Skip to main content
SpringerLink
Log in

Sex determination in platypus and echidna: autosomal location of SOX3 confirms the absence of SRY from monotremes

  • Published:
Chromosome Research Aims and scope Submit manuscript

Abstract

In eutherian (‘placental’ mammals, sex is determined by the presence or absence of the Y chromosome-borne gene SRY, which triggers testis determination. Marsupials also have a Y-borne SRY gene, implying that this mechanism is ancestral to therians, the SRY gene having diverged from its X-borne homologue SOX3 at least 180 million years ago. The rare exceptions have clearly lost and replaced the SRY mechanism recently. Other vertebrate classes have a variety of sex-determining mechanisms, but none shares the therian SRY-driven XX female:XY male system. In monotreme mammals (platypus and echidna), which branched from the therian lineage 210 million years ago, no orthologue of SRY has been found. In this study we show that its partner SOX3 is autosomal in platypus and echidna, mapping among human X chromosome orthologues to platypus chromosome 6, and to the homologous chromosome 16 in echidna. The autosomal localization of SOX3 in monotreme mammals, as well as non-mammal vertebrates, implies that SRY is absent in Prototheria and evolved later in the therian lineage 210-180 million years ago. Sex determination in platypus and echidna must therefore depend on another male-determining gene(s) on the Y chromosomes, or on the different dosage of a gene(s) on the X chromosomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bowles J, Schepers G, Koopman P (2000) Phylogeny of the SOX family of transcription factors based on sequence and structural indicators. Dev Biol 227: 239–55.

    Article  CAS  PubMed  Google Scholar 

  • Charlesworth B (1991) The evolution of sex chromosomes. Science 251: 1030–033.

    Article  CAS  PubMed  Google Scholar 

  • Delbridge ML, Lingenfelter PA, Disteche CM, Graves JAM (1999) The candidate spermatogenesis gene RBMY has a homologue on the human X chromosome. Nat Genet 22: 223–24.

    Article  CAS  PubMed  Google Scholar 

  • Delbridge ML, Longepied G, Depetris D, et al. (2004) TSPY, the candidate gonadoblastoma gene on the human Y chromosome, has a widely expressed homologue on the X - implications for Y chromosome evolution. Chromosome Res 12: 345–56.

    Article  CAS  PubMed  Google Scholar 

  • Delbridge ML, Wallis MC, Kirby PJ, Alsop AE, Grützner F, Graves JAM (2006) Assignment of SOX1 to platypus chromosome 20q by fluorescence in situ hybridization. Cytogenet Genome Res 112: 342L.

    Article  CAS  PubMed  Google Scholar 

  • Dewing P, Chiang CW, Sinchak K, et al. (2006) Direct regulation of adult brain function by the male-specific factor SRY. Curr Biol 16: 415–20.

    Article  CAS  PubMed  Google Scholar 

  • El-Mogharbel N, Wakefield M, Deakin JE, et al. (2007) DMRT gene cluster analysis in the platypus: new insights into genomic organization and regulatory regions. Genomics 89: 10–1.

    Article  CAS  PubMed  Google Scholar 

  • Ezaz T, Quinn AE, Miura I, Sarre SD, Georges A, Graves JAM (2005) The dragon lizard Pogona vitticeps has ZZ/ZW micro-sex chromosomes. Chromosome Res 13: 763–76.

    Article  CAS  PubMed  Google Scholar 

  • Ezaz T, Stiglec R, Veyrunes F, Graves JAM (2006a) Relationships between vertebrate ZW and XY sex chromosome systems. Curr Biol 16: R736–43.

    Article  CAS  Google Scholar 

  • Ezaz T, Valenzuela N, Grützner F, et al. (2006b) An XX/XY sex microchromosome system in a freshwater turtle, Chelodina longicollis (Testudines: Chelidae) with genetic sex determination. Chromosome Res 14: 139–50.

