Worm Breeder's Gazette 2(1): 21

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.

X-linked Recessive Lethals

P. Meneely, B. Herman

We are interested in X-linked recessive lethal (including sterile) 
mutations, which we call let, induced by EMS and balanced by Dp(X;V)1. 
Specifically, we are looking for mutants with the following genotype: 
unc-3 let/unc-3 let; Dp(X;V)1/+, where Dp(X;V)1 carries unc-3+ let+.  
Such animals segregate inviable or sterile uncs.  Dp(X;V)1 is retained 
in heterozygous form since homozygotes are gonadless.
Our procedure is to mutagenize unc-3/unc-3; (X;V)1/+ animals and 
screen the offspring of individual F2 wild-type animals for inviable 
or sterile uncs.  Wild-type sibs are kept to maintain the stock.  To 
establish that the mutation is X-linked, the wild-type sib is crossed 
to N2 males.  If the lethal acts early and is not sex-limited, there 
are no unc male offspring issuing from this cross.  In any case, wild-
type male offspring (putative genotype: unc-3 let/0;Dp(X;V)1) are back-
crossed to the wild-type sib.  If the lethal is X-linked, there will 
be no fertile unc hermaphrodite offspring.  Complementation testing is 
straightforward: unc-3 let(MN1)/0; Dp(X;V)1/+ males are crossed to unc-
3 let(MN2)/unc-3 let(MN2); Dp(X;V)1/+ hermaphrodites, and the progeny 
are screened for fertile unc hermaphrodites.
By this procedure, we have found 12 independent X-linked recessive 
lethals that fall into 10 complementation groups, with repeats in 2 
genes.  On the assumption that all genes in the region are equally 
mutable, we calculate, using the Poisson distribution, that there are 
roughly 26 essential genes in the region covered by Dp(X;V)1.  This 
would obviously be an underestimate if some genes are much more 
mutable than others (by virtue of being larger, for example).
The phenotypes of the lethals have so far been only crudely 
characterized.  Three of the 10 act early: no uncs are produced.  Five 
give uncs that hatch but are arrested at various larval stages, 
typically L2 or L3.  One mutant, let-9, gives uncs that grow to adults 
but are sterile.  Crossing these uncs to N2 males gives fertile wild-
type hermaphrodites (showing that the oocytes are rescuable by let-9+-
containing sperm) and unc males, which indicate either a sperm defect 
or an unusual sex-limited effect.  To test this, the unc-3 
odites were crossed to unc-3 
/+.  Unc hermaphrodites were among the 
progeny.  This result indicates that the let-9+ gene is essential in 
hermaphrodites for either spermatogenesis or for permitting endogenous 
sperm to fertilize - although it is not necessary for the sperm to 
carry let-9 in order to be capable of fertilization.  The remaining 
mutant exhibits a prolonged maternal effect: the uncs are fertile but 
their progeny die as larvae.  Crossing these uncs with N2 males gives 
wild-type hermaphrodites but no mature unc males.  Work on these 
mutants and others isolated more recently is continuing.
The same procedure that gives the X-linked recessives also gives two 
other classes of mutants separable from these on the backcross.  One 
type includes mutants found on LGV in the region where crossing over 
is suppressed by Dp(X;V)1.  Complementation and characterization of 
these is more involved than for the X, and saturation of the region 
appears less easy, so little work has been done on them so far.  The 
other mutant class includes lethals that map elsewhere but seem to be 
specific for unc-3 in their lethal action.  There appear to be a fair 
number of these, but we have done nothing with them.