Worm Breeder's Gazette 9(1): 73

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.

Molecular Analysis Of Dosage Compensation Continues

L. Donahue, B. Quarantillo, and W.B. Wood

Mutations in several unusual dpy genes appear to affect the general 
level of X-chromosome expression, implicating these genes in control 
of X chromosome dosage compensation (Hodgkin, 1983, Mol.  Gen.  Genet. 
192:452 Meneely and Wood, 1984, C.  elegans Newsletter, Vol. 8, #1, p.
6; Meneely and Wood, 1985 C.  elegans Meeting Abstracts, p. 90; De 
Long et al., ibid., p. 99; Meyer and Champness, ibid. p. 101).  For 
example, dpy-21 mutations appear to increase and dpy-22 mutations to 
decrease X expression by genetic tests.  To determine whether these 
effects are occurring at the RNA level, we have employed a 
quantitative RNA dot blot procedure to compare ratios of X-linked to 
autosomal transcripts between males and hermaphrodites and between dpy-
21 or dpy-22 and wild-type hermaphrodites, using gene-specific probes 
for the  X linked genes act-4 and myo-2 and the autosomal genes act-1, 
p. 100).  We have previously 
reported that adult males and hermaphrodites have the same amount of 
act-4 mRNA relative to act-1 or unc-54 mRNA (ibid.).  We have now 
shown that the same is true for myo-2 mRNA relative to myo-1 mRNA 
levels.  Expression of these two genes would seem unlikely to differ 
for physiological reasons between males and hermaphrodites, because 
both code for myosins of the pharynx, which is not a sexually 
dimorphic structure.  Therefore, the equivalence of these ratios in 
the two sexes supports the view that dosage compensation of these 
genes operates at the RNA level.  Conceivably, our results could be 
explained by special regulatory controls on act-4 and myo-2, operating 
outside of, or in addition to, the general X-chromosome dosage 
compensation mechanism.  To test this possibility, we are attempting 
to determine whether these genes, like other X-linked genes analyzed 
genetically, show dose-sensitive expression when present in extra 
copies because of a duplication or fewer copies because of a 
deficiency.  We have preliminary evidence from quantitative Southern 
blot analysis that act-4 is covered by the duplication mnDp57 (X;I), 
given to us by R.  Herman.  If we confirm this result, we shall assay 
act-4 expression in mnDp57-containing strains.  We are testing known 
duplications for extra copies of myo-2; so far we have found that this 
gene is not covered by mnDp10 (X;I).
We previously reported that in L1 animals a dpy-21 mutation did not 
affect the ratio of act-4 mRNA to unc-54 mRNA (ibid.).  We have now 
shown that in adult hermaphrodites, the dpy-21(e428) mutation 
increases the ratio of act-4 mRNA to unc-54 mRNA by a factor of 1.53 +-
.08 relative to the same ratio in N2.  We are presently testing the 
effect of dpy-21 in adult animals on myo-2 mRNA levels.  One possible 
reason for the difference in results between L1's and adults with act-
4 could be that the dpy-21 gene is not active prior to the L1 stage of 
development.  A more trivial possibility is that many of the animals 
in our L1 preparations were starved and could have degraded some of 
their RNA's by the time they were harvested.  We are attempting to 
test these and other possible reasons for the apparent difference.