ACTIVITY OF THE SEX-DETERMINING GENE tra-2 IS MODULATED TO ALLOW SPERMATOGENESIS IN THE C. ELEGANS HERMAPHRODITE

Tabitha Doniach ¹

¹ MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, England

In the nematode C. elegans, there are two sexes, the self-fertilizing hermaphrodite (XX) and the male (XO). The hermaphrodite is essentially a female that makes sperm for a brief period before oogenesis. Sex determination in C. elegans is controlled by a pathway of autosomal regulatory genes, the state of which is determined by the X:A ratio. One of these genes, tra-2, is required for hermaphrodite development, but not for male development, because null mutations in tra-2 masculinize XX animals but have no effect on XO males. Dominant, gain-of-function tra-2 mutations have now been isolated that completely feminize the germline of XX animals so that they make only oocytes and no sperm and, thus, are female. Most of the tra-2(dom) mutations do not correspondingly feminize XO animals, so they do not appear to interfere with control by her-1 , a gene thought to negatively regulate tra-2 in XO animals. Thus, these mutations appear to cause gain of tra-2 function in the XX animal only. Dosage studies indicate that 5 of 7 tra-2( dom) alleles are hypomorphic, so they do not simply elevate XX tra-2 activity overall. These properties suggest that in the wild type, tra-2 activity is under two types of control: (1) in males, it is inactivated by her-1 to allow male development to occur, and (2) in hermaphrodites, tra-2 is active but transiently inactivated by another, unknown, regulator to allow hermaphrodite spermatogenesis; this mode of regulation is hindered by the tra-2(dom) mutations, thereby resulting in XX females.

This article has been cited by other articles:

				D. F. Kelleher, C. E. de Carvalho, A. V. Doty, M. Layton, A. T. Cheng, L. D. Mathies, D. Pilgrim, and E. S. Haag Comparative Genetics of Sex Determination: Masculinizing Mutations in Caenorhabditis briggsae Genetics, March 1, 2008; 178(3): 1415 - 1429. [Abstract] [Full Text] [PDF]

				M. Shimada, K. Kanematsu, K. Tanaka, H. Yokosawa, and H. Kawahara Proteasomal Ubiquitin Receptor RPN-10 Controls Sex Determination in Caenorhabditis elegans Mol. Biol. Cell, December 1, 2006; 17(12): 5356 - 5371. [Abstract] [Full Text] [PDF]

				S. Jager, H. T. Schwartz, H. R. Horvitz, and B. Conradt The Caenorhabditis elegans F-box protein SEL-10 promotes female development and may target FEM-1 and FEM-3 for degradation by the proteasome PNAS, August 24, 2004; 101(34): 12549 - 12554. [Abstract] [Full Text] [PDF]

				V. Prahlad, D. Pilgrim, and E. B. Goodwin Roles for Mating and Environment in C. elegans Sex Determination Science, November 7, 2003; 302(5647): 1046 - 1049. [Abstract] [Full Text] [PDF]

				J. Hodgkin Exploring the Envelope: Systematic Alteration in the Sex-Determination System of the Nematode Caenorhabditis elegans Genetics, October 1, 2002; 162(2): 767 - 780. [Abstract] [Full Text] [PDF]

				S. T. Lamitina and S. W. L'Hernault Dominant mutations in the Caenorhabditis elegans Myt1 ortholog wee-1.3 reveal a novel domain that controls M-phase entry during spermatogenesis Development, January 11, 2002; 129(21): 5009 - 5018. [Abstract] [Full Text] [PDF]

				P.-J. Chen, S. Cho, S.-W. Jin, and R. E. Ellis Specification of Germ Cell Fates by FOG-3 Has Been Conserved During Nematode Evolution Genetics, August 1, 2001; 158(4): 1513 - 1525. [Abstract] [Full Text] [PDF]

				D. H. Lum, P. E. Kuwabara, D. Zarkower, and A. M. Spence Direct protein-protein interaction between the intracellular domain of TRA-2 and the transcription factor TRA-1A modulates feminizing activity in C. elegans Genes & Dev., December 15, 2000; 14(24): 3153 - 3165. [Abstract] [Full Text]

				E. S. Haag and J. Kimble Regulatory Elements Required for Development of Caenorhabditis elegans Hermaphrodites Are Conserved in the tra-2 Homologue of C. remanei, a Male/Female Sister Species Genetics, May 1, 2000; 155(1): 105 - 116. [Abstract] [Full Text]

				S. B. Sokol and P. E. Kuwabara Proteolysis in Caenorhabditis elegans sex determination: cleavage of TRA-2A by TRA-3 Genes & Dev., April 15, 2000; 14(8): 901 - 906. [Abstract] [Full Text]

				S. R. Thompson, E. B. Goodwin, and M. Wickens Rapid Deadenylation and Poly(A)-Dependent Translational Repression Mediated by the Caenorhabditis elegans tra-2 3' Untranslated Region in Xenopus Embryos Mol. Cell. Biol., March 15, 2000; 20(6): 2129 - 2137. [Abstract] [Full Text]

				R Clifford, M. Lee, S Nayak, M Ohmachi, F Giorgini, and T Schedl FOG-2, a novel F-box containing protein, associates with the GLD-1 RNA binding protein and directs male sex determination in the C. elegans hermaphrodite germline Development, January 12, 2000; 127(24): 5265 - 5276. [Abstract] [PDF]

				L. Saccomanno, C. Loushin, E. Jan, E. Punkay, K. Artzt, and E. B. Goodwin The STAR protein QKI-6 is a translational repressor PNAS, October 26, 1999; 96(22): 12605 - 12610. [Abstract] [Full Text] [PDF]

				A. Mehra, J. Gaudet, L. Heck, P. E. Kuwabara, and A. M. Spence Negative regulation of male development in Caenorhabditis elegans by a protein-protein interaction between TRA-2A and FEM-3 Genes & Dev., June 1, 1999; 13(11): 1453 - 1463. [Abstract] [Full Text]

				A. Puoti and J. Kimble The Caenorhabditis elegans Sex Determination Gene mog-1 Encodes a Member of the DEAH-Box Protein Family Mol. Cell. Biol., March 1, 1999; 19(3): 2189 - 2197. [Abstract] [Full Text] [PDF]

				J. M. Schumacher, A. Golden, and P. J. Donovan AIR-2: An Aurora/Ipl1-related Protein Kinase Associated with Chromosomes and Midbody Microtubules Is Required for Polar Body Extrusion and Cytokinesis in Caenorhabditis elegans Embryos J. Cell Biol., December 14, 1998; 143(6): 1635 - 1646. [Abstract] [Full Text] [PDF]

				E. Goodwin, K Hofstra, C. Hurney, S Mango, and J Kimble A genetic pathway for regulation of tra-2 translation Development, January 2, 1997; 124(3): 749 - 758. [Abstract] [PDF]

				A. Puoti, M. Gallegos, B. Zhang, M.P. Wickens, and J. Kimble Controls of Cell Fate and Pattern by 3' Untranslated Regions: The Caenorhabditis elegans Sperm/Oocyte Decision Cold Spring Harb Symp Quant Biol, January 1, 1997; 62(0): 19 - 24. [Abstract] [PDF]

				P. Kuwabara A novel regulatory mutation in the C. elegans sex determination gene tra-2 defines a candidate ligand/receptor interaction site Development, January 7, 1996; 122(7): 2089 - 2098. [Abstract] [PDF]

				P. Kuwabara and J Kimble A predicted membrane protein, TRA-2A, directs hermaphrodite development in Caenorhabditis elegans Development, January 9, 1995; 121(9): 2995 - 3004. [Abstract] [PDF]

				M D Perry, W Li, C Trent, B Robertson, A Fire, J M Hageman, and W B Wood Molecular characterization of the her-1 gene suggests a direct role in cell signaling during Caenorhabditis elegans sex determination. Genes & Dev., February 1, 1993; 7(2): 216 - 228. [Abstract] [PDF]

				C Kenyon The nematode Caenorhabditis elegans Science, June 10, 1988; 240(4858): 1448 - 1453. [Abstract] [PDF]

				T A Rosenquist and J Kimble Molecular cloning and transcript analysis of fem-3, a sex-determination gene in Caenorhabditis elegans. Genes & Dev., May 1, 1988; 2(5): 606 - 616. [Abstract] [PDF]

				J Hodgkin A genetic analysis of the sex-determining gene, tra-1, in the nematode Caenorhabditis elegans. Genes & Dev., September 1, 1987; 1(7): 731 - 745. [Abstract] [PDF]