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Snakes’s Eyeview of Adam and Eve

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Book cover Reproductive Immunology

Abstract

The fundamental molecular control of primary sex determination in higher vertebrates and in certain invertebrates is vested in morphologically distinct sex chromosomes, which are largely heterochromatic and rich in highly repetitive DNA. Snakes in particular provide unique opportunities to elucidate the mechanism involved in the evolution and function of these chromosomes as they offer a model system representing all stages in the evolution of sex chromosomes. Our discovery of sex chromosome associated highly conserved Bkm (Banded krait minor satellite DNA) DNA sequences made the beginning of our understanding of the molecular basis of sex determination. Recently a gene termed SRY was discovered and described as the testis determining factor (TDF). However, the absence of SRY and apparently all other Y sequences in majority of XX males, true XX hermaphrodites, and their presence in most of XY females with no detectable SRY mutation, hitherto remains unexplained. Our recent finding of a unique case of 47 XXY sex reversal with a typical female phenotype having a normal Y chromosome and the normal SRY, SOX9 and ZFY genes, strongly suggests the involvement of other sex determining gene(s) in the complex pathway of sex determination. By using the Bkm probe, we have isolated a novel gene (pß2) from a human testis cDNA library, which is present in both the sexes but is expressed specifically in the male (testis) irrespective of the nature of heterogamety (XX/XY or ZZ/ZW). It is also expressed in male mouse embryos at the onset of testis differentiation. These and other studies suggest that pß2 may be involved in the complex pathway of sex determination. The sex determining chromosomes (W/Y) remain condensed in all somatic cells but decondense extensively in the germ cells. We have identified and purified a sex and tissue-specific Bkm-binding protein (BBP) from snake oocytes which shows sex, tissue and developmental stage specific expression and is associated with the decondensed state of the sex determining chromosomes (Y/W). We have implicated the BBP in bringing about co-ordinated decondensation of the entire W/Y chromosome by binding to GATA repeats, which may serve as a switch for the activation of the genes present on these chromosomes. We have isolated sex and species specific repetitive DNA from mouse (M34) and human (102(d)2) which are distributed along the length of the Y-chromosome. These are expressed specifically in the testis in a developmentally regulated manner in the cell type which shows decondensation of the Y-chromosome.

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References

  1. Lyon M.F. Gene action in the X chromosome of Mouse (Mus musculus). Nature 1961: 190: 372–373.

    Google Scholar 

  2. Singh L. Evolution of karyotypes in snakes. Chromosoma (berl.) 1972; 38: 185–236.

    Article  CAS  Google Scholar 

  3. Singh L., Purdom I.F., Jones K.W. Satellite DNA and evolution of sex chromosomes. Chromosoma (Berl.) 1976; 59: 43–62.

    Article  CAS  Google Scholar 

  4. Singh L., Purdom I.F., Jones K.W., Behaviour of sex chromosome associated satellite DNA in somatic and germ cells in snakes. Chromosoma (Berl.) 1979; 71: 167–181.

    Article  CAS  Google Scholar 

  5. Singh L., Purdom I.F., Jones K.W., Sex chromosome associated satellite DNA: evolution and conservation. Chromosoma (Berl.) 1980; 79: 137–157.

    Article  CAS  Google Scholar 

  6. Jones K.W., Singh L., Conserved repeated DNA suquences in vertebrate sex chromosomes. Hum Genet 1981; 58: 46–53.

    Article  PubMed  CAS  Google Scholar 

  7. Singh L., Jones K.W., Sex reversal in mouse (Mus musculus) is caused by a recurrent non-reciprocal crossover involving the X and an aberrant Y chromosome. Cell. 1982; 28: 205–216.

    Article  PubMed  CAS  Google Scholar 

  8. Jacobs P.A., Strong J.A., A case of human intersexuality having a possible XXY sex determining mechanism. Nature 1959; 183: 302–303.

    Article  PubMed  CAS  Google Scholar 

  9. Ford C.E., Miller O.J., Polani P.E., de Almeida J.C., Briggs J.H. A sex-chromosome anomaly in a case of gonadal dysgenesis (Turner’s syndrome). Lancet 1959; 1: 711–713.

