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. 1983 Nov;105(3):633–650. doi: 10.1093/genetics/105.3.633

Enzyme Variation, Metabolic Flux and Fitness: Alcohol Dehydrogenase in DROSOPHILA MELANOGASTER

Richard J Middleton 1, Henrik Kacser 1
PMCID: PMC1202178  PMID: 6416922

Abstract

Although there are many in vitro studies of enzyme activity of genetic variants at the Adh locus in D. melanogaster, little is known about the corresponding metabolic activity in living flies. We report here such measurements of the metabolic flux in the conversion of ethanol to the two products, CO2 and lipids, for six different active genotypes, containing the predominant naturally recurring alleles and covering a threefold range of in vitro activity. In adult flies we have found nonsignificant differences between genotypes in metabolic flux when estimates for individual genotypes had standard errors of approximately 10% of the mean value. In vitro activities are, therefore, poor predictors of the physiological consequences of enzyme variation since such determinations ignore the interactions inherent in multienzyme systems. We have no evidence that heterozygote show overdominance either at the enzyme or the flux level. Since fitness differences between genotypes must be generated by physiological differences, investigations of polymorphisms should be based on in vivo studies.

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Selected References

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

  1. Birley A. J., Barnes B. W. Genetical variation for enzyme activity in a population of Drosophila melanogaster. III. Dominance relationships for alcohol dehydrogenase activity. Heredity (Edinb) 1975 Aug;35(1):121–126. doi: 10.1038/hdy.1975.73. [DOI] [PubMed] [Google Scholar]
  2. Clarke B. The contribution of ecological genetics to evolutionary theory: detecting the direct effects of natural selection on particular polymorphic loci. Genetics. 1975 Jun;79 (Suppl):101–113. [PubMed] [Google Scholar]
  3. Daly K., Clarke B. Selection associated with the alcohol dehydrogenase locus in Drosophila melanogaster: differential survival of adults maintained on low concentrations of ethanol. Heredity (Edinb) 1981 Apr;46(Pt 2):219–226. doi: 10.1038/hdy.1981.29. [DOI] [PubMed] [Google Scholar]
  4. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  5. Gibson J. Enzyme flexibility in Drosophila melanogaster. Nature. 1970 Aug 29;227(5261):959–960. doi: 10.1038/227959a0. [DOI] [PubMed] [Google Scholar]
  6. Harris H. Polymorphism and protein evolution. The neutral mutation-random drift hypothesis. J Med Genet. 1971 Dec;8(4):444–452. doi: 10.1136/jmg.8.4.444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Heinrich R., Rapoport T. A. Mathematical analysis of multienzyme systems. II. Steady state and transient control. Biosystems. 1975 Jul;7(1):130–136. doi: 10.1016/0303-2647(75)90050-7. [DOI] [PubMed] [Google Scholar]
  8. McKay J. Variation in activity and thermostability of alcohol dehydrogenase in Drosophila melanogaster. Genet Res. 1981 Jun;37(3):227–237. doi: 10.1017/s0016672300020231. [DOI] [PubMed] [Google Scholar]
  9. McKenzie J. A., McKechnie S. W. Ethanol tolerance and the Adh polymorphism in a natural population of Drosophila melanogaster. Nature. 1978 Mar 2;272(5648):75–76. doi: 10.1038/272075a0. [DOI] [PubMed] [Google Scholar]
  10. McKenzie J. A., Parsons P. A. Microdifferentiation in a natural population of Drosophila melanogaster to alcohol in the environment. Genetics. 1974 Jun;77(2):385–394. doi: 10.1093/genetics/77.2.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rapoport T. A., Heinrich R., Jacobasch G., Rapoport S. A linear steady-state treatment of enzymatic chains. A mathematical model of glycolysis of human erythrocytes. Eur J Biochem. 1974 Feb 15;42(1):107–120. doi: 10.1111/j.1432-1033.1974.tb03320.x. [DOI] [PubMed] [Google Scholar]
  12. Retzios A. D., Thatcher D. R. Chemical basis of the electrophoretic variation observed at the alcohol dehydrogenase locus of Drosophila melanogaster. Biochimie. 1979;61(5-6):701–704. doi: 10.1016/s0300-9084(79)80169-8. [DOI] [PubMed] [Google Scholar]
  13. Thatcher D. R., Sawyer L. Secondary-structure prediction from the sequence of Drosophila melanogaster (fruitfly) alcohol dehydrogenase. Biochem J. 1980 Jun 1;187(3):884–886. doi: 10.1042/bj1870884. [DOI] [PMC free article] [PubMed] [Google Scholar]

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