Key Takeaways:
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The presence of a Y chromosome does not make someone male, because it is not the Y chromosome but the genes it often (but not always) contains that influence male sexual development.
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When the genes encoding male sexual development cross-over to an X chromosome, you get XX (“chromosomally female”) individuals who proceed along male developmental pathways.
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When the genes encoding male sexual development mutate or are deleted, you get XY (“chromosomally male”) individuals who proceeds along female developmental pathways.
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All of the sex chromosome sets (including XX and XY) can mix-and-match with other sexual characteristics—such as genitals, gonads, and secondary sexual characteristics—to create a mosaic of sexual traits.
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The International Olympic Committee (IOC) determined in 1999 that the Y chromosome was “inconclusive” at sex determination.
Does the Y Chromosome Create a Sex Binary?
When it comes to understanding biological sex, most of us were taught a simple lie instead of a complex truth. The simple lie was the human sex is binary (“female”/”male”). The complex truth is that biological sex is far too complex to fit into that simplistic model.
Today, biology, endocrinology, physiology, genetics, neuroscience, and reproductive science confirm that biological sex is composed of a constellation of traits, none of which are binary.
Of course, there are specific sex traits that are more and less common across the human population, which is what gives us the impression of a sex binary. Meaning, there combinations for “male” and “female” traits that are substantially more likely to appear together. You can read about that here.
In particular, one of the sex traits that people mistakenly think is binary are chromosomes.
Specifically, there are two common misbeliefs around the chromosomes, which are that:
- Only XX and XY chromosomes exist.
- Anyone with a Y chromosome is “male”, regardless of how many Y’s they have.
Let’s dive into both of them misconceptions below.
Are XX and XY the Only Sex Chromosome Sets?
Sometimes you will hear people say, “Anyone who is XX is female, anyone who is XY is male.” But, is this actually rooted in science?
The short answer to this question is “no” and here’s why. On average, most people assigned male at birth tend to have XY chromosomes, while most people assigned female at birth tend to have XX chromosomes.
However, other sex chromosomal variations frequently exist as a result of the loss, damage, or addition of one or both of the sex chromosomes.
Specifically, the following sex chromosome variations are naturally occurring in humans:
- 45, X, also called Turner syndrome
- 45, X/46, also called XY mosaicism
- 46, XX/XY
- 47, XXX, also called Trisomy X
- 47, XXY, also called Klinefelter syndrome
- 47, XYY with normal phenotype
- 48, XXXX
- 48, XXXY
- 48, XXYY
- 49, XXXXY
- 49, XXXXX
- XX Male Syndrome
- XX Gonadal Dysgenesis
- XY Gonadal Dysgenesis
Where Gonadal Dysgenesis is listed above, it refers to reproductive tissue (gonads) being replaced by non-reproductive fibrous tissue during prenatal development.
Given that chromosomes are varied and diverse across the human species, we’ve disconfirmed the first misconception above. Let’s move onto the second one.
Does Having One (Or More) Y Chromosomes Make You Male?
Another thing people will sometimes say is, “Anyone with an Y chromosome is male, regardless of how many Y’s they have.”
In saying this, these people think that XY, XXYY, XXY, XYY, etc., should all be considered male, while XX, XXX, and XXXX should all be considered female. Thus, these individuals think that the presence or lack of a Y chromosome creates a sex binary (two options).
There are several incorrect understandings associated with this belief, as discussed below.
Problem 1: It is Not the Y Chromsome(s) but the Genes That Influence Sex
The major problem with this belief is that it not the Y chromosome that makes an person male, but the genes that are often—but not always—contained within that chromosome that have the potential to initiate a cascade of male sexual developmental pathways.
The reason that mutations can impact fetal sex development is that the sex determination genes don’t just have to be present, they have to express proteins and those proteins need active receptors to be able to bind them.
Here’s the simple schematic:
Chromosomes Contain Genes → Genes Express Proteins → Proteins Need Receptors to Bind Them → Biological Pathways Gets Activated
If gene deletions, mutations, duplication, or cross-over occur, then that sex development cascade gets altered. Similarly, if active receptors aren’t available, it gets altered. These events cause biological sex diversity known as intersex conditions.
It is important to understand that the default option during development is for all embryos to proceed along female sexual developmental pathways. Having said that, specific genes are necessary for complete ovarian development to take place (like FOXL2, RSPO1, and WNT4). Without them, atypical ovary development will occur.
Meaning, regardless of the presence or lack of a Y chromosome, all embryos have the same gonadal ridge tissue until about week 7 to week 8 of pregnancy.
The gonadal ridge is what eventually becomes the sex organs, meaning a testis, ovary, or blend of both. An example of blended gonad would be a ovotestis or a streak gonad. A person can also have one ovary and one testis.
Unless cues to initiate male development pathway are initiated, a fetus will continue along female sexual development pathways, regardless of whether or not a Y chromosome is present.
