Worm Breeder's Gazette 10(1): 128

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.

sdc-2: A New Locus Important for Sex Determination and Dosage Compensation in XX animals

C. Nusbaum and B. Meyer

We report here the identification and characterization of a new X-
linked locus important to both the processes of sex determination and 
dosage compensation in XX animals.  This gene has provisionally been 
named sdc-2 (sex determination and dosage compensation), by analogy 
with the gene sdc-1, also X-linked, in which lesions have been shown 
to disrupt both these processes.
The original allele of sdc-2, y15, was isolated as a recessive X-
linked, XX-specific lethal mutation.  Sex-specific lethality is 
commonly associated with mutations that disrupt dosage compensation.  
Consistent with sdc-2's involvement in dosage compensation is that 21 
more alleles have been isolated as suppressors of the XO-specific 
lethality of mutations in the gene xol-1.  The XO-specific lethality 
of xol-1 mutations seems to result from XO animals adopting the XX 
mode of dosage compensation (see Miller et al., this WBG).  
Suppression of xol-1 lethality by sdc-2 is likely to be by a mechanism 
in which the XX mode of dosage compensation can no longer be 
implemented.  As a result, X-linked gene expression returns to a 
normal male level, rescuing XO lethality, but causing a concurrent 
loss of viability in xol-1 ls.  Thus, sdc-2 
is likely to be important for the hermaphrodite mode of dosage 
All 21 alleles fail to complement the XX-specific lethality of y15.  
We have divided them into two classes.  Class I (13 alleles) are XX 
specific lethal mutations.  They are also lethal to XX animals in 
trans to the deficiency nDf19.  Class II (9 alleles) cause XX animals 
to display a phenotype of sexual transformation toward the male fate.  
Homozygous animals range from Egl hermaphrodites to nearly wild-type 
looking males, but most are intersexual pseudomales with slightly 
dumpy hermaphrodite-like bodies and imperfect male tails.  Homozygous 
strains cannot be maintained with the strongest alleles of this class 
since the Egl hermaphrodites produce broods consisting almost entirely 
of pseudomales.  For weaker alleles, homozygous strains may be 
maintained.  Fertile animals are somewhat short, slightly Dpy, Egl, 
and have protruding vulvae.  Similar Dpy, Egl and protruding vulva 
phenotypes are associated with the dosage compensation defect of sdc-1 
mutants.  Surviving animals bearing class II alleles in trans to nDf19 
are pseudomales; we are currently quantifying the extent of lethality 
associated with this interaction.  The strong class II allele y55 
fails to complement the XX-specific lethality of a class I allele, y39.
Rare trans-heterozygote survivors are pseudomale.
The division between the two classes of alleles is not strict, and 
is made primarily for convenience in thinking about groups of similar 
alleles.  Some class I alleles produce small numbers of pseudomales as 
homozygotes and also in trans to nDf19.  There is at least one class I 
allele that is lethal at 20 C but produces some pseudomales at 25 C.  
XO sdc-2 animals in all cases appear to be wild type males, both in 
the presence and absence of xol-1 mutations.
Alleles of both classes have been isolated by several members of 
this laboratory from both EMS and gamma-radiation induced mutagenesis, 
and a class I allele has been isolated from a mutator background.  
Both class I and class II alleles have been mapped by their phenotype 
of suppression of the XO-specific lethality of xol-1(y9).  Three-
factor crosses place them approximately midway between dpy-6 and unc-9.
All alleles fall within the deficiency interval defined by nDf19.  
The XX specific lethality of the y15 allele has been mapped by three-
factor crosses with dpy-6 and lin-14.  y15 lies to the left of, or 
very close to lin-14, and is not covered by the duplication stDp2.
Interactions between the XX transformer phenotype of class II sdc-2 
alleles and the genes of the major sex determination pathway have been 
explored.  In the strains her-1(e1520) 70);  
) (or (y54)), and her-1(e1520); )
, the her-1 mutation blocks the masculinizing effects of sdc-2 
mutations.  Thus, the XX transforming effect of class II sdc-2 
mutations acts through the major sex determination pathway and 
requires the wild type her-1 gene product for it to be expressed.  
Moreover, her-1; ) or her-1; ) 
individuals still exhibit the slightly Dpy, Egl and protruding vulva 
phenotypes associated with the dosage compensation defect.  In 
addition, XX animals of genotype her-1; ry 
class I (XX lethal) alleles of sdc-2 are inviable.  her-1 mutations 
clearly suppress the sex determination effects, but not the dosage 
compensation effects, of sdc-2 mutations.
sdc-2 mutations appear to cause inappropriate activation of the XO 
modes of dosage compensation and of sex determination in XX animals.  
As a result XX animals are inviable or masculinized (and perhaps both).
sdc-2 mutations appear to be epistatic to both sex determination and 
dosage compensation effects of lesions in xol-1: they suppress the XO 
specific lethality of xol-1, and xol-1 utants 
produce no XO hermaphrodites.  This is in contrast to suppression of 
xol-1 mutations by mutations in dpy-26, 
e epistatic only to dosage 
compensation effects of xol-1; these doubly mutant strains produce 
wild type XO hermaphrodites.  All of this is consistent with the 
notion that sdc-2 is essential in XX animals for the proper modes of 
both dosage compensation and sex determination.  sdc-1 mutations are 
fully epistatic to xol-1 mutations in a manner similar to sdc-2, 
although sdc-1 acts as a maternal-effect suppressor while sdc-2 is a 
simple recessive suppressor (see Miller et al., this WBG).
The effects of sdc-2 mutations on dosage compensation are being 
further investigated by both genetic and molecular methods.  
Interactions between sdc-2 mutations and mutations in the genes sdc-1, 
examined.  In addition, X-linked 
gene expression will be assayed by Northern blot analysis.
While the two classes of mutations discussed here have not 
rigorously been shown to occur at the same locus, complementation 
tests and initial mapping experiments strongly suggest that they 
disrupt the same function.  Reversion analysis and careful mapping 
will help to clarify this issue.  The formal possibility exists that 
the two classes of alleles comprise two closely linked loci that 
exhibit interactions in trans, but this can only truly be resolved at 
a molecular level.  Further experiments will establish whether the 
null phenotype of sdc-2 is indeed XX-specific lethality.