History and function of the SRY gene

Although the sex chromosome was discovered in 1921, its role in gender determination was only first recognized in the 60s from observations of abnormal karyotypes (Turner [XO] and Klinefelter [XXY, see below]). One indeed already knew that the Y chromosome, independent of how many X chromosomes were present, determined the differentiation of the gonads into testes. It is true that the factor that is responsible for determining maleness was suspected as being on the Y chromosome as a TDF (testis determining factor) but it was not found for a long time. It was only thanks to the DNA analysis of a "woman" with an XY karyotype and "three men" with an XX karyotype that the responsible gene was finally identified in 1985.

The sequencing and cloning of the DNA of these individuals made it possible, finally, to isolate the section that is responsible for determining gender. The tissue compatible antigen H-Y and the ZFY gene that initially were made responsible for gender determination could be excluded (this gene was missing in the male individuals), while the SRY gene that was on the short arm of the Y chromosome (Yp) was found in all three. The woman with the XY karyotype also exhibited this SRY gene – which was à priori contradictory – but it was confirmed that a mutation was involved that made the gene functionless.

The expression of the SRY gene coincided with the moment of the gender determination, since it is expressed in the somatic cells of the male genital ridge.

The transcription factor (protein made from 204 amino acids) that is coded by the SRY gene possesses an HMG (High Mobility Group) domain that makes it possible for it to bind with the DNA. The DNA forms a loop. This modification of the chromatin form permits the approach and interaction of transcription factors that, for their part, cause the expression of other genes, initiating the formation of the testes as well as the other male sex organs

However, the precise mechanisms are still unknown. It is also important to keep in mind that the gender differentiation is accomplished through a cascade of gene activations. Further factors are involved, then, before as well as after the SRY expression (Schematic diagram concerning the molecular factors involved in the development of the genital apparatus).