The SRY Gene Isn’t Always on the Y Chromosome
One of the genes that is usually, but not always, found on the Y chromosome is the SRY gene. It is critical for inducing male sexual development.
When SRY gene is active, it produces a DNA-binding protein called “Testis-Determining Factor”. As the name suggests, this protein is needed for the development of male gonads.
What is interesting is that in some cases, the SRY gene can cross-over from a Y chromosome to an X chromosome. When this happens, you get XX (“chromosomally female”) individual who will proceed along male developmental pathways.
Similarly, when the SRY gene gets mutated or deleted, you get an XY (“chromosomally male”) individual who will proceed along female developmental pathways.
Meaning, it is not the Y chromosomes but the sex determination genes that it usually (but not always) contains which have the potential to cue male sexual development.
Sex Determination Genes Are On Other Chromosomes Too
To make things more complex, there are also sex determination genes found on other chromosomes than the X and Y. Most people have 46 total chromosomes in total (23 pairs).
For example, DMRT1 is a critical sex determination gene found on the 9th chromosome. Just like SRY, it needs to be active to facilitate the development of male gonadal development (testes). When DMRT1 is inactive due to mutation or delete, then it cannot produce the DMRT1 protein.
In this case, an individual with a Y chromosome will not receive cues to promote male sexual development. Thus, DMRT1 mutation can cause partial or complete male-to-female sex reversal.[1,2]
Put simply, the DMRT1 gene is critical for male sex determination and without it the “default” female pathways take over.
Interestingly, DMRT1 upregulation (elevated production) appears to produces the opposite effect of female-to-male sex reversal. This has been studied in other species and is likely to occur in humans as well, because DMRT1 is a “dose dependent” protein.
Meaning, the amount of it you have matters for your sex determination.
To summarize, the presence of an active DMRT1 gene on chromosome 9 is required for male sexual development. If it is impacted by mutation or deletion, the presence of a Y chromosome will not cue male sexual development pathways.
Likewise, there is a gene called WNT4 that is required for ovarian pathways to be activated. In humans, duplications of this gene in XY individuals (“chromosomal males”) or loss of function mutations in XX individuals (“chromosomal females”) causes sex reversal.[3,4,5]
Once again, it is not the Y chromosome but a beautifully intricate cascade of gene activation that determines whether a person is female, male, or intersex.
Active Sex Hormone Receptors Are Also Required
Of course, active sex hormone receptors are also required for sexual development and not everyone produces them.
For example, people with complete androgen insensitivity syndrome (CAIS) have XY chromosomes, but they develop with female sexual characteristics because their hormone receptors are insensitive to androgens.
Because people with CAIS have a vagina, labia, and breasts, as well as undescended testes, if you tried to sex them, it would look like this:
- external genitals (vagina and labia) = “female”
- secondary sex markers (breasts) = “female”
- gonads (testes) = “male”
- chromosomes (XY) = “male”
A renowned person with partial androgen insensitivity syndrome (PAIS) is Castor Semenya, the renowned 800m Olympic runner. The International Olympic Committee (IOC) has not found a way to classify her sex because it varies across different biological sex markers, which is why they have defaulted to measuring her continually fluctuating androgen levels on a event-by-event basis.
Put simply, under many varied conditions, the Y chromosome’s presence will not facilitate the cascade of events needed during development to promote male sexual characteristics.
So it seems, human biology is complex and resists a chromosomal sex binary at every turn.
Problem 2: Sex Chromosomes Can Mix with Characteristics of the “Opposite” Sex
The second problem with thinking that the Y chromosome creates a sex binary is that even newborns born with a standard XX or XY sex chromosome set can present with characteristics typical of the “opposite” sex.
Specifically, sex chromosomes can mix-and-match with other sex markers—such as chromosomes, genitals, or sex hormones—to create a mosaic of sexual traits.
For example, either a fetus or the mother’s adrenal glands can produce elevated levels of androgens. When this happens, an XX (“female”) child can be born with a small penis. In some cases, these newborns may will appear to have a scrotum, due to the labia fusing together.
Similarly, an XY (“male”) child can be born with an enzyme deficiency, such as 5-alpha deficiency and 17-beta dehydrogenase deficiency. When this happens, that “male” infant can be born without a penis and labelled “female” at birth.
As mentioned above, active sex hormone receptors are required for sexual development and not everyone produces them. People with complete androgen insensitivity syndrome (CAIS) have XY chromosomes, but they develop with female sexual characteristics because the androgens present in their body cannot induce male sexual development.
Because not all individuals with a Y chromosome develop as “male”, people are medically incorrect when they say, “Anyone with an Y chromosome is male, regardless of how many Y’s they have.”
The Olympic Committee Rejected Chromosomal Analysis
Interestingly, chromosome testing was introduced by the International Olympic Committee in 1968. At that time, the committee tested for a Y-chromosome in an attempt to classify competitors.
