The third-chromosome mutation Killer of prune (K-pn) causes no phenotype by itself, but causes lethality in individuals homozygous for the nonlethal X-chromosome mutation prune (pn). We have recovered 12 gammaray-induced revertants of Killer o[prune. All of the revertants fail to complement a recessive cell lethal mutation in the abnormal wing ddscs (awd) gene. We present evidence that Killer o[prune is a mutation in the awd gene. First, revertant awd r's14 leads to reduced accumulation of the awd gene product, but does not affect flanking genes. Second, when a copy of the awd gene is cloned from Killer o[prtme homozygous flies and injected into embryos, transformants express the lethal interaction with prune. In individuals of the genotype pn; awdX'~°/awd+ the awd mRNA is present at normal levels but the awd polypeptide fails to accumulate. The absence of the awd gene product in such individuals is the cause of death. Although the awd polypeptide is a subunit of a cytoplasmic protein, its sequence is similar to subunit V of yeast cytochrome oxidase.

The abnormal wing disc locus, which is at salivary gland chromosome position 100C-D of the Drosophila melanogaster genome, has been identified by a recessive lethal mutation, awdb3, induced by hybrid dysgenesis. When homozygous, this mutation causes abnormal development of the brain, the ovaries, and the larger imaginal discs as described in the preceding paper (C.R. Dearolf, E. Hersperger, and A. Shearn, 1988, Dev. Biol. 129, 159-168). The DNA corresponding to this locus was isolated from a genomic library prepared from awdb3 heterozygotes by screening with a P-element probe. The awdb3 allele resulted from the insertion of a P-element fragment into a gene that encodes an 0.8-kb poly(A)+ RNA. In mutant larvae, that 0.8-kb transcript is replaced by two chimeric transcripts that are 0.7 and 1.3 kb in length, both of which contain P-element and awd sequences. The wild-type awd+ gene transcript is most abundant during the second and third larval instars but is found at a lower level during every developmental stage as well as in continuous cell lines. Thus the awd+ gene transcript can be detected in normal larvae at a developmental stage long before defects are expressed in mutant larvae. Moreover, some tissues, for example the salivary gland of nonmutant, third-instar larvae, contain high levels of this transcript, even though these tissues appear to develop normally in mutant larvae.