Skip to main content
PMC home page
Genetics logoLink to Genetics
. 1994 Aug;137(4):1071–1078. doi: 10.1093/genetics/137.4.1071

Drosophila Alcohol Dehydrogenase Polymorphism and Carbon-13 Fluxes: Opportunities for Epistasis and Natural Selection

A Freriksen 1, BLA de-Ruiter 1, W Scharloo 1, PWH Heinstra 1
PMCID: PMC1206054  PMID: 7982561

Abstract

The influence of genetic variations in Drosophila alcohol dehydrogenase (ADH) on steady-state metabolic fluxes was studied by means of (13)C NMR spectroscopy. Four pathways were found to be operative during 8 hr of ethanol degradation in third instar larvae of Drosophila. Seven strains differed by 18-25% in the ratio between two major pathway fluxes, i.e., into glutamate-glutamine-proline vs. lactate-alanine-trehalose. In general, Adh genotypes with higher ADH activity exhibit a twofold difference in relative carbon flux from malate into lactate and alanine vs. α,α-trehalose compared to low ADH activity genotypes. Trehalose was degraded by the pentose-phosphate shunt. The pentose-phosphate shunt and malic enzyme could supply NADPH necessary for lipid synthesis from ethanol. Lactate and/or proline synthesis may maintain the NADH/NAD(+) balance during ethanol degradation. After 24 hr the flux into trehalose is increased, while the flux into lipids declines in Adh(F) larvae. In Adh(S) larvae the flux into lipids remains high. This co-ordinated nature of metabolism and the genotype-dependent differences in metabolic fluxes may form the basis for various epistatic interactions and ultimately for variations in organismal fitness.

Full Text

The Full Text of this article is available as a PDF (804.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Choudhary M., Laurie C. C. Use of in vitro mutagenesis to analyze the molecular basis of the difference in Adh expression associated with the allozyme polymorphism in Drosophila melanogaster. Genetics. 1991 Oct;129(2):481–488. doi: 10.1093/genetics/129.2.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Clark A. G., Keith L. E. Variation among extracted lines of Drosophila melanogaster in triacylglycerol and carbohydrate storage. Genetics. 1988 Jul;119(3):595–607. doi: 10.1093/genetics/119.3.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cohen S. M. Enzyme regulation of metabolic flux. Methods Enzymol. 1989;177:417–434. doi: 10.1016/0076-6879(89)77024-5. [DOI] [PubMed] [Google Scholar]
  4. Cohen S. M., Ogawa S., Shulman R. G. 13C NMR studies of gluconeogenesis in rat liver cells: utilization of labeled glycerol by cells from euthyroid and hyperthyroid rats. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1603–1609. doi: 10.1073/pnas.76.4.1603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Heinstra P. W. Evolutionary genetics of the Drosophila alcohol dehydrogenase gene-enzyme system. Genetica. 1993;92(1):1–22. doi: 10.1007/BF00057503. [DOI] [PubMed] [Google Scholar]
  6. Heinstra P. W., Scharloo W., Thörig G. E. Physiological significance of the alcohol dehydrogenase polymorphism in larvae of Drosophila. Genetics. 1987 Sep;117(1):75–84. doi: 10.1093/genetics/117.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jeffrey F. M., Rajagopal A., Malloy C. R., Sherry A. D. 13C-NMR: a simple yet comprehensive method for analysis of intermediary metabolism. Trends Biochem Sci. 1991 Jan;16(1):5–10. doi: 10.1016/0968-0004(91)90004-f. [DOI] [PubMed] [Google Scholar]
  8. Laposata E. A., Lange L. G. Presence of nonoxidative ethanol metabolism in human organs commonly damaged by ethanol abuse. Science. 1986 Jan 31;231(4737):497–499. doi: 10.1126/science.3941913. [DOI] [PubMed] [Google Scholar]
  9. Laurie C. C., Bridgham J. T., Choudhary M. Associations between DNA sequence variation and variation in expression of the Adh gene in natural populations of Drosophila melanogaster. Genetics. 1991 Oct;129(2):489–499. doi: 10.1093/genetics/129.2.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Laurie C. C., Heath E. M., Jacobson J. W., Thomson M. S. Genetic basis of the difference in alcohol dehydrogenase expression between Drosophila melanogaster and Drosophila simulans. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9674–9678. doi: 10.1073/pnas.87.24.9674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lewontin R. C., Hubby J. L. A molecular approach to the study of genic heterozygosity in natural populations. II. Amount of variation and degree of heterozygosity in natural populations of Drosophila pseudoobscura. Genetics. 1966 Aug;54(2):595–609. doi: 10.1093/genetics/54.2.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Malloy C. R., Sherry A. D., Jeffrey F. M. Carbon flux through citric acid cycle pathways in perfused heart by 13C NMR spectroscopy. FEBS Lett. 1987 Feb 9;212(1):58–62. doi: 10.1016/0014-5793(87)81556-9. [DOI] [PubMed] [Google Scholar]
  13. Malloy C. R., Sherry A. D., Jeffrey F. M. Evaluation of carbon flux and substrate selection through alternate pathways involving the citric acid cycle of the heart by 13C NMR spectroscopy. J Biol Chem. 1988 May 25;263(15):6964–6971. [PubMed] [Google Scholar]
  14. Malloy C. R., Thompson J. R., Jeffrey F. M., Sherry A. D. Contribution of exogenous substrates to acetyl coenzyme A: measurement by 13C NMR under non-steady-state conditions. Biochemistry. 1990 Jul 24;29(29):6756–6761. doi: 10.1021/bi00481a002. [DOI] [PubMed] [Google Scholar]
  15. Middleton R. J., Kacser H. Enzyme variation, metabolic flux and fitness: alcohol dehydrogenase in Drosophila melanogaster. Genetics. 1983 Nov;105(3):633–650. doi: 10.1093/genetics/105.3.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Oudman L., Van Delden W., Kamping A., Bijlsma R. Polymorphism at the Adh and alpha Gpdh loci in Drosophila melanogaster: effects of rearing temperature on developmental rate, body weight, and some biochemical parameters. Heredity (Edinb) 1991 Aug;67(Pt 1):103–115. doi: 10.1038/hdy.1991.69. [DOI] [PubMed] [Google Scholar]
  17. Ovádi J. Physiological significance of metabolic channelling. J Theor Biol. 1991 Sep 7;152(1):1–22. [PubMed] [Google Scholar]
  18. Powers D. A., Lauerman T., Crawford D., DiMichele L. Genetic mechanisms for adapting to a changing environment. Annu Rev Genet. 1991;25:629–659. doi: 10.1146/annurev.ge.25.120191.003213. [DOI] [PubMed] [Google Scholar]
  19. Thomson M. S., Jacobson J. W., Laurie C. C. Comparison of alcohol dehydrogenase expression in Drosophila melanogaster and D. simulans. Mol Biol Evol. 1991 Jan;8(1):31–48. doi: 10.1093/oxfordjournals.molbev.a040630. [DOI] [PubMed] [Google Scholar]
  20. Vouidibio J., Capy P., Defaye D., Pla E., Sandrin J., Csink A., David J. R. Short-range genetic structure of Drosophila melanogaster populations in an Afrotropical urban area and its significance. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8442–8446. doi: 10.1073/pnas.86.21.8442. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES