• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Mar 1, 1994; 91(5): 1927–1931.

An SRY-related sequence on the marsupial X chromosome: implications for the evolution of the mammalian testis-determining gene.


The SRY gene on the human, mouse, and marsupial Y chromosomes is the testis-determining gene that initiates male development in mammals. The SRY protein has a DNA-binding domain (high mobility group or HMG box) similar to those found in the high-mobility-group proteins. SRY is specific for the Y chromosome, but many autosomal genes have been identified that possess a similar HMG box region; those with the most closely SRY-related box regions form a gene family now referred to as SOX genes. We have identified a sequence on the marsupial X chromosome that shares homology with SRY. Sequence comparisons show near-identity with the mouse and human SOX3 gene (formerly called a3), the SOX gene which is the most closely related to SRY. We suggest here that the highly conserved X chromosome-linked SOX3 represents the ancestral SOX gene from which the sex-determining gene SRY was derived. In this model SOX3/SRY divergence and the acquisition of a testis-determining role by SRY might have preceded (and initiated) sex chromosome differentiation or, alternatively, might have been a consequence of X chromosome-Y chromosome differentiation initiated at the locus of an original sex-determining gene(s), later superseded by SRY.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, Foster JW, Frischauf AM, Lovell-Badge R, Goodfellow PN. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature. 1990 Jul 19;346(6281):240–244. [PubMed]
  • Berta P, Hawkins JR, Sinclair AH, Taylor A, Griffiths BL, Goodfellow PN, Fellous M. Genetic evidence equating SRY and the testis-determining factor. Nature. 1990 Nov 29;348(6300):448–450. [PubMed]
  • Jäger RJ, Anvret M, Hall K, Scherer G. A human XY female with a frame shift mutation in the candidate testis-determining gene SRY. Nature. 1990 Nov 29;348(6300):452–454. [PubMed]
  • Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R. Male development of chromosomally female mice transgenic for Sry. Nature. 1991 May 9;351(6322):117–121. [PubMed]
  • Harley VR, Jackson DI, Hextall PJ, Hawkins JR, Berkovitz GD, Sockanathan S, Lovell-Badge R, Goodfellow PN. DNA binding activity of recombinant SRY from normal males and XY females. Science. 1992 Jan 24;255(5043):453–456. [PubMed]
  • Ferrari S, Harley VR, Pontiggia A, Goodfellow PN, Lovell-Badge R, Bianchi ME. SRY, like HMG1, recognizes sharp angles in DNA. EMBO J. 1992 Dec;11(12):4497–4506. [PMC free article] [PubMed]
  • Foster JW, Brennan FE, Hampikian GK, Goodfellow PN, Sinclair AH, Lovell-Badge R, Selwood L, Renfree MB, Cooper DW, Graves JA. Evolution of sex determination and the Y chromosome: SRY-related sequences in marsupials. Nature. 1992 Oct 8;359(6395):531–533. [PubMed]
  • Gubbay J, Collignon J, Koopman P, Capel B, Economou A, Münsterberg A, Vivian N, Goodfellow P, Lovell-Badge R. A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature. 1990 Jul 19;346(6281):245–250. [PubMed]
  • Griffiths R. The isolation of conserved DNA sequences related to the human sex-determining region Y gene from the lesser black-backed gull (Larus fuscus). Proc Biol Sci. 1991 May 22;244(1310):123–128. [PubMed]
  • Graves JA, Watson JM. Mammalian sex chromosomes: evolution of organization and function. Chromosoma. 1991 Nov;101(2):63–68. [PubMed]
  • Mitchell MJ, Woods DR, Wilcox SA, Graves JA, Bishop CE. Marsupial Y chromosome encodes a homologue of the mouse Y-linked candidate spermatogenesis gene Ube1y. Nature. 1992 Oct 8;359(6395):528–531. [PubMed]
