MOLECULAR ANALYSIS OF CUBITUS INTERRUPTUS (CI) MUTATIONS SUGGESTS AN EXPLANATION FOR THE UNUSUAL CI POSITION EFFECTS

The cubitus interruptus (ci) locus of Drosophila melanogaster is locat ed proximally on chromosome 4. In ci mutants cubital wing veins are in terrupted or absent. We have cloned this locus using a gypsy element a ssociated with the ci(1) mutation. Analysis of all extant ci mutations reveals that they contain conspicuous molecular alterations within a 13.7 kb region. Of the four homozygous viable mutations, three (ci(1), Ci(361), Ci(W)) have single insertions, while one (Ci(57g)) has a sma ll deletion, all located within a more restricted 1 kb region. The dom inant mutations, ci(D) and Ce-2 each contain two insertions within the 13.7 kb region. All these molecular alterations are located upstream of a transcript previously associated with the ci(D) mutation and thou ght to derive from a segment polarity gene. We induced revertants of t he dominant ci phenotype (wing vein interruption) in ci(D) and found m olecular alterations in this transcript (the cif transcript) in two re vertant alleles, thereby demonstrating this transcript's involvement i n the ci phenotype. The locations of the molecular alterations, togeth er with the results of the ci(D) reversion experiment, provide a conne ction between the dominant and recessive ci mutations and argue that a ll are likely to be alleles of the same complex locus, ci, not two sep arate loci as previously proposed. The ci phenotype of dominant and re cessive mutations can be explained by inappropriate expression of the cit transcript in the posterior wing compartment where the cubital vei n is affected, while loss of ci(+) function generates recessive lethal ity. Lack of repression of ci(+) transcription, through a pairing-depe ndent, trans-acting silencer element, can explain the unusual position effects associated.with ci (the Dubinin effect).