MECHANISMS OF GENE ACTION 273 



w hich t\\ o pigments are lost following a single gene mutation, represents 

 the simplest sort of pleiotropism. At the other extreme, consider a lethal 

 single gene mutation in the rat, cited by Griineberg, in which the first 

 observed effect is upon cartilage formation. The subsequent effects are 

 so manifold and diverse that Griineberg has provided a "pedigree of 

 causes of death, reproduced in Figure 10.1. 



It is to be expected then, that the analysis of gene action will be 

 greatly complicated by the integrated state of cellular and developmental 

 metabolism, by the remoteness of the phenotype from the primary action 

 of the gene, and by the number of interxening steps which can be in- 

 fluenced by other genes and by environmental factors. A fruitful ap- 

 proach would seem to require the choice of a trait directly determined 

 by a gene, in which interactions with other systems are minimal. 



The early studies of biochemical genetics (before 1940) played the 

 important role of demonstrating in a few favorable systems, such as plant 

 and animal pigments, that a specific gene mutation could lead to a block 

 at a particular step in the biosynthesis of a particular compound. But 

 investigators who attempted to carry this kind of analysis further in 

 higher organisms found the going difficult. 



A great ad\'ance in the search for systems suitable for the study of 

 gene action came with the development of microbial genetics. In 

 choosing the mold Neurospom for genetic inxestigation, Beadle and 

 Tatum were motivated precisely by the hope that a microorganism would 

 provide better access to the so-called primary gene products, the first 

 chemical products of gene action, than could be expected with any 

 higher organism. 



GENETIC BLOCK OF SINGLE-STEP REACTIONS 



Beadle and Tatum proposed the "one-gene-one-enzyme hypothesis 

 which states that a single gene acts by determining the specificity of a 

 particular enzyme, "and thereby controls in a primary way enzymatic 

 synthesis and other chemical reactions in the organism. On this 

 hypothesis, preferred traits to be sought in the study of primary gene 

 action are the presence, absence, or alteration of a particular enzyme 

 following mutation. 



It was expected that any enzymatically controlled reaction in the cell 

 would be blocked by a mutation which interfered with the activity of the 

 enzyme. On this hypothesis, then, to find the particular enzyme in each 

 instance, it was necessary first to identify which biosynthetic step had 

 been blocked as a result of a particular gene mutation. 



