Worm Breeder's Gazette 10(3): 8
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.
We recently reported the discovery of a new gene, dpy-29, which is required in XX animals for proper dosage compensation, and displays the same repertoire of mutant phenotypes as do dpy-26, sch, DeLong, Meyer Genetics, in press, see also Plenefisch et al. in WBG v10 n2). We have subsequently isolated eight additional alleles of dpy-29 (all of which map between unc-61 and unc-76 on LG V): six EMS induced alleles and one gamma-irradiation induced allele were obtained on the basis of their failure to complement dpy-29(y100am); one EMS induced allele was obtained as a suppressor of xol-1 XO-specific lethality. Preliminary characterization of these new alleles reveals that they result in the same phenotypes as the original dpy-29(y100am). Homozygous dpy-29 XX progeny of heterozygous mothers are Dpy; homozygous progeny of homozygous mothers are inviable, with rare Dpy escapees. XO animals appear unaffected. None of the alleles appear to promote X-chromosome nondisjunction as do mutations in dpy-26 and dpy-28. Finally, none of these dpy-29 mutations appear to result in sexual transformation of XX animals into males. We have previously reported the isolation of the sex transformation mutation y52, which also maps within the unc-61 and unc-76 interval of LG V (DeLong and Meyer WBG v10 n2). XX animals homozygous for y52 are wild-type in length and exhibit a range of phenotypes from Egl hermaphrodite to pseudomale. The most strongly transformed animals are incomplete males with a normal male body and gonad but a deformed tail with stunted rays. Complete transformation to a mating XX male can occur if the animal is also homozygous for a mutation in xol-1. her-1(e1520) is epistatic to y52, suggesting that y52 acts upstream of her-1 in the sex determination pathway. X-linked gene expression in y52 animals is indistinguishable from wild type (by the lin-14 assay). We have recently isolated three new tra mutations at this locus: two gamma-irradiation induced alleles were obtained on the basis of failure to complement y52; one EMS induced allele was obtained as a mating X.Y male in a xol-1 background. Although the dpy-29 mutations appear to affect only dosage compensation in XX animals and the tra mutations appear to affect only sex determination in XX animals, we performed complementation tests between the two since they map to the same small interval. y52 complements all dpy-29 alleles fully for dumpiness and lethality. Moreover, y52/dpy-29 cannot suppress the XO specific lethality of xol- 1. Unexpectedly, y52/dpy-29 XX animals are masculinized, the exact proportion ranging from 2% to 90% depending on the dpy-29 allele. The most transformed of these y52/dpy-29 animals are capable of mating if simultaneously homozygous for xol-1. Preliminary results suggest the proportion of transformed y52/dpy-29 XX animals shows no correlation with the extent of the dumpiness or XX-specific lethality of the dpy- 29 alleles. At least a second of these tra mutations, y121, also shows the same complementation pattern in trans to dpy-29 alleles (we are continuing to test all the possible combinations). Although the amber suppressor sup-7(st5) suppresses dpy-29(y100) for both dumpiness and lethality, dpy-29(y100am)/y52; ) XX animals are still transformed. The interaction between dpy-29 and the tra on V is specific; dpy-29 does not display a similar interaction with other transformation mutations. For example tra-1/+; 5sd)/dpy-29 are indistinguishable from tra-1/+ or her-1(n695sd)/+ respectively. The interactions between dpy-29 and the tightly linked tra mutation might be explained if the dpy-29 and the tra mutations represent separate neighboring genes, and all the extant alleles of dpy-29 are, for example, small deficiencies that alter not only dpy-29 but also the neighboring gene. Alternatively dpy-29 may be a cryptic sdc-like gene. That is, dpy-29 may be a gene which contains both sex- determination and dosage compensation functions required for the hermaphrodite modes of both processes. (The position of the y52 mutation in the hierarchy of sex-determination genes is consistent with this proposal.) If this latter case is true, any potential masculinization of dpy-29 XX might be masked by the dpy-29 dosage compensation defect. There is a precedent for such a phenomena. Mutations in dpy-21 or dpy-27 can suppress the masculinization of y52 XX animals, and substantial evidence has accumulated suggesting that the sex determination process is feminized in animals which over- express their X-linked genes. Thus any masculinizing effects mediated by dpy-29 mutations might be visible only in the absence of an elevation of X-chromosome expression. Both the ease of obtaining tra mutations and the complementation pattern seen between y52 and dpy-29 ( i.e., complementation for dosage compensation defects [dumpiness, lethality] and failure to complement for sex-determination defects [XX transformation]) suggest that the two functions are at least partially separable, unlike what has been observed with sdc-1 and sdc-2. We have not as yet identified any dpy-29 alleles that completely complement the tra function, nor have we identified any mutations which simultaneously display both an obvious sex determination and dosage compensation phenotypes. We have isolated two putative deficiencies of this region in an attempt to clarify the genetic interactions; however, whether dpy-29 and the tra mutations represent two functions within one gene or two separate neighboring genes probably cannot be determined merely from genetic evidence. A molecular approach may well be required to resolve this conundrum.