56 CELL HEREDITY 



rates of mutation. In multicellular organisms, these rates vary from 

 gene to gene, but together they form a class which averages about 10~^ 

 They are not to be compared directly with the rates of mutation in 

 microorganisms which are true rates; in intact higher organisms, the so- 

 called rates of mutation are only the frequencies of mutant gametes 

 expressed as per generation. As such they do not directly reflect the 

 mutation rate because clones of mutant cells result from one mutation. 

 As the mutant cells divide and new mutations occur, the frequency of 

 mutants continues to increase. Thus older organisms have more mutant 

 gametes than vounger ones. But even when the true rates of mutation 

 of mammalian somatic cells are estimated by enumerating papillae in 

 tissue culture, they are found to be high. 



It is possible that the absolute rates of mutation, or at least mutant 

 frequencies, are, in general, selected in the course of evolution to be 

 those maintaining the optimal proportion of mutants in the population. 

 Sexually reproducing higher organisms, for reasons of population gen- 

 etics, may maintain greater mutational loads than microorganisms. The 

 question of what constitutes an optimal mutational load is an important 

 one, especially now that man is increasing the level of radiation in his 

 environment, but it will not be discussed further at this point. 



The background of other genes, and probably of other kinds of hered- 

 itary determinants, controls the stability of a given gene. An example 

 is the case of mutation to yellow body color in the fruit fly where the 

 rate differs significantly in male and female. Similar examples exist in 

 which strain, not sex, is responsible. A most interesting case is that in 

 which one single gene determines the rate of mutation of another. Such 

 mutator genes are known in plants and animals, and in microorganisms. 

 Some are nonspecific and cause many different genes to increase their 

 mutation rates. In the corn plant, however, there is one which shows 

 a high degree of specificity; the mutator gene, Dt, increases only the 

 rate of mutation of gene a to its allele, A. All cells containing the 

 A gene form a purple pigment. It is interesting that gene Dt acts only 

 at a specific time in the formation of the kernel. We know this because 

 on the kernel surface there are purple patches of the same size; each 

 contains about the same number of cells, all derived from the one which 

 originally mutated (Figure 2.8). This is a case of the induction of a 

 specific mutation, apparently random in space but nonrandom in time. 

 Because it involves the influence of one gene on another, a specific 

 chemical mutagen is implicated but its nature is unknown. In other 

 cases, a gene may be unstable and mutate with a rate as high as 10~^ 

 per division, not because of other genes but perhaps for intrinsic reasons. 



Still other genes have not been observed to mutate at all; some of them 



