Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Establishing sexual dimorphism: conservation amidst diversity?

Nature Reviews Genetics volume 2, pages 175–185 (2001)Cite this article

Abstract

The molecular mechanisms that control sexual dimorphism are very different in distantly related animals. Did sex determination arise several times with different regulatory mechanisms, or is it an ancient process with little surviving evidence of ancestral genes? The recent identification of related sexual regulators in different phyla indicates that some aspects of sexual regulation might be ancient. Studies of sex-determining mechanisms are beginning to reveal how sexual dimorphism arises and evolves.

Key Points

  • Sex-determining pathways in different species are initiated by a surprising variety of genetic and environmental signals.

  • Sex chromosomes can evolve quickly and generally are not conserved at the molecular level, between distant species.

  • Experimental manipulations of Caenorhabditis elegans show how sex-determination mechanisms can be completely transformed by simple mutations in regulatory genes.

  • Comparisons of nematodes with insects indicate that sexual regulators that function upstream in the developmental hierarchy might evolve very rapidly, but that downstream genes are more highly conserved.

  • Flies, worms and mammals regulate the various aspects of sexual development with genes that contain the DM-domain DNA-binding motif.

  • The conservation of downstream sex-determining genes and the divergence of those upstream fits theoretical predictions.

  • Sexual regulation must be integrated with spatial and temporal regulation. The control of sexual dimorphism in the posterior of flies and worms illustrates how this can occur.

  • Short-range transcriptional repression seems to generate sexual dimorphism in worms, and might be a general mechanism in other species.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Somatic sex determination in flies and worms.
Figure 2: Mammalian sex determination.
Figure 3: Sexual dimorphism is controlled jointly by Hox genes and sexual regulators.
Figure 4: Sexually dimorphic regulation by short-range transcriptional repression.

Similar content being viewed by others

References

  1. Barton, N. H. & Charlesworth, B. Why sex and recombination? Science 281, 1986–1989 (1998).

    Article  CAS  PubMed  Google Scholar 

  2. Welch, D. M. & Meselson, M. Evidence for the evolution of bdelloid rotifers without sexual reproduction or genetic exchange. Science 288, 1211–1215 ( 2000).

    Article  CAS  Google Scholar 

  3. Marin, I. & Baker, B. S. The evolutionary dynamics of sex determination. Science 281, 1990– 1994 (1998).

    Article  CAS  PubMed  Google Scholar 

  4. Sinclair, A. H. et al. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346, 240–244 (1990).

    Article  CAS  PubMed  Google Scholar 

  5. Cline, T. W. & Meyer, B. J. Vive la difference: males vs females in flies vs worms. Annu. Rev. Genet. 30, 637–702 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. Fredga, K. in The Differences Between the Sexes (eds Short, R. V. & Balaban, E.) 419–431 (Cambridge Univ. Press, Cambridge, 1994).

    Google Scholar 

  7. Schutt, C. & Nothinger, R. Structure, function and evolution of sex-determining systems in dipteran insects. Development 127, 667–677 (2000).

    Article  CAS  PubMed  Google Scholar 

  8. Graves, J. A. Mammals that break the rules: genetics of marsupials and monotremes. Annu. Rev. Genet. 30, 233–260 (1996).

    Article  CAS  PubMed  Google Scholar 

  9. Charlesworth, B. The evolution of chromosomal sex determination and dosage compensation. Curr. Biol. 6, 149–162 ( 1996).

    Article  CAS  PubMed  Google Scholar 

  10. Hodgkin, J. Genetic sex determination mechanisms and evolution. Bioessays 14, 253–261 (1992).

    Article  CAS  PubMed  Google Scholar 

  11. Bull, J. J. Evolution of Sex Determining Mechanisms (Benjamin/Cummings, Menlo Park, California, 1983).

    Google Scholar 

  12. Stevanovic, M., Lovell-Badge, R., Collignon, J. & Goodfellow, P. N. SOX3 is an X-linked gene related to SRY. Hum. Mol. Genet. 2, 2013–2018 ( 1993).