    Article  PubMed  CAS  Google Scholar 

  10. Welshons W.J., Russel L.B. The Y chromosome as the bearer of male determining factors in the mouse. Proc. Natl. Acad. Sci. (USA) 1959; 45: 560–566.

    Article  CAS  Google Scholar 

  11. Cattanach B.M., Pollard C.E., Hawkes S.G. Sex reversed mice XX and XO males. Cytogenet 1971; 10: 318–337.

    Article  CAS  Google Scholar 

  12. Page D.C., Mosher R., Simpson E.M., Fisher E.M.C., Mardon G., Pollack J., McGillivray B., de la Chapelle A., Brown L.G. The sex-determining region of the human Y chromosome encodes a finger protein. Cell. 1987; 51: 1091–1104.

    Google Scholar 

  13. Koopman P., Gubbay J., Collignon J., Lovell-Badge R. Zfy gene expression pattern are not compatible with a primary role in mouse sex-determination. Nature 1989; 342: 940–942.

    Google Scholar 

  14. Sinclair A.H., Foster J.W., Spencer J.A., Page D.C., Palmer M., Goodfellow P.N., Graves J.A. Sequences homologous to ZFY, a candidate human sex determining gene, or autosomal in marsupials. Nature 1988; 336: 780–783.

    Article  PubMed  CAS  Google Scholar 

  15. Gubbay J., Collignon J., Koopman P., Capel B., Economou A., Munsterberg A., Vivan N., Goodfellow P.N., Lovell-Badge R. Agene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature 1990; 346: 245–250.

    Article  PubMed  CAS  Google Scholar 

  16. Koopman P., Gubbay J., Nigel V., Goodfellow P., Lovell-Badge R. Male development of chromosomally female mice transgenic for sry. Nature 1991; 351: 117–121.

    Article  PubMed  CAS  Google Scholar 

  17. Goodfellow P.N., Lovell-Badge R. SRY and sex determination in mammals. Ann. Rev. Genet 1993; 27: 71–92.

    Article  PubMed  CAS  Google Scholar 

  18. McElreavey K., Vilain E., Abbas N., Herskowitz I., Fellous M. A regulatory cascade hypothesis for mammalian sex determination: SRY represses a negative regulator of male development. Proc. Natl. Acad. Sci. (USA) 1993; 90: 3368–3372.

    Article  CAS  Google Scholar 

  19. Vilain E., Le Fiblec B., Morichon-Delvallez N., Brauner R., Dommergues M., Dumez Y., Jaubert F., Boucekkine C., McElreavey K., Vekemans M., Fellous M. SRY-negative XX fetus with complete male phenotype. Lancet 1994; 343: 240–241.

    Article  PubMed  CAS  Google Scholar 

  20. Cameron F.J., Sinclair A.H., Mutation in SRY and SOX9: Testis-determining genes. Hum. Mutation 1997; 9: 388–395.

    Article  CAS  Google Scholar 

  21. Graves JAM. Interactions between SRYand SOX genes in mammalian sex determination. BioEssays 1998; 20: 264–269.

    Article  PubMed  CAS  Google Scholar 

  22. Bardoni B., Zanaria E., Guioli S., Floridia G., Worley G., Tonini G., Ferrante E., Chiumello G., McCabe E.R.B., Fraccaro M., Zuffardi O., Camerino G. A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal. Nature Genet. 1994; 7: 497–501.

    Article  PubMed  CAS  Google Scholar 

  23. Ogata T., Matsuo N. Sex determining gene on the X chromosome short arm: dosage sensitive sex reversal. Acta. Paediatr Jpn. 1996; 38: 390–398.

    Article  PubMed  CAS  Google Scholar 

  24. Laporte J., Kioschis P., Hu L-J., Kretz C., Carlsson B., Poustka A., Mandel J.L., Dahl N. Cloning and characterization of an alternatively spliced gene in proximal Xq28 deleted in two patients with intersexual genitalia and myopathy. Genomics 1997; 41: 458–462.

    Article  PubMed  CAS  Google Scholar 

  25. Veitia R., Nunes M., Brauner R., Fenzy M.D., Flinois O.J., Jaubert F., Jacob S.L., Fellous M., McElreavey K. Deletions of distal 9p associated with 46, XY male to female sex reversal: definition of the breakpoints at 9p23.3-p24.1. Genomics 1997; 41: 271–274.

