Distribution of MR-induced sex-linked recessive lethal mutations in Drosophila melanogaster

In the ‘doubling-dose’ method currently used in genetic risk evaluation, two principle assumptions are made and these are: (1) there is proportionality between spontaneous and induced mutations and (2) the lesions that lead to spontaneous and induced mutations are essentially similar. The studies reported in this paper were directed at examining the validity of these two assumptions in Drosophila. An analysis was made of the distribution of sex-linked recessive lethals induced by MR, one of the well-studied mutator systems in Drosophila.

Appropriate genetic complementation tests with 15 defined X-chromosome duplications showed that MR-induced lethals occurred at many sites along the X-chromosome (in contrast to the known locus specificity of MR-induced visible-mutations); some, but not all these sites at which recessive lethals arose in the MR-system are the same as those known to be hot-spots for X-ray-induced lethals. With in situ hybridization we were able to demonstrate that a majority of MR-induced lethals is associated with a particular mobile DNA sequence, the P-element, i.e. they arose as a result of transposition.

The differences between the profiles of MR-induced and X-ray-induced recessive lethals, and the nature of MR-induced and X-ray-induced mutations, thus raise questions about the validity of the assumptions involved in the use of the ‘doubling-dose’ method.     

Mutagenic potential of permethrin in the Drosophila melanogaster (Diptera: Drosophilidae) sex-linked recessive lethal test

When permethrin was tested for mutagenicity in Drosophila melanogaster Meigen with the sex-linked recessive lethal test, it was nonmutagenic under conditions of this study. The frequencies of spontaneous mutation for permethrin and the negative control were 0.135% and 0.133%, respectively; the spontaneous mutation frequency for positive control was 12.6%. The difference between the mutation frequency of permethrin and the negative control was not significant.     

The effect of repeated microwave irradiation on the frequency of sex-linked recessive lethal mutations in Drosophila melanogaster

The effect of repeated microwave irradiation (2375 MHz, CW) on mutagenic changes in Drosophila melanogaster was investigated. Oregon-R males were exposed to sublethal doses of microwaves (15 W/cm2 for 60 min, 20 W/cm2 for 10 min, and 25 W/cm2 for 5 min) for 5 days. The Muller-5 cross was used to detect sex-linked recessive lethal mutations. 4 lethals were found in treated groups but their frequency was not significantly different from that of the control group. No cumulative effect of repeated exposures on the mortality of the treated males was observed; on the contrary, their mortality decreased with the number of exposures. Irradiation did not affect the sex ratio of the F1. A significant decrease in the number of F1 offspring was noted in the group exposed to the power density of 15 W/cm2. A negative thermal effect of microwaves on male germ cells was probably manifested by this long exposure.     

The first oncogene in Drosophila melanogaster

Discovered by Bridges in the 1930s, lethal (2) giant larvae was the first of more than 27 recessive oncogenes identified in Drosophila, which provides an excellent model to study neoplastic mechanisms due to the fact that homologs of human oncogenes and tumor suppressors have been isolated and most of the complexes and associated pathways are conserved. This review explores the potential of neoplastic studies in Drosophila to help understand the genomic mechanisms of neoplastic development in vertebrates and invertebrates. Starting from neoplasms and genetic mutations, the article introduces the reader to one of the possibilities that the studies on neoplastic mechanisms of oncogenes in Drosophila can provide a great understanding of the developmental progression in both vertebrates and invertebrates.     

l(1)hopscotch,a larval-pupal zygotic lethal with a specific maternal effect on segmentation in Drosophila

The maternal and zygotic effect phenotypes of mutations at the l(1)hopscotch (l(1)hop) locus are described. l(1)hop is located in 10B6-8 on the salivary gland chromosome map and 17 alleles have been characterized. A complex complementation pattern is observed among the 17 alleles. The lethal phase of null alleles of l(1)hop occurs at the larval-pupal interface associated with a small disc phenotype. Embryos produced from homozygous l(1)hop germline clones show segment specific defects. The extent of these defects depends upon both the strength of the allele and the paternal contribution. In the most extreme case embryos exhibit defects associated with five segments T2, T3, A4, A5, and A8. In the less extreme phenotype defects are only associated with A5. Thus, activity of l(1)hop⁺ is required both for the maintenance and continued cell division of diploid imaginal precursors and for the establishment of the full array of segments.     