    Article  CAS  PubMed  Google Scholar 

  13. Foster, J. W. & Graves, J. A. 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, 1927–1931 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lahn, B. T. & Page, D. C. Four evolutionary strata on the human X chromosome. Science 286, 964– 967 (1999).

    Article  CAS  PubMed  Google Scholar 

  15. Marin, I., Siegal, M. L. & Baker, B. S. The evolution of dosage-compensation mechanisms. Bioessays 22, 1106–1114 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. Marin, I., Franke, A., Bashaw, G. J. & Baker, B. S. The dosage compensation system of Drosophila is co-opted by newly evolved X chromosomes. Nature 383, 160– 163 (1996).

    Article  CAS  PubMed  Google Scholar 

  17. Bopp, D., Calhoun, G., Horabin, J. I., Samuels, M. & Schedl, P. Sex-specific control of Sex-lethal is a conserved mechanism for sex determination in the genus Drosophila . Development 122, 971– 982 (1996).

    Article  CAS  PubMed  Google Scholar 

  18. O'Neil, M. T. & Belote, J. M. Interspecific comparison of the transformer gene of Drosophila reveals an unusually high degree of evolutionary divergence. Genetics 131, 113–128 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Chandler, D. et al. Evolutionary conservation of regulatory strategies for the sex determination factor transformer-2. Mol. Cell. Biol. 17, 2908–2919 ( 1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Muller-Holtkamp, F. The Sex-lethal homologue in Chrysomya rufifacies is highly conserved in sequence and exon–intron organization. J. Mol. Evol. 41, 467–477 (1995).

    Article  CAS  PubMed  Google Scholar 

  21. Sievert, V., Kuhn, S. & Traut, W. Expression of the sex determining cascade genes Sex-lethal and doublesex in the phorid fly Megaselia scalaris. Genome 40, 211–214 ( 1997).

    Article  CAS  PubMed  Google Scholar 

  22. Meise, M. et al. Sex-lethal, the master sex-determining gene in Drosophila , is not sex-specifically regulated in Musca domestica. Development 125, 1487–1494 (1998).

    Article  CAS  PubMed  Google Scholar 

  23. Dauwalder, B., Amaya-Manzanares, F. & Mattox, W. A human homologue of the Drosophila sex determination factor transformer-2 has conserved splicing regulatory functions. Proc. Natl Acad. Sci. USA 93, 9004– 9009 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Beil, B., Screaton, G. & Stamm, S. Molecular cloning of htra2-β-1 and htra2-β-2 , two human homologues of tra-2 generated by alternative splicing . DNA Cell Biol. 16, 679– 690 (1997).

    Article  CAS  PubMed  Google Scholar 

  25. Tacke, R., Tohyama, M., Ogawa, S. & Manley, J. L. Human TRA2 proteins are sequence-specific activators of pre-mRNA splicing. Cell 93, 139–148 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. Shearman, D. C. & Frommer, M. The Bactrocera tryoni homologue of the Drosophila melanogaster sex-determination gene doublesex. Insect Mol. Biol. 7, 355–366 (1998).

    Article  CAS  PubMed  Google Scholar 

  27. Shimada, T. & Ohbayashi, F. Bombyx mori Bmdsx mRNA for BmDSX-M, complete cds, male specific (AB48544); and mRNA for BmDSX–F, complete cds, female specific (AB048543). GenBank ( 2000).[style?]

