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And finally, it wouldn’t be a genetics podcast about the disappearance of males if we didn’t address the perennial headline: that the Y chromosome is disappearing, and men will go extinct.
I swear I see articles about the disappearing Y chromosome popping up in the news every single year, and each one follows the same sort of logic. The Y chromosome used to be the same size as the X chromosome 166 million years ago. It’s since shrunk to just a third of the size with only about 55 genes compared to the X chromosome’s 900 genes. If we extrapolate from the rate it is shrinking, it’ll be completely gone in less than 5 million years. Oh no! Men will go extinct!
As well as questioning whether this is a) true and b) something to worry about, it’s also interesting to ask why the Y might be disappearing. Most chromosomes come in pairs, and each member of the pair contains pretty much the same information, give or take a few mutations or variations. To make an egg or sperm cell, a germ cell has to halve the number of chromosomes it has; in humans a normal cell has 46 chromosomes whereas an egg or sperm cell has only 23. We call this meiosis. But the cell doesn’t just pick one chromosome out of each pair and throw away the other. First it goes through a process called genetic recombination where enzymes cut the DNA up and swap pieces of DNA between the pair of chromosomes, creating two new chromosomes with completely new combinations of genes.
This process is super important at weeding out harmful mutations. Imagine if you had a hand of cards with some really good cards and some really bad cards, overall it would average out and maybe you would win your game with it, maybe it wouldn’t. But if you shuffled with the deck and now you had a hand of all really bad cards, you’d definitely lose your card game and that whole hand would be eliminated. Genetic recombination allows harmful mutations to be exposed to the game of natural selection, and they can be weeded out when they’re so harmful that the individual can’t survive or reproduce.
The Y chromosome, however, can’t go through this process. The Y chromosome doesn’t contain the same genes as the X chromosome with a few mutations here and there, it contains completely different genes. When two Xs get together in someone with XX chromosomes, they can recombine and get rid of the bad genes. But because you pretty much never get YY chromosome pairings, the poor old Y never gets the chance to dump all its bad mutations. It just accumulates and accumulates mutations until the genes are rendered completely useless and eventually disappear entirely.
And it’s not just that the Y can’t get rid of mutations, it also accumulates them more quickly too. Whereas females are born with all the eggs they can produce, males continuously produce sperm cells throughout their life, meaning cells in the testes are continuously dividing and dividing, each time opening up the possibility of generating a new mutation. Since the Y chromosome can only be inherited through sperm, they’re much more likely to be subject to this higher mutation rate.
With the double whammy of collecting more mutations and not being able to get rid of them, it’s not ridiculous to suggest that the Y chromosome might eventually become so mutation-addled that it disappears entirely. In fact, it’s already happened…in the Amami spiny rat. These rats just…don’t have a Y chromosome. They used to, 2 million years ago, but now it’s gone. Both females and males have just one X chromosome. But even without sex chromosomes, there are still males and females. So, how?
This was a conundrum that Asato Kuroiwa and her team at Hokkaido University in Japan set out to solve. The first step was sequencing the genome of several males and females and looking for genes that were only present in males, basically looking for genes that might have replaced the function of the SRY gene that had been lost as the Y chromosome disappeared. But they couldn’t find one.
Kuroiwa looked even closer at the genomes; there must be a difference somewhere. Then she spotted it. The male rats had a duplicated region right next to a gene called SOX9 on one copy of their chromosome 3, but only one of the pair of chromosomes had this duplication. And what is this SOX9 gene? Well it only happens to be one of the key genes that the SRY region activates when it's barking its orders to masculinise the embryo, telling the embryo to grow testes.
The duplicated region next to the SOX9 gene boosts the activity of SOX9, which means it has the exact same effect that the SRY gene has in triggering testes development. Two different parts of the genome, same result. If you’re a spiny rat and you inherit a copy of chromosome 3 with the duplication, you’re a male. If neither of your chromosome 3s have the duplication, you’re a female. Chromosome 3 has essentially become the new X and Y chromosomes.
We can now piece together the clues and figure out how the Amami spiny rat lost its Y chromosome. 2 million years ago, all male rats would have had a Y chromosome, then at some point this duplication occurred and some rats would have had both a Y chromosome with the SRY gene and a copy of chromosome 3 with the overactive SOX9 gene. Two genes doing the same job. And once you’ve got redundancy like that, it doesn’t matter if the Y chromosome dwindles away and disappears completely. The SRY gene can gradually mutate itself into oblivion safe in the knowledge that the overactive SOX9 gene will step up to the reins.
So that’s how one species of rat is able to lose the Y chromosome without any problems. But what about humans?
Well the Y chromosome isn’t as helpless to mutations as I’ve perhaps made it out to be. Although it can’t undergo recombination with the X chromosome (except at the very tips), it can so-to-speak recombine with itself or go through what we call gene conversion. The Y chromosome has an unusually high number of palindromes, DNA sequences that read the same forwards as they do backwards, like the words ‘civic’, or ‘refer’ or ‘solos’, or even phrases like ‘Never odd or even’.
Imagine a mutation happened and the phrase said ‘Never add or even’. Well if you knew that it was supposed to be a palindrome, you could use the back half to predict what the first half should say and correct the mistake. And not only does the Y chromosome have lots of these palindromes, it also just has a lot of duplications that all result in there being multiple copies of the important genes. Between them, these act as a back-up. Sure, the Y chromosome might be particularly prone to mistakes and errors, but it can just use the back-up copies of the genes to correct those mistakes as and when they occur.
So yes, the Y chromosome is slowly shrinking, but it’s doing its best to keep itself present and correct. And even if the Y chromosome does disappear, either the SRY gene could hop onto a different chromosome, making that chromosome the ‘new Y chromosome’, or, as we’ve seen with the rats, another region of the genome entirely could take over the role of the SRY gene, so the species can continue to have males without a Y chromosome. So don’t worry men, you’ll be sticking around for at least a few more millennia yet.
