by Katherine J. Wu
figures by Daniel Utter

Let’s talk about sex.

Seriously. Not intercourse, though – more about how genetic sex is programmed during development. Sexual identity has been in the news often lately, and unsurprisingly so: the past few years have yielded sweeping reforms in civil rights, spurring new conflicts surrounding everything from age-old battles in gender equality to legislation enforcing anti-transgender bathrooms. It’s a complicated subject, to say the least. With regards to science, we don’t know enough about gender identity to draw any conclusions about its biological underpinnings, and certainly not about what is “right” or “wrong.” We are only now beginning to fully understand how mammalian sexual identity has evolved, and its dependence on the sex determination systems that allow biological development of sexual characteristics in different organisms.

The sex determination we’ll discuss today is (unfortunately?) not the dogged resolve to copulate. Most multicellular organisms, humans included, use sexual reproduction to reproduce. Compared to asexual reproduction, in which cells can simply create carbon copies of themselves, sexual reproduction allows for the introduction of genetic diversity into a population. In most sexually reproducing organisms, there are two sexes – but the ways in which these sexes are determined and the ways in which they manifest vary greatly. What are the ways in which sexual characteristics are encoded? Why are there so many systems for one seemingly common result?


We were all taught the classic recipe in grade school: an X chromosome from mom and an X chromosome from dad will yield a genetic female, while an X chromosome from mom and a Y chromosome from dad will yield a genetic male. The XY sex determination system (Figure 1A) is certainly what’s most familiar to us, and it’s used in most other mammals, as well as a few select insects and plants. Briefly, human cells all carry chromosomes, which carry our genes. When egg meets sperm, each parent contributes 22 non-sex chromosomes and one sex chromosome – always an X from the mother, and either an X or Y from the father. Thus, the contribution from the father determines the sex of the baby[1].

Following fertilization, a fetus begins to develop. At first, its sexual organs manifest as a genderless gonad, or sex gland – basically a small, thick ridge of tissue near what will become the abdomen. The “default” sex (i.e., without any other further input) is actually female – however, the presence of a gene called SRY on the Y chromosome initiates the release of testosterone and the formation of male sex organs. SRY is a transcription factor – a genetic element that can turn on the expression of other genes. In this way, SRY is like the master switch to turn on the suite of “male” genes in a developing organism. Thus, the presence of a single Y chromosome switches on the male pathway, something that is clear in what’s called Klinefelter Syndrome, in which individuals carry two X chromosomes and one Y chromosome, but develop testes and appear generally “male.” Without the presence of a Y chromosome, and thus without SRY, cells secrete estrogen instead of testosterone, and an XX baby develops female sexual organs.

It seems like a pretty clear system – but it wouldn’t be biology without exceptions and extra rules muddying the waters. When it comes to sex chromosomes, X’s and Y’s are not the only ingredients available. Many other sex determination systems exist, and the concept of “male” vs. “female” isn’t quite as simple as humans once thought.

The Birds and the Bees (and Some Other Things Too)

Unsurprisingly, with the immense variation observed in our natural world, more than one sex determination system exists. Ours, XY, is not even predominant. A few key examples tend to predominate: the ZW system in birds, XO in insects, haplodiploidy, and environmental sex determination systems.

The ZW system (Figure 1B) exists in birds and some reptiles, and operates opposite of XY: females get the mixed set of sex chromosomes (ZW), while males are ZZ. Thus, unlike in humans, the mother’s contribution determines the sex of the progeny[2]. Just as the mammalian Y chromosome carries the male-determining SRY, the avian W chromosome carries similar master switches FET1 and ASW, which are necessary for female development of the offspring, which will otherwise “default” to male.

In the XO sex determination system (Figure 1C), which is found in several insects, females are still XX, but instead of carrying a Y chromosome, males simply carry a single X – the “O” in “XO” indicates the absence of a second sex chromosome. Each sperm carries either an X chromosome or no sex chromosome at all – but once again, as in XY, the father’s contribution determines the sex of the offspring.

