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. 1987 Jan;115(1):107–119. doi: 10.1093/genetics/115.1.107

Gain-of-Function Mutations of fem-3, a Sex-Determination Gene in Caenorhabditis elegans

M Kathryn Barton 1, Timothy B Schedl 1, Judith Kimble 1
PMCID: PMC1203045  PMID: 3557107

Abstract

We have isolated nine gain-of-function (gf) alleles of the sex-determination gene fem-3 as suppressors of feminizing mutations in fem-1 and fem-2. The wild-type fem-3 gene is needed for spermatogenesis in XX self-fertilizing hermaphrodites and for male development in both soma and germ line of XO animals. Loss-of-function alleles of fem-3 transform XX and XO animals into females (spermless hermaphrodites). In contrast, fem-3(gf) alleles masculinize only one tissue, the hermaphrodite germ line. Thus, XX fem-3(gf) mutant animals have a normal hermaphrodite soma, but the germ line produces a vast excess of sperm and no oocytes. All nine fem-3(gf) alleles are temperature sensitive. The temperature-sensitive period is from late L4 to early adult, a period just preceding the first signs of oogenesis. The finding of gain-of-function alleles which confer a phenotype opposite to that of loss-of-function alleles supports the idea that fem-3 plays a critical role in germ-line sex determination. Furthermore, the germ-line specificity of the fem-3( gf) mutant phenotype and the late temperature-sensitive period suggest that, in the wild-type XX hermaphrodite, fem-3 is negatively regulated so that the hermaphrodite stops making sperm and starts making oocytes. Temperature shift experiments also show that, in the germ line, sexual commitment appears to be a continuing process. Spermatogenesis can resume even after oogenesis has begun, and oogenesis can be initiated much later than normal.

