No one gene, of course, determines something as complex as sex. There are genes for our external and internal genitalia, our gonads (testes and ovaries) and for a variety of other attributes we identify with our differences in gender. When the human genome project is completed in less than a decade, I would not be surprised to find more than a thousand such genes among our 75,000 genes. There is, however, one gene that starts the early embryo in one direction or the other. This gene, discovered several years ago, is called SRY, an abbreviation for the sex-determining region of the Y chromosome. All normal males and females have two sex chromosomes in addition to 44 other chromosomes in each of their body cells.. Normal males have an X and a Y; normal females have two X chromosomes. The Y has very few genes. It is about one tenth the size of the X. One of these genes is the SRY. When it is present at fertilization, the developing embryo will become a male. It does so through the product of the SRY gene which converts the neutral gonads in the embryo into testes. Once testes form, the direction is inexorable and the normal XY embryo produces what one expects to find in a normal male. The absence of SRY (as in normal XX females) leads to female development.
The SRY gene has been isolated and sequenced which means that its structure is known as a sequence of nucleotides. In mice, when XX fertilized eggs are injected with the SRY gene, the newborn mice are anatomically and behaviorally male. They are sterile because other genes needed for making sperm are missing. In the human Y chromosome, a cluster of such genes associated with making sperm have also been identified. That region is called DAZ, an abbreviation for deleted in azoospermia. The term arose because a small portion of males who are sterile and produce no spermatozoa lack a region of their Y chromosome. Those genes are in the process of being sequenced.
Occasionally a small piece of the X and Y chromosomes get swapped when sperm are being made. This happens only about once in 50,000 sperm produced. This can lead to XX males or XY females. Usually XX males are normal except for the lack of spermatozoa. They contain the SRY gene which can be detected by a chemical analysis of the X chromosomes. Since they lack the genes of the DAZ region they make no sperm. Similarly XY females are usually females at birth and they are normal girls until they reach puberty when they fail to mature into women. They require hormone therapy to achieve their puberty and femininity but since they lack ovaries they are sterile. With in vitro fertilization, however, they can be surrogate mothers using a relative’s eggs or a donor’s eggs. XY females lack the SRY gene and thus their gonads were shifted to ovaries. These ovaries fail to mature because they only have one X and they need two X chromosomes to make working ovaries.
One of the pleasures of studying science is how powerful it is to explain what seems impossible or a contradiction to common sense. We expect males to be XY and females to be XX. When XX males and XY females were first encountered, this was a shock. As the tools of biochemistry became more sophisticated, the mechanisms producing these altered chromosomes were worked out. As biologists learn how genes make embryos, the understanding of how our body is put together becomes clear. It is a breathtaking picture that is emerging and the young scientists of the first decades of the twenty-first century will startle us with their findings.