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.
Full Text
The Full Text of this article is available as a PDF (1.7 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Deak I. I., Bellamy P. R., Bienz M., Dubuis Y., Fenner E., Gollin M., Rähmi A., Ramp T., Reinhardt C. A., Cotton B. Mutations affecting the indirect flight muscles of Drosophila melanogaster. J Embryol Exp Morphol. 1982 Jun;69:61–81. [PubMed] [Google Scholar]
- Deak I. I. Mutations of Drosophila melanogaster that affect muscles. J Embryol Exp Morphol. 1977 Aug;40:35–63. [PubMed] [Google Scholar]
- Dibb N. J., Brown D. M., Karn J., Moerman D. G., Bolten S. L., Waterston R. H. Sequence analysis of mutations that affect the synthesis, assembly and enzymatic activity of the unc-54 myosin heavy chain of Caenorhabditis elegans. J Mol Biol. 1985 Jun 25;183(4):543–551. doi: 10.1016/0022-2836(85)90170-6. [DOI] [PubMed] [Google Scholar]
- Epstein H. F., Ortiz I., Mackinnon L. A. The alteration of myosin isoform compartmentation in specific mutants of Caenorhabditis elegans. J Cell Biol. 1986 Sep;103(3):985–993. doi: 10.1083/jcb.103.3.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Falkenthal S., Graham M., Wilkinson J. The indirect flight muscle of Drosophila accumulates a unique myosin alkali light chain isoform. Dev Biol. 1987 May;121(1):263–272. doi: 10.1016/0012-1606(87)90158-8. [DOI] [PubMed] [Google Scholar]
- Falkenthal S., Parker V. P., Mattox W. W., Davidson N. Drosophila melanogaster has only one myosin alkali light-chain gene which encodes a protein with considerable amino acid sequence homology to chicken myosin alkali light chains. Mol Cell Biol. 1984 May;4(5):956–965. doi: 10.1128/mcb.4.5.956. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fekete E., Szidonya J. Abnormalities of ultrastructure and calcium distribution in the flight muscle of a flightless mutant of Drosophila melanogaster. Acta Biol Acad Sci Hung. 1979;30(1):47–57. [PubMed] [Google Scholar]
- Geyer P. K., Fyrberg E. A. 5'-flanking sequence required for regulated expression of a muscle-specific Drosophila melanogaster actin gene. Mol Cell Biol. 1986 Oct;6(10):3388–3396. doi: 10.1128/mcb.6.10.3388. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenwald I., Horvitz H. R. A visible allele of the muscle gene sup-10X of C. elegans. Genetics. 1986 May;113(1):63–72. doi: 10.1093/genetics/113.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harrington W. F., Rodgers M. E. Myosin. Annu Rev Biochem. 1984;53:35–73. doi: 10.1146/annurev.bi.53.070184.000343. [DOI] [PubMed] [Google Scholar]
- Hinton C W. The Behavior of an Unstable Ring Chromosome of Drosophila Melanogaster. Genetics. 1955 Nov;40(6):951–961. doi: 10.1093/genetics/40.6.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Homyk T., Jr, Szidonya J., Suzuki D. T. Behavioral mutants of Drosophila melanogaster. III. Isolation and mapping of mutations by direct visual observations of behavioral phenotypes. Mol Gen Genet. 1980;177(4):553–565. doi: 10.1007/BF00272663. [DOI] [PubMed] [Google Scholar]
- Homyk T., Sheppard D. E. Behavioral Mutants of DROSOPHILA MELANOGASTER. I. Isolation and Mapping of Mutations Which Decrease Flight Ability. Genetics. 1977 Sep;87(1):95–104. doi: 10.1093/genetics/87.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Homyk T., Sinclair D. A., Wong D. T., Grigliatti T. A. Recovery and Characterization of Temperature-Sensitive Mutations Affecting Adult Viability in DROSOPHILA MELANOGASTER. Genetics. 1986 Jun;113(2):367–389. doi: 10.1093/genetics/113.2.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hotta Y., Benzer S. Mapping of behaviour in Drosophila mosaics. Nature. 1972 Dec 29;240(5383):527–535. doi: 10.1038/240527a0. [DOI] [PubMed] [Google Scholar]
- Judd B. H., Shen M. W., Kaufman T. C. The anatomy and function of a segment of the X chromosome of Drosophila melanogaster. Genetics. 1972 May;71(1):139–156. doi: 10.1093/genetics/71.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karlik C. C., Fyrberg E. A. Two Drosophila melanogaster tropomyosin genes: structural and functional aspects. Mol Cell Biol. 1986 Jun;6(6):1965–1973. doi: 10.1128/mcb.6.6.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kidd S., Lockett T. J., Young M. W. The Notch locus of Drosophila melanogaster. Cell. 1983 Sep;34(2):421–433. doi: 10.1016/0092-8674(83)90376-8. [DOI] [PubMed] [Google Scholar]
- Koana T., Hotta Y. Isolation and characterization of flightless mutants in Drosophila melanogaster. J Embryol Exp Morphol. 1978 Jun;45:123–143. [PubMed] [Google Scholar]
