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. 1993 Mar;133(3):543–560. doi: 10.1093/genetics/133.3.543

Molecular Cloning and Duplication of the Nematode Sex-Determining Gene Tra-1

J Hodgkin 1
PMCID: PMC1205342  PMID: 8384144

Abstract

The autosomal sex-determining gene tra-1 plays a major role in controlling sexual phenotype in the nematode Caenorhabditis elegans. This gene is the terminal global regulator in a well-characterized cascade of sex-determining genes. It governs all aspects of somatic sexual differentiation, and it also has important functions in governing germ-line differentiation. Previous genetic analyses have led to the characterization of many loss-of-function (masculinizing) and gain-of-function (dominant feminizing) alleles, and to models for the functions and regulation of tra-1. The gene was cloned by identifying linked transposon insertions, about 200 kb away from tra-1. From this starting point a series of YAC, cosmid and phage clones were assembled into a genomic walk covering over 400 kb. Much of this region was found to be unrepresented in the cosmid database that covers most of the C. elegans genome. This deficit is largely or wholly due to the presence of sequences that cannot be cloned in rec(+)bacterial hosts. The ratio of physical map distances to recombinational map distances in the tra-1 region of the genome appears to be unusually low, indicating considerable local map expansion. The location of tra-1 within the cloned region was determined using a variety of tra-1 mutations that are associated with physical rearrangements of the gene. One of these is a 14-kb deletion, which behaves as a null allele. Another rearrangement, eDp24, is a tandem duplication of 22 kb. Genetic analysis demonstrates that eDp24 carries two incomplete copies of tra-1, and that these copies appear to interact, suggesting some form of negative autoregulation at this locus. Three variant forms of the tra-1 locus have been identified in different natural isolates of C. elegans.