Figure 1: Five (of many) sex determination systems. A. XY system In humans, females are XX and males are XY. B. ZW system In birds, females are ZW and males are ZZ. C. XO system In insects, females have two sex chromosomes, but males have only one sex chromosome (while retaining two copies of all non-sex chromosomes). D. Haplodiploidy In honeybees, females again have two sex chromosomes while males have one, but in this case, males have only one copy of every chromosome. E. Thermal regulation In some reptiles, the temperature of the surrounding environment determines the sex of the offspring.
Figure 1: Five (of many) sex determination systems. A. XY system In humans, females are XX and males are XY. B. ZW system In birds, females are ZW and males are ZZ. C. XO system In insects, females have two sex chromosomes, but males have only one sex chromosome (while retaining two copies of all non-sex chromosomes). D. Haplodiploidy In honeybees, females again have two sex chromosomes while males have one, but in this case, males have only one copy of every chromosome. E. Thermal regulation In some reptiles, the temperature of the surrounding environment determines the sex of the offspring.

After this, things start to get a little weirder. Honeybees utilize the system of haplodiploidy (Figure 1D), in which unfertilized eggs (which carry only one set of chromosomes and are thus haploid) develop into males and fertilized eggs (which carry two sets of chromosomes and are thus diploid) develop into females. Importantly, this is distinct from the XO system, where progeny inherit two copies of all non-sex chromosomes, regardless of sex; in haplodiploidy, males inherit only one copy of all chromosomes, sex and non-sex (Figure 2A).

Honeybee colonies typically center around a single fertile queen, serviced by an army of male drones and female workers. The queen lays a vast number of eggs, some of which are fertilized and develop into females. Those that remain unfertilized develop into males. Thus, in this system, males have no fathers and can produce no sons. Furthermore, if a queen chooses only one drone to mate with, all her daughters will share 75% of their genes with each other (unlike in humans, where siblings share 50% of their genes) because they each inherit the full set of their father’s genes, rather than just half. While this system seems vastly overcomplicated, it is believed to have been evolved to promote the social nature of honeybees: as a female worker, it turns out to be more evolutionarily advantageous to protect your sisters (with whom you share 75% of your genes) than it is to produce daughters of your own (with whom you share only 50% of your genes) (Figure 2B). Thus, the community structure revolves around the queen. This is an interesting case where the genetically determined sex of individuals shapes their role within the larger community.

Figure 2: Sex determination in honeybees. A. Honeybee haplodiploidy Fertilized eggs inherit a set of chromosomes from their mother and a set of chromosomes from their father, and are always female. Unfertilized eggs receive half their mother’s chromosomes and are always male; males have no fathers. B. Sisters before mothers Each daughter receives all her father’s chromosomes and half her mother’s chromosomes. Thus, sisters are more related to one another (75%) than they each are to their mothers (50%).
Figure 2: Sex determination in honeybees. A. Honeybee haplodiploidy Fertilized eggs inherit a set of chromosomes from their mother and a set of chromosomes from their father, and are always female. Unfertilized eggs receive half their mother’s chromosomes and are always male; males have no fathers. B. Sisters before mothers Each daughter receives all her father’s chromosomes and half her mother’s chromosomes. Thus, sisters are more related to one another (75%) than they each are to their mothers (50%).

Finally, there exist systems in which sex determination isn’t dependent on chromosomes at all. In alligators and some turtles, the temperature at which the egg is incubated during a sensitive period determines sex: lower temperatures produce females, higher temperatures produce males (the phenomenon of “cool chicks” and “hot dudes”) (Figure 1E). However, this rule does not hold true in every species – sometimes the opposite rule is in effect, or temperatures at either extreme produce one sex, while an intermediate temperature produces the other. Some snails and fish are actually able to reverse sex midway through life, depending on environmental conditions, in a process called sex reversal. Thus, genetic sex is a far more fluid process than one might assume.