  28. de Bono, M. & Hodgkin, J. Evolution of sex determination in Caenorhabditis: unusually high divergence of tra-1 and its functional consequences. Genetics 144, 587– 595 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kuwabara, P. E. Interspecies comparison reveals evolution of control regions in the nematode sex-determining gene tra-2. Genetics 144, 597–607 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kuwabara, P. E. & Shah, S. Cloning by synteny: identifying C. briggsae homologues of C. elegans genes. Nucleic Acids Res. 22, 4414–4418 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Streit, A. et al. Homologs of the Caenorhabditis elegans masculinizing gene her-1 in C. briggsae and the filarial parasite Brugia malayi. Genetics 152, 1573– 1584 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ventura-Holman, T., Seldin, M. F., Li, W. & Maher, J. F. The murine fem1 gene family: homologs of the Caenorhabditis elegans sex-determination protein FEM-1. Genomics 54, 221– 230 (1998).

    Article  CAS  PubMed  Google Scholar 

  33. Raymond, C. S. et al. Evidence for evolutionary conservation of sex-determining genes. Nature 391, 691– 695 (1998).

    Article  CAS  PubMed  Google Scholar 

  34. Erdman, S. E. & Burtis, K. C. The Drosophila doublesex proteins share a novel zinc finger related DNA binding domain. EMBO J. 12, 527–535 ( 1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhu, L. et al. Sexual dimorphism in diverse metazoans is regulated by a novel class of intertwined zinc fingers. Genes Dev. 14, 1750–1764 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Baker, B. S. & Ridge, K. Sex and the single cell: on the action of major loci affecting sex determination in Drosophila melanogaster. Genetics 94, 383–423 ( 1980).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Coschigano, K. T. & Wensink, P. C. Sex-specific transcriptional regulation by male and female doublesex proteins of Drosophila . Genes Dev. 7, 42– 54 (1993).

    Article  CAS  PubMed  Google Scholar 

  38. An, W. & Wensink, P. C. Integrating sex- and tissue-specific regulation within a single Drosophila enhancer. Genes Dev. 9, 256–266 ( 1995).Together with reference 37 , this paper shows that the two sex-specific isoforms of Dsx bind the same DNA site and have opposite effects on the transcription of the Yp1 yolk-protein gene.

    Article  CAS  PubMed  Google Scholar 

  39. Yi, W. & Zarkower, D. Similarity of DNA binding and transcriptional regulation by Caenorhabditis elegans MAB-3 and Drosophila melanogaster DSX suggests conservation of sex determining mechanisms. Development 126, 873–881 (1999).

    Article  CAS  PubMed  Google Scholar 

  40. Shen, M. M. & Hodgkin, J. mab-3, a gene required for sex-specific yolk protein expression and a male-specific lineage in C. elegans. Cell 54, 1019– 1031 (1988).

    Article  CAS  PubMed  Google Scholar 

  41. Yi, W., Ross, J. M. & Zarkower, D. mab-3 is a direct tra-1 target gene that regulates diverse aspects of C. elegans male sexual behavior. Development 127, 4469–4480 ( 2000).

    Article  CAS  PubMed  Google Scholar 

  42. Nef, S. & Parada, L. F. Hormones in male sexual development . Genes Dev. 14, 3075–3086 (2000).

    Article  CAS  PubMed  Google Scholar 

  43. Jost, A. Recherches sur le differentiation sexuelle de l'embryo de lapin. Arch. Anat. Microsc. Morphol. Exp. 36, 117– 121 (1947).

    Google Scholar 

  44. Jost, A. Studies on sex differentiation in mammals. Rec. Prog. Horm. Res. 8, 379–418 ( 1953).

    Google Scholar 

  45. Zimmermann, S. et al. Targeted disruption of the Insl3 gene causes bilateral cryptorchidism. Mol. Endocrinol. 13, 681 –691 (1999).

    Article  CAS  PubMed  Google Scholar 

  46. Nef, S. & Parada, L. F. Cryptorchidism in mice mutant for Insl3. Nature Genet. 22, 295– 299 (1999).

    Article  CAS  PubMed  Google Scholar 

  47. Nachtigal, M. W. et al. Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression. Cell 93, 445–454 (1998).Shows that Sf1 and Wt1 synergistically activate Müllerian inhibiting substance and that Dax1 antagonizes this activation in transfected cells. Provides evidence for physical interaction between Sf1 and Wt1 and between Sf1 and Dax1.

