DNA Basics

What is the big difference about the X and Y chromosomes that make the difference between male and female people? Do the cells just generate differently?

-An elementary school student from California

March 14, 2012

You're right that it just isn't having an X and a Y chromosome that makes a male (or that having two X's makes you a female).  It is what our cells do with these chromosomes that makes a baby grow as a boy or a girl.

Specifically, there is a gene on the Y chromosome called SRY that makes the big difference. This gene tells a baby to be a boy. Without the SRY gene, babies develop into girls.

One way we know about this important gene is that there are some rare cases where someone has two X's but also has an SRY gene. These people look male.  And there are cases where an XY person has an SRY that doesn't work or is missing. These people look female.

But we also know the SRY gene isn't enough.  There are lots of genes needed to make a boy.

What the SRY gene does is start something called a gene cascade.  This is sort of like an avalanche.

The SRY gene turns on some boy making genes that turn on some more boy making genes and so on. Eventually you get a whole different set of genes working differently than they would without the SRY gene there.

If one of the genes is missing in this avalanche, the whole thing can come to a halt.  You can end up looking somewhere between a man and a woman and if the SRY gene is missing or doesn't work, then the avalanche won't start at all. The baby will develop as a girl.

So in a sense the "boy" cells do generate differently from the "girl" cells.  Each has a different gene program turned on that leads to being a boy or a girl.

But as you'll see, all the genes on the Y chromosome aren't enough to make a boy.  Lots of the other chromosomes are involved too.

It Takes a Village (of Genes) to Make a Boy

Most people have 23 pairs of chromosomes. The numbered pairs (1-22) are called autosomes, and they are the same in boys and girls.
The 23rd pair is the sex chromosomes.  These are the ones that are different in boys and girls.  Boys have an X and a Y and girls have two X chromosomes.

image3 Scattered across all of these chromosomes are over 20,000 different genes. Each gene has the instructions for doing a particular thing in a cell.  All of these different genes work together to make you.

Both boys and girls share almost all of the same set of genes.  The difference is the 80 or so on the Y chromosome.  Only boys have those.

But these 80 aren't enough to make a male.  Genes on lots of the other chromosomes are involved too.

Let's look at a quick example to give you a feel for what I mean.  One of the first genes that SRY turns on or activates is called SOX9.  This gene is found on chromosome 17.
This means boys and girls both have this gene.  It is just that without SRY, it stays off.

There are at least 5 other genes that come on early that have instructions for becoming a boy. They are located on different chromosomes like the X chromosome and chromosomes 9, 11, 17, and 19.  Some of them are turned on by SRY or by genes like SOX9.

This is actually how lots of things work in cells.  Every cell has the potential to be a muscle, a blood cell, or any of the other hundreds of cell types.  Cell type is determined by what genes are on and off.

Being a boy is a bit different though.  Not only are genes used differently, but there are also a few extra genes needed to make a boy.

Even though boys have their own genes, one of the most important is a shared gene called the androgen receptor or AR.  And believe it or not, the silly thing is actually on the X chromosome.

Halfway There

A key step in making a boy is getting some testosterone made.  I am sure you've heard of testosterone.  It is what gets turned on at puberty to make boys hairier, deeper voiced and more aggressive (among other things).
But it is also turned on early in development to make a baby a boy.  One of the key jobs of SRY and its related genes is to get testosterone made so the AR gene can do its job.  And AR is responsible for making many of the parts of a boy that identify him as a boy.

Sometimes, though, someone can get a copy of the AR gene that isn't working quite right.  Now the boy making process doesn't go all the way to the end.  This is called Androgen Insensitivity syndrome or AIS.

So people with AIS have an X and a Y chromosome. They just don't make it all the way to being a boy because because AR can't do its job.  The gene avalanche is slowed down or stopped early.  And the earlier it is stopped, the less like a traditional boy the person will look.

There are two types of AIS, partial and complete. People who have complete AIS are genetically boys (XY), but they have the physical characteristics of a girl.
People who have partial AIS are also genetically boys (XY). They have some of the physical characteristics of a girl and some of a boy.

Even though this gene is on the X chromosome, it obviously plays a key role in making someone a boy.  So you're right, a boy's cells are programmed differently than a girl's.  But it takes more than a Y to make a boy.

Jessica Profato, Stanford University

A nice video explaining how cells can be different even though they share the exact same DNA.

The SRY gene on the Y chromosome causes an avalanche of boy genes to get turned on.

SRY turns on genes that turn on other boy making genes.
(Image from Nature.com)

The AR gene on the X chromosome is critical for making a boy.