HOROWITZ AND LEUPOLD 



Others proceed normally. It is inferred 

 that the role of the gene is to function 

 in the synthesis of the enzyme which 

 catalyses this reaction. 



It has not yet been possible to ana- 

 lyse all, or even the majority, of the 

 known Neurospom mutants in the de- 

 tail we have just outlined, while in a 

 few cases the analysis has been carried 

 still farther by showing that the mu- 

 tants are in fact lacking in particular 

 enzymes (Mitchell and Lein, 1948; 

 Fincham, in press). Out of approxi- 

 mately 500 nutritional mutants which 

 are, or have been, in the Pasadena 

 collection, 84 per cent require sin- 

 gle, known chemical substances for 

 growth. The remaining 16 per cent 

 have not responded to any of the in- 

 dividual substances tested, but do grow 

 on complex media. It is very likely that 

 many of the strains in this unanalysed 

 group require individual compounds 

 which have not been tested, others 

 may have multiple requirements re- 

 sulting from multiple mutations, while 

 some may have multiple requirements 

 resulting from the mutation of multi- 

 functional genes. 



The one gene-one enzyme hypo- 

 thesis has been suggested as the sim- 

 plest interpretation of the large class 

 of mutants whose growth requirement 

 is known to be satisfied by a single 

 growth factor. Are there any grounds 

 for suspecting that these mutants may 

 not, in spite of appearances, represent 

 mutations of unifunctional genes? 



One basis for criticism of the one 

 gene-one enzyme interpretation is the 

 difficulty of excluding in every in- 

 stance the alternative hypothesis that 

 the given gene controls not one, but 

 several sequential steps in the affected 

 pathway. This interesting idea appears 

 rather improbable, however, in view 

 of the cumulative evidence from series 

 of mutants which shows that each gene 

 can be assigned to a particular step in 



211 



a sequence of reactions; and it is vir- 

 tually excluded in those cases where it 

 has been possible, by enzyme studies, 

 to define the reaction precisely. 



A second ground for suspicion of 

 the one gene-one enzyme interpreta- 

 tion rests on the fact that closer study 

 of the mutants shows that they are 

 not in all cases restored to a fully nor- 

 mal phenotype when supplied with 

 the required growth substance. While 

 all of the lethal consequences of the 

 mutation are avoided, a residue of 

 non-lethal effects may remain. In some 

 cases, these residual effects are readily 

 accounted for— partial sterility, for ex- 

 ample, when the mutant carres a chro- 

 mosomal rearrangement. Others are 

 not so easily understood. One of the 

 commonest residual effects is a sensi- 

 tivity toward certain natural sub- 

 stances—frequently amino acids. The 

 first reported instance of this phenome- 

 non was that described by Doermann 

 (1944), who found that growth of all 

 of the then known lysine-requiring 

 mutants— a series involving at least 

 three loci— is competitively inhibited 

 by L-arginine in the medium. The 

 growth of wild type Neurospora is not 

 affected by arginine. Many similar 

 cases are now known. A significant 

 feature of this phenomenon is that the 

 inhibition may, as in the case cited, ex- 

 tend to a whole class of genetically 

 different, but biochemically related 

 mutants, indicating that the effect is 

 not locus-specific but is inherent in the 

 mechanism of utilization of theexog- 

 enously provided growth substance. 

 A third residual effect which has been 

 encountered is sterility in crosses in 

 which both parents carry the same 

 mutant allele. One interpretation is 

 that in these cases the gene performs a 

 specific function, possibly independent 

 of its vegetative biochemical function, 

 in connection with zygote formation 

 or maturation. Some recent prelimi- 



