scholarly journals THE α-GLYCEROPHOSPHATE IN DROSOPHILA MELANOGASTER II. GENETIC ASPECTS

Genetics ◽  
1972 ◽  
Vol 71 (1) ◽  
pp. 127-138
Author(s):  
Stephen J O'Brien ◽  
Ross J Macintyre
Keyword(s):  
Drosophila Melanogaster ◽  
Energy Production ◽  
Null Alleles ◽  
Electrophoretic Variant ◽  
Electrophoretic Variants ◽  
Glycerophosphate Dehydrogenase ◽  
Naturally Occurring ◽  
Relative Viability ◽  
Null Mutants ◽  
Independent Mutant

ABSTRACT Seven alleles of the α-Glycerophosphate dehydrogenase-1 (αGpdh-1) locus of Drosophila melanogaster have been described. These include two naturally occurring electrophoretic variants, one EMS-induced electrophoretic variant, and four EMS-induced "null" or "zero" mutants. With the electrophoretic variants, the locus was mapped to II-20.5 ± 2.5. A complementation matrix was prepared utilizing the null mutants. Three of the four mutants and a deletion of the locus (Grell 1967) exhibit dosage dependency. The dosage independent mutant exhibits complementation with two of the other null alleles. Flies genetically deficient in α-glycerophosphate dehydrogenase are fertile, but their relative viability is severely diminished. Such flies also lose the ability to sustain flight, an observation consistent with the enzyme's function in energy production. The levels of mitochondrial α-glycerophosphate oxidase, measured in flies genetically deficient in the cytoplasmic enzyme, were normal.

A genetic analysis of the alpha-glycerophosphate oxidase locus in Drosophila melanogaster.

Genetics ◽  
1988 ◽  
Vol 120 (3) ◽  
pp. 755-766
Author(s):  
M B Davis ◽  
R J MacIntyre
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Analysis ◽  
Structural Gene ◽  
Mitochondrial Enzyme ◽  
Synthetic Lethal ◽  
Lethal Phenotype ◽  
Cytoplasmic Enzyme ◽  
Glycerophosphate Dehydrogenase ◽  
Null Mutants

Abstract The gene for alpha-glycerophosphate oxidase, the nuclear encoded mitochondrial enzyme of the alpha-glycerophosphate cycle (alpha GP); has been mapped in Drosophila melanogaster. Several interstitial deficiencies in region 50c-53AB of chromosome 2R were used to localize the structural gene to 52D2-5. In addition, mutations of alpha GPO were generated; alpha GPO mutants are viable yet flightless. Interactions of alpha GPO with alpha-glycerophosphate dehydrogenase (alpha GPDH), the cytoplasmic enzyme of the alpha GP cycle, were investigated through the synthesis of a series of alpha GPDHnull-alpha GPOnull double mutants. Of the six double null mutants constructed, four alpha GPDH-alpha GPO double nulls are viable and flightless. Two double mutants, however, exhibit an allelic-dependent synthetic lethal phenotype.

scholarly journals THE α-GLYCEROPHOSPHATE CYCLE IN DROSOPHILA MELANOGASTER

1974 ◽  
Vol 63 (3) ◽  
pp. 864-882 ◽  
Author(s):  
Stephen J. O'Brien ◽  
Yoshio Shimada
Keyword(s):  
Drosophila Melanogaster ◽  
Oxidative Phosphorylation ◽  
Adult Life ◽  
Respiratory Control ◽  
Premature Mortality ◽  
Pyridine Nucleotide ◽  
Null Alleles ◽  
Wild Type ◽  
Relative Viability ◽  
In The Wild

"Null" mutations previously isolated at the αGpdh-1 locus of Drosophila melanogaster, because of disruption of the energy-producing α-glycerophosphate cycle, severely restrict the flight ability and relative viability of affected individuals. Two "null" alleles, αGpdh-1BO-1-4, and αGpdh-1BO-1-5, when made hemizygous with a deficiency of the αGpdh-1 locus, Df(2L)GdhA, were rendered homozygous by recombination with and selective elimination of the Df(2L)GdhA chromosome. After over 25 generations, a homozygous αGpdh-1BO-1-4 stock regained the ability to fly despite the continued absence of measurable αGPDH activity. Inter se heterozygotes of three noncomplementing αGpdh-1 "null" alleles and the "adapted" αGpdh-1BO-1-4 homozygotes were examined for metabolic enzymatic activities related to the energy-producing and pyridine nucleotide-regulating functions of the α-glycerophosphate cycle in Drosophila. The enzyme functions tested included glyceraldehyde-3-phosphate dehydrogenase, cytoplasmic and soluble malate dehydrogenase, lactate dehydrogenase, mitochondrial NADH oxidation, oxidative phosphorylation, and respiratory control with the substrates α-glycerophosphate, succinate, and pyruvate. These activities in any of the mutant genotypes in early adult life were indistinguishable from those in the wild type. There was, however, a premature deterioration and atrophy of the ultrastructural integrity of flight muscle sarcosomes observed by electron microscopy in the "null" mutants. These observations were correlated with a decrease in state 3 mitochondrial oxidation with α-glycerophosphate, succinate, and pyruvate, as well as with loss of respiratory control in adults as early as 2 wk after eclosion. Such observations, which normally are seen in aged dipterans, were accompanied by premature mortality of the mutant heterozygotes. The adapted αGpdh-1BO-1-4 was identical with wild type in each of the aging characters with the single exception of lowered rates of mitochondrial oxidative phosphorylation.

scholarly journals Direct measurement of in vivo flux differences between electrophoretic variants of G6PD from Drosophila melanogaster.