    Article  CAS  Google Scholar 

  • Ferguson-Smith MA (2007) The evolution of sex chromosomes and sex determination in vertebrates and the key role of DMRT1. Sex Dev 1: 2–1.

    Article  CAS  PubMed  Google Scholar 

  • Flannery TF, Groves CP (1998) A revision of the genus Zaglossus (Monotremata, Tachyglossidae), with description of new species and subspecies. Mammalia 62: 367–96.

    Article  Google Scholar 

  • Ford CE, Jones KW, Polani PE, de Almeida JC, Briggs JH (1959) A sex chromosome anomaly in a case of gonadal dysgenesis (Turner’s syndrome). Lancet i: 711–13.

    Article  Google Scholar 

  • Foster JW, Brennan FE, Hampikian GK, et al. (1992) Evolution of sex determination and the Y chromosome: SRY-related sequences in marsupials. Nature 359: 530–31.

    Article  Google Scholar 

  • Foster JW, Graves JAM (1994) An SRY-related sequence on the marsupial X chromosome: Implications for the evolution of the mammalian testis-determining gene. Proc Natl Acad Sci USA 91: 1927–931.

    Article  CAS  PubMed  Google Scholar 

  • Grafodatskaya D, Rens W, Wallis MC, et al. (2007) Search for the sex determining switch in monotremes: Mapping WT1, SF1, LHX1, LHX9, FGF9, WNT4, RSPO1 and GATA4 in platypus. Chromosome Res 15: 777–85.

    Article  CAS  PubMed  Google Scholar 

  • Graves JAM (1995) The evolution of mammalian sex chromosomes and the origin of sex determining genes. Philos Trans R Soc Lond B Biol Sci 350: 305–11.

    Article  CAS  PubMed  Google Scholar 

  • Graves JAM (1998) Interactions between SRY and SOX genes in mammalian sex determination. Bioessays 20: 264–69.

    Article  CAS  PubMed  Google Scholar 

  • Graves JAM (2006) Sex chromosome specialization and degeneration in mammals. Cell 124: 901–14.

    Article  PubMed  Google Scholar 

  • Grützner F, Rens W, Tsend-Ayush E, et al. (2004) In the platypus a meiotic chain of ten sex chromosomes shares genes with the bird Z and the mammal X chromosomes. Nature 432: 913–17.

    Article  PubMed  Google Scholar 

  • Hanley NA, Hagan DM, Clement-Jones M, et al. (2000) SRY, SOX9 and DAX1 expression patterns during human sex determination and gonadal development. Mech Dev 91: 403–07.

    Article  CAS  PubMed  Google Scholar 

  • Harley VR, Clarkson MJ, Argentaro A (2003) The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9 [SRY-related high-mobility group (HMG) box 9]. Endocr Rev 24: 466–87.

    Article  CAS  PubMed  Google Scholar 

  • Harry JL, Koopman P, Brennan FE, Graves JAM, Renfree MB (1995) Widespread expression of the testis-determining gene SRY in a marsupial. Nat Genet 11: 347–49.

    Article  CAS  PubMed  Google Scholar 

  • Hori T, Asakawa S, Itoh Y, Shimizu N, Mizuno S (2000) Wpkci encoding an altered form of PKCI is conserved widely on the avian W chromosome and expressed early in female embryos: implication of its role in female sex determination. Mol Biol Cell 11: 3645–660.

    CAS  PubMed  Google Scholar 

  • Huang B, Wang S, Ning Y, Lamb AN, Bartley J (1999) Autosomal XX sex reversal caused by duplication of SOX9. Am J Med Genet 87: 349–53.

    Article  CAS  PubMed  Google Scholar 

  • Itoh Y, Kampf K, Arnold AP (2006) Assignment of human X-linked genes to a zebrafinch microchromosome by in situ hybridization of BAC clones. Cytogenet Genome Res 112: 342M.

    Article  CAS  PubMed  Google Scholar 

  • Jacobs PA, Strong JA (1959) A case of human intersexuality having a possible XXY sex-determining mechanism. Nature 183: 302.