Mitotic chromosome organization of neuroblastomas induced by the recessive oncogene Lethal(2)giant larvae 4 of Drosophila melanogaster

Mitotic chromosomes in neuroblastomas of Drosophila melanogaster homozygous for the recessive oncogene Lethal(2)giant larvae ⁴ were studied at different larval ages. There was a progressive increase in mitotically active cells with increasing period of tumorous growth. The karyotype of the neuroblastomas generally remained stable. The metaphase chromosomes of the neuroblastomas, however, showed widely varying levels of condensation ranging from highly condensed to highly extended. Staining with the AT-specific fluorescent dye Hoechst 33258 showed extensive resolution of AT-rich heterochromatic blocks in the third and Y chromosomes suggesting their lack of coalescence in the extended metaphases of neuroblastomas. Our results suggest aberrant condensation as a major chromosomal lesion in Drosophila neuroblastomas.     

The interaction between daughterless and sex-lethal in triploids: a lethal sex-transforming maternal effect linking sex determination and dosage compensation in Drosophila melanogaster

Regulation of Drosophila sex determination and X-chromosome dosage compensation in response to the X-chromosome/autosome (X/A) balance of the zygote is shown to require proper functioning of both the da+ gene in the mother and the Sxl+ gene in the zygote. Previous studies led to the hypothesis that zygotic Sxl+ alleles are differentially active in females (XXAA) vs males (XYAA) in response to the X/A balance, and that maternal da+ gene product acts as a positive regulator in this connection. Sxl+ activity was proposed to impose the female developmental sequence on cells which would follow the male sequence in its absence. Important predictions of this proposal are verified. This study focuses primarily on the phenotype of triploid intersexes (XXAAA, X/A = 0.67). They are shown here to survive effects of da and Sxl mutations that would be lethal to diploids. The ambiguous X/A signal of intersexes normally causes them to develop as phenotypic mosaics of male and female tissue. Loss of maternal da+ or zygotic Sxl+ gene function shifts their somatic sexual phenotype to the male alternative. A gain-of-function mutation at Sxl has the opposite effect, imposing female development regardless of the maternal genotype with respect to da. It also reduces their rate of X-linked gene expression. The effects of a duplication of Sxl+ resemble those of the constitutive Sxl allele, but are less extreme. The role of these genes in the process of X-chromosome dosage compensation is inferred indirectly from the strict dependence of the mutations' lethal effects on the X/A balance in haploids, diploids, and triploids, and more directly from the effects of the mutations on the phenotypes of the X-linked neomorphic mutations, Bar and Hairy-wing. The relationship of da+ and Sxl+ gene functions to those of other sex-specific lethal loci in D. melanogaster, and to sex determination mechanisms in other species, is discussed.     

Sex-linked recessive lethal test of Drosophila melanogaster after exposure to 50-Hz magnetic fields.

To determine whether a 50-Hz magnetic field will induce mutations, a sex-linked recessive lethal test of Drosophila melanogaster was performed. Adult flies were exposed at an rms flux density of 500 mu T or 5 mT to the homogeneous field of a Helmholtz coil. The ambient field to which controls were exposed was less than 1 mu T. Exposures took place continuously for 13 to 14 days, which correspond to the life cycle of Drosophila at 25 degrees C. About 10,000 X-chromosomes were tested at each flux density. Recessive lethal mutation rates of 0.13, 0.21, and 0.18 percent were observed, respectively, for control, 500-mu T, and 5-mT conditions. By the Kastenbaum-Bowman significance test, the recessive lethal mutation rates in the 500-mu T and 5-mT conditions did not differ from the mutation rate of controls.     

