254 ERNST FREESE 



a. The Huilwr M iiitunnir Spvnjiritii. 'V\w I'cactix'ity of a ^^ivcii 

 nucleotide pair toward a mutagen dcjx'iids on its location in the J)NA, 

 as we have already seen for the induction of forward mutations (Section 

 V,A). Mutants containing the same type of base pair change at different 

 sites may thus give ajipreciably dilTeicnt rates of reversion. However, 

 this variable mutagenic si)ecificity can only influence the height of the 

 mutagenic response and cannot make an A-T base pair rcs])ond to a 

 mutagen that attacks only G or C, etc. If one finds two distinct classes 

 of mutants, those that are much and others that are little (or not) 

 inducible by a given mutagen, the corresponding mutations must be 

 fundamentally different. This bipartition is most simply explained by 

 assuming that the mutations of the two classes differ by the type of base 

 pair cliange by which they arose; the higher mutagenic specificity would 

 then only control the relative strength of the response within each class. 



h. Suppressor Mutations. Since reverse mutations occur so rarely they 

 can be observed only on selective media on which the original mutant 

 cannot multiply. All strains which can grow under these selective 

 conditions are called revertants of the original mutant. They may arise 

 by "back mutations" to the standard genotype, i.e., the original sequence 

 of nucleotide pairs in DNA, or by "suppressor mutations." The latter do 

 not return the genome to the standard state but nevertheless restore the 

 growth of the organism partially and sometimes even completely. Such 

 suppressor mutations may occur in the same functional region as the 

 original mutation (intragenic suppressor mutations) or in a tliffcrent 

 functional region (extragenic suppressor inutations). 



The extragenic suppressor mutations usually restore the growth of 

 the organism only ])artially and then can be distinguished from back 

 mutations on growth plates. Their presence is furthermore revealed 

 readily by crosses of a revertant to the standard ty])e organism. These 

 extragenic suppressor mutations may be non-si:)ecific or specific for the 

 original mutational site; they have interesting i)i'operties which go 

 beyond the scope of this paper. For the rll region with which we are here 

 mainly concerned extragenic suppressor nuitations do not seem to exist. 

 This follows from the fact that 10% of the spontaneous rll mutants do 

 not revert at all, which excludes non-specific supi^ressors, and that 

 specific extragenic suppressor nuitations have so far not been found. 



I shall therefore limit the further discussion to back mutations and 

 intragenic suppressor mutations. Let us consider the case in which the 

 functional region contains tlu^ infoi'ination for a ])olypeptide that is the 

 whole or a part of an enzyme. Some mutations may alter the enzyme 

 such that the change of no amino acids in the polypeptide can repair 

 the damage, except the restoration of the original amino acid sequence. 