    Article  CAS  PubMed  Google Scholar 

  48. Swain, A., Narvaez, V., Burgoyne, P., Camerino, G. & Lovell-Badge, R. Dax1 antagonizes Sry action in mammalian sex determination. Nature 391, 761–767 (1998).

    Article  CAS  PubMed  Google Scholar 

  49. Vainio, S., Heikkila, M., Kispert, A., Chin, N. & McMahon, A. P. Female development in mammals is regulated by Wnt-4 signalling. Nature 397, 405–409 (1999).

    Article  CAS  PubMed  Google Scholar 

  50. 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 90, 3368–3372 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Swain, A. & Lovell-Badge, R. Mammalian sex determination: a molecular drama. Genes Dev. 13, 755– 767 (1999).

    Article  CAS  PubMed  Google Scholar 

  52. Capel, B. The battle of the sexes. Mech. Dev. 92, 89–103 (2000).

    Article  CAS  PubMed  Google Scholar 

  53. Gubbay, J. et al. 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 346, 245–250 (1990).

    Article  CAS  PubMed  Google Scholar 

  54. Koopman, P., Gubbay, J., Vivian, N., Goodfellow, P. & Lovell-Badge. R. Male development of chromosomally female mice transgenic for Sry. Nature 351, 117– 121 (1991).Provides formal proof that Sry is sufficient to induce male development in an XX mammal.

    Article  CAS  PubMed  Google Scholar 

  55. Tucker, P. K. & Lundrigan, B. L. Rapid evolution of the sex determining locus in Old World mice and rats. Nature 364, 715–717 (1993).

    Article  CAS  PubMed  Google Scholar 

  56. Whitfield, L. S., Lovell-Badge, R. & Goodfellow, P. N. Rapid sequence evolution of the mammalian sex-determining gene SRY. Nature 364, 713– 715 (1993).

    Article  CAS  PubMed  Google Scholar 

  57. Kent, J., Wheatley, S. C., Andrews, J. E., Sinclair, A. H. & Koopman, P. A male-specific role for SOX9 in vertebrate sex determination. Development 122, 2813–2822 (1996).

    Article  CAS  PubMed  Google Scholar 

  58. Morais da Silva, S. et al. Sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds . Nature Genet. 14, 62– 68 (1996).

    Article  CAS  PubMed  Google Scholar 

  59. Oreal, E. et al. Early expression of AMH in chicken embryonic gonads precedes testicular SOX9 expression. Dev. Dyn. 212, 522–532 (1998).

    Article  CAS  PubMed  Google Scholar 

  60. Spotila, L. D., Spotila, J. R. & Hall, S. E. Sequence and expression analysis of WT1 and Sox9 in the red-eared slider turtle, Trachemys scripta. J. Exp. Zool. 281, 417–427 (1998).

    Article  CAS  PubMed  Google Scholar 

  61. Moreno-Mendoza, N., Harley, V. R. & Merchant-Larios, H. Differential expression of SOX9 in gonads of the sea turtle Lepidochelys olivacea at male- or female-promoting temperatures . J. Exp. Zool. 284, 705– 710 (1999).

    Article  CAS  PubMed  Google Scholar 

  62. Western, P. S., Harry, J. L., Graves, J. A. & Sinclair, A. H. Temperature-dependent sex determination: upregulation of SOX9 expression after commitment to male development. Dev. Dyn. 214 , 171–177 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Foster, J. W. et al. Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature 372 , 525–530 (1994).

