Worm Breeder's Gazette 11(2): 118
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
The cumulative genetic evidence continues to support the proposal that dpy-29, like sdc-1 and sdc-2, is required in XX animals for the proper control of both sex determination and dosage compensation. However, unlike the sdc genes, the dosage compensation and sex- determination functions of dpy-29 appear to be independently mutable. Furthermore, null or near null alleles of dpy-29 do not normally masculinize XX animals, rather, the cryptic Tra phenotype can only be seen in certain genetic backgrounds. The tra V mutations, which cause recessive masculinization of XX animals, appear to result from loss of only the sex-determination function of the gene. One dpy-29 allele appears to disrupt only the dosage-compensation function, the remaining dpy-29 alleles appear to disrupt both gene functions. dpy-29 is required for the XX mode of dosage compensation. Mutations in dpy-29 result in recessive XX-specific dumpiness and XX- specific maternal effect lethality; the lethality ranges from 72% to 98%. Phenotypically, mutations in dpy-29 resemble mutations in the dosage compensation dpy genes dpy-26, he lin-14 assay we have shown that mutations in dpy-29 result in elevated levels of X-linked gene expression. Like other mutations that disrupt the XX mode of dosage compensation, mutations in dpy-29 rescue xol-1 XO animals. dpy-29 is required for hermaphrodite sexual development. dpy-29 differs from the dosage compensation dpy genes in two ways: 1) dpy-29 mutations, like sdc-1 and sdc-2 mutations, suppress the lethality of xol-1 XO animals, resulting in rescued animals that are male. By contrast, dpy-26, s suppress the lethality of xol-1 XO animals but result in rescued animals that are hermaphrodite. 2) dpy-29 mutations also differs from dpy-26, s in their effects on the sexual phenotype of 2X:3A animals. dpy-29(y100) 2X:3A animals, like dpy(+) 2X:3A animals, are usually male; by contrast, dpy-26, imals are feminized. The masculinizing effect of dpy-29 mutations can be seen directly when placed in trans to tra(y52). dpy-29/tra V XX animals range from 0 to 99% masculinized, depending on the dpy-29 allele. This masculinization is specific to mutations in these two genes; dpy-29 mutations show no dominant masculinization with mutations in tra-1 or tra-2. tra V mutations show no dominant masculinization with mutations in dpy-26, dpy-28, nodpy-29 rs to act upstream of her-1. her-1(+) is required for the masculinization of tra V XX animals and for the masculinization of dpy-29/tra V XX animals. This result, combined with the observation that dpy-29 mutations suppress the XO- specific lethality of xol-1 mutations, indicates that dpy-29 acts at the same point of the sex-determination pathway as sdc-1 and sdc-2.The dosage-compensation and the sex- determination functions of dpy-29 are independently mutable. The extent of masculinization of the dpy-29 alleles is unrelated to the strength of the dosage compensation defect, which is measured by extent of the XX-specific maternal-effect lethality. For example, both dpy-29(y144) and dpy-29(y100) have the same level of maternal- effect lethality (97%), however 99% of dpy-29(y144)/tra V animals are masculinized, whereas only 3% of dpy-29(y100)/tra V animals are masculinized. By a cis-trans test, dpy-29 and tra V mutations are in the same gene. Three independent tra V dpy-29 mutants were obtained by inducing dpy- 29 mutations on a tra V chromosome (two different tra V alleles were used). All three double mutants are phenotypically indistinguishable from strong dpy-29 mutations: XX animals are fully hermaphrodite and exhibit a strong maternal-effect lethality (96% - 98%). We have evidence that the original tra V mutation is still present in two of the double mutants. For one double mutant, a Tra non-Dpy recombinant was obtained after screening 17,000 progeny of tra V dpy-29/+ mothers. In another double mutant, the dpy-29 mutation was shown to be suppressible by sup-7(st5). The tra V dpy-29; ed animals are pseudomales, in contrast to the tra V dpy-29 mutant animals which, when viable, are hermaphrodites. [See Figure 1] Mutations in dpy-29 probably represent the null phenotype. Mutations in dpy-29 that have strong cryptic masculinizing effects resemble a deficiency in trans to tra(y52). 99% of Df/tra progeny of Df/tra mothers and 99% of dpy-29/tra progeny of dpy-29/tra mothers are fully masculinized. However only approximately 50% of Df/tra or dpy- 29/tra progeny of tra/+ mothers are masculinized. The XX masculinization of mutations in tra V is suppressible by XXX and mutations in dpy-26, erpretation that dpy-29 mutations represent the null phenotype of tra V requires that, in dpy-29 mutants, the dosage compensation defect suppresses the masculinization caused by the sex determination defect. Not only have we shown this to be true for dpy-29 as described in the cis-trans test above, but we have found that mutations in dpy-26, c the effect of dpy-29 mutations by completely suppressing the masculinization of mutations in tra V. That is, homozygous dpy; tra( y52) XX animals are hermaphrodites. In a similar vein, we have found that him-5 XX animals are dumpy hermaphrodites. The dosage compensation dpy genes also cause a dominant suppression of the masculinization of tra(y52). dpy/+; tra(y52) progeny of dpy/+; tra(y52)/+ mothers are frequently hermaphrodite. For example: 100% of dpy-27/+; tra(y52) or yDf10/+; tra(y52) XX animals are hermaphrodite; 70% of dpy-28/+; tra(y52) + animals are hermaphrodite; and 30% of dpy- 26/+; tra(y52) or 58% of sDf21/+; tra(y52) XX animals are hermaphrodite. Suppression is not seen in the next generation however dpy/+; tra(y52) progeny of dpy/+; tra(y52) mothers are fully masculinized. These results are similar to the results described earlier for both a deficiency of dpy-29 and dpy-29 mutations in trans to tra(y52). Unexpectedly, we have found that dpy-26, se a maternal-effect suppression of the masculinization of tra(y52). dpy/+; tra(y52) progeny of dpy; tra(y52) mothers are mostly hermaphrodite. This is very different from the results seen with dpy-29, which shows little or no maternal- effect suppression of tra(y52). There is considerable evidence showing that disruption of dosage compensation in XX animals is associated with suppression of masculinization in sexually transformed animals. For example, mutations in dpy-26, the masculinization of her-1(n695sd) and her-1(y101sd). In addition, sdc- 1(y67) XX animals become more strongly transformed when the dosage- compensation defect is suppressed by y63. Thus, although feedback between sex-determination and dosage compensation is not novel, the dpy-29 mutations provide a dramatic demonstration of this feedback operating within a single locus.