  • Graves JA, Schmidt MM. Mammalian sex chromosomes: design or accident? Curr Opin Genet Dev. 1992 Dec;2(6):890–901. [PubMed]
  • Reed KC, Mann DA. Rapid transfer of DNA from agarose gels to nylon membranes. Nucleic Acids Res. 1985 Oct 25;13(20):7207–7221. [PMC free article] [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Sinclair AH, Wrigley JM, Marshall Graves JA. Autosomal assignment of OTC in marsupials and monotremes: implications for the evolution of sex chromosomes. Genet Res. 1987 Oct;50(2):131–136. [PubMed]
  • Ewens WJ, Griffiths RC, Ethier SN, Wilcox SA, Graves JA. Statistical analysis of in situ hybridization data: derivation and use of the zmax test. Genomics. 1992 Apr;12(4):675–682. [PubMed]
  • Stevanović M, Lovell-Badge R, Collignon J, Goodfellow PN. SOX3 is an X-linked gene related to SRY. Hum Mol Genet. 1993 Dec;2(12):2013–2018. [PubMed]
  • Whitfield LS, Lovell-Badge R, Goodfellow PN. Rapid sequence evolution of the mammalian sex-determining gene SRY. Nature. 1993 Aug 19;364(6439):713–715. [PubMed]
  • Chandra HS. Is human X chromosome inactivation a sex-determining device? Proc Natl Acad Sci U S A. 1985 Oct;82(20):6947–6949. [PMC free article] [PubMed]
  • Page DC, Mosher R, Simpson EM, Fisher EM, Mardon G, Pollack J, McGillivray B, de la Chapelle A, Brown LG. The sex-determining region of the human Y chromosome encodes a finger protein. Cell. 1987 Dec 24;51(6):1091–1104. [PubMed]
  • Hamvas RM, Zinn A, Keer JT, Fisher EM, Beer-Romero P, Brown SD, Page DC. Rps4 maps near the inactivation center on the mouse X chromosome. Genomics. 1992 Feb;12(2):363–367. [PubMed]
  • Schneider-Gädicke A, Beer-Romero P, Brown LG, Nussbaum R, Page DC. ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation. Cell. 1989 Jun 30;57(7):1247–1258. [PubMed]
  • Watson JM, Frost C, Spencer JA, Graves JA. Sequences homologous to the human X- and Y-borne zinc finger protein genes (ZFX/Y) are autosomal in monotreme mammals. Genomics. 1993 Feb;15(2):317–322. [PubMed]
  • Pamilo P, Bianchi NO. Evolution of the Zfx and Zfy genes: rates and interdependence between the genes. Mol Biol Evol. 1993 Mar;10(2):271–281. [PubMed]
  • Shimmin LC, Chang BH, Li WH. Male-driven evolution of DNA sequences. Nature. 1993 Apr 22;362(6422):745–747. [PubMed]
  • Salido EC, Yen PH, Koprivnikar K, Yu LC, Shapiro LJ. The human enamel protein gene amelogenin is expressed from both the X and the Y chromosomes. Am J Hum Genet. 1992 Feb;50(2):303–316. [PMC free article] [PubMed]
  • Legouis R, Hardelin JP, Levilliers J, Claverie JM, Compain S, Wunderle V, Millasseau P, Le Paslier D, Cohen D, Caterina D, et al. The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules. Cell. 1991 Oct 18;67(2):423–435. [PubMed]
  • Yen PH, Marsh B, Allen E, Tsai SP, Ellison J, Connolly L, Neiswanger K, Shapiro LJ. The human X-linked steroid sulfatase gene and a Y-encoded pseudogene: evidence for an inversion of the Y chromosome during primate evolution. Cell. 1988 Dec 23;55(6):1123–1135. [PubMed]
  • Mitchell MJ, Woods DR, Tucker PK, Opp JS, Bishop CE. Homology of a candidate spermatogenic gene from the mouse Y chromosome to the ubiquitin-activating enzyme E1. Nature. 1991 Dec 12;354(6353):483–486. [PubMed]
  • Tucker PK, Lundrigan BL. Rapid evolution of the sex determining locus in Old World mice and rats. Nature. 1993 Aug 19;364(6439):715–717. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • OMIM
    OMIM record citing PubMed
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...