MUTATION AND PHENOTYPIC VARIATION IN PHAGES 309 



Luria's analysis, furthermore, suggested that the mutants form 

 geometric clones originating at all times during phage growth, 

 which partly justifies the method of calculation. However, the 

 rates measured in this way are complex functions of the large, 

 unknown number of possible sites of mutation (Hershey and 

 Rotman, 1948; Benzer, 1957), and are not therefore very 

 interesting. Hershey (1946a) estimated, by a crude method that 

 is nevertheless free from many types of complication, the rate of 

 reversion from r to r+ in one of the mutants. The rate fell be- 

 tween 10~^ and 10~^ per phage per generation. This is probably 

 the rate for a single locus, since the reverse mutations tend to 

 occur at or near the site of the original one (Hershey and Rotman, 

 1948). However, the rates of reversion at different r loci vary 

 over a wide range (Hershey and Rotman, 1948; Benzer, 1957). 



Mutations affecting host range (specificity of adsorption) in 

 T2 show several characteristics in common with the r mutations 

 (Streisinger and Franklin, 1956). Mutations from h to A+ occur 

 at many closely linked loci with an over-all frequency of the 

 order 10^'* per phage per generation. The rates at individual 

 loci must be considerably lower and not too dissimilar from each 

 other. Reversions from h+ to h, on the other hand, invariably 

 occur at or near the site of the original mutation to /?+. The 

 reversion frequency varies greatly for different h^ mutants. 

 Thus the A'phenotype (like the r+) seems to call for a rigidly 

 specified genetic configuration that is relatively stable. The h+ 

 phenotype (like the r) can be produced by many different con- 

 figurations, many of which are extremely unstable. In both h 

 and r systems, the distinction between "forward" and "reverse" 

 mutations is real, though the distinction between "wild" and 

 "mutant," of course, is somewhat arbitrary. These conclusions 

 were first clearly stated by Streisinger and Franklin. 



Adams (1953a) estimated the rate of the mutation to heat 

 stability in T5 at 10~^ to 10~^ per phage per generation. 



These facts seem to permit only a few generalizations. First, 

 mutation rates at individual loci can vary anywhere between an 

 upper limit necessary for the persistence of the phage type, and a 



