Functional interactions between unlinked muscle genes within haploinsufficient regions of the Drosophila genome.

Abstract

Mutations in 13 genes affecting muscle development in Drosophila have been examined in pairwise combinations for evidence of genetic interactions. Heterozygous combinations of mutations in five genes, including the gene coding for myosin heavy chain, result in more severe phenotypes than respective single heterozygous mutant controls. The various mutant interactions include examples showing allele-specific intergenic interactions, gene specific interactions, and allele-specific intragenic complementations, suggesting that some interactions result from the manner in which mutant gene products associate. Interactions that result from alterations in "+" gene copy number were also uncovered, suggesting that normal myofibril development requires that the relative amounts of respective gene products produced be tightly regulated. The importance of the latter parameter is substantiated by the finding that all five interacting loci map to disperse haploinsufficient or haplolethal regions of the genome. The implications of the present findings are discussed in relation to pursuing the phenomena involving genetic interactions to identify new genes encoding interacting myofibrillar proteins, to examine the nature of intermolecular interactions in mutant and normal development and to decipher the quantitative and temporal regulation of a large family of functionally related gene products.

Ifm(2)2 is a myosin heavy chain allele that disrupts myofibrillar assembly only in the indirect flight muscle of Drosophila melanogaster.

“…Our results, in addition to the recombination mapping which placed the Ifm(2)2 mutation within 1.9 kb of the Mhc ~ mutation (Homyk and Emerson, 1988), indicate that Ifm(2)2 is a tissue-specific null allele of the muscle-specific MHC gene which fails to synthesize MHC mRNA and protein only in the IFM. The other muscles are unaffected by this mutation.…”

“…Gold sections were collected and stained with 2 % uranyl acetate and Reynold's lead citrate before viewing. lfm(2)2 Is a Mutation in the MHC Gene lfm(2)2 maps within 0.007 map units of a Drosophila MHC null allele, Mhc ~, which contains a deletion of intron 4 and exon 5 spanning nucleotides 4,155-4,255 3' from the transcription start site (Homyk and Emerson, 1988;O'Donnell and Bernstein, 1988). Because of the tight linkage of this mutation with the Mhc j allele (within 1,900 nucleotides assuming that 1 map unit approximates 275 kb of DNA [Kidd et al, 1983]), it is reasonable to suggest that Ifm(2)2 is an Mhc allele.…”

“…Abbreviations used in this paper: IFM, indirect flight muscle; MHC, myosin heavy chain; MLC-I or -2, myosin light chain-1 or -2; MLC-ALK, myosin alkali light chain; TDT, tergotrochanteral muscle. Mogami and Hotta (1981) have reported the isolation of a mutation, Ifm(2)2, mapping within 0.007 map units of the single copy sarcomeric myosin heavy chain (MHC) gene on the second chromosome at band 36B (Bernstein et al, 1983;Homyk and Emerson, 1988) that possesses dominant flightless behavior and is homozygous viable. This mutation affects the accumulation of a different subset of proteins than the rsd mutation.…”

Specific Myosin Heavy Chain Mutations Suppress Troponin I Defects in Drosophila Muscles

“…Three point mutations and the H20 deficiency chromosome were chosen to observe effects of specific amino acid changes or reduction in MHC levels upon the hdp 2 phenotypes. Homyk and Emerson (1988) had previously described a negative interaction between two of these alleles (Mhc 5 and Mhc 8 ) and hdp 2 . Our data corroborated that Mhc 5 is lethal in combination with hdp 2 /Y, but showed a reduced viability, rather than complete lethality, between Mhc 8 and hdp 2 /Y (Table III).…”

How do heterogametic females survive without gene dosage compensation?

“…These results do not imply thai dose relationships are not important subsequently, but it appears that most genes showing dose-dependent effects later in development contribute to multicomponent structures such as ribosomes (Kongsuwan el al. 1985"1, spliceosomes (Last et al 1987, the organized cytoskeleton (Regan and Fuller 1988) and the muscle (Homyk and Emerson 1988) in which stoichiometric ratios may be important. For example, many Mimae mutations in Drosophila lead to growth retardation because the ribosomes are defective (Kongsuwan et al 19851.…”