Genetics ◽  
1992 ◽  
Vol 132 (3) ◽  
pp. 783-787
Author(s):  
J Labate ◽  
W F Eanes
Keyword(s):  
Drosophila Melanogaster ◽  
Steady State ◽  
Adaptive Significance ◽  
Electrophoretic Variants ◽  
Naturally Occurring ◽  
Steady State Kinetics ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
In Vivo Flux ◽  
Pathway Flux

Abstract Demonstrating that naturally occurring enzyme polymorphisms significantly impact metabolic pathway flux is a fundamental step in examining the possible adaptive significance of such polymorphisms. In earlier studies of the glucose-6-phosphate dehydrogenase (G6PD) polymorphism in Drosophila melanogaster, we used two different methods, exploiting both genotype-dependent interactions with the 6Pgd locus, and conventional steady-state kinetics to examine activity differences between the two common allozymes. In this report we use 1-14C- and 6-14C-labeled glucose to estimate directly genotype-dependent flux differences through the pentose shunt. Our results show that G6pdA genotype possesses statistically lower pentose shunt flux than G6pdB at 25 degrees. We estimate this to be about a 32% reduction, which is consistent with the two former studies. These results reflect a significant responsiveness of pentose shunt flux to activity variation at the G6PD-catalyzed step, and predict that the G6PD allozymes generate a polymorphism for pentose shunt flux.

scholarly journals GENETIC ANALYSIS OF ASPARTATE AMINOTRANSFERASE ISOZYMES FROM HYBRIDS BETWEEN DROSOPHILA MELANOGASTER AND DROSOPHILA SIMULANS AND MUTAGEN-INDUCED ISOZYME VARIANTS

Genetics ◽  
1976 ◽  
Vol 83 (4) ◽  
pp. 753-764
Author(s):  
E H Grell
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Analysis ◽  
Genetic Map ◽  
Aspartate Aminotransferase ◽  
Electrophoretic Variants ◽  
F1 Hybrid ◽  
Naturally Occurring ◽  
Chromosome Arm ◽  
Ordinary Type ◽  
Low Activity

ABSTRACT The aspartate aminotransferases (designated GOT1 and GOT2) are two enzymes of Drosophila melanogaster for which naturally occurring electrophoretic variants were not found. There is an electrophoretic difference between D. melanogaster and D. simulans. Since the F1 hybrid offspring of these species are sterile, a genetic analysis of the ordinary type cannot be done on differences between the two species. A method was devised to make "partial hybrids" in which one chromosome arm is homozygous for melanogaster genes in an otherwise hybrid background. By using this method, Got1 was localized to 2R and Got2 to 2L. Once a gene can be assigned to a chromosome, it may be followed in crossing schemes and mutations from mutagen treatments may be looked for. At the locus of Got1 a mutation with low activity was recovered and designated Got1lo. It was located at a genetic map position of 75 on 2R. A Got2 mutant with a greater migration to the anode was recovered and designated Got2J. It was located at a genetic map position of 3.0, and in the salivary chromosome was between 22B1 and 22B4 inclusive.

MUTATION AND DISEASE IN MAN

1978 ◽  
Vol 20 (3) ◽  
pp. 295-306 ◽  
Author(s):  
James V. Neel
Keyword(s):  
Point Mutation ◽  
Protein Level ◽  
Genetic Disease ◽  
Null Alleles ◽  
Receptor Protein ◽  
Mutation Pressure ◽  
Electrophoretic Variants ◽  
Technical Advances ◽  
Impaired Health ◽  
Null Mutants

Efforts to evaluate the burden of genetic disease maintained by mutation pressure are reviewed, Various individuals and committees have suggested that approximately 1800 per 100,000 liveborn infants will ultimately exhibit clearly defined disease due to chromosomal or point mutation. Direct estimates of human chromosomal and point mutation now permit the identification of about 370 per 100,000 liveborn infants with defect due to mutation in the preceding generation. Recent technical advances permit the study of mutation to shift to the protein level. In Amerindians, mutations resulting in electrophoretic variants of a series of proteins of the blood serum and erythrocyte occur at at rate of 1.6 × 10−3/locus/generation. While it is debatable what proportion of electrophoretic variants result in impaired health as heterozgotes or homozgotes in man, we are increasingly aware of disease due to an absence of enzyme or receptor protein due to homozygosity for "null" alleles. A conservative calculation of the possible impact of these "null" mutations on health proceeds as follows: if the rate of mutation to electrophoretic variants in man is only 1.0 × 10−5/locus/generation, and if in man the ratio of nulls to electrophoretic variants is only 2:1 rather than 5:1 of Drosophila, then null mutants with respect to protein should be 2.0 × 10−5/locus/generation. There are perhaps 5,000 proteins in man whose absence can lead to disease. It is clear we are just beginning to recognize a class of mutations whose impact on health in toto may exceed the commonly visualized gross phenotypic abnormalities. However, many of the conceptuses homozygous for these null mutations may be eliminated in utero and not come to clinical attention.

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