Studies on the induction of sex-linked recessive lethal mutations in Drosophila melanogaster by nitroheterocyclic compounds

24 nitroheterocyclic compounds were investigated for their capacity to induce sex-linked recessive lethals in Drosophila, by the adult feeding technique, and in some cases injection or larval-feeding methods. Out of 9 5-nitroimidazoles, ZK 26.173 and ZK 25.095 (moxnidazole) were clearly active whereas nimorazole and ronidazole were marginally mutagenic. Out of 10 5-nitrofurans, nitrovin, furazolidone and furaltadone were unambiguously mutagenic, whereas nitrofurantoin was a borderline case. Nitrofurans were active at lower molar concentrations than nitroimidazoles. Out of a group of 5 related nitro compounds (2 nitrothiophenes, picrolonic acid, niridazole and 4-NQO), only 4-NQO was clearly mutagenic, when fed to larvae. Experiments with germ-free flies showed that, for ZK 26.173 and furazolidone, the gut flora of Drosophila do not play a role in the activation of the compounds to mutagenic metabolites. Furazolidone, 4-NAO, ZK 26.173, ZK 25.095 and furaltadone were tested in mal and cin strains, both of which lack xanthine dehydrogenase and aldehyde oxidase. The latter enzyme and xanthine oxidase are known to carry out nitro reduction in mammalian tissues. For ZK 26.173, the mutation frequencies were drastically reduced in the enzyme-deficient strains, indicating the involvement of one of these enzymes in the activation of this substance.     

wiser tsl : a recessive X-linked temperature-sensitive lethal mutation that affects the wings and the eyes in Drosophila melanogaster

In this study, we characterize a recessive X-linked temperature-sensitive mutation of the gene CG32711. The mutation, named wiser ^tsl (wings scalloped-eyes rough), was isolated from a dysgenic cross and is due to a natural P element insertion within the 5′ regulatory region of the gene. Mutant (wiser ^tsl ) individuals exhibit wing notching, rough eyes, tarsal malformations and reduced life-span. At 29°C they die at larval and late pharate stages or during eclosion. The CG32711 (wiser) gene is mainly expressed in the ventral midline cells, the peripheral neural system, the hemocytes and the tracheal system of embryos. It is also expressed in nurse cells of adult female ovaries. Our results show that the wiser gene is alternatively spliced generating two mRNAs, which share the same open reading frame, while western analysis identified two protein isoforms. Their expression pattern depends on the stage of development and the culture temperature. wiser ^tsl and wild-type individuals display different expression patterns of the two isoforms and this difference most probably accounts for the mutant phenotype. Our results indicate that wiser is a vital gene for the development of Drosophila melanogaster which has no orthologs outside the Drosophilidae. Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. bankit1003537 EU071463–bankit1003860 EU071464.     

The effect of sexual harassment on lethal mutation rate in female Drosophila melanogaster

The rate by which new mutations are introduced into a population may have far-reaching implications for processes at the population level. Theory assumes that all individuals within a population have the same mutation rate, but this assumption may not be true. Compared with individuals in high condition, those in poor condition may have fewer resources available to invest in DNA repair, resulting in elevated mutation rates. Alternatively, environmentally induced stress can result in increased investment in DNA repair at the expense of reproduction. Here, we directly test whether sexual harassment by males, known to reduce female condition, affects female capacity to alleviate DNA damage in Drosophila melanogaster fruitflies. Female gametes can repair double-strand DNA breaks in sperm, which allows manipulating mutation rate independently from female condition. We show that male harassment strongly not only reduces female fecundity, but also reduces the yield of dominant lethal mutations, supporting the hypothesis that stressed organisms invest relatively more in repair mechanisms. We discuss our results in the light of previous research and suggest that social effects such as density and courtship can play an important and underappreciated role in mediating condition-dependent mutation rate.