Abstract
This article appeals to a recent theory of enzyme evolution to show that the properties, neutral or adaptive, which characterize the observed allelic variation in natural populations can be inferred from the functional parameters, substrate specificity, and reaction rate. This study delineates the following relations between activity variables, and the forces—adaptive or neutral—determining allelic variation: (1) Enzymes with broad substrate specificity: The observed polymorphism is adaptive; mutations in this class of enzymes can result in increased fitness of the organism and hence be relevant for positive selection. (2) Enzymes with absolute substrate specificity and diffusion-controlled rates: Observed allelic variation will be absolutely neutral; mutations in this class of enzymes will be either deleterious or have no effect on fitness. (3) Enzymes with absolute or group specificity and nondiffusion-controlled rates: Observed variation will be partially neutral; mutants which are selectively neutral may become advantageous under an appropriate environmental condition or different genetic background. We illustrate each of the relations between kinetic properties and evolutionary states with examples drawn from enzymes whose evolutionary dynamics have been intensively studied.
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References
Dean A (1994) Fitness, flux and phantoms in temporally variable environments. Genetics 136:1481–1495
Demetrius L (1992) Thermodynamic perturbations of molecular systems. J Chem Phys 97(9):6663–6665
Demetrius L (1995) Evolutionary dynamics of enzymes. Protein Eng 8(8): 152–167
Demetrius L (1997) Enzyme catalysis: structure-activity relations. Preprint
Dykhuizen DE, Hartl D (1983) Functional effects of PGI allozymes in E. Coli. Genetics 105:1–18
Ewens WJ (1972) The sampling theory for selectively neutral alleles. Theor Popul Biol 3:86–112
Eyring H, Lin SH, Lin SM (1985) Basic chemical kinetics. John Wiley, New York
Fersht A (1985) Enzyme structure and function. WH Freeman, New York
Getzoff ED, Cabelli E, Fisher C, Parge HE, Viezzoli M, Banci L, Hallewell RA (1992) Faster superoxide dismutase mutants designed by enhancing electrostatic guidance. Nature 358:347–351
Gillespie JH (1987) Molecular evolution and the neutral theory. Oxf Surv Evol Biol 4:10–37
Hardy LW, Kirsch J (1984) Diffusion-limited component of reactions catalyzed by Bacillus cereus β-lactamase I. Biochemistry 23:1275–1282
Harris H (1966) Enzyme polymorphisms in man. Proc R Soc Lond [Biol] 164:298–310
Hartl D, Dykhuizen D, Dean A (1985) Limits of adaptation: the evolution of selective neutrality. Genetics 111:655–674
Hilbish TJ, Koehn RK (1985) The physiological basis of natural selection at the Lap locus. Evolution 39:1302–1317
Hudson R, Kreitman M, Aguadé M (1987) A test for neutral molecular evolution based on nucleotide data. Genetics 166:153–159
Hudson R, Bailey K, Skarecky D, Kwiatowski J, Ayala F (1994) Evidence for positive selection in the superoxide dismutase (SOD) region of Drosophila melanogaster. Genetics 136(4): 1329–1340
Kacser H, Burns J (1987) The molecular basis of dominance. Genetics 97:639–666
Koshland D (1976) The role of flexibility in enzyme action. Cold Spring Harb Symp Quant Biol 28:473–480
Jencks WP (1975) Binding energy, specificity, and enzyme catalysis⥭he Circe effect. Adv Enzymol 43:219–410
Kimura M (1968) Evolutionary rate at the molecular level. Nature 217:624–626
Kimura M (1971) Theoretical foundations of population genetics at the molecular level. Theor Popul Biol 2:174–208
Kimura M, Ohta T (1971) Protein polymorphism as a phase of molecular evolution. Nature 229:467–469
Lewontin RC, Hubby JL (1966) A molecular approach to the study of genetic heterozygosity in natural populations of Drosophila pseudoobscura. Genetics 54:595–609
Oakeshott JG, Gibson JB, Anderson PR, Knibb WR, Anderson DG, Chambers GK (1982) Alcohol dehydrogenase and glycerol-3phosphate dehydrogenase clines in Drosophila melanogaster on different continents. Evolution 36:86–96
Richmond R, Gilbert D, Sheehan K, Granko M, Butterworth F (1980) Esterase-6 and reproduction in D. melanogaster. Science 207: 1483–1485
Savageau MA (1976) Biochemical systems analysis: a study of function and design in molecular biology. Addison-Wesley, Reading, MA
Sawyer SA (1994) Inferring selection and mutation from DNA sequences: the McDonald-Kreitman test revisited. In: Golding B (ed) Non-neutral evolution. Chapman and Hall, pp 77–88, New York
Simopoulos T, Jencks WP (1994) Alkaline phosphatase is an almost perfect enzyme. Biochemistry 33:10375–10380
Tipper DJ, Strominger J (1965) Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine. Proc Natl Acad Sci USA 54:1133–1141
Watt WB (1977) Adaptation at specific loci. 1. Natural selection on phosphoglucoisomerase of Colias butterflies: biochemical and population aspects. Genetics 87:177–194
Watt WB (1983) Adaptation at specific loci. II. Demographic and biochemical elements in the maintenance of the Colias PGI polymorphism. Genetics 103:691–724
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Demetrius, L. Selective neutrality and enzyme kinetics. J Mol Evol 45, 370–377 (1997). https://doi.org/10.1007/PL00006242
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DOI: https://doi.org/10.1007/PL00006242