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Selected References

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  1. Chalker A. F., Leach D. R., Lloyd R. G. Escherichia coli sbcC mutants permit stable propagation of DNA replicons containing a long palindrome. Gene. 1988 Nov 15;71(1):201–205. doi: 10.1016/0378-1119(88)90092-3. [DOI] [PubMed] [Google Scholar]
  2. Collins J., Saari B., Anderson P. Activation of a transposable element in the germ line but not the soma of Caenorhabditis elegans. Nature. 1987 Aug 20;328(6132):726–728. doi: 10.1038/328726a0. [DOI] [PubMed] [Google Scholar]
  3. Coulson A., Sulston J., Brenner S., Karn J. Toward a physical map of the genome of the nematode Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7821–7825. doi: 10.1073/pnas.83.20.7821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Coulson A., Waterston R., Kiff J., Sulston J., Kohara Y. Genome linking with yeast artificial chromosomes. Nature. 1988 Sep 8;335(6186):184–186. doi: 10.1038/335184a0. [DOI] [PubMed] [Google Scholar]
  5. Greenwald I. lin-12, a nematode homeotic gene, is homologous to a set of mammalian proteins that includes epidermal growth factor. Cell. 1985 Dec;43(3 Pt 2):583–590. doi: 10.1016/0092-8674(85)90230-2. [DOI] [PubMed] [Google Scholar]
  6. Hodgkin J. A genetic analysis of the sex-determining gene, tra-1, in the nematode Caenorhabditis elegans. Genes Dev. 1987 Sep;1(7):731–745. doi: 10.1101/gad.1.7.731. [DOI] [PubMed] [Google Scholar]
  7. Hodgkin J., Barnes T. M. More is not better: brood size and population growth in a self-fertilizing nematode. Proc Biol Sci. 1991 Oct 22;246(1315):19–24. doi: 10.1098/rspb.1991.0119. [DOI] [PubMed] [Google Scholar]
  8. Hodgkin J. More sex-determination mutants of Caenorhabditis elegans. Genetics. 1980 Nov;96(3):649–664. doi: 10.1093/genetics/96.3.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hodgkin J., Papp A., Pulak R., Ambros V., Anderson P. A new kind of informational suppression in the nematode Caenorhabditis elegans. Genetics. 1989 Oct;123(2):301–313. doi: 10.1093/genetics/123.2.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hodgkin J. Sex determination compared in Drosophila and Caenorhabditis. Nature. 1990 Apr 19;344(6268):721–728. doi: 10.1038/344721a0. [DOI] [PubMed] [Google Scholar]
  11. Hodgkin J. Sex determination in the nematode C. elegans: analysis of tra-3 suppressors and characterization of fem genes. Genetics. 1986 Sep;114(1):15–52. doi: 10.1093/genetics/114.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hodgkin J. Two types of sex determination in a nematode. Nature. 1983 Jul 21;304(5923):267–268. doi: 10.1038/304267a0. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Hunter C. P., Wood W. B. The tra-1 gene determines sexual phenotype cell-autonomously in C. elegans. Cell. 1990 Dec 21;63(6):1193–1204. doi: 10.1016/0092-8674(90)90415-b. [DOI] [PubMed] [Google Scholar]
  15. Kuwabara P. E., Kimble J. Molecular genetics of sex determination in C. elegans. Trends Genet. 1992 May;8(5):164–168. doi: 10.1016/0168-9525(92)90218-s. [DOI] [PubMed] [Google Scholar]
  16. Liao L. W., Rosenzweig B., Hirsh D. Analysis of a transposable element in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3585–3589. doi: 10.1073/pnas.80.12.3585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mains P. E., Sulston I. A., Wood W. B. Dominant maternal-effect mutations causing embryonic lethality in Caenorhabditis elegans. Genetics. 1990 Jun;125(2):351–369. doi: 10.1093/genetics/125.2.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miller D. M., Shen M. M., Shamu C. E., Bürglin T. R., Ruvkun G., Dubois M. L., Ghee M., Wilson L. C. elegans unc-4 gene encodes a homeodomain protein that determines the pattern of synaptic input to specific motor neurons. Nature. 1992 Feb 27;355(6363):841–845. doi: 10.1038/355841a0. [DOI] [PubMed] [Google Scholar]
  19. Murray N. E., Brammar W. J., Murray K. Lambdoid phages that simplify the recovery of in vitro recombinants. Mol Gen Genet. 1977 Jan 7;150(1):53–61. doi: 10.1007/BF02425325. [DOI] [PubMed] [Google Scholar]
  20. Pulak R. A., Anderson P. Structures of spontaneous deletions in Caenorhabditis elegans. Mol Cell Biol. 1988 Sep;8(9):3748–3754. doi: 10.1128/mcb.8.9.3748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rommens J. M., Iannuzzi M. C., Kerem B., Drumm M. L., Melmer G., Dean M., Rozmahel R., Cole J. L., Kennedy D., Hidaka N. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989 Sep 8;245(4922):1059–1065. doi: 10.1126/science.2772657. [DOI] [PubMed] [Google Scholar]
  22. Rosenquist T. A., Kimble J. Molecular cloning and transcript analysis of fem-3, a sex-determination gene in Caenorhabditis elegans. Genes Dev. 1988 May;2(5):606–616. doi: 10.1101/gad.2.5.606. [DOI] [PubMed] [Google Scholar]
  23. Ruvkun G., Ambros V., Coulson A., Waterston R., Sulston J., Horvitz H. R. Molecular genetics of the Caenorhabditis elegans heterochronic gene lin-14. Genetics. 1989 Mar;121(3):501–516. doi: 10.1093/genetics/121.3.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schedl T., Graham P. L., Barton M. K., Kimble J. Analysis of the role of tra-1 in germline sex determination in the nematode Caenorhabditis elegans. Genetics. 1989 Dec;123(4):755–769. doi: 10.1093/genetics/123.4.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Spence A. M., Coulson A., Hodgkin J. The product of fem-1, a nematode sex-determining gene, contains a motif found in cell cycle control proteins and receptors for cell-cell interactions. Cell. 1990 Mar 23;60(6):981–990. doi: 10.1016/0092-8674(90)90346-g. [DOI] [PubMed] [Google Scholar]
  26. Villeneuve A. M., Meyer B. J. The regulatory hierarchy controlling sex determination and dosage compensation in Caenorhabditis elegans. Adv Genet. 1990;27:117–188. doi: 10.1016/s0065-2660(08)60025-5. [DOI] [PubMed] [Google Scholar]
  27. Wyman A. R., Wertman K. F. Host strains that alleviate underrepresentation of specific sequences: overview. Methods Enzymol. 1987;152:173–180. doi: 10.1016/0076-6879(87)52017-1. [DOI] [PubMed] [Google Scholar]
  28. 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]

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