Disease relevance of tra-1

• The functional importance of the TRA-1-TRA-2 physical interaction is supported by genetic interactions between tra-1(0) and tra-2(mx) mutations: a reduction of tra-1 gene dose from two copies to one copy enhances the tra-2(mx) feminization phenotype, but has no apparent somatic effect [1].
• Using the Caenorhabditis elegans sex determining tra-1 gene as a probe we have identified two tra-1 related genes in the genome of O. volvulus [2].

High impact information on tra-1

• The transcription pattern reveals that alternative mRNA processing governs the number of zinc fingers in the resulting tra-1 protein [3].
• The tra-1 gene determines sexual phenotype cell-autonomously in C. elegans [4].
• By analyzing a large number of tra-1 genetic mosaics we have shown that, with the expected exception of vulval induction by the hermaphrodite gonad, tra-1 functions cell-autonomously, consistent with a role as an intracellular component of a signaling pathway [4].
• Epistasis analysis is most consistent with a model in which mab-3 is controlled by tra-1, the last switch gene known to act in the somatic sex determination pathway [5].
• In these strains the autosomes carrying the tra-1 locus are in effect homomorphic Z and W sex chromosomes, and the sexes are homogametic ZZ males and heterogametic ZW females, in contrast to the wild-type arrangement of homogametic XX hermaphrodites and heterogametic X0 males [6].

Biological context of tra-1

• By analyzing double mutants it has been shown that fem-1(+) is part of the sex-determination pathway and has two distinct functions: (1) in the soma it prevents the action of tra-1, thereby allowing male development to occur, and (2) in the germline it is necessary for spermatogenesis in both sexes [7].
• Two alleles of tra-1 produce almost complete transformation, to a fertile male phenotype; such transformed animals are useful for analyzing sex-linked genes [8].
• Mab-3 is a direct tra-1 target gene regulating diverse aspects of C. elegans male sexual development and behavior [9].
• Twenty-three mutations were isolated after chemical mutagenesis and found to fall into both expected classes (four dominant tra-1 mutations and eight recessive xol-1 mutations) and novel classes [10].
• A low level of both spermatogenesis and oogenesis can occur in the absence of tra-1 activity [11].

Anatomical context of tra-1

• Paradoxically, tra-2(mx) mutations feminize the XX germ line, as do tra-1 mutations mapping to the TRA-2 binding domain [12].

Regulatory relationships of tra-1

• All dpy-21 alleles show hermaphroditization effects in XO males that carry a duplication of part of the X chromosome and also partially suppress a transformer (tra-1) mutation that converts XX animals into males [13].

Other interactions of tra-1

• These fall into three autosomal complementation groups, termed tra-1, tra-2, and tra-3 [8].
• All alleles of tra-1 and tra-2 are recessive; the one known allele of tra-3 is both recessive and maternal in effect [8].
• The same mutations also suppress certain alleles of another sex determination gene, tra-1, and of a morphogenetic gene, dpy-5 [14].
• Furthermore, after transformation into fertile hermaphrodites by a her-1 mutation, XO animals were more radiosensitive than XX her-1 animals; and XX animals transformed into fertile males by a tra-1 mutation did not show increased radiosensitivity [15].
• The feminization phenotype induced by deletion of the rpn-10 gene was rescued by knockdown of tra-2, one of sexual fate decision genes promoting female development, and its downstream target tra-1, indicating that the TRA-2-mediated sex determination pathway is crucial for the Deltarpn-10-induced sterile phenotype [16].

Analytical, diagnostic and therapeutic context of tra-1

• First, northern analyses and RT-PCR experiments indicate that expression of fog-3 is controlled by tra-1 [17].
• Molecular cloning and duplication of the nematode sex-determining gene tra-1 [18].

References