Chromosome Research

, 15:949

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

  • M. C. Wallis
  • P. D. Waters
  • M. L. Delbridge
  • P. J. Kirby
  • A. J. Pask
  • F. Grützner
  • W. Rens
  • M. A. Ferguson-Smith
  • J. A. M. Graves
Article
First Online:
Received:
Revised:
Accepted:

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.

Key words

Ornithorhynchus anatinus platypus sex determination SOX3 SRY Tachyglossus aculeatus 

References

  1. 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.CrossRefPubMedGoogle Scholar
  2. Charlesworth B (1991) The evolution of sex chromosomes. Science 251: 1030–033.CrossRefPubMedGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 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.CrossRefPubMedGoogle Scholar
  7. 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.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. Ezaz T, Stiglec R, Veyrunes F, Graves JAM (2006a) Relationships between vertebrate ZW and XY sex chromosome systems. Curr Biol 16: R736–43.CrossRefGoogle Scholar
  10. 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.CrossRefGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. Flannery TF, Groves CP (1998) A revision of the genus Zaglossus (Monotremata, Tachyglossidae), with description of new species and subspecies. Mammalia 62: 367–96.CrossRefGoogle Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.CrossRefGoogle Scholar
  15. 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.CrossRefPubMedGoogle Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. Graves JAM (1998) Interactions between SRY and SOX genes in mammalian sex determination. Bioessays 20: 264–69.CrossRefPubMedGoogle Scholar
  19. Graves JAM (2006) Sex chromosome specialization and degeneration in mammals. Cell 124: 901–14.CrossRefPubMedGoogle Scholar
  20. 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.CrossRefPubMedGoogle Scholar
  21. 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.CrossRefPubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 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.CrossRefPubMedGoogle Scholar
  24. 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.PubMedGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 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.CrossRefPubMedGoogle Scholar
  27. Jacobs PA, Strong JA (1959) A case of human intersexuality having a possible XXY sex-determining mechanism. Nature 183: 302.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. 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.CrossRefPubMedGoogle Scholar
  31. 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.CrossRefPubMedGoogle Scholar
  32. 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
  33. 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
  34. 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
  35. 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
  36. Lovell-Badge R, Canning C, Sekido R (2002) Sex-determining genes in mice: building pathways. Novartis Found Symp 244: 4–8.Google Scholar
  37. 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.CrossRefPubMedGoogle Scholar
  38. Mayer A, Mosler G, Just W, Pilgrim C, Reisert I (2000) Developmental profile of Sry transcripts in mouse brain. Neurogenetics 3: 25–0.CrossRefPubMedGoogle Scholar
  39. Muller HJ (1914) A gene for the fourth chromosome of Drosophila. J Exp Zool 17: 325–36.CrossRefGoogle Scholar
  40. 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.CrossRefPubMedGoogle Scholar
  41. 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.PubMedGoogle Scholar
  42. Ohno S (1967) Sex Chromosomes and Sex-linked Genes, Springer-Verlag, Berlin.Google Scholar
  43. Pannetier M, Tilly G, Kocer A, et al. (2006) Goat SRY induces testis development in XX transgenic mice. FEBS Lett 580: 3715–720.CrossRefPubMedGoogle Scholar
  44. 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.CrossRefPubMedGoogle Scholar
  45. 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.CrossRefGoogle Scholar
  46. 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.CrossRefGoogle Scholar
  47. Polanco JC, Koopman P (2006) Sry and the hesitant beginnings of male development. Dev Biol 302: 13–4.CrossRefPubMedGoogle Scholar
  48. 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.CrossRefPubMedGoogle Scholar
  49. 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.CrossRefPubMedGoogle Scholar
  50. 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.CrossRefPubMedGoogle Scholar
  51. 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.CrossRefPubMedGoogle Scholar
  52. 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
  53. 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.CrossRefPubMedGoogle Scholar
  54. Ross MT, Grafham DV, Coffey AJ, et al. (2005) The DNA sequence of the human X chromosome. Nature 434: 325–37.CrossRefPubMedGoogle Scholar
  55. 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.CrossRefPubMedGoogle Scholar
  56. 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.CrossRefPubMedGoogle Scholar
  57. Smith CA, McClive PJ, Western PS, Reed KJ, Sinclair AH (1999) Evolution: conservation of a sex-determining gene. Nature 402: 601–02.CrossRefPubMedGoogle Scholar
  58. 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.CrossRefPubMedGoogle Scholar
  59. 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.CrossRefPubMedGoogle Scholar
  60. 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.CrossRefPubMedGoogle Scholar
  61. 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.CrossRefGoogle Scholar
  62. 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.CrossRefPubMedGoogle Scholar
  63. 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.CrossRefPubMedGoogle Scholar
  64. Valenzuela N, Lance VA (2004) Temperature-dependent Sex Determination in Vertebrates, Smithsonian Books, New York.Google Scholar
  65. 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.CrossRefPubMedGoogle Scholar
  66. 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.CrossRefPubMedGoogle Scholar
  67. 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.CrossRefPubMedGoogle Scholar
  68. 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.CrossRefPubMedGoogle Scholar
  69. Wrigley JM, Graves JAM (1988) Karyotypic conservation in the mammalian order monotremata (subclass Prototheria). Chromosoma 96: 231–47.CrossRefPubMedGoogle Scholar
  70. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • M. C. Wallis
    • 1
  • P. D. Waters
    • 1
  • M. L. Delbridge
    • 1
  • P. J. Kirby
    • 1
    • 2
  • A. J. Pask
    • 3
  • F. Grützner
    • 1
    • 4
  • W. Rens
    • 5
  • M. A. Ferguson-Smith
    • 5
  • J. A. M. Graves
    • 1
  1. 1.Comparative Genomics Group, Research School of Biological Sciencesthe Australian National UniversityCanberraAustralia
  2. 2.National Institute of Environmental Health SciencesResearch Triangle ParkDurhamUSA
  3. 3.Department of Zoologythe University of MelbourneMelbourneAustralia
  4. 4.School of Molecular and Biomedical Sciencethe University of AdelaideAdelaideAustralia
  5. 5.Cambridge Resource Centre for Comparative Genomics, Department of Veterinary MedicineUniversity of CambridgeCambridgeUK

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