TRANSPOSON-INDUCED REARRANGEMENTS IN THE DUPLICATED LOCUS PH OF DROSOPHILA-MELANOGASTER CAN CREATE NEW CHIMERIC GENES FUNCTIONALLY IDENTICAL TO THE WILD-TYPE

Variation in the number of gene copies can play a major role in changi ng the coding capacities of eukaryotic genomes. Different mechanisms, such as unequal recombination or transposon-induced chromosome rearran gements, are believed to be responsible for these events. We have used the direct tandem duplication at the complex locus polyhomeotic (pit) of Drosophila melanogaster as a model system to study functional redu ndancy associated with chromosomal rearrangements, such as duplication s or deletions. The locus covers 28.6 kb and comprises two independent units, ph proximal and ph distal, which are not only similar on the m olecular level, but appear to be functionally redundant [Dura et al., Cell 51 (1987) 829-839; Deatrick et al., Gene 105 (1991) 185-195]. We present a molecular and phenotypic analysis of two hypomorphic pit mut ants, ph(2) and ph(4), induced during hybrid dysgenesis. Each correspo nds to an internal deletion in the ph locus that overlaps both transcr iption units. We show that the deletions are likely due to a P/M hybri d dysgenesis-induced rearrangement between proximal and distal ph, tha t created a single new chimerical pit gene. At least one of the breakp oints must be located in a 1247-bp region that is rich in single seque nce, and 100% identical between proximal and distal ph. Junction point s between units are in the protein-coding regions, but could not be ex actly localized on the genomic sequence of either mutant, because of t he precise molecular mechanism that caused the deletions. Protein prod ucts of the hybrid genes contain the same functional domains as either wild-type (wt) product. Homeotic transformation frequencies in the ph (2) and ph(4) strains suggest that the mutants are functionary equival ent in vivo. Temperature-sensitivity studies and phenotypic rescue by a wt transgene indicate that the ph(2) and ph(4) loci encode proteins which appear to be functionally indistinguishable from the wt. The amo unt, not the proximal or distal origin, of the pit product seems cruci al for correct development. The mechanisms involved in these particula r mutational events and their possible implications in genome and DNA evolution are discussed.