Sex is pretty simple: you’re either male or female, right? Nope! Turns out it’s not nearly that straightforward. In fact, it’s pretty darned complicated.
That’s why a recent update at AncestryDNA is so welcome. Like me, you may not have even noticed when it happened, but the DNA kit details now refer to “Assigned sex at birth” rather than “Sex”.
This is a big deal, because sex is more than skin deep. What you learned in school is still true: most of us either have two X chromosomes (denoted XX) and female anatomy or one X and one Y chromosome (XY) and male anatomy. But it’s not the whole truth.
A child can have a single X (X0), three Xs (XXX), two Xs and a Y (XXY), or other combinations (XXXY, XYY, etc.). What’s more, someone can have a Y chromosome and female anatomy, no Y and male anatomy, ambiguous anatomy, or even anatomy that does not align with their gender identity.
To understand why, we need to take a deep dive into what DNA actually does.
At its core, DNA is a set of instructions on how to build and operate a body. For humans, you can think of it as a 23-volume set of loose-leaf binders (chromosomes 1–22 plus the X chromosome), with an optional section for some individuals (the Y chromosome).
Each page (gene) in a binder (chromosome) gives instructions for one part of the system. The X chromosome has about 900 genes and is essential to life. The body can’t operate without it. Everyone has at least one X chromosome.
The Y chromosome, on the other hand, is much smaller and has only about 55 genes. It’s not essential; half the human population does just dandy without one, after all.
There is one gene usually found on the Y chromosome that is key to male anatomy, though. That gene is called SRY or sometimes TDS for testis-determining region. SRY is what’s called a regulatory gene; it tells other genes when to take action, a bit like a manager in an office directs other employees in their specific roles. SRY is, in fact, upper-level management, because it controls other regulatory genes.
SRY and Anatomical Sex
Early in development, the SRY gene initiates a cascade of events that usually results in male anatomy. If SRY does not function properly because of mutation, an XY fetus can have female appearance. In other words, that child will be “chromosomally male” but anatomically female.
The biology gets even more interesting. SRY isn’t always found on the Y chromosome. It can sometimes end up on the X chromosome. We don’t typically think of the X and Y chromosomes crossing over, but it’s normal at their very tips.
The so-called pseudoautosomal regions (PARs) are highlighted in yellow in the figure below. Note where SRY is. It’s just beyond the PAR, meaning that if a bit too much of the PAR swaps during sperm production, SRY can end up on an X chromosome.
A Y chromosome that has lost its SRY gene to crossing over will lead to female anatomy, and an X chromosome with SRY will induce male anatomy. It’s also possible for SRY to end up on another chromosome entirely through an event called transposition.
Returning to the binder analogy, the “page” for SRY can sometimes get removed from the Y binder and put into another one. The instructions it gives are the same, though.
So, SRY Makes a Male?
Whoa Nellie! Not so fast. Remember that SRY is the genetic equivalent of an executive manager. If the staff don’t do their jobs, the project still doesn’t meet its goals.
One way that SRY delivers its message to the rest of the body is through hormones called androgens. Testosterone is an androgen. At high enough levels, androgens tell cells to develop male characteristics, both the obvious anatomical ones (genitalia) and secondary sexual traits like facial hair, muscle mass, and so on.
Androgens are made by a chemical assembly line, with each step regulated by a different gene. If any of those genes don’t function properly, not enough of the “make-a-male” instruction gets out.
Even if the message gets out, it’s not always heard. Body cells receive the message via special proteins called androgen receptors. If the receptors don’t function properly, cells won’t receive the androgen signals and can’t respond. People with androgen insensitivity can be anatomically male, female, or something in between, depending on degree of insensitivity.
There’s Still So Much to Learn
We’ve seen above that sex isn’t so simple; external anatomy might not align with one’s genetic makeup for any number of reasons. What’s more, people with these conditions may not show symptoms until puberty, if at all.
And we’ve just scratched the surface. There’s still plenty about anatomy, brain development, and gender identity that geneticists haven’t worked out yet. It’s no wonder that some of us identify in ways that don’t fit the stereotypes associated with our genitalia. It’s all part of the normal human rainbow.
That’s why AncestryDNA’s move toward inclusivity is so important. While the presence of a Y chromosome may be important to genealogy, it’s not necessarily important to who we are. And although a simple check-box can never reflect all of human diversity, I’m glad to see Ancestry acknowledge that we are not always the sex assigned based on anatomy at birth.