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The SRY protein is a monomeric 203 residues long polypeptide. It is a transcriptionnal factor, more precisely a transcriptionnal activator of the Müllerian Inhibiting Substance (MIS gene). It is encoded by the testis-determining sex gene and is itself involved in the sex determination in mammels by being responsible for the male sexual developement.

History

After centuries of unfounded theories mainly based on environmental factors, the first molecular theory concerning the sex determination appeared in 1891. At this time, the german biologist Hermann Henking was studying sperm formation in wasps. He noticed that some wasp sperm cells own 12 chromosomes whereas some only own 11. As this chromosome look different from the others during the meiosis process, he suspected it to play a role in sex determination, without any proof. He called it the "X chromosome". Ten years later, Clarence Erwin McClung saw that the X chromosome behaved differently during the meiosis and was only present in half the sperm cells of grasshoppers. As the main characteristic that varies in 50/50 proportions among zygotes is the sex, McClung suspected the X chromosome to be implicated in sexual development. In 1905, Nettie Stevens discovered the "Y chromosome" (and so, the female XX and male XY patterns) while she was counting the chromosomes of beetles under the microscope. ^[1] During the next decades, a few theories were in competition. In 1921, Calvin Bridges's works on Drosophila melanogaster seemed to reveal that male characters acquisition is due to a genic balance between the genes contained in the X chromosome and those contained in the autosomes ^[2]. In 1930, Ronald Fisher introduced the first Y-based control of sex theory by proposing two different models : either all the genes responsible for the male characters are located on the Y chromosome or there is a Y-located gene which regulates the expression of genes elsewhere in the genome. ^[3] As Alfred Jost had shown the testosterone produced by the testis is responsible for the entire male phenotype acquisition^[4], in 1988, Goodfellow and Darling proposed that there is a gene on the Y chromosome which drives the development of the testis.^[5]

It has been shown that a mutation of SRY increase male to female sex reversal for 15% REF NECESSAIRE

SRY gene

The SRY gene encodes the SRY protein. It is located on the Y chromosom.

Structure

The SRY-HMG domain

SRY-HMG stands for Sex determining Region Y - High Mobility Domain It is a approximately 80 residues domain. It mediates minor groove DNA binding proteins. Twisted L shape : Concave surface. 3 helices & N and C end strands. Binds the DNA by its minor groove. 2 kinds of HMG domain:

• HMG1
• HMG2

General structure of SRY

3 domains:

• N-term domain
• Central domain
• C-term domain

Structure of the DNA target site

Function

Sex determining

It acts like a sex determinator thanks to it transcriptionnal activity. It inhibits the developpement of female sex structure in th embryonnic individual.

Implication - Future for SRY ?

Disease

Relevance

Structural highlights

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