Clinical genetics / edited by Arnold Sorsby.

Date:
1953
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Clinical genetics / edited by Arnold Sorsby. Source: Wellcome Collection.

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    LEVELS OF EFFECT IN GENE MUTATION some of its physico-chemical properties, notably the /?Н optima and the responses to various inhibitors, show characteristic differences from those of succinic dehy¬ drogenase from other sources. The status of the one gene-one enzyme hypothesis is that it is still a useful hypothesis and that it will remain so as long as it appears profitable to see to what extent gene substitutions are correlated with enzyme alterations. Just as an inactive primary product, such as an enzyme, may possibly be activated completely or partially by isolation from the organized cell system, so the reversal may occur by mutation of other genes which thus appear to suppress the mutant character. The best known mutation of this kind is the suppressor of a pyrimidine requirement studied by Houlahan and Mitchell in 1947. The most interesting feature of this case is that the suppressor acts towards three different alleles, each with a characteristic physiology, two being temperature sensitive and the third producing an absolute requirement for pyrimidine at all temperatures. Besides such specific suppressors, there exists the possibility of non-specific suppressors, Ике some in Drosophila, which make two or more non-alleHc mutants more or less normal. Secondary eflfects on physiology and chemistry The various biochemical mutants have an obvious utility in efforts to work out chains of synthesis, the process of which has been indicated above. It is more appropriate now to consider in general the kinds of alteration in the physiology and chemistry of an organism consequent upon a gene change in such a reaction chain. Consider a simple synthetic chain СД ОД.E. A block at reaction 3, in which С is normally converted to D, would result in an absolute or conditional requirement for a growth factor subsequent to the block. Presumably D or E or any compound readily convertible to them in the organism would satisfy the requirement. The requirement would be absolute if the block existed under all conditions suitable for growth of the normal wild type, con¬ ditional or partial if it existed only under certain conditions. The former is characteristic of most of the biochemical mutants so far studied, the latter is characteristic of the few which are temperature sensitive and perhaps also of the one or two pH sensitive mutants which have been reported. As regards the relation of the growth response of the mutant to the concentration of the added growth factor, several diff'erent patterns are found. Various possible types that might be expected are illustrated in Fig. 47. The response of a lysineless mutant (/y-3. Fig. 46) to lysine is, according to Doermann's data of 1944 like the A (or possibly the B) pattern. There is an appreciable response to a small amount of lysine, the magnitude of the response being about linearly related to the concentration of lysine until other factors begin to be limiting, when the curve falls off and becomes steady at about the growth rate of the wild type. The responses of mutants, which require leucine or para-aminobenzoic acid respec¬ tively, are similar. A different type of growth response, namely C, appears to be shown by mutants requiring histidine. Small concentrations of histidine produce little or no growth. Germination of conidia starts, growth is at first rapid and then abruptly ceases. Above a threshold value growth continues, though often at a diminishing rate, to the exhaustion of the medium and above a somewhat greater 127