MECHANISMS OF GENE ACTION 297 



and the complementation units reflect the relative ease or difficulty of 

 aggregation of these chains as a function of distance between the altered 

 sites. 



The experiments required to test these proposals hav.e not yet been 

 reported. If complementation does occur by reassortment or aggrega- 

 tion of polypeptide chains, then physical studies of the enzymes should 

 reveal this. On the other hand, none of the proposed mechanisms ac- 

 counts for all the biological observations, and it seems likely that further 

 analysis of complementation may provide some new insights into the 

 mechanism of gene action. 



SUPPRESSION 



Another phenomenon, which may in some instances result from the 

 same process as complementation, is called suppression. The term is 

 a poorly chosen and misleading one, but since it is in current usage, we 

 shall employ it here. Geneticists use the term suppression to refer to a 

 change in a mutant phenotype in the direction of the wild type following 

 mutation at some second locus, not the site of the primary mutation. 

 Thus, a suppressor mutation reverses the phenotypic effect of a primary 

 mutation. Phenotypically, it resembles a reversion, and can be distin- 

 guished from it often by slow growth but definitively by genetic analysis 

 to determine whether one locus or two are involved. 



There may be many different biochemical mechanisms leading to rever- 

 sal of the mutant phenotype. Three such mechanisms have been demon- 

 strated: (1) synthesis of the required compound by an alternate pathway, 

 thereby avoiding the blocked step; (2) removal of an inhibitor present 

 in the primary mutant strain; and (3) formation of an active enzyme. 

 Of these, the third is particularly interesting for the analysis of primary 

 gene action, and it may be related in mechanism to complementation. 



The tryptophane synthetase system provides examples of mechanisms 

 2 and 3. In Neuruspora, strain td-24 is temperature-sensitive, having 

 an absolute growth requirement for tryptophane at 25° C but not at 

 30° C. At both temperatures, cultures form large amounts of CRM. 

 Two different unlinked genes, su-24 and su-S, are each able to restore 

 some enzyme activity. CRM isolated from cultures of td-24 grown at 

 either temperature can be restored to enzymatic activity in vitro by 

 removing a bound inhibitor. This activated enzyme from td-24 differs 

 from the wild-type enzyme in being more sensitive to metal ion inactiva- 

 tion. The enzyme isolated from suppressed strains td-24 sn-24 or from 



