Chromosomal control: How X and Y chromosomes control genetic sex determination
Image Courtesy of Hannah Davis (CC BY-SA 4.0)
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In the rare event that I am invited to parties, my party trick is that I can sex a fruit fly from 2 metres away. Of course I then have to explain that I can do this for exactly one species of fruit fly - Drosophila melanogaster - the subject of my PhD, and that ‘sexing a fly’ means determining its sex (is it female or male) and nothing to do with having intercourse with it. Unsurprisingly after displaying this skill, it is an even rarer event that the hosts invite me back to future parties.
My social life aside, sex determination is something that happens every second of every day around the world. If a species has two sexes, and most animal species do, then every time a sperm and egg cell fuse, that resulting offspring has a decision to make: should I develop into a male or a female? Should my stem cells divide and specialise into testis cells or ovary cells?
For some animals, it goes even further than what’s in their gonads or between their legs. Think about the difference between a peacock and a peahen, or a male lion and a lioness. This is what we call ‘sexual dimorphism’, where females and males look strikingly different from one another in size, shape and colour. Sexual dimorphism is how I’m able to tell a male fruit fly from a female fruit fly - though they’re only about 1mm long, females are twice the size of males and have a white belly, whereas males have a black bottom.
There’s obviously a lot riding on the decision, so how does a fertilised egg cell decide whether it’s male or female? Well for humans, you guessed it: it’s down to the X and Y chromosomes. Got two X chromosomes? You’re genetically female. Got one X and one Y chromosome? You’re genetically male. But why is that the case?
You may have heard that “all embryos start off female, and if a Y chromosome is present it becomes male, if a Y chromosome isn’t present, it remains female”. Usually this comes up whenever someone questions why men have nipples. And it’s kinda true, but as is often the case, the biology is a bit more complicated than that.
For the first few weeks of development, human embryos are neither male nor female, or you could say they are both male and female, depending on how you want to look at it. All human embryos grow a Mullerian duct that can develop into the cervix, uterus and fallopian tubes, but they also grow a Wollfian duct that can develop into the seminal vesicles, epididymis and vas deferens. That is to say they have both female bits and male bits.
Then around week 5 or 6, the influence of the X and Y chromosomes kicks in. The Y chromosome contains a very important gene called the sex-determining region Y, or SRY gene for short, that sets the embryo on the road to biological maleness. Fun fact - Robin Lovell-Badge, who we heard from in our last episode talking about the ethics of genome editing was one of the co-discoverers of this gene, and it was only discovered in 1990! Which to me seems like an incredibly recent discovery for such an important gene.
The SRY gene makes a protein that activates a whole bunch of male-specific transcription factors, which basically run around the rest of the genome shouting things like “Turn those non-specific gonads into testes! Ramp up testosterone production! Get rid of that Mullerian duct so we don’t grow a uterus!”
Of course, that can only happen if the SRY gene is present. Without the SRY gene barking orders to become male, the embryo develops as female, although this is far from the passive act that the ‘all embryos are default female’ would have you believe. Becoming female is just as active and complicated a process as becoming male, as the embryo starts ramping up female transcription factors, getting rid of the Wollfian duct and turning the gonads into ovaries.
This also explains some of the rare conditions we see known collectively as differences of sex development. Just because you’ve got a Y chromosome doesn’t automatically mean that you’ll develop into a typical biological male- if your SRY gene isn’t working properly it can lead to someone who is genetically male developing typically female reproductive organs. And sometimes the SRY gene will hop onto the X chromosome instead of the Y chromosome - in this case it would mean that someone who appeared to be genetically female with two X chromosomes would still head down the male reproductive pathway.
Overall though, we say that humans as a species have chromosomal sex determination. Just like all the other mammals, it’s our X and Y chromosomes that determine whether we become biologically female or male. Other groups of animals also use sex chromosomes, but they have a different system to our XX and XY. Birds, as well as some species of fish, crustaceans and insects for example use the ZW system where if you’ve got two Z chromosomes, you’re male, but if you’re ZW you’re female.
However, chromosomes are far from the only system of sex determination there is. And once a species has settled on a form of sex determination, it’s not necessarily guaranteed that it’s going to stick with it.
Genetic Mechanisms of Sex Determination | Learn Science at Scitable
Temperature-dependent sex determination - Wikipedia
Temperature-Dependent Sex Determination in Reptiles | The Embryo Project Encyclopedia
Environmental Sex Determination - Developmental Biology - NCBI Bookshelf
