How do chromosomes determine the sex of an individual?

It took scientists a long time to work out the puzzle of how sex chromosomes determine an individual's sex. Here's the evidence:

• X + X = FEMALE
• Y + X = MALE
• X + 0 = FEMALE (Turner Syndrome)
• Y + X + X = MALE (Klinefelter Syndrome)

What's the key feature? What chromosomes do the males have that the females don't have?

All the males have a Y chromosome!

BUT --- how does it work?

To figure this out, scientists carefully studied the chromosomes from people whose karyotypes were puzzling. Some of these individuals appeared female, but had a Y chromosome in their karyotype. Similarly, some individuals appeared male but had two X chromosomes in their cells. What was going on?

As discussed in Using karyotypes to predict genetic disorders, chromosomes can be broken and exchange DNA. In fact, chromosome exchanges, or recombination, occur normally as part of meiosis.

When scientists looked at the DNA of the individuals whose sex chromosomes did not seem to predict their sex, they found that a small piece of the Y chromosome was transferred to the X chromosome of the apparently male individuals who were XX. Similarly, the same piece of the Y chromosome was missing and replaced with a piece of the X chromosome in individuals who were XY but appeared female.

The region of the Y chromosome that was added or missing is called the SRY (Sex determining Region on the Y). This region can be transferred to the X chromosome in a rare recombination event during meiosis. The resulting sperm carry an X chromosome but direct the development of an embryo as a male, since they also contain the SRY region.