Unsurprisingly, testing for a Y chromosome was ended in 1999 because it was shown to be “inconclusive” at sex determination.
Specifically, the committee ran into problems because:
- People can have XX chromosomes and a penis (called an “XX male”).
- People can have XX chromosomes and a vagina, but possess male internal organs, commonly an undescended testes. (This was the debate around 800m star, Caster Semenya, for example.)
- People can can have XX chromosomes and a vagina but “overproduce” testosterone, called hyperandrogenism. (In recent years, this has been common among mid-distance runners at the Olympic level.)
Given this, how should these individuals be “sexed”?
As these examples illuminate, the presence of one (or more) Y chromosomes does not create a sex binary.
Why The Y Chromosome Doesn’t Determine Sex
Given the complexity we just discussed, let’s summarize the findings. In most but not all individuals, the Y chromosome will contain specific genes to code for proteins that influence male developmental pathways, instead of female developmental pathways.
However, many things can disrupt or alter this process, giving us biological sex diversity.
Whether an individual’s sex organs turn out to be female, male, or intersex depends on a cascade of interactive events. Thus, biological sex cannot be isolated to a single trait, like a Y chromosome.
Rather, sex is better understood as a constellation of traits, of which there are at least 10 relevant markers. Because biology is beautifully diverse, none of them are binary.
Biological markers of sex include:
- Chromosomes – Types of chromosomal expression.
- Gonads – Organs that produce gametes (testes or ovaries).
- Hormones –Types and level of hormone secretion, which vary within and across the sexes.
- Secondary Sex Characteristics – Features that appear during puberty, but are not involved with reproduction.
- External Genitalia – Genitals visible outside the body.
- Internal Genitalia – Genitals present within the body.
- Gametes – Reproductive cells in humans.
- Gene Expression –Levels and types of gene expression. Genes dictate the proteins made by the body. Known genes that impact sex include DMRT1, SRY (produces Testis-Determining Factor), and Foxl 2.
- Brain Structure – Brain structure characteristics (including the ratio of white matter to grey matter) and brain activation patterns vary by sex.
- Hormone Receptor Sensitivity – The response to sex hormones can vary, depending on receptor sensitivity. Some individuals may be partially or completely insensitive to hormones, negating their effect.
To Summarize
To summarize, the presence of a Y chromosome does not make someone male, because it is not the chromosome but a series of events involving genes, proteins, and receptors that determine biological sex. Also, chromosomes are only one of multiple sex markers that in aggregate constitute a person’s sex as female, male, or a blend of both (intersex/undefined).
Footnotes
1. Zarkower, D. and Murphy, M.W. (2021) “Dmrt1: An ancient sexual regulator required for human gonadogenesis,” Sexual Development, 16(2-3), pp. 112–125. Available at: https://doi.org/10.1159/000518272. [Article link]
2. Raymond, C. (1999) “A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators,” Human Molecular Genetics, 8(6), pp. 989–996. Available at: https://doi.org/10.1093/hmg/8.6.989. [Article link]
3. Elejalde BR, Opitz JM, de Elejalde MM, Gilbert EF, Abellera M, et al. Tandem dup (1p) within the short arm of chromosome 1 in a child with ambiguous genitalia and multiple congenital anomalies. Am J Med Genet. 1984;17:723–[PubMed]
4. Jordan BK, Mohammed M, Ching ST, Délot E, Chen XN, et al. Up-regulation of WNT-4 signaling and dosage-sensitive sex reversal in humans. Am J Hum Genet. 2001;68:1102–9. [PMC free article]
5. Mandel H, Shemer R, Borochowitz ZU, Okopnik M, Knopf C, et al. SERKAL syndrome: an autosomal-recessive disorder caused by a loss-of-function mutation in WNT4. Am J Hum Genet. 2008;82:39–47. [PMC free article]
Did this help you to better understand the role of the Y chromosome in biological sex determination? Ask your questions in comments below.
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*This article is part of a Biological Sex and Gender Diversity Series published by Cade Hildreth, B.A., M.S. You can read the other articles here:
AUTHOR BIO: Cade Hildreth attended Dartmouth College & Smith College for Undergraduate Studies in Biology and then acquired a Master’s Degree in Biochemistry and Molecular Biology with Specialization in Biotechnology & Bioinformatics from Georgetown University, where they were Valedictorian. Cade is the Founder/President of BioInformant.com, the world’s largest stem cell industry news site that attracts nearly one million views per year and serves all-star clients that include GE Healthcare, Pfizer, and Goldman Sachs. Cade has authored over one-thousand articles about the stem cells, interviewed hundreds of executives from across the industry, and presented at stem cell conferences worldwide. As an expert on stem cells, Cade has been interviewed by the Wall Street Journal, Los Angeles Business Journal, Xconomy, and Vogue Magazine, as well as cited in Tony Robbin’s his best selling book, Life Force. Cade owns a portfolio of income-producing residential and commercial properties across the U.S.