    Article  CAS  PubMed  Google Scholar 

  64. Wagner, T. et al. Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell 79, 1111–1120 ( 1994).

    Article  CAS  PubMed  Google Scholar 

  65. Bishop, C. E. et al. A transgenic insertion upstream of Sox9 is associated with dominant XX sex reversal in the mouse. Nature Genet. 26, 490–494 (2000). A fortuitous transgene insertion far upstream of the Sox9 gene causes constitutive expression of Sox9 in XX embryos and results in fully male development, showing clearly the importance of Sox9 in mammals. The insertion might interfere with a negative regulatory element, consistent with the regulatory hypothesis described in reference 50.

    Article  CAS  PubMed  Google Scholar 

  66. Raymond, C. S., Kettlewell, J. R., Hirsch, B., Bardwell, V. J. & Zarkower, D. Expression of Dmrt1 in the genital ridge of mouse and chicken embryos suggests a role in vertebrate sexual development. Dev. Biol. 215, 208– 220 (1999).

    Article  CAS  PubMed  Google Scholar 

  67. De Grandi, A. et al. The expression pattern of a mouse doublesex-related gene is consistent with a role in gonadal differentiation. Mech. Dev. 90, 323–326 ( 2000).

    Article  CAS  PubMed  Google Scholar 

  68. Smith, C. A., McClive, P. J., Western, P. S., Reed, K. J. & Sinclair, A. H. Conservation of a sex-determining gene. Nature 402, 601–602 (1999).

    Article  CAS  PubMed  Google Scholar 

  69. Moniot, B., Berta, P., Scherer, G., Sudbeck, P. & Poulat, F. Male specific expression suggests role of DMRT1 in human sex determination. Mech. Dev. 91, 323–325 (2000).

    Article  CAS  PubMed  Google Scholar 

  70. Kettlewell, J. R., Raymond, C. S. & Zarkower, D. Temperature-dependent expression of turtle Dmrt1 prior to sexual differentiation. Genesis 26, 174–178 (2000).

    Article  CAS  PubMed  Google Scholar 

  71. Marchand, O. et al. DMRT1 expression during gonadal differentiation and spermatogenesis in the rainbow trout, Oncorhynchus mykiss. Biochim. Biophys. Acta 1493, 180–187 (2000).

    Article  CAS  PubMed  Google Scholar 

  72. Raymond, C. S. et al. A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators. Hum. Mol. Genet. 8, 989–996 ( 1999).

    Article  CAS  PubMed  Google Scholar 

  73. Nanda, I. et al. 300 million years of conserved synteny between chicken Z and human chromosome 9. Nature Genet. 21, 258 –259 (1999).

    Article  CAS  PubMed  Google Scholar 

  74. Raymond, C. S., Murphy, M. W., O'Sullivan, M. G., Bardwell, V. J. & Zarkower, D. Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation. Genes Dev. 14, 2587 –2595 (2000).A mouse knockout shows that Dmrt1 is required for postnatal testis differentiation, by affecting both Sertoli-cell and germ-cell development.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Crocker, M., Coghill, S. B. & Cortinho, R. An unbalanced autosomal translocation (7;9) associated with feminization. Clin. Genet. 34, 70– 73 (1988).

    Article  CAS  PubMed  Google Scholar 

  76. Ogata, T. et al. Impaired male sex development in an infant with molecularly defined partial 9p monosomy: implication for a testis forming gene(s) on 9p. J. Med. Genet. 34, 331–334 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ion, R. et al. Failure of testicular development associated with a rearrangement of 9p24.1 proximal to the SNF2 gene. Hum. Genet. 102, 151–156 (1998).

    Article  CAS  PubMed  Google Scholar 

  78. Ottolenghi, C. et al. The region on 9p associated with 46,XY sex reversal contains several transcripts expressed in the urogenital system and a novel doublesex -related domain. Genomics 64, 170– 178 (2000).

    Article  CAS  PubMed  Google Scholar 

  79. Wilkins, A. S. Moving up the hierarchy: a hypothesis on the evolution of a genetic sex determination pathway. BioEssays 17, 71– 77 (1995).Proposes that sex-determining pathways, particularly those of nematodes, have evolved by the sequential addition of upstream regulators, so helping to explain the extreme molecular differences between these pathways and the evolution of the negatively acting Caenorhabditis elegans pathway.

