200 



CHAPTER 23 



point mutations would usually occur in 

 clusters, even if within a cluster the same gene 

 did not always mutate to the same allele. 

 But many point mutants occur singly, and 

 others, which appear in a cluster and seem to 

 be identical, can usually be accounted for on 

 the basis that a single cell containing the mu- 

 tant gene divided a number of times before 

 the tests to detect the mutant condition were 

 made. While such data do not prove that 

 point mutation is instantaneous, they indi- 

 cate that it is usually completed within one 

 cell generation and is, in this respect, more a 

 quick than a gradual change. However, the 

 number of point mutations obtained from X 

 ray or ultraviolet ray treatments is reduced, 

 if a posttreatment of certain types of visible 

 light or of chemical substances is given im- 

 mediately. Such posttreatments produce 

 photo- or chemorecovery from point muta- 

 tion. This proves that the point mutation 

 process is often not completed for some 

 minutes. It is only after the point mutation 

 process is completed that the new genetic 

 alternative is about as stable as the old. 



While the point mutants which arise at 

 the present time are just about as stable as 

 their parent genes, or other genes in the geno- 

 type, this should not be taken to mean that 

 all allelic and nonallelic genes have the same 

 spontaneous mutation rate. A representa- 

 tive sample of specific loci in Drosopliila gives 

 an average of one point mutation at a given 

 locus in each 200,000 germ cells tested. In 

 mice, the per locus rate is about twice this, or 

 one in 100,000. In man, scoring mutants 

 that are detected when in heterozygous condi- 

 tion, the per locus rate is one per 50,000 to 

 100,0000 germ cells per generation. Within 

 each species, the different loci studied had 

 about the same order of mutability. Never- 

 theless, some genes are definitely more mu- 

 table than others, and those that seem to be 

 very mutable are called "mutable genes." 

 The latter will be discussed in Chapter 25. 

 The average spontaneous point mutation 



rate per genome has been estimated for Dro- 

 sophi/a, mouse, and man. In Drosophila, one 

 gamete in twenty (or one zygote in ten) con- 

 tains a new detectable point mutant which 

 arose in that generation. In mice, this fre- 

 quency is about one in ten gametes, while in 

 man this rate is about one in five gametes (or 

 two in five zygotes). 



The point mutations which occur sponta- 

 neously — that is, during the course of ob- 

 servations made under natural conditions — 

 bear no obvious relation to the environment, 

 either with respect to the locus affected or to 

 the type of alternative produced. However, 

 modifications in the environment do influ- 

 ence point mutation rate. For example, 

 changes in temperature can change point mu- 

 tation rate, each rise of 10° C, in the range of 

 temperatures to which individuals are usually 

 exposed, producing about a fivefold increase 

 in mutation rate. This rate of increase is 

 similar to, though somewhat higher than, 

 what is obtained in ordinary chemical reac- 

 tions with an increase in temperature. Vio- 

 lent temperature changes in either direction 

 produce an even greater effect upon point 

 mutation rate. Actually, it is found that 

 detrimental environmental conditions of al- 

 most any kind cause an increase in point 

 mutation rate. 



Certain physical and chemical agents 

 which raise the mutation rate enormously 

 are called mutagens. All high-energy radia- 

 tions (see Chapter 21) are mutagenic as are 

 many highly reactive chemical substances, in- 

 cluding mustard gas and its derivatives, and 

 also peroxides, epoxides, and carbamates. 

 The point mutation rates obtained with muta- 

 gens may be 150 times the spontaneous rate, 

 and the loci affected and the types of mutant 

 alternatives produced are not radically differ- 

 ent from those which are involved in sponta- 

 neous mutation. One can speak of a spec- 

 trum of spontaneous point mutations, how- 

 ever, in that certain loci are normally some- 

 what more mutable than others. Ionizing 



