairs.
You can also count the number of genes, but we don’t know all the genes on every chromosome and some genes use more base pairs than others.
The human X chromosome contains 154Mbp and has 804 known genes
The human Y chromosome is significantly shorter than the X chromosome, this image of a karyotype shows the difference in length! The Y chromosome is 64.5Mbp long and contains 63 known genes. 29 of these genes are in the pseudoautosomal region, leaving 34 known genes on the Y chromosome that are only present in people with a Y chromosome.
Of those 34 genes, 24 are also present elsewhere in the genome, normally on the X. Nine of these genes are associated with spermatogenesis and not important in embryo development, and the last one is the key to the Y chromosome’s normal action.
Only one gene? So what does it do?
The gene is known as either SRY, for Sex-determining Region of the Y chromosome, or TDF for Testes Determining Factor. Which gives a good clue about what it does.
Around six weeks after conception this gene activates and causes an up-regulation in the production of the SOX-9 transcription factor, which then transcribes other previously inactive genes which increase SOX-9 production forming a positive feedback loop, and the high levels of SOX-9 causes the non-determined gonads to become testes and production of anti-Müllerian hormone (AMH). The testes then release testosterone, which causes up-regulation of other genes which cause the rest of the male external genitalia to form, formation of the prostate, and the anti-Müllerian hormone inhibits the development of the female genitalia.
All of that is a long way of saying the gene on the Y chromosome just activates genes elsewhere, all the genes related to the development of reproductive organs are elsewhere in the human genome.
So the SRY gene doesn’t recombine, so has to be on the Y chromosome right?
Unfortunately nothing about biology is that clean cut. Most of the time the non-pseudoautosomal regions of the Y chromosome is exempt from DNA recombination. Most of the time.
However sometimes this does happen and SRY gets swapped on to the X chromosome, leading to “XX male syndrome” if the X chromosome is inherited, or Swyer syndrome if the SRY-less Y is inherited.
It’s estimated that around one in every 20,000 births with a male phenotype has two X chromosomes, and in 90% of those they have the SRY gene active. However it’s likely underreported as most people with XX male syndrome have no medical issues except infertility (remember those spermatogenesis genes on the Y chromosome?), so if they did not seek medical help for infertility, a karyotype was not done, or through some other mechanism they retained fertility, they would never be picked up.
The remaining 10% are SRY negative and tend to have more problems, as the lack of the SRY gene causes some reproductive system development to fail or only partially complete. However this is not always the case, there’s a documented case of an SRY-negative man with normal masculinisation who was only discovered when seeking help for infertility.
Swyer syndrome is much less common, less than one in every 100,000 births with a female phenotype. This is due to the X chromosome’s behaviour being even more complicated.
A short diversion in to the mystery of the X chromosome.
If you remember basic biology, the intensity of gene expression is due to the number of copies you have. Each chromosome is a pair, and if the gene is on both you get a stronger expression than if only one has the gene. For example I only have one functional copy of the gene for the CYP2D6 enzyme, a liver enzyme that metabolises many medications. This means my response to those medications is different to someone with two functioning copies.
However around half the human population has only one X chromosome, so does that mean they only get half the gene expression of those with two?
Well no. It turns out the body has a solution - X chromosome inactivation! During foetal development one of the X chromosomes is picked and deactivated, so we all only have one functioning X chromosome. However early in development it requires two functioning X chromosomes to develop the undifferentiated gonads in to ovaries.
Because of this with Swyer syndrome you get a female phenotype without fully functional ovaries, so generally hormone replacement is required to go through puberty and people with Swyer syndrome are infertile, but there are very few known cases of Swyer syndrome.
And all this means?
The Y chromosome contains very few genes, and only one of them is involved in determining which genitals someone is born with. At least one in every 20,000 people born with a male phenotype has an XX karyotype. 90% of those would show an SRY genotype, but 10% would not. Which goes to show that biology is complicated, messy, and doesn’t care to be put in to neat little boxes.
There’s a lot more to this. I’ve entirely skipped over intersex conditions - what happens if SRY activates but AMH doesn’t? If testosterone is what causes the genes responsible for external genitalia to activate, what happens if the testosterone receptors don’t work right? How about SOX-9 not activating when SRY does? There’s a lot of moving parts to this puzzle and they can all change in ways we don’t expect.
References
Since this isn’t academic research, you can find all of this on Wikipedia:
https://en.wikipedia.org/wiki/Y_chromosome
https://en.wikipedia.org/wiki/X_chromosome
https://en.wikipedia.org/wiki/XX_male_syndrome
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