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Published June 1944 | public
Journal Article Open

The ornithine cycle in Neurospora and its genetic control


It has been emphasized by Haldane (1) that for studies of intermediary metabolism "the new science of genetics furnishes a very powerful method." Such a method is founded upon the general premises that genes control many of the chemical reactions within an organism, and that gene mutations by blocking a reaction chain at various points may, in effect, resolve a metabolic process into some of its constituent stages. For instance, the genetics of such diseases as alcaptonuria and cystinuria have elucidated certain problems in human metabolic processes (2), and studies in the genetics of plant pigments have increased the knowledge of of the biochemistry of anthocyanins (3). But the study of metabolism by way of genetic differences in naturally occurring populations is limited not only by the low rate of mutation but also by the lethal character of most mutations of genes controlling vital functions. By increasing the mutation rate of an organism, through irradiation or otherwise, it is possible to create a number of genetic blocks at various steps in the syntheses of substances or in other processes of metabolism. The problem of preserving mutations ordinarily lethal has been met by Beadle and Tatum (4) in a general course of procedure developed around work with the ascomycetous mold Neurospora. The wild type of this organism is able to carry out all the syntheses essential to its normal growth and reproduction if biotin, inorganic salts, and a suitable source of carbon are available. Strains of Neurospora are irradiated with x-ray or ultraviolet rays on the assumption that mutations will be induced in genes controlling the syntheses of such substances as vitamins and amino acids. Mutant strains of this kind cannot grow on merely inorganic salts, sugar, and biotin, "minimal medium," but can be expected to grow if the product of the blocked synthesis is added to the minimal medium. From irradiated Neurospora there has been isolated in this laboratory a series of mutant strains which require for growth the presence of arginine in the culture medium. A study of the specific biochemical characteristics of members of this group of mutants has made it possible to demonstrate in Neurospora crassa an ornithine cycle similar to that proposed by Krebs and Henseleit (5) as occurring in mammalian liver, and to assign various steps in the cycle to the influence of particular single genes. To our knowledge the ornithine cycle has not previously been demonstrated in plants.

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Copyright © 1944 by the American Society for Biochemistry and Molecular Biology. (Received for publication, February 15, 1944) This work was supported by grants from the Rockefeller Foundation and the Nutrition Foundation, Inc. The authors wish to express their indebtedness to members of the Genetics Laboratories for the finding and the identification of the mutants described in this paper. The work of producing and isolating some of the mutant strains was supported by a grant from the Research Corporation. The microanalysis of ornithuric acid was carried out by Dr. A. J. Haagen-Smit and Dr. G. Oppenheimer of the California Institute of Technology. [A.M.S. was a] Nutrition Foundation Fellow at Stanford University.


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