    Article  CAS  PubMed  Google Scholar 

  • Just W, Rau W, Akhverdian M, et al. (1995) Sex determination in Ellobius lutescens and E. tancrei in the absence of the Y chromosome and the Sry gene. Nat Genet 11: 117–18.

    Article  CAS  PubMed  Google Scholar 

  • Kim Y, Kobayashi A, Sekido R, et al. (2006) Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biol 4: e187.

    Article  PubMed  Google Scholar 

  • Kirby PJ, Waters PD, Delbridge M, et al. (2002) Cloning and mapping of platypus SOX2 and SOX14: insights into SOX group B evolution. Cytogenet Genome Res 98: 96–00.

    Article  CAS  PubMed  Google Scholar 

  • Koopman P, Münsterberg A, Capel B, Vivian N, Lovell-Badge R (1990) Expression of a candidate sex -determining gene during mouse testis differentiation. Nature 348: 450–52.

    Article  CAS  PubMed  Google Scholar 

  • Koopman P, Schepers G, Brenner S, Venkatesh B (2004) Origin and diversity of the Sox transcription factor gene family: genome-wide analysis in Fugu rubripes. Gene 328: 177–86.

    Google Scholar 

  • Kuroiwa A, Uchikawa M, Kamachi Y, et al. (2002) Chromosome assignment of eight SOX family genes in chicken. Cytogenet Genome Res 98: 189–93.

    Google Scholar 

  • Lahr G, Maxson SC, Mayer A, Just W, Pilgrim C, Reisert I (1995) Transcription of the Y chromosome gene, Sry, in adult mouse brain. Brain Res Mol Brain Res 33: 179–82.

    Google Scholar 

  • Laumonnier F, Ronce N, Hamel BC, et al. (2002) Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency. Am J Hum Genet 72: 1450–455.

    Google Scholar 

  • Lovell-Badge R, Canning C, Sekido R (2002) Sex-determining genes in mice: building pathways. Novartis Found Symp 244: 4–8.

    Google Scholar 

  • Matsubara K, Tarui H, Toriba M, et al. (2006) Evidence for different origin of sex chromosomes in snakes, birds, and mammals and step-wise differentiation of snake sex chromosomes. Proc Natl Acad Sci USA 103: 18190–8195.

    Article  CAS  PubMed  Google Scholar 

  • Mayer A, Mosler G, Just W, Pilgrim C, Reisert I (2000) Developmental profile of Sry transcripts in mouse brain. Neurogenetics 3: 25–0.

    Article  CAS  PubMed  Google Scholar 

  • Muller HJ (1914) A gene for the fourth chromosome of Drosophila. J Exp Zool 17: 325–36.

    Article  Google Scholar 

  • O’Neill M, Binder M, Smith C, et al. (2000) ASW, a gene with conserved avian W-linkage and female specific expression in chick embryonic gonad. Dev Genes Evol 210: 243–49.

    Article  PubMed  Google Scholar 

  • Ogata M, Ohtani H, Igarashi T, Hasegawa Y, Ichikawa Y, Miura I (2003) Change of heterogametic sex from male to female in the frog. Genetics 164: 613–20.

    CAS  PubMed  Google Scholar 

  • Ohno S (1967) Sex Chromosomes and Sex-linked Genes, Springer-Verlag, Berlin.

    Google Scholar 

  • Pannetier M, Tilly G, Kocer A, et al. (2006) Goat SRY induces testis development in XX transgenic mice. FEBS Lett 580: 3715–720.

    Article  CAS  PubMed  Google Scholar 

  • Parma P, Radi O, Vidal V, et al. (2006) R-spondin1 is essential in sex determination, skin differentiation and malignancy. Nat Genet 38: 1304–309.

