|Sex determining region Y|
PDB rendering based on 1hry.
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|RNA expression pattern|
This intronless gene encodes a transcription factor that is a member of the high mobility group (HMG)-box family of DNA-binding proteins. This protein is the testis determining factor (TDF), also referred to as the SRY protein, which initiates male sex determination. Mutations in this gene give rise to XY females with gonadal dysgenesis (Swyer syndrome); translocation of part of the Y chromosome containing this gene to the X chromosome causes XX male syndrome.
During gestation, the cells of the primordial gonad that lie along the urogenital ridge are in a bipotential state, meaning they possess the ability to become either male cells (Sertoli and Leydig cells) or female cells (follicle cells and Theca cells). SRY initiates testis differentiation by activating male-specific transcription factors that allow these bipotenital cells to differentiate and proliferate. SRY accomplishes this by upregulating SOX9, a transcription factor with a DNA-binding site very similar to SRY's. SOX9 in turn upregulates fibroblast growth factor 9 (Fgf9), which is necessary for proper Sertoli cell diferentiation. Fgf9 then feeds back and upregulates SOX9. SOX9 can also upregulate itself by binding to its own enhancer region. This is known as a feed-forward loop, where a gene product can feed back and increase its own expression. Once proper SOX9 levels are reached, the bipotential cells of the gonad begin to differentiate into Sertoli cells. Additionally, cells expressing SRY will continue to proliferate to form the primordial testis. While this contitutes the basic series of events, this brief review should be taken with caution since there are many more factors that influence sex differentation.
Since its discovery, the importance of the SRY gene in sex determination has been extensively documented:
One of the most controversial uses of this discovery was as a means for gender verification at the Olympic Games, under a system implemented by the International Olympic Committee in 1992. Athletes with a SRY gene were not permitted to participate as females, although all athletes in whom this was "detected" at the 1996 Summer Olympics were ruled false positives and were not disqualified. In the late 1990s, a number of relevant professional societies in United States called for elimination of gender verification, including the American Medical Association, the American Academy of Pediatrics, the American College of Physicians, the American College of Obstetricians and Gynecologists, the Endocrine Society and the American Society of Human Genetics, stating that the method used was uncertain and ineffective. The screening was eliminated as of the 2000 Summer Olympics.
Individuals with XY genotype and functional SRY gene can have a female phenotype, where the underlying cause is androgen insensitivity syndrome (AIS). SRY is essential for 'maleness', loss of SRY gene from Y chromosome means XY individuals that are normally male will have female characteristics (Swyer syndrome).
SRY has been linked to the fact that men are more likely than women to develop dopamine-related diseases such as schizophrenia and Parkinson's disease. SRY makes a protein that controls concentrations of dopamine, the neurotransmitter that carries signals from the brain that control movement and coordination.
SRY arose from a gene duplication of the X chromosome bound gene SOX3, a member of the Sox family. This duplication occurred after the split between monotremes and therians. Monotremes lack SRY and have a ZW-like sex determination system, likely involving DMRT1, whereas therians (marsupials and placental mammals) use the XY sex determination system. SRY is a rapidly evolving gene.