    Article  PubMed  CAS  Google Scholar 

  26. Wikie A.O.M., Campbell F.M., Daubeney P., Grant D.B., Daniels R.J., Mullarkey M., Affara N.A., Fitchett M., Huson S.M. Complete and partial X.Y. sex reversal associated with terminal deletion of 10q: report of two cases and literature review. Am. J. Med. Genet. 1993; 46: 597–600.

    Article  Google Scholar 

  27. Tommerup N., Schempp W., Meinecke P., Pederson S., Bolund L., Brandt C., Goodpasture C., Guldberg P., Held K.R., Reinwein H., et al. Assignment of an autosomal sex reversal locus (SRA1) and compomelic dysplasia (CMPD1) to 17q24. l-q25.1. Nature Genet. 1993; 4: 170–174.

    Article  PubMed  CAS  Google Scholar 

  28. Thangaraj K., Gupta N.J., Chakravarty B., Singh L. A 47, XXY female. Lancet 1998; 352: 1121.

    Article  PubMed  CAS  Google Scholar 

  29. Klinefelter H.P., Reifenstein E.C., Albright F. Syndrome characterized by gynecomastia, aspermatogenesis without a-leydigism, and increased excretion of follicle stimulating hormone. J. Clin. Endocrinol 1942; 2: 615–627.

    Article  CAS  Google Scholar 

  30. Netley C. Personality in 47.XXY males during adolescence. Clin. Genet. 1991; 39: 409–418.

    Article  PubMed  CAS  Google Scholar 

  31. Maaswinkel-Mooij P.D., van Zwieten P., Mollevanger P., van Noort E., Beverstock G. A girl with 71, XXXXY karyotype, Clin Genet. 1992; 41: 96–99.

    Article  PubMed  CAS  Google Scholar 

  32. Petit P., Moerman P., Fryns J.P. Full 69, XXY triploidy and sex-reversal: a further example of true hermaphroditism associated with multiple malformations. Clin. Genet. 1992; 41: 175–177.

    Article  PubMed  CAS  Google Scholar 

  33. Ferguson-Smith M.A., Cooke A., Affara N.A., Boyd E., Tolmie J.L. Genotype-phenotype correlations in XX males and their bearing on the current theories of sex determination. Hum. Genet. 1990; 84: 198–202.

    Article  PubMed  CAS  Google Scholar 

  34. Jager R.J., Anvret M., Hall. K., Scherer G. A human XY female with a frame shift mutation in the candidate testis-determining gene SRY. Nature 1990; 348: 452–454.

    Article  PubMed  CAS  Google Scholar 

  35. Tournaye H., Staessen C., Liebaers I., Van-Assche E., Devroey P., Bonduelle M., Van-Steirteghem A. Testicular sperm recovery in nine 47, XXY Klinefelter patients. Hum. Reprod. 1996; 11: 1644–1649.

    Article  PubMed  CAS  Google Scholar 

  36. Sano K., Terashima K., Tanaka Y., Saski Y., Four cases of true hermaphroditism. Hinyokika 1995; 41: 73–77.

    CAS  Google Scholar 

  37. Poulat F., Soullier S., Goze C., Heitz F., Calas B., Berta P., Description and functional implications of a novel mutation in the sex-determining gene SRY. Hum Mutat. 1994; 3: 200–204.

    Article  PubMed  CAS  Google Scholar 

  38. Wagner T., Wirth J., Meyer J., Zabel B., Held M., Zimmer J., Pasantes J., Bricarelli F.D., Keutel J., Hustert E., Wolf U., Tommerup N., Schempp W., Scherer G., Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY related gene SOX9. Cell 1994; 79: 1111–1120.

    Article  PubMed  CAS  Google Scholar 

  39. Hawkins J.R., Taylor A., Berta P., Levilliers J. van der Auwera B., Goodfellow P.N. Mutation analysis of SRY: nonsense and missence mutations in XY sex reversal. Hum. Genet 1992; 88: 471–474.

    Article  PubMed  CAS  Google Scholar 

  40. Hassold T., Pettay D., May K., Robinson A. Analysis of non-disjunction in sex chromosome tetrasomy and pentasomy. Hum Genet. 1990; 85: 648–650.

