Gene and Point Mutations 



199 



detecting changes in individual genes, there- 

 fore, is by the phenotypic changes these pro- 

 duce. Since, at present, we recognize a gene 

 operationally as the smallest unit of genetic 

 material whose recombination can be de- 

 tected phenotypically, we must determine the 

 characteristics of mutation in single genes 

 from the phenotypic changes produced in 

 recombinationally detected genes. Accord- 

 ingly, it is clear that we shall not be able to 

 determine from such phenotypic changes 

 whether single gene mutation involves the 

 recombinational gene in toto, or one portion 

 or site within it, or many different sites within 

 it. If gene mutation requires a change in the 

 entire gene, then the material composition 

 of the genes detected by recombination and 

 by mutation would be identical. If, on the 

 other hand, the recombinationally detected 

 gene contains within it one or more sites at 

 which mutation can occur, the basic recombi- 

 national unit of genetic material would be 

 larger than the basic mutational unit of the 

 genetic material. In the absence of critical 

 evidence as to which of these alternatives ob- 

 tains, we shall continue to consider the muta- 

 tional and recombinational genes to be ma- 

 terially equivalent, as we have assumed since 

 page 14, where we invoked the law of parsi- 

 mony. 



As already mentioned in Chapter 1, any 

 given gene is rather stable, being faithfully 

 replicated many thousands of times before a 

 detectable mutation occurs in it. You should 

 recognize, however, that the greater the sensi- 

 tivity of our tests for detecting mutations, 

 the larger will be the rate of mutation ob- 

 served (recall the detection of isoallelism on 

 p. 65). It remains probable, therefore, that 

 there are transmissible modifications of single 

 genes which escape our present modes of de- 

 tection. Nevertheless, within the limits of our 

 present methods of analysis, the gene ap- 

 pears to be a very stable entity. 



The studies to be considered next started 

 with the collection of all detectable mutants of 



genes which were being investigated singly or 

 in combinations. The mutants obtained were 

 then analyzed. Some of the mutations in- 

 volving a given locus proved to be based upon 

 ploidy changes, not involving chromosome 

 breakage; others proved to be associated 

 with gross or small chromosomal rearrange- 

 ments. These types were eliminated from 

 further consideration. Then, sometimes, all 

 genetic and cytological tests known were ap- 

 plied in order also to eliminate the minutest 

 chromosomal rearrangements, including, for 

 example, tiny duplications or deficiencies. 

 The remainder of mutations was then as- 

 sumed, for lack of evidence to the contrary, 

 to comprise in considerable portion mutations 

 involving a single gene (gene mutations) or 

 involving at most only a few genes (intergenic 

 mutations). The mutations remaining, then, 

 behaved as though they occurred at a single 

 point in the genetic and cytological maps, 

 and they were, therefore, called point muta- 

 tions. (Note that gene mutation includes 

 losses of single whole genes.) 



Let us discuss now those discovered charac- 

 teristics of spontaneous and induced point 

 mutations which are likely to apply to gene 

 mutation. Point mutation can occur in a 

 vast number of different genes, so that this 

 process is not restricted to a very limited type 

 of gene. It might be thought that the con- 

 ditions causing point mutation could be of 

 such a nature that, in the diploid cell, both 

 members of a pair of alleles would tend to 

 respond by mutation. But, when point mu- 

 tation does occur in a diploid cell, it is found 

 that only one gene of the pair present is af- 

 fected. The fact that only one member of a 

 pair of genes mutates, though both are lo- 

 cated in the same nucleus, demonstrates that 

 the point mutation process is a very localized, 

 submicroscopic event. 



Is point mutation a rapid or a gradual 

 change? If it were typically a gradual change, 

 or one which involved an instability of the 

 gene for more than one cell generation, then 



