Mutational Loads and Their Consequences 



245 



the environment in a given territory will 

 eventually change, so that a nonmutating 

 population that is successful at one time will 

 normally eventually face extinction in the 

 future. Mutation, therefore, is the price 

 paid by a population for future adaptiveness 

 in the same or a different environment. We 

 can now appreciate that mutation and selec- 

 tion, together with genetic drift and migra- 

 tion, represent the principal factors responsi- 

 ble for the origin of more adaptive genotypes. 

 We can also appreciate better the advan- 

 tage that genetic recombination provides in 

 speeding up the production of adaptive 

 genotypes, and the importance of the genetic 

 regulation of mutability. 



In view of what has already been presented, 

 it is not at all difficult to predict the conse- 

 quences of increasing the mutation rate in 

 human beings. There can be no doubt that 

 the exposure of human populations, to man- 

 made penetrating radiations and certain 

 reactive chemical substances, is increasing 

 his mutation rate. Manmade, as well as 

 spontaneous, mutations can occur in either 

 the somatic line or the germ line. Somatic 

 mutations are, of course, restricted to the per- 

 son in which they occur. The earlier the 

 mutation occurs in a person's life history, 

 the larger will be the sector of somatic tissue 

 to which the mutated cell gives rise. 



Suppose a mutagen causes mutation in a 

 certain percentage of all cells. If these mu- 

 tant cells are in an adult they will usually be 

 surrounded by nonmutant ones, of the same 

 tissue, whose action would usually suffice 

 to produce a near-normal effect. A smaller 

 number of cells would be mutated in an 

 embryo than in an adult. However, the 

 mutant embryonic cells could later give rise 

 to whole tissues or organs which would be 

 defective, and in which no compensatory 

 action of normal tissue would be possible. 

 Furthermore, insofar as many mutants af- 

 fect the rate of cell division, the earlier in de- 

 velopment they occur, the more abnormal 



will be the size of the structure to be pro- 

 duced. It becomes understandable, then, 

 even if developmental and postdevelopmental 

 stages are equally mutable, that somatic 

 mutations are more damaging to the indi- 

 vidual, the earlier they occur in its develop- 

 ment. 



Almost all somatic damage is done by 

 newly arisen mutants in heterozygous condi- 

 tion, since mutation involves loci which are 

 usually nonmutant in the other genome. 

 Although somatic mutants cannot be trans- 

 mitted to the next generation, they can 

 lower the reproductive potential of their car- 

 riers, and in this way affect the gene pool for 

 the next generation. 



Mutational damage to somatic cells de- 

 pends upon whether or not the cell subse- 

 quently divides. Certain highly differenti- 

 ated cells in the human body, hke nerve cells, 

 or the cells of the inner lining of the small in- 

 testine, do not divide. It is ordinarily diffi- 

 cult to detect mutations in such cells, since 

 they have no progeny cells which can be 

 classified as mutant and nonmutant. Such 

 cells may be more or less mutable than cells 

 which still retain the ability to divide, but 

 in any case a variety of mutations can occur 

 in them. These can include point mutations 

 that inactivate genes or change the type of 

 allele that is present, as well as structural 

 rearrangements of all sizes. Nevertheless, 

 the cell will remain euploid or nearly euploid 

 because no cell division follows. Accord- 

 ingly, phenotypic detriment to nondividing 

 cells must be due almost entirely to point 

 mutants in heterozygous condition and to 

 position effect. (It is likely that position ef- 

 fect occurs in human beings.) Although the 

 functioning of nondividing cells may be 

 considerably impaired for these reasons, so 

 that they may behave as though they were 

 aging prematurely, their sudden and imme- 

 diate death due to mutation is probably very 

 rare. 



The same mutations can occur in somatic 