    Article  CAS  PubMed  Google Scholar 

  • Pask A, Renfree MB, Graves JAM (2000a) The human sex-reversing ATRX gene has a homologue on the marsupial Y chromosome, ATRY: implications for the evolution of mammalian sex determination. Proc Natl Acad Sci USA 97: 13198–3202.

    Article  CAS  Google Scholar 

  • Pask AJ, Harry JL, Renfree MB, Graves JAM (2000b) Absence of SOX3 in the developing marsupial gonad is not consistent with a conserved role in mammalian sex determination. Genesis 27: 145–52.

    Article  CAS  Google Scholar 

  • Polanco JC, Koopman P (2006) Sry and the hesitant beginnings of male development. Dev Biol 302: 13–4.

    Article  PubMed  Google Scholar 

  • Quinn AE, Georges A, Sarre SD, Guarino F, Ezaz T, Graves JAM (2007) Temperature sex reversal implies sex gene dosage in a reptile. Science 316: 411.

    Article  CAS  PubMed  Google Scholar 

  • Raverot G, Weiss J, Park SY, Hurley L, Jameson JL (2005) Sox3 expression in undifferentiated spermatogonia is required for the progression of spermatogenesis. Dev Biol 283: 215–25.

    Article  CAS  PubMed  Google Scholar 

  • Raymond CS, Kettlewell JR, Hirsch B, Bardwell VJ, Zarkower D (1999) Expression of Dmrt1 in the genital ridge of mouse and chicken embryos suggests a role in vertebrate sexual development. Dev Biol 215: 208–20.

    Article  CAS  PubMed  Google Scholar 

  • Reed KJ, Sinclair AH (2002) FET-1: a novel W-linked female specific gene up-regulated in the embryonic chicken ovary. Mech Dev 119: S87–0.

    Article  PubMed  Google Scholar 

  • Rens W, O’Brien PC, Fairclough H, Graves JAM, Ferguson-Smith MA (2004) Resolution and evolution of the duck-billed platypus karyotype with an X1Y1X2Y2X3Y3X4Y4X5Y5 male sex chromosome constitution. Proc Natl Acad Sci USA 101: 16257–6261.

    Google Scholar 

  • Rens W, O’Brien PC, Grützner F, et al. (2007) The multiple sex chromosomes of platypus and echidna are not completely identical and several share homology with the avian Z. Genome Biol 8: R243.

    Article  CAS  PubMed  Google Scholar 

  • Ross MT, Grafham DV, Coffey AJ, et al. (2005) The DNA sequence of the human X chromosome. Nature 434: 325–37.

    Article  CAS  PubMed  Google Scholar 

  • Shetty S, Griffin DK, Graves JAM (1999) Comparative painting reveals strong chromosome homology over 80 million years of bird evolution. Chromosome Res 7: 289–95.

    Article  CAS  PubMed  Google Scholar 

  • Sinclair AH, Berta P, Palmer MS, et al. (1990) A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346: 240–44.

    Article  CAS  PubMed  Google Scholar 

  • Smith CA, McClive PJ, Western PS, Reed KJ, Sinclair AH (1999) Evolution: conservation of a sex-determining gene. Nature 402: 601–02.

    Article  CAS  PubMed  Google Scholar 

  • Soullier S, Hanni C, Catzeflis F, Berta P, Laudet V (1998) Male sex determination in the spiny rat Tokudaia osimensis (Rodentia: Muridae) is not Sry dependent. Mamm Genome 9: 590–92.

    Article  CAS  PubMed  Google Scholar 

  • Südbeck P, Schmitz ML, Baeuerle PA, Scherer G (1996) Sex reversal by loss of the C-terminal transactivation domain of human SOX9. Nat Genet 13: 230–32.

    Article  PubMed  Google Scholar 

  • Sutou S, Mitsui Y, Tsuchiya K (2001) Sex determination without the Y chromosome in two Japanese rodents Tokudaia osimensis osimensis and Tokudaia osimensis spp. Mamm Genome 12: 17–1.