    Article  CAS  PubMed  Google Scholar 

  80. Waxman, D. & Peck, J. R. Pleiotropy and the preservation of perfection. Science 279, 1210– 1213 (1998).

    Article  CAS  PubMed  Google Scholar 

  81. Kopp, A., Duncan, I. & Carroll, S. B. Genetic control and evolution of sexually dimorphic characters in Drosophila. Nature 408, 553–559 (2000).Shows how the differential regulation of the bric-a-brac (bab ) gene by Dsx and AbdB contributes to sexually dimorphic patterning in Drosophila species and how sexual selection is likely to have affected the evolution of bab regulation.

    Article  CAS  PubMed  Google Scholar 

  82. Hodgkin, J. A. & Brenner, S. Mutations causing transformation of sexual phenotype in the nematode Caenorhabditis elegans . Genetics 86, 275– 287 (1977).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kenyon, C. A gene involved in the development of the posterior body region of C. elegans . Cell 46, 477–487 (1986).

    Article  CAS  PubMed  Google Scholar 

  84. Zhao, C. & Emmons, S. W. A transcription factor controlling development of peripheral sense organs in C. elegans. Nature 373, 74–78 ( 1995).

    Article  CAS  PubMed  Google Scholar 

  85. Emmons, S. W. in Cell Lineage and Fate Determination (ed. Moody, S. A.) 139– 155 (Academic, San Diego, California, 1999).

    Book  Google Scholar 

  86. Wrischnik, L. A. & Kenyon, C. J. The role of lin-22, a hairy/enhancer of split homolog, in patterning the peripheral nervous system of C. elegans. Development 124, 2875–2888 ( 1997).

    Article  CAS  PubMed  Google Scholar 

  87. Branford, W. W., Benson, G. V., Ma, L., Maas, R. L. & Potter, S. S. Characterization of Hoxa-10/Hoxa-11 transheterozygotes reveals functional redundancy and regulatory interactions. Dev. Biol. 224, 373–387 ( 2000).

    Article  CAS  PubMed  Google Scholar 

  88. Hsieh-Li, H. M. et al. Hoxa11 structure, extensive antisense transcription, and function in male and female fertility. Development 121, 1373–1385 (1995).

    Article  CAS  PubMed  Google Scholar 

  89. Rijli, F. M. et al. Cryptorchidism and homeotic transformations of spinal nerves and vertebrae in Hoxa-10 mutant mice. Proc. Natl Acad. Sci. USA 92, 8185–8189 ( 1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Satokata, I., Benson, G. & Maas, R. Sexually dimorphic sterility phenotypes in Hoxa10-deficient mice. Nature 374, 460–463 (1995).

    Article  CAS  PubMed  Google Scholar 

  91. Katoh-Fukui, Y. et al. Male-to-female sex reversal in M33 mutant mice. Nature 393, 688–692 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  92. Conradt, B. & Horvitz, H. R. The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell 93, 519– 529 (1998).

    Article  CAS  PubMed  Google Scholar 

  93. Sulston, J. E. & Horvitz, H. R. Post-embryonic cell lineages of the nematode Caenorhabditis elegans. Dev. Biol. 56, 110–156 ( 1977).

    Article  CAS  PubMed  Google Scholar 

  94. Trent, C., Tsung, N. & Horvitz, H. R. Egg-laying defective mutants of the nematode Caenorhabditis elegans. Genetics 104, 619–647 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Conradt, B. & Horvitz, H. R. The TRA-1A sex determination protein of C. elegans regulates sexually dimorphic cell deaths by repressing the egl-1 cell death activator gene. Cell 98 , 317–327 (1999). An impressive genetic demonstration in C. elegans that TRA-1 regulates the sexually dimorphic expression of egl-1 in one cell type by acting on an enhancer element located 5.6 kb downstream of the egl-1 coding region.

