THE CHEMICAL BASIS OF HEREDITY 29 



the rapid advances being made in this field. In actuahty, most genetic 

 investigations have been undertaken with chromosomal genes, par- 

 ticularly in the studies of recombination. In studies of mutation, the 

 genetic elements have not always been identified. 



The existence of the gene has been inferred from observations of diff^er- 

 ences in heritable traits of individuals in a pedigree. Thus observations 

 of altered phenotypes have provided the raw material from which the 

 science of genetics was constructed. Before proceeding to a more de- 

 tailed analysis of the genetic unit, then, let us summarize what is known 

 of the action of genes in determining the phenotypes by which they are 

 identified. 



How do genes act? When one observes the extraordinary precision of 

 heredity — the extent to which progeny resemble their parents, embryos 

 develop identically, species differ consistently — one feels convinced that 

 the directing role of hereditary determinants must be pervasive, encom- 

 passing a great variety of activities. The perpetuation of the complexi- 

 ties of subcellular organization, the synthesis of small molecules and of 

 specific macromolecules at the right time and in the right place, must 

 demand a very high level of integration; presumably all this is under 

 gene control. Viewed from the vantage point of the finished product, the 

 analysis of gene action looks bewilderingly complex. 



On the other hand, if one considers the problem of gene action in a 

 single-celled microorganism, and further simplifies matters by surveying 

 the effects of known gene mutations, the picture becomes somewhat less 

 blurred. This approach was developed in a forceful way with the sys- 

 tematic investigation of mutants of the bread mold, Neurospora, by 

 Beadle and Tatum. They, and subsequently many others, isolated 

 mutant strains called auxotrophs, each of which had acquired, as a result 

 of a single gene mutation, a growth requirement for some particular 

 compound, generally an amino acid, vitamin, purine, or pyrimidine, not 

 required by the parental strain. These mutants were studied bio- 

 chemically to locate the metabolic effect of each mutation. 



For example, in one experiment, fifteen mutant strains were isolated 

 which required arginine for growth. Biochemists supplied the informa- 

 tion that the last few steps in arginine synthesis in mammalian liver 

 involved the compounds, ornithine and citrulline, as shown in Figure 

 1.11. The mutants, tested for their ability to grow with any of these 

 compounds, fell into three groups: those which could use only arginine 

 (Group 1), those that could use either arginine or citrulline (Group 2), 

 and those that could use any one of the three compounds equally well for 

 growth (Group 3). It was further noted that mutants of Group 1 ac- 

 cumulated citrulline, supporting the growth of Group-2 mutants which, 



