XY sex-determination system

The XY sex-determination system is the sex-determination system found in humans, most other mammals, some insects (Drosophila) and some plants (Ginkgo). In this system, females have two of the same kind of sex chromosome (XX), and are called the homogametic sex. Males have two distinct sex chromosomes (XY), and are called the heterogametic sex. However, an opposite scheme is found in birds.

The XY sex determination system was first described independently by Nettie Stevens and Edmund Beecher Wilson in 1905.

Ancient ideas on sex determination
Since ancient times, people have believed that the sex of an infant is determined by how much heat a man's sperm had during insemination. Aristotle wrote that: ...the semen of the male differs from the corresponding secretion of the female in that it contains a principle within itself of such a kind as to set up movements also in the embryo and to concoct thoroughly the ultimate nourishment, whereas the secretion of the female contains material alone. If, then, the male element prevails it draws the female element into itself, but if it is prevailed over it changes into the opposite or is destroyed. Aristotle claimed that the male principle was the driver behind sex determination, such that if the male principle was insufficiently expressed during reproduction, the fetus would develop as a female. In contrast, modern genetics has developed a view on sex determination in which no one single factor is responsible for determining sex; a number of pro-male, anti-male and pro-female genes being responsible, though the largest factor is whether the male's gamete carries an x or y chromosome.

Beginnings of genetics of sex
Edmund Beecher Wilson and Nettie Stevens are credited with discovering, in 1905, the chromosomal XY sex-determination system; the fact that males have XY sex chromosomes and females have XX sex chromosomes.

The first clues to the existence of a factor that determines the development of testis in mammalians came from experiments carried out by Alfred Jost, who castrated embryonic rabbits in utero and noticed that they all developed as female. In the wake of Jost's experiments, C. E. Ford and his team discovered that the Y gene was needed for a fetus to develop as male when they examined patients with Turner's syndrome, who grew up as phenotypic females, and found them to be X0 (hemizygous for X and no Y). All these observations lead to a consensus that a dominant gene that determines testis development (TDF) must exist on the mammalian chromosome Y.

The search for a testis-determining factor (TDF) lead a team of scientists in 1990 to discover a region of the Y chromosome that is necessary for the male sex determination, which was named SRY (Sex-determining Region of the Y chromosome).

Mechanisms
Some species (including most mammals) have a gene or genes on the Y-chromosome that determine maleness. In the case of humans, a single gene (SRY) on the Y-chromosome acts as a signal to set the developmental pathway towards maleness. Other mammals use several genes on the Y-chromosome for that same purpose. Not all male-specific genes are located on the Y-chromosome.

Other species (including most Drosophila species) use the presence of two X chromosomes to determine femaleness. One X chromosome gives putative maleness. The presence of Y-chromosome genes is required for normal male development.

Humans, as well as some other organisms, can have a chromosomal arrangement that is contrary to their phenotypic sex, that is, XX males or XY females. See, for example, XX male syndrome and androgen insensitivity syndrome.

Birds have a similar system of sex determination (ZW sex-determination system), in which it is the females that are heterogametic (ZW), while males are homogametic (ZZ).

Recent studies on the genetic factors that influence gender traits
For a long time, biologists believed that the female form was the default template for the mammalian fetuses of both sexes. After the discovery of the testis-determining gene SRY, many scientists shifted to the theory that the genetic mechanism that determines a fetus to develop into a male form was initiated by the SRY gene, which was thought to be responsible for the production of testosterone and its overall effects on body and brain development. This perspective still shared the classical way of thinking; that in order to produce two sexes, nature has developed a default female pathway and an active pathway by which male genes would initiate the process of determining a male sex, as something that is developed in addition to and based on the default female form. This view is no longer considered accurate by most scientists who study the genetics of sex. In an interview for the Rediscovering Biology website, researcher Eric Vilain described how the paradigm changed since the discovery of the SRY gene: For a long time we thought that SRY would activate a cascade of male genes. It turns out that the sex determination pathway is probably more complicated and SRY may in fact inhibit some anti-male genes.

The idea is instead of having a simplistic mechanism by which you have pro-male genes going all the way to make a male, in fact there is a solid balance between pro-male genes and anti-male genes and if there is a little too much of anti-male genes, there may be a female born and if there is a little too much of pro-male genes then there will be a male born.

We [are] entering this new era in molecular biology of sex determination where it's a more subtle dosage of genes, some pro-males, some pro-females, some anti-males, some anti-females that all interplay with each other rather than a simple linear pathway of genes going one after the other, which makes it very fascinating but very complicated to study.

In mammals, including humans, the SRY gene is responsible with triggering the development of non-differentiated gonads into testes, rather than ovaries. However, there are cases in which testes can develop in the absence of an SRY gene (see sex reversal). In these cases, the SOX9 gene, involved in the development of testes, can induce their development without the aid of SRY. In the absence of SRY and SOX9, no testes can develop and the path is clear for the development of ovaries. Even so, the absence of the SRY gene or the silencing of the SOX9 gene are not enough to trigger sexual differentiation of a fetus in the female direction. A recent finding indicates that ovary development and maintenance is an active process, regulated by the expression of a "pro-female" gene, FOXL2. In an interview for the TimesOnline edition, study co-author Robin Lovell-Badge explained the significance of the discovery: We take it for granted that we maintain the sex we are born with, including whether we have testes or ovaries. But this work shows that the activity of a single gene, FOXL2, is all that prevents adult ovary cells turning into cells found in testes.

Implications for human health and social policy
Looking into the genetic determinants of human sex can have wide-ranging consequences. Scientists have been studying different sex determination systems in fruit flies and animal models to attempt an understanding of how the genetics of sexual differentiation can influence biological processes like reproduction, ageing and disease. Since many of the same genetic mechanisms involved in determining sexually dimorphic traits have been preserved during evolution to this day in fruitflies, mice, and humans, understanding how these genetic mechanisms work can lead to improved healthcare that takes into account sex differences. The research could also lead to changes in how people understand and perceive sex differences.