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D A Sinclair

Publications and source records attributed to D A Sinclair.

47 records · Page 3Linked to original sources
PubMed1992

Genetic analysis of the additional sex combs locus of Drosophila melanogaster.

Additional sex combs (Asx) is a member of the Polycomb group of genes, which are thought to be required for maintenance of chromatin structure. To better understand the function of Asx, we have isolated nine new alleles, each of which acts like a gain of function mutation. Asx is required for normal determination of segment identity. AsxP1 shows an unusual phenotype in that anterior and posterior homeotic transformations are seen in the same individuals, suggesting that AsxP1 might upset chromatin structure in a way that makes both activation and repression of homeotic genes more difficult. Analysis of embryonic and adult phenotypes of Asx alleles suggests that Asx is required zygotically for determination of segment number and polarity. The expression pattern of even-skipped is altered in Asx mutant embryos, suggesting that Asx is required for normal expression of this gene. We have transposon-tagged the Asx gene, and can thus begin molecular analysis of its function.

Alleles↗
PubMed1991

Informational redundancy of tRNA(4Ser) and tRNA(7Ser) genes in Drosophila melanogaster and evidence for intergenic recombination.

Variant tRNA genes have been widely observed in multicellular eukaryotes. Recent biochemical studies have shown that some of them are expressed in a tissue- or a stage-specific manner. These findings would thus imply that certain modified tRNAs may be crucial for the development of the organism. Using Drosophila melanogaster as a model, we have taken a combined genetic and molecular approach to examine critically the possible biological functions of tRNA(4, 7Ser) genes. We showed that at least 50% of the total templates can be deleted from the genome without inducing abnormal phenotypes such as Minute, or a decrease in viability. In addition, two of the tRNASer variant genes that are unique in sequence are also completely dispensable. This strongly implies that even though they may be expressed in vivo, they play no essential role in the development of the fruitfly. By comparison with some of the corresponding tRNA genes in another sibling species, Drosophila erecta, our results suggest strongly that the variants are products non-reciprocal exchanges among the tRNA(4, 7Ser), genes. Such intergenic recombination events may have a major influence in the concerted evolution of the two gene families.

Animals↗
PubMed1989

Characterization of mutations that enhance position-effect variegation in Drosophila melanogaster.

Several mutants that enhance the gene inactivation associated with position-effect variegation [E(var) mutants] have been characterized. These include three ethyl methanesulfonate (EMS)-induced lesions and a second chromosome duplication. Each of the EMS mutations maps to a discrete euchromatic site on the third chromosome. One is located within the chromosomal region occupied by a cluster of Su(var) mutations. All four E(var) mutants enhance the inactivation of several different variegators and therefore they appear to influence position-effect variegation generally. However, the enhancement caused by the single site E(var) mutations is less striking than that caused by the duplication or by loss of the Y chromosome. The interaction between the E(var) mutants and selected Su(var) mutations, as well as the effects of extra Y heterochromatin on E(var) expression, have also been investigated. Based on the results of these studies, various hypothetical functions of the E(var)+ products are suggested.

Alleles↗
PubMed1987

Isolation and characterization of second chromosome mutagen-sensitive mutations in Drosophila melanogaster.

We have undertaken the study of a collection of 32 Drosophila melanogaster mus strains selected on the basis of developmental sensitivity to the DNA-damaging agents, methyl methanesulfonate (MMS), N-acetyl-2-aminofluorene (AAF), nitrogen mustard (HN2), and gamma-radiation. In total, 18 of these strains are sensitive to MMS. In turn, 14 of these exhibit unconditional MMS sensitivity (one of the latter mutants is lethal at 29 degrees C), whereas the other 4 are sensitive to MMS only at higher temperatures. Detailed analysis of the 7 strongest MMS-sensitive strains reveals that they identify 4 new second chromosome mus loci. Two mus loci are each represented by two alleles. One mutant (mus205B1) is allelic to a previously characterized mus locus. Different MMS-sensitive mutants display patterns of mutagen cross-sensitivity (to AAF, HN2, benzo[a]pyrene (BP), and gamma-rays) that parallel the range of responses seen in previously recovered X-linked and autosomal mus loci. In general, mutations that are strongly sensitive to MMS are also sensitive to one or both of the procarcinogens, AAF and BP, as opposed to HN2 and gamma-radiation. In contrast, the moderately MMS-sensitive mutations are sensitive to HN2 and gamma-rays, but not to AAF or BP. Of the 14 mus strains that are not sensitive to MMS, 5 are sensitive to AAF, another 5 are sensitive to HN2, and the remaining 4 are sensitive to gamma-rays.

