CHAPTER 16 



organs which arc defective; in such cases 

 there is no compensator) action of normal 

 tissue. Furthermore, since many mutants 

 affect the rate of cell division, the earlier 

 in development they occur, the more ab- 

 normal the si/e o\' the resulting structure 

 will be. It is understandable, then — assum- 

 ing that cells at all stages are equally mutable 

 — that the earlier somatic mutations occur 

 in the development of an individual, the 

 more damaging they will be to him. 



Newly arisen mutants produce almost all 

 their somatic damage when heterozygous, 

 since mutation involves loci which are usu- 

 ally nonmutant in the other genome. Al- 

 though somatic mutants cannot be trans- 

 mitted to the next generation, they can lower 

 the reproductive potential of their carriers, 

 thus affecting the gene pool of the next 

 generation. 



The damage which new mutants produce 

 in a somatic cell depends upon whether or 

 not the cell subsequently divides. Certain 

 highly differentiated cells in the human body, 

 like nerve cells or the cells of the inner lining 

 of the small intestine, do not divide. In 

 such cases, it is ordinarily difficult to detect 

 mutations since the cells have no progeny 

 classifiable as mutant or nonmutant. Non- 

 dividing cells may be more or less mutable 

 than those retaining the ability to divide. 

 In any event, a variety of mutations can 

 occur in nondividing cells, including point 

 mutations which inactivate or change the 

 type of allele present, as well as structural 

 rearrangements of all sizes. Nevertheless, 

 the nondividing cell remains euploid or 

 nearly euploid, and the phenotypic detriment 

 produced must be due almost entirely to 

 point mutants in heterozygous condition and 

 to shifts in gene position. Although this 

 may considerably impair the functioning of 

 nondividing cells and give the impression 

 that they are aging prematurely, their sud- 

 den and immediate death due to mutation 

 is probably very rare. 



Although the same kinds of mutations 

 occur in somatic cells that subsequently di- 

 vide and in those that do not, nuclear divi- 

 sion can result in gross aneuploidy (Chapters 

 I I and 12). Accordingly, most of the phe- 

 notypic damage of induced mutants in divid- 

 ing cells is the result of aneuploidy — mostly 

 the consequence of single breakages that fail 

 to restitute. It should be noted that all 

 known agents causing point mutation also 

 break chromosomes. 



Germinal Mutations 



Since somatic cells comprise a population 

 produced by asexual reproduction (cell divi- 

 sion), the preceding discussion of the effects 

 of somatic mutation is appropriate to this 

 chapter. Consider next, in a general way, 

 the consequences of increasing the frequency 

 of mutations in the human germ line. The 

 earlier that mutation occurs in the germ line, 

 the greater the portion of all germ cells 

 carrying the new mutant will be. Of course, 

 the upper limit of gametes carrying a par- 

 ticular induced mutant is usually fifty per 

 cent. Consider the effect of exposing the 

 gonads of each generation to an additional 

 constant amount of high-energy radiation 

 (Figure 16-3). The load of mutants pro- 

 duced spontaneously is presumably at equi- 

 librium — the rate of mutant origin equals 

 the rate of mutant loss via genetic death. 

 Beginning with the first generation to receive 

 the additional radiation exposure, the mu- 

 tant load increases with each generation 

 until a new equilibrium is reached; at this 

 point the higher number of genetic deaths 

 per generation equals the higher number of 

 new mutants produced each generation. If 

 the additional radiation exposure ceases at 

 some still later generation, the mutational 

 load will decrease gradually (because of 

 variations in persistence) via genetic deaths, 

 until the old spontaneous equilibrium is 

 reached again. 



