THE 3 DOMINANT FEMALE-STERILE MUTATIONS OF THE DROSOPHILA OVO GENE ARE POINT MUTATIONS THAT CREATE NEW TRANSLATION-INITIATOR AUG CODONS

The Drosophila ovo gene, which encodes a putative transcription factor (Ovo) with TFIIIA-like zinc fingers, is required for female germline survival and proper oogenesis, Three dominant female-sterile ovo(D) mu tations cause ovarian abnormalities that define an allelic series, wit h ovo(D1) displaying the stronger phenotype and ovo(D3) the weaker. We report here that all three ovo(D) mutations are point mutations that create new in-frame methionine codons in the 5' part of ovo. There are two types of overlapping ovo transcription units, ovo alpha and ovo b eta. By using various ovo-lacZ reporter genes, we determined that the long Ovo isoforms starting at methionine M1, present in transcripts ov o alpha, are expressed at low levels only in mature oocytes, Short Ovo isoforms are translated from methionine M373, the first in-frame star t codon present in transcript ovo beta, and correspond to the activity defined by recessive loss of function ovo mutations. The new AUGs cre ated in ovo(D) mutations all are located upstream of the M373 initiati on site. Our results support the hypothesis that they can substitute f or M373 as translation starts and initiate the synthesis of Ovo protei ns that have extra amino acids at their N termini. We propose that pre mature expression of long Ovo protein isoforms occurs in ovo(D) mutant s and interferes with wild-type Ovo function in controlling female ger mline differentiation.