We have reported that the five
let-60 dominant multivulva (Muv) mutations (formerly known as
lin-34 dominant Muv mutations) are amber suppressible (Beitel et al., Nature 348:1990). For example 93% of let- 60
(n1046) animals are Muv, while 11% of
let-60(
n1046); ) animals are Muv. Using the genomic sequence of
let-60 generously provided by Min Han and Paul Sternberg (Cell 63:1990), we sequenced the entire
let-60 open reading frame of all five
let-60 Muv alleles. These alleles all contain the identical G -> A transition mutation that results in a Glu for Gly substitution at amino acid 13. The stop codon at the end of the coding sequence of both the wildtype and mutant alleles is not an amber codon. Thus, it is not obvious why these mutations are amber-suppressible. We suspect that the suppression is indirect and involves changes in the animal's general physiology or changes in the level or nature of a gene product(s) that is involved in
let-60 function. The former interpretation is supported by the ability of the apparently unrelated mutations
unc-22(
e66) and
lon-2(
e678) to decrease the penetrance of the Muv phenotype and for
dpy-20(
e1282) to increase the penetrance of the Muv phenotype ( see below). While there is no reason to expect that amber suppressors will often cause indirect suppression, our results reaffirm the need for prudence in interpreting results of suppression studies. [See Figure 1]