In the last newsletter, we described genetic studies of the
unc-93 locus and suggested that, although rare alleles of
unc-93 such as
e1500 confer a striking uncoordinated and egg-laying defective phenotype, the phenotype resulting from null alleles is wild-type. One possible and intriguing explanation for the wild-type null phenotype of
unc-93 is that in the absence of the
unc-93 pathway, an alternative pathway(s) still functions. A specific example of such redundancy is that another gene product may be able to substitute directly for the
unc-93 product, i.e.
unc-93 may be a member of a multigene family. The
e1500 mutation, which is semidominant, may result in a product that is toxic; elimination of the toxic product restores the wild-type phenotype. The genetic property that originally attracted our attention spontaneous (intragenic) reversion ( see previous Newsletters)--may be an indicator of other genes with wild-type null phenotypes. For example,
unc-58(
e665) X ('shaker') reverts spontaneously, and experiments similar to those described for
e1500 have indicated that the null phenotype of
unc-58 is wild-type. Bob Waterston has informed us that
unc-92(
st15) V, which reverts spontaneously, may also have a wild-type null phenotype. The rate of spontaneous reversion (10 ) seen for
e1500 and
e665 probably reflects the normal rate of spontaneous mutagenesis. As other genes with wild-type null phenotypes are identified, some of the genetic strategies we have used for our analysis of
unc-93 may be applicable. For example, we generated deficiencies of
unc-93 and
sup-9 (a recessive extragenic suppressor of
e1500) by exploiting the observation that
e1500/null is mutant: [See Figure 1] Many of the wild-type animals obtained using the above procedures were shown to harbor deficiencies by recessive lethality and by failure to complement neighboring markers (intragenic revertants and dominant suppressors of
e1500 were distinguishable from deficiencies by these criteria). The map below shows the deficiencies of
unc-93 we have generated. The protocol used for
unc-93 deficiencies may be modified for more general applicability (i.e., for genes that are not also suppressed by extragenic suppressors): mutant males may be irradiated and directly mated with marked revertants hermaphrodites, or revertant males may be mated with irradiated mutant hermaphrodites. The protocol used for deficiencies of
sup-9 may also be modified: irradiated mutant males may be mated with marked suppressed hermaphrodites, or suppressed males may be mated with irradiated mutant hermaphrodites. [See Figure 2]