    Article  PubMed  CAS  Google Scholar 

  41. Villamar M., Benitez J., Fernandez E., Ayuso C., Ramos C. Parental origin of chromosomal non-disjunction in a 49, XXXXY male using recombinant-DNA techniques. Clin. Genet. 1989; 36: 152–155.

    Article  PubMed  CAS  Google Scholar 

  42. Sinclair A.H., Berta P., Palmer M.S., Hawkins J.R., Griffiths H.L., Smith M.J., Foster J.W., Frischauf A.M., Lovell-Badge R., Goodfellow P.N. A gene from the human sex determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 1990; 346: 240–244.

    Article  PubMed  CAS  Google Scholar 

  43. Singh L., Phillips C., Jones K.W. The conserved nucleotide sequences of Bkm which define Sxr-in the mouse are transcribed. Cell 1984; 36: 111–120.

    Article  PubMed  CAS  Google Scholar 

  44. Singh L., Panicker S.G., Nagaraj R., Majumdar K.C. Functional significance of molecular organization of sex chromosomes. Proc. Indian Natl. Sci. Acad. 1994; B60: 455–470.

    Google Scholar 

  45. Singh L., Panicker S.G., Nagaraj R., Majumdar K.C., Banded krait minor-satellite (Bkm)-associated Y chromosome specific repetitive DNA in mouse. Nucleic Acids Res 1994; 22: 2289–2295.

    Article  PubMed  CAS  Google Scholar 

  46. Singh L., Wadhwa R., Naidu S., Nagaraj R., Ganesan M. Sex-and tissue-specific Bkm (GATA)-binding protein in the germ cells of heterogametic sex. J. Biol. Chem. 1994; 269: 25321–25327.

    PubMed  CAS  Google Scholar 

  47. Orkin S.H. GATA-binding transcription factors in hematopoietic cells. Blood 1992; 80: 575–581.

    PubMed  CAS  Google Scholar 

  48. Singh L., Biological significance of minisatellites. Electrophoresis 1995; 16: 1586–1595.

    Article  PubMed  CAS  Google Scholar 

  49. Laverriere A.C., MacNeil C., Mueller C., Poclmann R.E., Burch J., Evans T. GATA-4 5 6, a subfamily of three transcription factors transcribed in developing heart and gut. J. Biol. Chem. 1994; 269: 23177–23184.

    PubMed  CAS  Google Scholar 

  50. Viger R.S., Mertinet C., Trasler J.M., Nemer M. Transcription factor GATA-4 is expressed in a sexually dimorphic fashion during mouse gonadal development and is a potent activator of the Mullerian inhibiting substance promoter. Development 1998; 125: 2665–2675.

    PubMed  CAS  Google Scholar 

  51. Pardo V.F., Lee C.H., Zahod L., Vekemans M., Nishiyoka Y. Molecular characterization of a mouse Y chromosomal repetitive sequence that detects transcripts in the testis. Cytogenet Cell Genet. 1992; 61: 37–90.

    Google Scholar 

  52. Styrna J., Kla G.J., Moriwaki K. Influence of partial deletion of the Y chromosome on mouse sperm phenotype. J. Reprod. Fertil. 1991; 92: 187–195.

    Article  PubMed  CAS  Google Scholar 

  53. Xian M., Azuma S., Naito K., Kuneida T., Moriwaki K., Toyoda Y, Effect of partial deletions of the Y chromosome on in vitro fertilizing ability of mouse spermatozoa. Biol. Reprod. 1992; 47: 549–553.p

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India

    Lalji Singh, N. H. Pathak, A. J. Rachel & K. Thangaraj

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  1. Lalji Singh
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  2. N. H. Pathak
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  3. A. J. Rachel
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  4. K. Thangaraj
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Editors and Affiliations

  1. Gamete Antigen Laboratory, National Institute of Immunology, New Delhi, India

    Satish K. Gupta (Chief) (Chief)

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© 1999 Springer Science+Business Media Dordrecht

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Singh, L., Pathak, N.H., Rachel, A.J., Thangaraj, K. (1999). Snakes’s Eyeview of Adam and Eve. In: Gupta, S.K. (eds) Reproductive Immunology. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4197-0_13

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  • DOI: https://doi.org/10.1007/978-94-011-4197-0_13

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-5825-4

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