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Selected References

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  1. Amati P, Meselson M. Localized Negative Interference in Bacteriophage. Genetics. 1965 Mar;51(3):369–379. doi: 10.1093/genetics/51.3.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Amundsen S. K., Taylor A. F., Chaudhury A. M., Smith G. R. recD: the gene for an essential third subunit of exonuclease V. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5558–5562. doi: 10.1073/pnas.83.15.5558. [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. Carl P. L. Escherichia coli mutants with temperature-sensitive synthesis of DNA. Mol Gen Genet. 1970;109(2):107–122. doi: 10.1007/BF00269647. [DOI] [PubMed] [Google Scholar]
  5. Chaudhury A. M., Smith G. R. A new class of Escherichia coli recBC mutants: implications for the role of RecBC enzyme in homologous recombination. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7850–7854. doi: 10.1073/pnas.81.24.7850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Emmerson P. T., Howard-Flanders P. Cotransduction with thy of a gene required for genetic recombination in Escherichia coli. J Bacteriol. 1967 May;93(5):1729–1731. doi: 10.1128/jb.93.5.1729-1731.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ennis D. G., Fisher B., Edmiston S., Mount D. W. Dual role for Escherichia coli RecA protein in SOS mutagenesis. Proc Natl Acad Sci U S A. 1985 May;82(10):3325–3329. doi: 10.1073/pnas.82.10.3325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gellert M. DNA topoisomerases. Annu Rev Biochem. 1981;50:879–910. doi: 10.1146/annurev.bi.50.070181.004311. [DOI] [PubMed] [Google Scholar]
  9. Gellert M., O'Dea M. H., Itoh T., Tomizawa J. Novobiocin and coumermycin inhibit DNA supercoiling catalyzed by DNA gyrase. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4474–4478. doi: 10.1073/pnas.73.12.4474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Glassberg J., Meyer R. R., Kornberg A. Mutant single-strand binding protein of Escherichia coli: genetic and physiological characterization. J Bacteriol. 1979 Oct;140(1):14–19. doi: 10.1128/jb.140.1.14-19.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gottesman M. M., Hicks M. L., Gellert M. Genetics and function of DNA ligase in Escherichia coli. J Mol Biol. 1973 Jul 15;77(4):531–547. doi: 10.1016/0022-2836(73)90221-0. [DOI] [PubMed] [Google Scholar]
  12. Hirsh D., Vanderslice R. Temperature-sensitive developmental mutants of Caenorhabditis elegans. Dev Biol. 1976 Mar;49(1):220–235. doi: 10.1016/0012-1606(76)90268-2. [DOI] [PubMed] [Google Scholar]
  13. Hodgkin J. A., Brenner S. Mutations causing transformation of sexual phenotype in the nematode Caenorhabditis elegans. Genetics. 1977 Jun;86(2 Pt 1):275–287. [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Jarvik J., Botstein D. Conditional-lethal mutations that suppress genetic defects in morphogenesis by altering structural proteins. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2738–2742. doi: 10.1073/pnas.72.7.2738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kimble J., Hodgkin J., Smith T., Smith J. Suppression of an amber mutation by microinjection of suppressor tRNA in C. elegans. Nature. 1982 Sep 30;299(5882):456–458. doi: 10.1038/299456a0. [DOI] [PubMed] [Google Scholar]
  17. Kleckner N., Ross D. G. recA-dependent genetic switch generated by transposon Tn10. J Mol Biol. 1980 Dec 5;144(2):215–221. doi: 10.1016/0022-2836(80)90033-9. [DOI] [PubMed] [Google Scholar]
  18. Kobayashi I., Murialdo H., Crasemann J. M., Stahl M. M., Stahl F. W. Orientation of cohesive end site cos determines the active orientation of chi sequence in stimulating recA . recBC-mediated recombination in phage lambda lytic infections. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5981–5985. doi: 10.1073/pnas.79.19.5981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kobayashi I., Stahl M. M., Fairfield F. R., Stahl F. W. Coupling with packaging explains apparent nonreciprocality of Chi-stimulated recombination of bacteriophage lambda by RecA and RecBC functions. Genetics. 1984 Dec;108(4):773–794. doi: 10.1093/genetics/108.4.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lam S. T., Stahl M. M., McMilin K. D., Stahl F. W. Rec-mediated recombinational hot spot activity in bacteriophage lambda. II. A mutation which causes hot spot activity. Genetics. 1974 Jul;77(3):425–433. doi: 10.1093/genetics/77.3.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lindahl G., Sironi G., Bialy H., Calendar R. Bacteriophage lambda; abortive infection of bacteria lysogenic for phage P2. Proc Natl Acad Sci U S A. 1970 Jul;66(3):587–594. doi: 10.1073/pnas.66.3.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Little J. W., Mount D. W. The SOS regulatory system of Escherichia coli. Cell. 1982 May;29(1):11–22. doi: 10.1016/0092-8674(82)90085-x. [DOI] [PubMed] [Google Scholar]
  23. Lundblad V., Taylor A. F., Smith G. R., Kleckner N. Unusual alleles of recB and recC stimulate excision of inverted repeat transposons Tn10 and Tn5. Proc Natl Acad Sci U S A. 1984 Feb;81(3):824–828. doi: 10.1073/pnas.81.3.824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nash H. A. LambdaattB-attP, a lambda derivative containing both sites involved in integrative recombination. Virology. 1974 Jan;57(1):207–216. doi: 10.1016/0042-6822(74)90121-4. [DOI] [PubMed] [Google Scholar]
  25. Ponticelli A. S., Schultz D. W., Taylor A. F., Smith G. R. Chi-dependent DNA strand cleavage by RecBC enzyme. Cell. 1985 May;41(1):145–151. doi: 10.1016/0092-8674(85)90069-8. [DOI] [PubMed] [Google Scholar]
  26. Sarthy P. V., Meselson M. Single burst study of rec- and red-mediated recombination in bacteriophage lambda. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4613–4617. doi: 10.1073/pnas.73.12.4613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schultz D. W., Taylor A. F., Smith G. R. Escherichia coli RecBC pseudorevertants lacking chi recombinational hotspot activity. J Bacteriol. 1983 Aug;155(2):664–680. doi: 10.1128/jb.155.2.664-680.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Shibata T., DasGupta C., Cunningham R. P., Radding C. M. Purified Escherichia coli recA protein catalyzes homologous pairing of superhelical DNA and single-stranded fragments. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1638–1642. doi: 10.1073/pnas.76.4.1638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Smith S. R. Miscellaneous: In praise of the Basuto pony. Br Med J (Clin Res Ed) 1983 Dec 24;287(6409):1985–1987. doi: 10.1136/bmj.287.6409.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Stahl F. W., McMilin K. D., Stahl M. M., Malone R. E., Nozu Y., Russo V. E. A role for recombination in the production of "free-loader" lambda bacteriophage particles. J Mol Biol. 1972 Jul 14;68(1):57–67. doi: 10.1016/0022-2836(72)90262-8. [DOI] [PubMed] [Google Scholar]
  31. Stahl F. W., Stahl M. M., Malone R. E., Crasemann J. M. Directionality and nonreciprocality of Chi-stimulated recombination in phage lambda. Genetics. 1980 Feb;94(2):235–248. doi: 10.1093/genetics/94.2.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Taylor A. F., Schultz D. W., Ponticelli A. S., Smith G. R. RecBC enzyme nicking at Chi sites during DNA unwinding: location and orientation-dependence of the cutting. Cell. 1985 May;41(1):153–163. doi: 10.1016/0092-8674(85)90070-4. [DOI] [PubMed] [Google Scholar]
  33. Weil J. Reciprocal and non-reciprocal recombination in bacteriopahge lambda. J Mol Biol. 1969 Jul 28;43(2):351–355. doi: 10.1016/0022-2836(69)90276-9. [DOI] [PubMed] [Google Scholar]

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