The fact that genetic sex can be directed by the flip of a single switch may be surprising. Sex is complex – but then again, there are a lot of other factors at play and, clearly, environment can have a big influence on how sex expresses itself. Additionally, there are many documented cases of humans with a genetic sex that appears “contrary” to their physical appearance. For instance, we know of genetically XX persons who have developed testes and external characteristics of men, and genetic XYs who develop as females. An example of the latter case occurs in Swyer Syndrome, often when there is a mutation in the SRY gene. While the rest of the Y chromosome is left intact, a malfunctioning SRY means that the male “switch” is never flipped, and the indifferent gonads do not get signals to become testes. Swyer Syndrome patients develop externally as female, but do not have ovaries and are infertile.

Finally, inheriting extra or too few chromosomes can considerably alter how sex manifests. Klinefelter is a common example, as well as Turner Syndrome (XO), where a sex chromosome is missing, often leading to developmental defects. Thus, all it takes is a small genetic change to turn SRY, or any of the genes it targets, on (or off).

(De)Generation Y

We know very little about how sexual reproduction and sex determination systems evolved – the theories are, of course, difficult to test. But another important question is, once sexual reproduction did evolve, why did it branch off in so many ways? And, perhaps more pressingly, is it still evolving in ways that could affect us?

The answers are still mostly elusive. There has been some indication that the XY and ZW systems are still connected to a common ancestor, even though they manifested a complete reversal somewhere down the line. One small but interesting line of evidence lies in the platypus, which encodes a whopping 10 sex chromosomes (males are XYXYXYXYXY instead of XY – apparently, size matters to platypodes) that bear great similarity to the bird Z chromosome, but technically operate under XY sex determination rules. Interestingly, though, the platypus Y lacks SRY. Thus, platypodes may end up being the “missing link” between these two systems.

Furthermore, analysis of the Y chromosome has indicated that it probably evolved from the X chromosome, acquiring some literal “man power” along the way. This “differentiation” event solidly distinguished the roles of the two chromosomes, and they began to evolve away from each other over time. In its current state, the Y chromosome is much smaller than the X chromosome, and appears to have lost the unnecessary X genes[3] along the way. Y continues to exhibit signs of this (very, very slow) Y degeneration as time progresses. In fact, the XO sex determination system is believed to have arisen from complete loss of an effective Y chromosome that was ultimately discarded for its relative inefficiency. There’s no need for panic, though, XY readers – your Y chromosome is unlikely to be going anywhere anytime soon, or maybe ever. Complete loss of Y is a pretty extreme event, and much evidence has accumulated that the loss of genes from the Y chromosome will ultimately plateau.

Plenty of Fish (Sexes) in the Sea

Sex determination in humans is fairly well established. But our system is neither the dominant mode of sex determination, nor a more “correct” version of it. A final lesson comes in with the fairly new discovery of polygenic sex determination (PSD), wherein multiple genes and chromosomes contribute to the ultimate sex of offspring. This can take the form of XY and ZW systems being combined into the same species, for instance. Domesticated cantaloupes (yes, the fruit) produce four sexes, and there is some evidence that several species of fish rely on PSD). This system is still poorly understood, but importantly, the added variation on each side of the equation indicates that even genetic sex is often not a binary trait. Perhaps it’s time to rethink our preconceptions about the divides between “male” and “female.”

Katherine Wu is a third-year graduate student in the Biological and Biomedical Sciences Program at Harvard University and is, as far as she knows, XX and not XY.

[1] … Making King Henry VIII’s decision to behead a bunch of his wives for failing to bear him sons a little misinformed. Oops. Not that he could have known at the time – no one did. So, moot point.

[2] If only Anne Boleyn had been a pigeon.

[3] For the most part, the genes on the X chromosome only need to be present in one copy, hence the favoring of “loss” of duplicates on the Y chromosome. In fact, in women, who have two X chromosomes, one X chromosome in each cell is packaged into a dormant state called a Barr body. This actually happens at random in each cell (that is, it’s not always the X from mom or the X from dad that’s turned off – it can be one or the other), resulting in “mosaicism.” This is actually how the coats of calico cats are patterned, and why the vast majority of calicos are female! Cool fact: if you stumble upon a male calico cat, it is almost certainly XXY.

Further reading

  1. To learn more about why honeybees can’t produce males from fertilized eggs, check out this brief article:
  2. An excellent review on the evolution of sex determination:

Featured image from Wikimedia Commons.

13 thoughts on ““I’m XY and I Know It”: Sex Determination Systems 101

  1. On strictly medical terms. there are 3 things that are possible, the baby has vagina or a penis. or in VERY RARE cases has a different condition that due to how nature decides to shape the human body, can end differently, usually denoted as a defect. modern practices have become better at solving this issue however.
    As a surgeon, i apologize if i seem slightly absorbed, but i have to take a firm stance on this topic. currently the two most logical medical solutions to gender are:
    1. you are what you are born with, body modifications are to be treated as nothing more than cosmetic. I can somewhat agree as whether you have a penis or vagina at this current time, you still carry either XY or XX in your genes and your size/muscle growth will reflect it.
    2. you are what you are equipped with at the current time. this is rather simple. if you have a penis, you don’t go in the women’s restrooms and vice-versa. this stemmed from what seemed to be a rise in alleged cross-sex rape cases from both sexes, in public restrooms. I see the point here, if you have a little girl. you don’t want her to have an encounter with a man in the women’s restrooms.
    Both seem pretty understandable.
    but the one thing that i cannot accept is the talk of non-binary gender spectrum things.
    gender isn’t a spectrum. you have male and female. subcategories of this are male and female. if your trans, then you are still either male or female. you are not nonbinary gender fluid whatever. i’m not saying your less human, but i am saying that you are not as to who you claim to be. i guess at this point we have to go as far as to say it like this:
    look at your hand right now. it is made of cells. those cells came from DNA. which is either XY or XX. nothing more, nothing less. both sexes have their far share of problems the other cannot fully understand, neither has it easy. but moving away from your self in order to feel like your self IS IN FACT a very bad mental state to be in. sure, it works for a moment. you get lost in the illusion and feel more free. but take a moment to put the illusion aside and reflect on your life choices and their consequences.
    physicality and medicality should always be put over opinions and politics. so its like a direct slap in the face that large, reputable universities, whose job it is to provide students with this valuable knowledge have turned. they are abandoning everything they once were for nothing.
    more people know what gender studies are than the are people who know what STEM even means. that should be a pretty large indicator right there.
    the fact that this is even a thing to discuss sickens me. we could have spent this time gaining a deeper understanding of cancer, or figuring out how to purify nuclear waste, build an animal shelter, go donate blood, go plant something. imagine all the time and money this new culture has demanded that could have went to better more productive things that have a practical purpose.

    1. Looking at the first and third comentors it would appear they are experiencing the back fire effect.
      1)Our first commentator jumps to calling this junk science. Not really helpful or insightful. The point was to get people thinking about gender and how we as humans perceive it.

      2)Our third commentator speaks of medical terms, but deviates from medical to personal matters and then includes scare tactics i.e. rape. Please don’t ignore that a disturbed individual will do horrible things regardless of what sign is on a bathroom door. It was also not mentioned that same sex rape happens.

      Both the article and the surgeon miss 2 conditions that make the gender based on DNA not so simple.
      A) Intersex, a condition where a person does not fit into a nice neat column A or B of gender/sex organs. So XX is a girl and XY is a boy. Neat, easy, no thought. Just look at you hand, well what if your hand’s DNA reads XXY or XYY. Not so neat and simple right. Is check their pants they say. Ah that can be a problem too. Many who have XXY do not hconditionnizable genitals. So what to do?
      B) the second condition chimerism is when one person hold DNA of more than one more individual. So that hand may not be XX like the rest of you. Google thus one if you’ve never heard of it. The part that makes this interesting is there was no way of telling if you have this without testing multiple parts of the body’s DNA. So yes, it is possible you’re brain (or at least the part of it) could be XY and the rest if you is XX. The thing is medical science can only guess at how many people have this particular condition since it requires multiple DNA tests and I don’t see many people signing up invasive surgery to have their brain tested just because they feel different.

