UNSW Embryology

Week 1 Male Sex Determination (sry)

© Dr Mark Hill (2008)

Acknowledgements

Male Sex Determination (sry)

Found in 1990 on the Y chromosome, the sry gene encodes a "testis determining factor" a 204aa protein (Mr 23884 Da).

Sry acts as a transcriptional activator (HMG type-high mobility group) binding to DNA and initiating male sex determination then regulating male development. The protein sequence is shown on this current page and the full genebank entry can also be seen. The sry protein has a HMG box that binds DNA by intercalating in the minor groove. Read about the mapping of the testis determining factor which is SRY.

The actual gene targets of SRY are still being determined but at least one downstream gene Sox9 has been identified. Another gene Dax1 (nuclear hormone-receptor superfamily member) when expressed as a transgene will antagonize Sry and also force dosage-sensitive sex reversal.

space fill model of SRY protein

original image source

Y chromosome

What else is the Y Chromosome good for?

As well as containing the SRY gene the Y chromosome has been used more recently to estimate the evolutionary age of Humans. Using comparative studies the researchers have found that our ancestors came out of Africa more recently (50,000 years ago) than previously determined by mitochondrial studies.

• Recent common ancestry of human Y chromosomes: Evidence from DNA sequence data. Russell Thomson, Jonathan K. Pritchard, Peidong Shen, Peter J. Oefner, and Marcus W. Feldman Proc. Natl. Acad. Sci. USA, Vol. 97, Issue 13, 7360-7365, June 20, 2000.
• Population genetic implications from sequence variation in four Y chromosome genes. Peidong Shen*,, Frank Wang*, Peter A. Underhill, Claudia Franco*, Wei-Hsien Yang*, Adriane Roxas*, Raphael Sung*, Alice A. Lin, Richard W. Hyman*, Douglas Vollrath, Ronald W. Davis*, L. Luca Cavalli-Sforza, and Peter J. Oefner*Proc. Natl. Acad. Sci. USA, Vol. 97, Issue 13, 7354-7359, June 20, 2000
• Genome, diversity, and origins: The Y chromosome as a storyteller. Jaume Bertranpetit Proc. Natl. Acad. Sci. USA, Vol. 97, Issue 13, 6927-6929, June 20, 2000.

Human sry Protein Sequence

 

        10         20         30         40         50         60 
         |          |          |          |          |          | 
MQSYASAMLS VFNSDDYSPA VQENIPALRR SSSFLCTESC NSKYQCETGE NSKGNVQDRV
                  
        70         80         90        100        110        120 
         |          |          |          |          |          | 
KRPMNAFIVW SRDQRRKMAL ENPRMRNSEI SKQLGYQWKM LTEAEKWPFF QEAQKLQAMH
                  
       130        140        150        160        170        180 
         |          |          |          |          |          | 
REKYPNYKYR PRRKAKMLPK NCSLLPADPA SVLCSEVQLD NRLYRDDCTK ATHSRMEHQL
                  
       190        200
         |          |
GHLPPINAAS SPQQRDRYSH WTKL
                  
                  

Sequence 60-128 is the HMG box.

In a human XY female, there is mutation giving a F to S conversion at position 109.
(Acc# S53156)

Developmental Abnormalities

Defects in sry lead to 46,XY complete gonadal dysgenesis ( "XY FEMALES" or Swyer Syndrome). This leads to rapid gonadal degeneration leaving only "streak gonads" of fibrous tissue and ovarian stroma. At puberty there is no development of secondary sexual characteristics. These patients have female external genitalia, in contrast 46,XY partial gonadal dysgenesis patients have ambiguous genitalia.

OMIM Entry- GONADAL DYSGENESIS, XY FEMALE TYPE; GDXY
OMIM Entry- GONADAL DYSGENESIS, XY TYPE

References

• A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif Sinclair,A.H., Berta,P., Palmer,M.S., Hawkins,J.R., Griffiths,B.L., Smith,M.J., Foster,J.W., Frischauf,A.M., Lovell-Badge,R. and Goodfellow,P.N. Nature 346 (6281), 240-244 (1990)
• A human XY female with a frame shift mutation in the candidate testis-determining gene SRY. Jager RJ, Anvret M, Hall K, Scherer GNature 1990 Nov 29;348(6300):452-4 Abstract
• Genetic evidence equating SRY and the testis-determining factor. Berta P, Hawkins JR, Sinclair AH, Taylor A, Griffiths BL, Goodfellow PN, Fellous M Nature 1990 Nov 29;348(6300):448-50 Abstract
• The molecular biology of SRY and its role in sex determination in mammals. Koopman P Reprod Fertil Dev 1995;7(4):713-22 Abstract
• Dax1 antagonizes Sry action in mammalian sex determination. Swain A, Narvaez V, Burgoyne P, Camerino G, Lovell-Badge R Nature 1998 Feb 19;391(6669):761-7 Abstract
• Sex in the 90s: SRY and the switch to the male pathway. Capel B Annu Rev Physiol 1998;60:497-523
• Sry and Sox9: mammalian testis-determining genes. Koopman P Cell Mol Life Sci 1999 Jun;55(6-7):839-56 Centre for Molecular and Cellular Biology, University of Queensland, Brisbane, Australia. Abstract p.koopman@cmcb.uq.edu.au
• OMIM- SEX-DETERMINING REGION Y; SRY

Quick Links

Week 1 Pages:

Introduction | Abnormalities | Gamete formation | Cell division | Fertilization | Zygote | Blastocyst | Male sex determination| X inactivation | References | Text only page | WWW Links |

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