    Article  CAS  PubMed  Google Scholar 

  • Teranashi M, Shimada Y, Hori T, et al. (2001) Transcripts of the MHM region on the chicken Z chromosome accumulate as non-coding RNA in the nucleus of female cells adjacent to the DMRT1 locus. Chromosome Res 9: 147–65.

    Article  Google Scholar 

  • Toder R, Wilcox SA, Smithwick M, Graves JAM (1996) The human/mouse imprinted genes IGF2, H19, SNRPN and ZNF127 map to conserved autosomal clusters in a marsupial. Chromosome Res 4: 295–00.

    Article  CAS  PubMed  Google Scholar 

  • Tsend-Ayush E, O'Sullivan LA, Grutzner FS, et al. (2005) RBMX gene is essential for brain development in zebrafish. Dev Dyn 234: 682–88.

    Article  CAS  PubMed  Google Scholar 

  • Valenzuela N, Lance VA (2004) Temperature-dependent Sex Determination in Vertebrates, Smithsonian Books, New York.

    Google Scholar 

  • Wallis MC, Delbridge ML, Pask AJ, et al. (2007) Mapping platypus SOX genes; autosomal location of SOX9 excludes it from sex determining role. Cytogenet Genome Res 116: 232–34.

    Article  CAS  PubMed  Google Scholar 

  • Waters PD, Delbridge ML, Deakin JE, et al. (2005) Autosomal location of genes from the conserved mammalian X in platypus (Ornithorhynchus anatinus): implications for mammalian sex chromosome evolution. Chromosome Res 13: 401–10.

    Article  CAS  PubMed  Google Scholar 

  • Waters PD, Wallis MC, Graves JAM (2007) Mammalian sex — Origin and evolution of the Y chromosome and SRY. Semin Cell Dev Biol 18: 389–00.

    Article  CAS  PubMed  Google Scholar 

  • Watson JM, Spencer JA, Riggs AD, Graves JAM (1990) The X chromosome of monotremes shares a highly conserved region with the eutherian and marsupial X chromosomes despite the absence of X chromosome inactivation. Proc Natl Acad Sci USA 87: 7125–129.

    Article  CAS  PubMed  Google Scholar 

  • Wrigley JM, Graves JAM (1988) Karyotypic conservation in the mammalian order monotremata (subclass Prototheria). Chromosoma 96: 231–47.

    Article  CAS  PubMed  Google Scholar 

  • Yamada K, Koyama Y, Komatsubara M (2004) Comprehensive search for chicken W chromosome-linked genes expressed early in female embryos from the female-minus-male subtracted cDNA microarray. Chromosome Res 12: 741–54.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. F. Grützner

    Present address: School of Molecular and Biomedical Science, the University of Adelaide, Adelaide, SA 5005, Australia

Authors and Affiliations

  1. Comparative Genomics Group, Research School of Biological Sciences, the Australian National University, Canberra, ACT 2601, Australia

    M. C. Wallis, P. D. Waters, M. L. Delbridge, P. J. Kirby, F. Grützner & J. A. M. Graves

  2. National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, 27709, USA

    P. J. Kirby

  3. Department of Zoology, the University of Melbourne, Melbourne, VIC 3010, Australia

    A. J. Pask

  4. Cambridge Resource Centre for Comparative Genomics, Department of Veterinary Medicine, University of Cambridge, Cambridge, CB3 0ES, UK

    W. Rens & M. A. Ferguson-Smith

Authors
  1. M. C. Wallis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. D. Waters
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. L. Delbridge
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. J. Kirby
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. J. Pask
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. Grützner
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. W. Rens
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. A. Ferguson-Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J. A. M. Graves
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. C. Wallis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wallis, M.C., Waters, P.D., Delbridge, M.L. et al. Sex determination in platypus and echidna: autosomal location of SOX3 confirms the absence of SRY from monotremes. Chromosome Res 15, 949–959 (2007). https://doi.org/10.1007/s10577-007-1185-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10577-007-1185-3

Key words

Search

Navigation