170 



CELL HEREDITY 



TABLE 6.3 



Average Numbers of Revertants Found Among 10'' Mutants Altered af 



Various Sites within a Single Cistron 



(After Freest', 1959, Pror. Nat. Acad. Sci. 45:622, and Streisiiigcr and i'raiiklin, 

 1956, C. S. //. Symp. (.hianl. Hiol.. 21:103) 



Phage 74 rll->Tll' Phage T2 h^-*h 



rill 

 rll4 



rll7 

 ; 131 

 r 157 

 r215 



283 

 0.20 

 1.7 

 1.2 



763 

 0.002 



h^23 

 /i+37 

 h+34 



0.3 

 0.3 

 0.3 

 0.5 



1.0 

 1000 

 1000 



various mutable sites will revert from the recessive state to wild type. 

 Table 6.3 indicates that these rates may vary ten-thousand-fold. When 

 the revertants were crossed with wild types, no mutants were found 

 among sufficient progeny to indicate that the reverted site was within 

 0.1-0.2 map units of the original mutant site; these reversions are either 

 true back mutations or they are due to very closely linked suppressors. 

 The rates of forward mutation from wild type to the mutant state shown 

 in the table are so high as to make the frequency of mutants among the 

 r"*" or h parents ca. 10"^^. This suggests that there is only one state of 

 the DNA in each of these cistrons that yields the r^ and the h pheno- 

 types, and that the various sites listed in the table are located within 

 these cistrons. Since each of these sites, when mutant, impairs the func- 

 tion of the cistron and causes the phenotypes r or h^, the rates of muta- 

 tion from r^ -^r and h~^h^ are the sums of the rates of change of many 

 mutons and, as a consequence, are high. The rates of reversion, which 

 determine the frequencies of mutants shown in Table 6.3, are, on the 

 other hand, unique for the rate with which a particular site changes 

 back to that one condition which allows the cistron to function. Since 

 there are numerous classes of reversion rates, the stahilitv of a muton must 

 involve more than the likelihood of a substitution of one of four bases 

 by another. Even if all changes were caused by base substitutions only, 

 the chance of such an event would be determined by the nature of the 

 neighboring bases or other structural features of the polynucleotide 

 it.self. All this speaks for a considerable chemical heterogeneity within 

 a functional unit. 



Even within a segment of the gene where no recombination has 

 been observed, a variety of changes can occur which differ in stability. 



