Spontaneous mutation of some genes was studied in haploid adenine and leucine auxotrophic yeast Saccharomyces. It was shown that a decrease in the amount of adenine (from 500 to 0 mg l-1) or leucine (from 300 to 0.3 mg l-1) in the medium, simultaneously with the transition from repression to derepression of the biosynthesis of these metabolites, resulted in a 15- to 150-fold increase in the reversion rate of genes ade 2 and leu2, respectively, for different strains. At the same time the mutation rate of suppressor genes varied relatively little (up to five-fold), and that of gene lys did not change at all. It was also demonstrated (on gene leu2) that the mutation rate is determined by the composition of the nutrient medium at the time of the S-phase of the cell cycle and it does not depend on the cultivation conditions during the presynthetic period. We discuss the hypothesis that derepressed genes mutate with a significantly higher rate than genes in the repressed state.
1. The Hill coefficient (nH), an often-used measure of deviations from hyperbolic behaviour (nonhyperbolicity) in kinetic and binding systems, is usually estimated from the maximum or minimum slope of the Hill plot. The method depends strongly on the assumed magnitude of the asymptotic velocity (V) or binding (P) whose evaluation may be difficult in nonlinear/co-operative systems. Therefore, alternative procedures were devised for the estimation nH which do not require the prior knowledge of V or P.2. When pairs of velocity/binding readings (v and w) are obtained at concentrations of c and ac, respectively (where a is a fixed constant), then the relation between w and v is described by a hyperbola, provided that Hill's equation is valid. In this case, linearizing plots, v/w versus v, w versus, w/v, and l/w versus l/v, can be used for the estimation of the degree of the equation. However, if the Hill expression is applicable, these methods are not efficient and traditional procedures, particularly nonlinear regression, should be used.3. The 'linearizing' plots of the Hill equation can be applied advantageously for the evaluation of the Hill slope and of nH also in the general case, when the Hill expression is actually not valid, provided that deviations from hyperbolic behaviour are positive. Appropriately extrapolated intercepts of the first two plots estimate anH. Furthermore, the slope of the third plot yields, similarly to the method of Kurganov et al., a continuous measure of the Hill slope (including its maximum) at all concentrations. The agreement is, at positive nonhyperbolicities, excellent between theoretical values of Hill slopes and coefficients and those estimated by the proposed methods. 4.A coefficient of nonhyperbolicity (4) is defined for 2nd-degree rate equations which provides a quantitative measure of positive or negative deviation from first-degree, hyperbolic characteristics. It is closely related to the Hill coefficient.The Hill coefficient is frequently used as a measure of co-operativity in kinetic and binding systems. It is usually evaluated from the slope of a line which is fitted to data represented in the so-called Hill plot.This procedure implies that the observations depicted in a Hill plot can be characterized by a straight line. In some cases, this is quite a reasonable assumption. In others, it is merely an approximation and not always a good one. In many of these instances, the data are better described by an elongated S-shaped curve, the slope of which is unity at very low and very high substrate concentrations [l] and deviates from this value at intermediate concentrations.Application of the Hill plot requires the assumption of a value for the asymptotic (usually maximum) velocity or binding which is approached at very high concentrations. Estimation of this quantity often involves substantial uncertainty even in the simplest case of hyperbolic kinetic and binding relationships [2,3]. With more complicated relations, for which the question of co-operativity becomes relevant a...
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