How do genes make us?

"You were born with male genes. You're a man. Period."

If you've followed any discussions about transsexual women competing in sport, you must have heard this complaint. It is false, and any biologist would be troubled by such a black-and-white statement. Let's unravel it a bit and see why.

Your chromosomal makeup is called a karotype. Humans with a normal karotype have 46 chromosomes, 23 from each parent. Normally, your DNA hangs around in each of your cells in a big tangled mass of DNA and proteins called chromatin. When one of your cells starts to to copy itself, the DNA snaps into structures called chromosomes.

In humans, you get one copy of each chromosome from each of your parents. The egg from your mother carries 23 chromosomes, and so does the sperm from your father that fertilizes the egg and leads to somebody like you. Total: 46 chromosomes.

In 22 of the 23 chromosomes, you just get one copy from your mother and one from your father. The sex chromosomes, X and Y, are the exception. You always get an X chromosome from your mother, because women who can bear children do not have Y chromosomes: they have one X chromosome from their mother, and one from their father. Men who can father children always have a Y chromosome. So, when your father's body created the sperm with just half of the chromosomes of a normal cell, there's something like a 50% chance that the sperm has an X chromosome, and a 50% chance that it has a Y chromosome. Since only one sperm can fertilize an egg--and this, again, has exceptions--you either end up with a child that has two X chromosomes (one from mom and one from dad) or one X and one Y chromosome (one each from mom and dad). The genetic shorthand for this is 46,XX and 46,XY (46 total chromosomes, plus the sex-specific genes).

The Y chromosome is very tiny compared to the other chromosomes, and as far as we can tell it carries relatively few genes when compared to powerhouse chromosomes like the X. The primary responsibility of the Y chromosome genes is for the production and sustenance of the male body. It doesn't do much else. When you think about it, with the only difference being the tiny Y chromosome, XX and XY people are far more alike than they are different.

The plot thickens! Chromosomal sex is not as simple as 46,XX and 46,XY. There are genetic variations like XXY, XYY, and XXXY. There are also 46,XY people who have some broken genes on the Y chromosome that mean that their bodies do not respond to testosterone, so they are chromosomally 46,XY but never develop physically like a male. You can see how it gets sticky. Estimates are that as many as 1 percent of humans are neither 46,XX nor 46,XY. With very few exceptions, the most you can say about genetics is that your genes and related genetic material has a certain percentage chance of creating a trait in a body.

Most transsexual women have an 46,XY karotype, and most develop male characteristics. However, science's best informed guess is that at some point during their development--either before birth or during early childhood--the environment causes something to "break" in the brain, forming a female gender identity and a male body.

A few Y chromosome genes are very active during development. The most well-known gene is called SRY: sex-determining region Y. Physically, early in development before birth, we start with the same bits. Around six weeks after conception, the SRY gene activates and starts to create testes instead of ovaries.

See, genetics is more complicated than just what genes you have. There's a relatively new field called epigenetics, which describes the biochemistry that turns genes on and off. Interestingly, we are starting to see that epigenetic variants can cross several generations of sexual reproduction: the things your grandmother ate can affect which of your genes are active and which aren't. You might have your grandmother's gene, but it's not like you get a clean copy: you get the one that was set up in her body when she gave birth to your parent.

One of the genes you have produces a protein called an androgen receptor. Androgens are the "male" hormones, like testosterone and DHT, and receptors are like little locks that are open and activated when the testosterone key is inserted. You have other genes that create enzymes--little molecules that help biochemical reactions happen--that are responsible for converting other steroids to testosterone. With the combination of the lock (the androgen receptor) and the key (the androgen like testosterone), testosterone can work its magic, and cause the transcription of other genes. That's how testosterone does its job.

So your genes are not deterministic. Without testosterone, the genes that are activated by testosterone are not active. So if you remove the major source of testosterone--which transsexual women do when they remove their testes and go on hormone replacement therapy--the body becomes physiologically female. There is little use for the Y chromosome at all. It basically goes dormant.