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. 1989 Apr;121(4):869–876. doi: 10.1093/genetics/121.4.869

Models of Quantitative Variation of Flux in Metabolic Pathways

P D Keightley 1
PMCID: PMC1203671  PMID: 2721937

Abstract

As a model of variation in a quantitative character, enzyme activity variation segregating in a population is assumed to affect the flux in simple metabolic pathways. The genetic variation of flux is partitioned into additive and nonadditive components. An interaction component of flux variance is present because the effect of an allelic substitution is modified by other substitutions which change the concentrations of shared metabolites. In a haploid population, the proportion of interaction variance is a function of the gene frequencies at the loci contributing to the flux variation, enzyme activities of mutant and wild type at variable loci and activities at nonvariable loci. The proportion of interaction variance is inversely related to the ratio of mutant to wild-type activities at the loci controlling the enzyme activities. The interaction component as a function of gene frequencies is at a maximum with high mutant allele frequencies. In contrast, the dominance component which would apply to a diploid population is maximal as a proportion of the total when mutant alleles are at low frequencies. Unless there are many loci with large differences in activity between the alleles, the interaction component is a small proportion of the total variance. Data on enzyme activity variation from natural and artificial populations suggest that such variation generates little nonadditive variance despite the highly interactive nature of the underlying biochemical system.

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Selected References

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  1. Bannister D. W., Lee A., Whitehead C. C., Griffin H. D. Lipogenic enzyme activity and fructose 2,6-bisphosphate concentration in livers of two lines of domestic fowl (Gallus domesticus) selected for different body fat content. Int J Biochem. 1984;16(12):1301–1305. doi: 10.1016/0020-711x(84)90232-5. [DOI] [PubMed] [Google Scholar]
  2. Bulfield G., Moore E. A., Kacser H. Genetic variation in activity of the enzymes of glycolysis and gluconeogenesis between inbred strains of mice. Genetics. 1978 Jul;89(3):551–561. doi: 10.1093/genetics/89.3.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. CLELAND W. W. The kinetics of enzyme-catalyzed reactions with two or more substrates or products. I. Nomenclature and rate equations. Biochim Biophys Acta. 1963 Jan 8;67:104–137. doi: 10.1016/0006-3002(63)91800-6. [DOI] [PubMed] [Google Scholar]
  4. Dykhuizen D. E., Dean A. M., Hartl D. L. Metabolic flux and fitness. Genetics. 1987 Jan;115(1):25–31. doi: 10.1093/genetics/115.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Graf J. D., Ayala F. J. Genetic variation for superoxide dismutase level in Drosophila melanogaster. Biochem Genet. 1986 Apr;24(3-4):153–168. doi: 10.1007/BF00502785. [DOI] [PubMed] [Google Scholar]
  6. Johnson W. G., Hong J. L., Knights S. M. Variation in ten lysosomal hydrolase enzyme activities in inbred mouse strains. Biochem Genet. 1986 Dec;24(11-12):891–909. doi: 10.1007/BF00554527. [DOI] [PubMed] [Google Scholar]
  7. Johnson W. G., Hong J. L. Variation in alpha-L-fucosidase properties among 28 inbred mouse strains: six strains have high enzyme activity and heat-stabile enzyme with a variant pH-activity curve; twenty-two strains have low activity and heat-labile enzyme. Biochem Genet. 1986 Jun;24(5-6):469–483. doi: 10.1007/BF00499100. [DOI] [PubMed] [Google Scholar]
  8. Kacser H., Burns J. A. The control of flux. Symp Soc Exp Biol. 1973;27:65–104. [PubMed] [Google Scholar]
  9. Kacser H., Burns J. A. The molecular basis of dominance. Genetics. 1981 Mar-Apr;97(3-4):639–666. doi: 10.1093/genetics/97.3-4.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kacser H. The control of enzyme systems in vivo: elasticity analysis of the steady state. Biochem Soc Trans. 1983 Jan;11(1):35–40. doi: 10.1042/bst0110035. [DOI] [PubMed] [Google Scholar]
  11. Keightley P. D., Kacser H. Dominance, pleiotropy and metabolic structure. Genetics. 1987 Oct;117(2):319–329. doi: 10.1093/genetics/117.2.319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kojima K. ROLE OF EPISTASIS AND OVERDOMINANCE IN STABILITY OF EQUILIBRIA WITH SELECTION. Proc Natl Acad Sci U S A. 1959 Jul;45(7):984–989. doi: 10.1073/pnas.45.7.984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. LaPorte D. C., Walsh K., Koshland D. E., Jr The branch point effect. Ultrasensitivity and subsensitivity to metabolic control. J Biol Chem. 1984 Nov 25;259(22):14068–14075. [PubMed] [Google Scholar]
  14. Laurie-Ahlberg C. C. Genetic, ontogenetic, and tissue-specific variation of dipeptidases in Drosophila melanogaster. Biochem Genet. 1982 Jun;20(5-6):407–424. doi: 10.1007/BF00484692. [DOI] [PubMed] [Google Scholar]
  15. Laurie-Ahlberg C. C., Maroni G., Bewley G. C., Lucchesi J. C., Weir B. S. Quantitative genetic variation of enzyme activities in natural populations of Drosophila melanogaster. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1073–1077. doi: 10.1073/pnas.77.2.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miyashita N., Laurie-Ahlberg C. C. Developmental variation in effects of the second and third chromosomes on the activities of the glucose 6-phosphate and 6-phosphogluconate dehydrogenases in Drosophila melanogaster. Biochem Genet. 1986 Jun;24(5-6):447–467. doi: 10.1007/BF00499099. [DOI] [PubMed] [Google Scholar]
  17. Savageau M. A. Biochemical systems analysis. I. Some mathematical properties of the rate law for the component enzymatic reactions. J Theor Biol. 1969 Dec;25(3):365–369. doi: 10.1016/s0022-5193(69)80026-3. [DOI] [PubMed] [Google Scholar]
  18. Whitehead C. C., Hood R. L., Heard G. S., Pym R. A. Comparison of plasma very low density lipoproteins and lipogenic enzymes as predictors of fat content and food conversion efficiency in selected lines of broiler chickens. Br Poult Sci. 1984 Apr;25(2):277–286. doi: 10.1080/00071668408454867. [DOI] [PubMed] [Google Scholar]

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