    Article  CAS  PubMed  Google Scholar 

  96. Ambros, V. & Horvitz, H. R. Heterochronic mutants of the nematode Caenorhabditis elegans. Science 226 , 409–416 (1984).

    Article  CAS  PubMed  Google Scholar 

  97. Arango, N. A., Lovell-Badge, R. & Behringer, R. R. Targeted mutagenesis of the endogenous mouse Mis promoter: in vivo definition of genetic pathways of vertebrate sexual development. Cell 99, 409– 419 (1999).An elegant study using in vivo mutagenesis of conserved binding sites in the Mis promoter and careful quantification of Mis expression to assess the importance of its regulation by Sf1 and Sox9. Shows that the Sox9 site is essential for Mis expression and that the Sf1 site is less important.

    Article  CAS  PubMed  Google Scholar 

  98. Viger, R. S., Mertineit, C., Trasler, J. M. & Nemer, M. Transcription factor GATA-4 is expressed in a sexually dimorphic pattern during mouse gonadal development and is a potent activator of the Müllerian inhibiting substance promoter. Development 125, 2665–2675 (1998).

    Article  CAS  PubMed  Google Scholar 

  99. Waterbury, J. A., Jackson, L. L. & Schedl, P. Analysis of the doublesex female protein in Drosophila melanogaster: role on sexual differentiation and behavior and dependence on intersex. Genetics 152, 1653–1667 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Jiang, M. et al. Genome-wide analysis of developmental and sex-regulated gene expression profiles in Caenorhabditis elegans. Proc. Natl Acad. Sci. USA 98, 218–223 (2001).

    Article  CAS  PubMed  Google Scholar 

  101. Bowles, J., Bullejos, M. & Koopman, P. A subtractive gene expression screen suggests a role for vanin-1 in testis development in mice. Genesis 27, 124–135 (2000).

    Article  CAS  PubMed  Google Scholar 

  102. Hodgkin, J. Two types of sex determination in a nematode. Nature 304, 267–268 (1983). A simple and effective demonstration that the sex-determination mechanism can be changed from XX/XO to ZZ/ZW by a pair of mutations in a single gene, resulting in a stable and fertile strain.

    Article  CAS  PubMed  Google Scholar 

  103. Miller, L. M., Plenefisch, J. D., Casson, L. P. & Meyer, B. J. xol-1: a gene that controls the male modes of both sex determination and X chromosome dosage compensation in C. elegans. Cell 55, 167–183 (1988).

    Article  CAS  PubMed  Google Scholar 

  104. Meyer, B. J. Sex in the worm; counting and compensating X-chromosome dose. Trends Genet. 16, 247–253 (2000).

    Article  CAS  PubMed  Google Scholar 

  105. Gray, S., Szymanski, P. & Levine, M. Short-range repression permits multiple enhancers to function autonomously within a complex promoter. Genes Dev. 8, 1829–1838 (1994).

    Article  CAS  PubMed  Google Scholar 

  106. Gray, S. & Levine, M. Transcriptional repression in development . Curr. Opin. Cell Biol. 8, 358– 364 (1996).

    Article  CAS  PubMed  Google Scholar 

  107. Small, S., Arnosti, D. N. & Levine, M. Spacing ensures autonomous expression of different stripe enhancers in the even-skipped promoter. Development 199, 762–772 (1993).

    Google Scholar 

  108. Chen, P. & Ellis, R. E. TRA-1A regulates transcription of fog-3, which controls germ cell fate in C. elegans. Development 127, 3119–3129 (2000).

    Article  CAS  PubMed  Google Scholar 

  109. Cai, H. N., Arnosti, D. N. & Levine, M. Long-range repression in the Drosophila embryo . Proc. Natl Acad. Sci. USA 93, 9309– 9314 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Usui-Aoki, K. et al. Formation of the male-specific muscle in female Drosophila by ectopic fruitless expression. Nature Cell Biol. 2, 500–506 ( 2000).

