192 



CHAPTER 14 



Study o\ a representative sample ol specific 

 loci in Drosophila reveals an average ol one 



point mutation at a given locus in each 200,- 

 000 germ cells tested. In mice the per locus 

 frequency is about twice this, or one in 

 100,000. In man. by scoring the mutants 

 detected in heterozygous condition, the per 

 locus rate is found to be one per 50.000 to 

 100,000 germ cells per generation. Within 

 a species, different loci have about the same 

 order of mutability. Even though some 

 genes are definitely more mutable than 

 others, the average spontaneous point muta- 

 tion rate per genome per generation can be 

 estimated for Drosophila, mouse, and man. 

 In one Drosophila generation, one gamete 

 in twenty (or one zygote in ten) contains 

 a new detectable point mutant. In mice, this 

 frequency is about one in ten gametes, 

 whereas in man it is about one in five gam- 

 etes (or two in five zygotes). 



The point mutations which occur spon- 

 taneously — that is, under natural conditions 

 — bear no obvious relation to the environ- 

 ment, either with respect to the locus af- 

 fected or the type of alternative produced. 

 Modifications in the environment do, how- 

 ever, influence point mutation frequency. 

 For example, in the range of temperatures 

 to which individuals are usually exposed, 

 each rise of 10 C produces about a fivefold 

 increase in point mutation frequency. The 

 magnitude of this increase is similar to, al- 

 though somewhat greater than, that obtained 

 with an increase in temperature in ordinary 

 chemical reactions. Violent temperature 

 changes in either direction produce an even 

 greater effect upon point mutation fre- 

 quency. Actually, detrimental environmen- 

 tal conditions of almost any kind increase 

 point mutation frequency. 



Physical and chemical agents which raise 

 the mutation frequency enormously are 

 called mutagens. All high-energy radia- 

 tions (see Chapter 13) are mutagenic (see 

 Figure 13-3) as are many highly reactive 



chemical substances including: mustard gas 

 and its derivatives; peroxides; epoxides; and 

 carbamates. The point mutation frequencies 

 obtained with radiation and certain chemical 

 mutagens can be 150 times the spontaneous 

 frequency. One speaks of a "spectrum of 

 spontaneous point mutations in that, as men- 

 tioned, certain loci are normally somewhat 

 more mutable than others. The loci affected 

 and the types of mutant alternatives pro- 

 duced by ionizing radiation are not radically 

 different from those involved in spontaneous 

 mutation. That these radiations produce a 

 mutational spectrum much like the sponta- 

 neous one is expected, since radiant energy 

 is more or less randomly distributed in the 

 nucleus and generally enhances many differ- 

 ent kinds of chemical reactions. The point- 

 mutational spectra for different chemicals 

 are somewhat different from each other as 

 well as from the spectra induced by radia- 

 tion mutagens or by spontaneous factors. 

 These differences can be attributed to the 

 nonrandom penetration of these chemical 

 substances into the nucleus, or to their spe- 

 cific capacities for combining with different 

 nuclear chemicals, or both. Nevertheless, 

 the frequency of point mutation, which in- 

 creases linearly with the dose of ionizing 

 radiation (although the frequency is in- 

 fluenced by the amount of oxygen present), 

 probably also increases linearly with the nu- 

 clear dose of many different chemical muta- 

 gens. So point mutation probably has no 

 threshold dose with chemical mutagens, and 

 the number of point mutations produced by 

 a given total dose is constant, other things 

 being equal, regardless of the rate of de- 

 livery. 



For ultraviolet light — which is not a highly 

 energetic radiation — the situation is differ- 

 ent. Here the probability for the individual 

 unit or quantum of energy inducing point 

 mutation is considerably less than 100 per 

 cent. Moreover, because several quanta can 

 cooperate to produce mutation, ultraviolet 