      The real reason this is all being discussed is that gender matters to society. If male amd female were true equals then it would not matter if you were male, female, or inbetween. We have constructed roles and expectations based upon our (perceived) gender. It’s not about whether you are male or females; it’s the notion of conforming to assigned roles. It’s not about genitalia. It’s not about not about restrooms any more than it was about fountains or where you could sit in a bus. It IS about human beings. If you have never been discriminated against because of the way you look or act you will never unstand what it is like. I don’t want people to see my skin tone or hair and expect me to be something just because of my genetics. Treating people a certain way just because of their genetics is not a good idea, just ask a Jew.
      Unfortunately for us all what it comes down to is that humans see a thing that is different and don’t understand. What is not understood is feared; what is feared becomes hated. Thus what we hate we destroy.

      1. I could not stop laughing while reading your reply Lauren. As the facts stand this is all there is XX and XY. Everything else is physical or mentally retardation, or people in serious need of professional counselling. Which is less than .001 of 1% of the world population, without even needing to look it up to do the research. Which sums everything both of you have said. Nice and tidy. Truth is if gender was fluid, then so is race, which then means both are only a state of mind. Which in that case I identify as a polka dotted apache helicopter, and you should respect that. Then I should also be able to say I identify as a woman to be able to apply for and get a small business administration loan for Women-owned businesses, from the government which is specifically an advantage only for women. From the Funny part is that will never happen because people only want equal rights as long as it is in their favor. Fun world we live in. I probably wouldn’t have gone that far, but you brought in religion in your reply and lost credibility.

      2. Lauren, humans have diseases, we all know a man is XY and a woman is XX, if we find a XYZT that is not standard or normal, it is an abnormality.
        Bottom line is that people do not change who they are just by thinking or feeling sth.
        I can wake up tomorrow felling I am a Bear, dressing as a bear, hibernating as a bear but this DOES NOT make me a bear, I respect the feeling and freedom of a bear-man to be who he wants to be, but it is a disease and I am not obligated to call him Mr. BEAR and pretend I am blind

    2. So Will what if you were born with a vagina and have a XY chromosome?

      What if you were born with a penis and have a XX chromosome?

      Than what’s your gender?

    3. Will, that you have a medical degree and are clearly against expanding your knowledge and learning continuation is terrifying.

  2. A couple different thoughts here, and I hope I can keep them coherent. All of the discussion of sex determination is interesting. I understand that certain species of plants and animals use different systems to determine biological sex. Also, that certain systems can be non-binary, etc. That being said, we are are not talking about bees, or melons, or fish or turtles. We are talking about human beings. XXY and XYY are mutations and defects of the genetic code. To use these disorders in an argument for non-binary gender is intellectually dishonest. The larger problem here really has nothing to do with gender. For the most part it is still OK to shame people for being fat, or poor, or not as smart, or just plain different. People will make fun and discriminate based on so many things. Growing up is hard, adolescence is hard, and there are a lot of challenges out there. Legislation that singles out trans people for humiliation are not good laws and are not good for society. That being said, I do not believe in non-binary fluid gender. I hate the use of the word “assigned” when talking about biological sex. Physically, you are either a boy or a girl, and anything else is an anomaly. But it’s probably good policy to have gender neutral bathrooms. It makes the line go more quickly. To Will’s point, my niece claimed that she is really a boy, and is transitioning FTM. She was always saying that she is lost, not fitting in, and that changing her gender would make everything better. She is an 18 year old girl, still developing as a person but now taking a whole bunch of hormones. And guess what? She is still lost, and doesn’t know what she is going to be doing with her life. Furthermore, the hormones have made her snarky and straight up obnoxious. Not fitting in can be very painful, but it would seem to me that when those around you don’t know who/what you are – that isolation would seem to be more painful. If you are feeling insecure about your identity, learn to accept yourself for who you are not transition into something that you are not. If the Queen of England had balls, then she would be the King……

  3. I greatly appreciate this blog post. It’s very informative.

    Is there a good journal article that summarizes the current science on sex determination in humans that deals with all the various issues like SRY migrating to the X chromosome that can give rise to XX males and similar situations where XY individuals can turn out to be biologically female?

Leave a Reply

Your email address will not be published. Required fields are marked *