Molecular organization and alternative splicing in zipper, the gene that encodes the Drosophila non-muscle myosin II heavy chain

Genomic sequence of the entire zipper gene, that encodes non-muscle myosin II heavy chain (MHC) in Drosophila melanogaster, reveals a new, differentially spliced exon in this essential locus and identifies a molecular lesion that is responsible for a severe embryonic lethal zipper allele. There are two alternative splices in the head domain. The first is present in the 5' untranslated sequence which, when employed, produces an N-terminal extension of 45 amino acids (aa). This splicoform produces a protein that is stable in flies but less prevalent than the isoform that lacks the extension. The second alternative exon (40 aa) is close to the nucleotide binding pocket. The position, size and sequence of this exon is conserved in D. simulans and putative alternative exons of different size (7 to 16 aa) but identical position have been reported for other myosins throughout phylogeny. The functional significance of neither alternative splice is clear. Sequence analysis of genomic DNA identifies the lesion responsible for ZipIIF107, one of the original severe embryonic lethal zipper alleles. Our primary structural data confirm and correct our previous sequence of the cDNA, establish the spatial relationship between zipper and unzipped (the gene originally thought to have been disrupted in zipper mutations), and provide a high resolution template for the precise mapping of mutations.