    Article  CAS  PubMed  Google Scholar 

  111. Janzen, F. J. & Paukstis, G. L. Environmental sex determination in reptiles: ecology, evolution, and experimental design . Q. Rev. Biol. 66, 149– 179 (1991).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The author thanks V. Bardwell, B. Charlesworth, E. Coucouvanis, J. Simon and three referees for critical reading of the manuscript; S. Carroll, A. Kopp and J. Hodgkin for sharing results before publication; and apologizes to those whose work could not be cited due to space limitations. Work in the Zarkower laboratory is supported by grants from the National Institutes of Health.

Author information

Authors and Affiliations

  1. Department of Genetics, Cell Biology and Development University of Minnesota, Minneapolis, 55455, Minnesota, USA

    David Zarkower

Authors
  1. David Zarkower
    View author publications

    You can also search for this author in PubMed Google Scholar

Related links

Related links

DATABASE LINKS

Sry

Sox3

Sxl

tra

tra-2

dsx

her-1

fem-1

fem-2

tra-1

Fem1a

Fem1b

mab-3

Dax1

Wnt4a

Sox9

Dmrt1

Abd-B

bab

mab-5

lin-32

hairy

lin-22

Hoxa10

Hoxa11

M33

egl-1

lin-28

WT1

SF1

GATA-4

Yp1

FURTHER INFORMATION

bdelloid rotifers

ENCYCLOPEDIA OF LIFE SCIENCES

Sex determination

Gonadal induction

Glossary

BDELLOID ROTIFER

(or simply bdelloids, from the Greek word for leech). Microscopic aquatic animals. Most species creep on a surface by alternately moving their front and back ends, such as in an inchworm or a leech.

HETEROGAMETIC SEX

The sex that produces gametes with different sex chromosomes. In XX/XY sex determination, the male is heterogametic, and in ZZ/ZW sex determination, the female is heterogametic.

G-BANDING

(Giemsa banding). One of several methods for staining chromosomes, which produces light and dark bands characteristic for each homologous chromosome pair, so that individual chromosomes can be distinguished and examined for abnormalities in structure and number.

RNA INTERFERENCE

(RNAi). This is a process by which double-stranded RNA specifically silences the expression of homologous genes through degradation of their cognate mRNA.

SEX COMBS

Specialized rows of sensory bristles on the foreleg of male fruitflies, which are used during courtship to grip the female.

SENSORY RAYS

Specialized sense organs in the nematode male tail, consisting of two sensory neurons and a structural cell. Used to locate and copulate with females.

SERTOLI CELLS

Cells in the testis that produce secreted factors, including Müllerian inhibiting substance, and act as 'nurse cells' to provide nourishment to the early sperm cells.

HOX PROTEINS

Transcription factors that are expressed in specific patterns, which are important for determining regional identity along the anterioposterior axis in the embryo.

DEUTEROSTOME/PROTOSTOME

The two principal divisions of the animal phyla, based on how the mouth forms in the embryo.

PLEIOTROPY

The phenomenon in which a single gene is responsible for several distinct and seemingly unrelated phenotypic effects.

HYPODERMIS

The cellular layer that underlies and secretes the cuticle that forms the outer coating of a nematode or arthropod.

BASIC HELIX–LOOP–HELIX

A common dimerization and DNA-binding motif. The helices mediate dimerization, and the adjacent basic region is required for DNA binding.

CRYPTORCHIDISM

The failure of the testicles to descend from the abdominal cavity into the scrotum by one year of age (in humans).

HETEROCHRONY

An evolutionary change in phenotype based on an alteration in the timing of developmental events.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zarkower, D. Establishing sexual dimorphism: conservation amidst diversity?. Nat Rev Genet 2, 175–185 (2001). https://doi.org/10.1038/35056032

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35056032

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing