Skip to main content
PMC home page
Genetics logoLink to Genetics
. 2001 Aug;158(4):1513–1525. doi: 10.1093/genetics/158.4.1513

Specification of germ cell fates by FOG-3 has been conserved during nematode evolution.

P J Chen 1, S Cho 1, S W Jin 1, R E Ellis 1
PMCID: PMC1461761  PMID: 11514443

Abstract

Rapid changes in sexual traits are ubiquitous in evolution. To analyze this phenomenon, we are studying species of the genus Caenorhabditis. These animals use one of two different mating systems-male/hermaphroditic, like the model organism Caenorhabditis elegans, or male/female, like C. remanei. Since hermaphrodites are essentially females that produce sperm for self-fertilization, elucidating the control of cell fate in the germ line in each species could provide the key to understanding how these mating systems evolved. In C. elegans, FOG-3 is required to specify that germ cells become sperm. Thus, we cloned its homologs from both C. remanei and C. briggsae. Each species produces a single homolog of FOG-3, and RNA-mediated interference indicates that FOG-3 functions in each species to specify that germ cells develop as sperm rather than as oocytes. What factors account for the different mating systems? Northern analyses and RT-PCR data reveal that the expression of fog-3 is always correlated with spermatogenesis. Since the promoters for all three fog-3 genes contain binding sites for the transcription factor TRA-1A and are capable of driving expression of fog-3 in C. elegans hermaphrodites, we propose that alterations in the upstream sex-determination pathway, perhaps acting through TRA-1A, allow spermatogenesis in C. elegans and C. briggsae XX larvae but not in C. remanei.

Full Text

The Full Text of this article is available as a PDF (593.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barton M. K., Kimble J. fog-1, a regulatory gene required for specification of spermatogenesis in the germ line of Caenorhabditis elegans. Genetics. 1990 May;125(1):29–39. doi: 10.1093/genetics/125.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bogdan J. A., Adams-Burton C., Pedicord D. L., Sukovich D. A., Benfield P. A., Corjay M. H., Stoltenborg J. K., Dicker I. B. Human carbon catabolite repressor protein (CCR4)-associative factor 1: cloning, expression and characterization of its interaction with the B-cell translocation protein BTG1. Biochem J. 1998 Dec 1;336(Pt 2):471–481. doi: 10.1042/bj3360471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974 May;77(1):71–94. doi: 10.1093/genetics/77.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. C. elegans Sequencing Consortium Genome sequence of the nematode C. elegans: a platform for investigating biology. Science. 1998 Dec 11;282(5396):2012–2018. doi: 10.1126/science.282.5396.2012. [DOI] [PubMed] [Google Scholar]
  5. Chen P. J., Singal A., Kimble J., Ellis R. E. A novel member of the tob family of proteins controls sexual fate in Caenorhabditis elegans germ cells. Dev Biol. 2000 Jan 1;217(1):77–90. doi: 10.1006/dbio.1999.9521. [DOI] [PubMed] [Google Scholar]
  6. Chen P., Ellis R. E. TRA-1A regulates transcription of fog-3, which controls germ cell fate in C. elegans. Development. 2000 Jul;127(14):3119–3129. doi: 10.1242/dev.127.14.3119. [DOI] [PubMed] [Google Scholar]
  7. Clifford R., Lee M. H., Nayak S., Ohmachi M., Giorgini F., Schedl T. 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. 2000 Dec;127(24):5265–5276. doi: 10.1242/dev.127.24.5265. [DOI] [PubMed] [Google Scholar]
  8. Doniach T. Activity of the sex-determining gene tra-2 is modulated to allow spermatogenesis in the C. elegans hermaphrodite. Genetics. 1986 Sep;114(1):53–76. doi: 10.1093/genetics/114.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ellis R. E., Kimble J. Control of germ cell differentiation in Caenorhabditis elegans. Ciba Found Symp. 1994;182:179–192. doi: 10.1002/9780470514573.ch10. [DOI] [PubMed] [Google Scholar]
  10. Ellis R. E., Kimble J. The fog-3 gene and regulation of cell fate in the germ line of Caenorhabditis elegans. Genetics. 1995 Feb;139(2):561–577. doi: 10.1093/genetics/139.2.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fire A., Xu S., Montgomery M. K., Kostas S. A., Driver S. E., Mello C. C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998 Feb 19;391(6669):806–811. doi: 10.1038/35888. [DOI] [PubMed] [Google Scholar]
  12. Fitch D. H., Bugaj-Gaweda B., Emmons S. W. 18S ribosomal RNA gene phylogeny for some Rhabditidae related to Caenorhabditis. Mol Biol Evol. 1995 Mar;12(2):346–358. doi: 10.1093/oxfordjournals.molbev.a040207. [DOI] [PubMed] [Google Scholar]
  13. Frohman M. A., Dush M. K., Martin G. R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. doi: 10.1073/pnas.85.23.8998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goodwin E. B., Okkema P. G., Evans T. C., Kimble J. Translational regulation of tra-2 by its 3' untranslated region controls sexual identity in C. elegans. Cell. 1993 Oct 22;75(2):329–339. doi: 10.1016/0092-8674(93)80074-o. [DOI] [PubMed] [Google Scholar]
  15. Guo S., Kemphues K. J. par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Cell. 1995 May 19;81(4):611–620. doi: 10.1016/0092-8674(95)90082-9. [DOI] [PubMed] [Google Scholar]
  16. Guéhenneux F., Duret L., Callanan M. B., Bouhas R., Hayette S., Berthet C., Samarut C., Rimokh R., Birot A. M., Wang Q. Cloning of the mouse BTG3 gene and definition of a new gene family (the BTG family) involved in the negative control of the cell cycle. Leukemia. 1997 Mar;11(3):370–375. doi: 10.1038/sj.leu.2400599. [DOI] [PubMed] [Google Scholar]
  17. Haag E. S., Kimble J. 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. 2000 May;155(1):105–116. doi: 10.1093/genetics/155.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Halloran N., Du Z., Wilson R. K. Sequencing reactions for the applied biosystems 373A Automated DNA Sequencer. Methods Mol Biol. 1993;23:297–315. doi: 10.1385/0-89603-248-5:297. [DOI] [PubMed] [Google Scholar]
  19. Hansen D., Pilgrim D. Molecular evolution of a sex determination protein. FEM-2 (pp2c) in Caenorhabditis. Genetics. 1998 Jul;149(3):1353–1362. doi: 10.1093/genetics/149.3.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hansen D., Pilgrim D. Sex and the single worm: sex determination in the nematode C. elegans. Mech Dev. 1999 May;83(1-2):3–15. doi: 10.1016/s0925-4773(99)00024-6. [DOI] [PubMed] [Google Scholar]
  21. Horvitz H. R., Brenner S., Hodgkin J., Herman R. K. A uniform genetic nomenclature for the nematode Caenorhabditis elegans. Mol Gen Genet. 1979 Sep;175(2):129–133. doi: 10.1007/BF00425528. [DOI] [PubMed] [Google Scholar]
  22. Jin S. W., Kimble J., Ellis R. E. Regulation of cell fate in Caenorhabditis elegans by a novel cytoplasmic polyadenylation element binding protein. Dev Biol. 2001 Jan 15;229(2):537–553. doi: 10.1006/dbio.2000.9993. [DOI] [PubMed] [Google Scholar]
  23. Jones D. H. Panhandle PCR. PCR Methods Appl. 1995 Apr;4(5):S195–S201. doi: 10.1101/gr.4.5.s195. [DOI] [PubMed] [Google Scholar]
  24. Kuwabara P. E. Interspecies comparison reveals evolution of control regions in the nematode sex-determining gene tra-2. Genetics. 1996 Oct;144(2):597–607. doi: 10.1093/genetics/144.2.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kuwabara P. E., Okkema P. G., Kimble J. Germ-line regulation of the Caenorhabditis elegans sex-determining gene tra-2. Dev Biol. 1998 Dec 1;204(1):251–262. doi: 10.1006/dbio.1998.9062. [DOI] [PubMed] [Google Scholar]
  26. Marín I., Baker B. S. The evolutionary dynamics of sex determination. Science. 1998 Sep 25;281(5385):1990–1994. doi: 10.1126/science.281.5385.1990. [DOI] [PubMed] [Google Scholar]
  27. McKearin D., Christerson L. Molecular genetics of the early stages of germ cell differentiation during Drosophila oogenesis. Ciba Found Symp. 1994;182:210–222. doi: 10.1002/9780470514573.ch12. [DOI] [PubMed] [Google Scholar]
  28. Raymond C. S., Shamu C. E., Shen M. M., Seifert K. J., Hirsch B., Hodgkin J., Zarkower D. Evidence for evolutionary conservation of sex-determining genes. Nature. 1998 Feb 12;391(6668):691–695. doi: 10.1038/35618. [DOI] [PubMed] [Google Scholar]
  29. Rose T. M., Schultz E. R., Henikoff J. G., Pietrokovski S., McCallum C. M., Henikoff S. Consensus-degenerate hybrid oligonucleotide primers for amplification of distantly related sequences. Nucleic Acids Res. 1998 Apr 1;26(7):1628–1635. doi: 10.1093/nar/26.7.1628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rouault J. P., Prévôt D., Berthet C., Birot A. M., Billaud M., Magaud J. P., Corbo L. Interaction of BTG1 and p53-regulated BTG2 gene products with mCaf1, the murine homolog of a component of the yeast CCR4 transcriptional regulatory complex. J Biol Chem. 1998 Aug 28;273(35):22563–22569. doi: 10.1074/jbc.273.35.22563. [DOI] [PubMed] [Google Scholar]
  31. Rudel D., Kimble J. Conservation of glp-1 regulation and function in nematodes. Genetics. 2001 Feb;157(2):639–654. doi: 10.1093/genetics/157.2.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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. 1988 Sep 23;54(7):1019–1031. doi: 10.1016/0092-8674(88)90117-1. [DOI] [PubMed] [Google Scholar]
  34. Streit A., Li W., Robertson B., Schein J., Kamal I. H., Marra M., Wood W. B. Homologs of the Caenorhabditis elegans masculinizing gene her-1 in C. briggsae and the filarial parasite Brugia malayi. Genetics. 1999 Aug;152(4):1573–1584. doi: 10.1093/genetics/152.4.1573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sutton K. A. Molecular mechanisms involved in the differentiation of spermatogenic stem cells. Rev Reprod. 2000 May;5(2):93–98. doi: 10.1530/ror.0.0050093. [DOI] [PubMed] [Google Scholar]
  36. Wyckoff G. J., Wang W., Wu C. I. Rapid evolution of male reproductive genes in the descent of man. Nature. 2000 Jan 20;403(6767):304–309. doi: 10.1038/35002070. [DOI] [PubMed] [Google Scholar]
  37. Zarkower D., Hodgkin J. Molecular analysis of the C. elegans sex-determining gene tra-1: a gene encoding two zinc finger proteins. Cell. 1992 Jul 24;70(2):237–249. doi: 10.1016/0092-8674(92)90099-x. [DOI] [PubMed] [Google Scholar]
  38. de Bono M., Hodgkin J. Evolution of sex determination in caenorhabditis: unusually high divergence of tra-1 and its functional consequences. Genetics. 1996 Oct;144(2):587–595. doi: 10.1093/genetics/144.2.587. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES