SRY

Sex determining region Y

PDB rendering based on 1hry.
Identifiers
Symbols SRY; TDF; TDY
External IDs OMIM: 480000 MGI: 98660 HomoloGene: 48168 GeneCards: SRY Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 6736 21674
Ensembl ENSG00000184895 ENSMUSG00000069036
UniProt Q05066 Q2T9H0
RefSeq (mRNA) NM_003140.1 NM_011564
RefSeq (protein) NP_003131.1 NP_035694
Location (UCSC) Chr Y:
2.65 – 2.66 Mb		 Chr Y:
1.95 – 1.95 Mb
PubMed search [1] [2]

SRY (Sex-determining region Y) is a sex-determining gene on the Y chromosome in the therians (placental mammals and marsupials).[1]

This intronless gene encodes a transcription factor that is a member of the SOX (SRY-like box) gene family of DNA-binding proteins. This protein is the therian testis determining factor (TDF), referred to as the sex-determining region Y protein or 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.[2]

Contents

Molecular Biology of testis determination

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 bipotential 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 differentiation. Fgf9 then feeds back and upregulates SOX9. SOX9 can also upregulate itself by binding to its own enhancer region (positive feedback loop). 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 constitutes the basic series of events, this brief review should be taken with caution since there are many more factors that influence sex differentiation.

Effect upon anatomical sex

Since its discovery, the importance of the SRY gene in sex determination has been extensively documented:

SRY and the Olympics

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, stating that the method used was uncertain and ineffective.[4] The screening was eliminated as of the 2000 Summer Olympics.[4][5][6]

SRY-related diseases and defects

Individuals with XY genotype and functional SRY gene can have an outwardly female phenotype due to an underlying 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.[7]

Evolution

SRY may have arisen from a gene duplication of the X chromosome bound gene SOX3, a member of the Sox family.[8] 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.[9] SRY is a rapidly evolving gene.[10] A small number of mammals lack this gene entirely and use an alternative form of sex determination.[11]

Interactions

SRY has been shown to interact with the androgen receptor.[12]

See also

References

  1. ^ Wallis MC, Waters PD, Graves JA (June 2008). "Sex determination in mammals - Before and after the evolution of SRY". Cell. Mol. Life Sci. 65 (20): 3182–95. doi:10.1007/s00018-008-8109-z. PMID 18581056. 
  2. ^ "Entrez Gene: SRY sex determining region Y". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6736. 
  3. ^ Biason-Lauber A, Konrad D, Meyer M, DeBeaufort C, Schoenle EJ (May 2009). "Ovaries and Female Phenotype in a Girl with 46,XY Karyotype and Mutations in the CBX2 Gene". Am. J. Hum. Genet. 84 (5): 658–63. doi:10.1016/j.ajhg.2009.03.016. PMC 2680992. PMID 19361780. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2680992. Lay summary – New Scientist. 
  4. ^ a b Facius GM (2004-08-01). "The Major Medical Blunder of the 20th Century". Gender Testing. facius-homepage.dk. http://www.123hjemmeside.dk/Facius/7031466. Retrieved 2011-06-12. 
  5. ^ Elsas LJ, Ljungqvist A, Ferguson-Smith MA, Simpson JL, Genel M, Carlson AS, Ferris E, de la Chapelle A, Ehrhardt AA (2000). "Gender verification of female athletes". Genet. Med. 2 (4): 249–54. doi:10.1097/00125817-200007000-00008. PMID 11252710. 
  6. ^ Dickinson BD, Genel M, Robinowitz CB, Turner PL, Woods GL (October 2002). "Gender verification of female Olympic athletes". Med Sci Sports Exerc 34 (10): 1539–42; discussion 1543. doi:10.1097/00005768-200210000-00001. PMID 12370551. 
  7. ^ Dewing, P; Chiang CW, Sinchak K, Sim H, Fernagut PO, Kelly S, Chesselet MF, Micevych PE, Albrecht KH, Harley VR, Vilain E (Feb 21 2006). "Direct regulation of adult brain function by the male-specific factor SRY". Current Biology 16 (4): 415–20. doi:10.1016/j.cub.2006.01.017. PMID 16488877. 
  8. ^ Katoh K, Miyata T (1999). "A heuristic approach of maximum likelihood method for inferring phylogenetic tree and an application to the mammalian SOX-3 origin of the testis-determining gene SRY". FEBS Lett 463 (1–2): 129–32. doi:10.1016/S0014-5793(99)01621-X. PMID 10601652. 
  9. ^ Veyrunes F, Waters PD, Miethke P et al. (2008). "Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes". Genome Res 18 (6): 965–73. doi:10.1101/gr.7101908. PMC 2413164. PMID 18463302. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2413164. 
  10. ^ Bowles J, Schepers G, Koopman P (2000). "Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators". Dev Biol 227 (2): 239–55. doi:10.1006/dbio.2000.9883. PMID 11071752. 
  11. ^ Kuroiwa A, Handa S, Nishiyama C, Chiba E, Yamada F, Abe S, Matsuda Y (June 2011). "Additional copies of CBX2 in the genomes of males of mammals lacking SRY, the Amami spiny rat (Tokudaia osimensis) and the Tokunoshima spiny rat (Tokudaia tokunoshimensis)". Chromosome Res 19 (5): 635–44. doi:10.1007/s10577-011-9223-6. PMID 21656076. 
  12. ^ Yuan X, Lu ML, Li T, Balk SP (December 2001). "SRY interacts with and negatively regulates androgen receptor transcriptional activity". J. Biol. Chem. 276 (49): 46647–54. doi:10.1074/jbc.M108404200. PMID 11585838. 

Further reading

External Links