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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    CHAPTER 10 П.—Chemical Genetics D. G. Catcheside The means by which the genes determine particular characters is the subject matter of physiological genetics. It is anticipated that it may become possible to describe this in completely chemical or biochemical terms, but at present the connexion between gene and character is still largely unknown. A fruitful approach is a careful analysis in chemical terms of the changes in character wrought by a change in one or more genes. This subject of chemical genetics has made use of the most varied biological material, from the pigments of flowers (Lawrence to the metabolic derangements in some congenital human diseases (Garrod, 1923). Alkaptonuria in man is a classic in chemical genetics, being the first instance in which a particular gene was related to a specific and known biochemical reaction. One characteristic symptom is the blackening of the urine on exposure to air, a reaction due to 2-5-dihydroxyphenylacetic acid, also known as homo- gen tisic acid and alkapton. Soon after the rediscovery of Mendel's work in 1900, it was recognized that alkaptonuria behaved in inheritance as a simple mendeHan recessive. Some time later it was found that the blood serum of normal individuals contains an enzyme capable of catalysing the breakdown of homogentisic acid and that this enzyme was apparently absent from the sera of alkaptonurics. Thus it was estabHshed that a single gene change resulted in the absence or inactivity of a specific enzyme and that this in turn led to the failure of a particular bio¬ chemical reaction. Several other inherited metabolic defects involving the meta¬ bolism of the amino acids tyrosine and phenylalanine are now known and are discussed elsewhere (Chapter 11). They all support an interpretation of gene action in terms of a one gene-one reaction hypothesis. Many of these materials suffer from some experimental disability or other, and in almost all respects the work on the chemical genetics of mould fungi, especially that on Neurospora, commenced by Beadle and Tat um, is the most promising. This fungus may be gorwn under completely defined conditions and a great range of chemical characters may be analysed genetically. It is proposed to confine the rest of this account to the principles of chemical genetics as illustrated by the Neurospora work. CHEMICAL MUTANTS OF NEUROSPORA This work began with the hypothesis that any mutation which interfered with an essential process of intermediate metaboHsm would render the strain carrying it incapable of growth on a medium sufiicient to support the normal wild type, and that it should be possible to obtain growth of the mutant strain if the deficient 121