- Landel C. P., Krause M., Waterston R. H., Hirsh D. DNA rearrangements of the actin gene cluster in Caenorhabditis elegans accompany reversion of three muscle mutants. J Mol Biol. 1984 Dec 15;180(3):497–513. doi: 10.1016/0022-2836(84)90024-x. [DOI] [PubMed] [Google Scholar]
- Lefevre G., Johnson T. K. Evidence for a Sex-Linked Haplo-Inviable Locus in the Cut-Singed Region of DROSOPHILA MELANOGASTER. Genetics. 1973 Aug;74(4):633–645. doi: 10.1093/genetics/74.4.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lefevre G., Watkins W. The question of the total gene number in Drosophila melanogaster. Genetics. 1986 Aug;113(4):869–895. doi: 10.1093/genetics/113.4.869. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindsley D. L., Sandler L., Baker B. S., Carpenter A. T., Denell R. E., Hall J. C., Jacobs P. A., Miklos G. L., Davis B. K., Gethmann R. C. Segmental aneuploidy and the genetic gross structure of the Drosophila genome. Genetics. 1972 May;71(1):157–184. doi: 10.1093/genetics/71.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lucchesi J. C. Synthetic lethality and semi-lethality among functionally related mutants of Drosophila melanfgaster. Genetics. 1968 May;59(1):37–44. doi: 10.1093/genetics/59.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mahaffey J. W., Coutu M. D., Fyrberg E. A., Inwood W. The flightless Drosophila mutant raised has two distinct genetic lesions affecting accumulation of myofibrillar proteins in flight muscles. Cell. 1985 Jan;40(1):101–110. doi: 10.1016/0092-8674(85)90313-7. [DOI] [PubMed] [Google Scholar]
- Miklos G. L., Kelly L. E., Coombe P. E., Leeds C., Lefevre G. Localization of the genes shaking-B, small optic lobes, sluggish-A, stoned and stress-sensitive-C to a well-defined region on the X-chromosome of Drosophila melanogaster. J Neurogenet. 1987 Jan;4(1):1–19. doi: 10.3109/01677068709102329. [DOI] [PubMed] [Google Scholar]
- Mogami K., Hotta Y. Isolation of Drosophila flightless mutants which affect myofibrillar proteins of indirect flight muscle. Mol Gen Genet. 1981;183(3):409–417. doi: 10.1007/BF00268758. [DOI] [PubMed] [Google Scholar]
- Okamoto H., Hiromi Y., Ishikawa E., Yamada T., Isoda K., Maekawa H., Hotta Y. Molecular characterization of mutant actin genes which induce heat-shock proteins in Drosophila flight muscles. EMBO J. 1986 Mar;5(3):589–596. doi: 10.1002/j.1460-2075.1986.tb04251.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Park E. C., Horvitz H. R. C. elegans unc-105 mutations affect muscle and are suppressed by other mutations that affect muscle. Genetics. 1986 Aug;113(4):853–867. doi: 10.1093/genetics/113.4.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perrimon N., Engstrom L., Mahowald A. P. Developmental genetics of the 2C-D region of the Drosophila X chromosome. Genetics. 1985 Sep;111(1):23–41. doi: 10.1093/genetics/111.1.23. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roehrdanz R. L., Lucchesi J. C. Mutational Events in the Triplo- and Haplo-Lethal Region (83de) of the DROSOPHILA MELANOGASTER Genome. Genetics. 1980 Jun;95(2):355–366. doi: 10.1093/genetics/95.2.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rozek C. E., Davidson N. Drosophila has one myosin heavy-chain gene with three developmentally regulated transcripts. Cell. 1983 Jan;32(1):23–34. doi: 10.1016/0092-8674(83)90493-2. [DOI] [PubMed] [Google Scholar]
- Simpson P. Maternal-Zygotic Gene Interactions during Formation of the Dorsoventral Pattern in Drosophila Embryos. Genetics. 1983 Nov;105(3):615–632. doi: 10.1093/genetics/105.3.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Suzuki D. T. Temperature-sensitive mutations in Drosophila melanogaster. Science. 1970 Nov 13;170(3959):695–706. doi: 10.1126/science.170.3959.695. [DOI] [PubMed] [Google Scholar]
- Tanouye M. A., Ferrus A., Fujita S. C. Abnormal action potentials associated with the Shaker complex locus of Drosophila. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6548–6552. doi: 10.1073/pnas.78.10.6548. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tarasoff M., Suzuki D. T. Temperature-sensitive mutations in drosophila melanogaster. VI. Temperature effects on development of sex-linked recessive lethals. Dev Biol. 1970 Nov;23(3):492–509. doi: 10.1016/0012-1606(70)90112-0. [DOI] [PubMed] [Google Scholar]
- Zabin I., Villarejo M. R. Protein complementation. Annu Rev Biochem. 1975;44:295–313. doi: 10.1146/annurev.bi.44.070175.001455. [DOI] [PubMed] [Google Scholar]