Animals↗
PubMed1985

Investigation of the nature of P-induced male recombination in Drosophila melanogaster.

The present study consists of an investigation of P-induced male recombination in Drosophila melanogaster from a number of perspectives. In an initial set of experiments, male recombination induced by several different P strains was examined on both major autosomes. The ability of these P strains to evoke recombination is striking; in many cases it exceeded that of radiation treatment. Also of interest is the apparent nonrandom chromosomal distribution of P-exchange breakpoints. The data suggest that both recombinagenic capacity and distribution pattern of exchange breakpoints may be P-strain specific. In addition to these findings, we have confirmed previous indications that P-induced exchange is reasonably symmetrical and that it frequently occurs during premeiotic stages of spermatogenesis. Moreover, we have established that radiation and P background act additively with regard to the induction of male recombination. The second part of the work involved an analysis of heterochromatic vs. euchromatic recombination induced by several recombinagenically potent P strains. Results of these experiments have confirmed our earlier findings concerning the recombinagenic capacity of p strains. More importantly, it would appear that P-induced exchange in heterochromatin is rare. The induction of various kinds of mutations was also monitored in several of these experiments. The results indicate that the mutagenic potential of the P strains is substantial and of particular interest, that certain types of mutations are P-strain specific. For example, rare heterochromatic lesions were recovered exclusively in the experiment using the h12 strain, whereas a novel pleiotropic mutation occurred at a high frequency only in the T-007 experiment. Our findings are discussed within the context of a model of P-induced exchange.

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PubMed1982

RNA-DNA hybridization analyses of tRNA-Val-3b in Drosophila melanogaster.

Transfer RNA was extracted from 50-300 mg of adult flies and specifically labeled in vitro. The level of individual isoacceptors was quantitated by efficient annealing to Drosophila tRNA genes carried on recombinant DNA plasmids immobilized on nitrocellulose filters. The level of tRNAVal3b in the tRNA isolated from flies deficient in the major tRNAVal3b loci has been examined. The results show that deletion of the major tRNAVal3b loci resulted in a reduction of approximately 50% in the level of tRNAVal3b but did not produce the Minute phenotype; furthermore the effects of deficiencies at two loci were approximately additive.

Animals↗
PubMedDate not supplied

Genetic and developmental analysis of a temperature-sensitive minute mutation of Drosophila melanogaster.

A temperature-sensitive (ts) third chromosome Minute (M) mutation, designated Q-III, has been recovered and characterized. Q-III heterozygotes raised at 29 degrees exhibit all of the dominant traits of M mutants including small bristles, rough eyes, prolonged development, reduced viability and interactions with several unrelated mutations. Q-III homozygotes raised at 29 degrees are lethal; death occurs primarily during the first larval instar. When raised at 22 degrees, Q-III heterozygotes are phenotypically normal and Q-III homozygotes display moderate M traits. In addition, Q-III elicits ts sterility and maternal-effect lethality. As is true of M lesions, the dominant traits of Q-III are not expressed in triploid females raised at 29 degrees. Complementation tests suggest that Q-III is a ts allele of M(3)LS4, which is located in 3L near the centromere.--Reciprocal temperature-shift experiments revealed that the temperature-sensitive period (TSP) of Q-III lethality is polyphasic, extending from the first instar to the latter half of pupation. Heat-pulse experiments further resolved this into two post-embryonic TSPs: one occurring during the latter half of the second larval instar, and the other extending from the larval/pupal boundary to the second half of pupation. In addition, heat pulses elicited a large number of striking adult phenotypes in Q-III individuals. These included pattern alterations such as deficiencies and duplications and other morphological defects in structures produced by the eye-antennal, leg, wing and genital imaginal discs and the abdominal histoblasts. Each defect or pattern alteration is associated with a specific TSP during development.--We favor the interpretation that most of the major Q-III defects, particularly the structural duplications and deficiencies, result from temperature-induced cell death in mitotically active imaginal anlagen, while the small macrochaete phene probably results from the direct effects of Q-III on bristle synthesis. The hypothesis that the Q-III locus specifies a component required for protein synthesis is discussed, and it is concluded that this hypothesis can account for the pleiotropy of Q-III, and that perhaps it can be extended to M loci in general.

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