EFFECT OF AN INCREASE IN MUTATION RATE 323 



as to hamper ever more individuals, until they finally make their ''kill" 

 and so become eliminated. For this reason the total harm done by a 

 so-called small mutation is in the end as great as that done by a large, 

 fully lethal mutation. It follows that, to know the total damage done to 

 a population by a given mutagenic agent, we have to know the total 

 number of mutations produced, including even the smallest on equal 

 terms with the largest [see Haldane (21)]. The detection of these ''small 

 mutations" is, however, a matter of the greatest technical difficulty, if 

 not impossible, except through very special and laborious techniques, 

 some of which should be so set up as to utilize their effects en masse and 

 others, as a countercheck, so devised as to analyze a small sample of 

 them individually [Muller (53)]. Nevertheless, it is already evident that 

 these mutations are considerably more numerous than the "large" ones, 

 and that they must therefore contribute correspondingly more to the 

 sum of biological ills. 



Another point of importance in regard to the mode of action of mu- 

 tant genes in affecting a population concerns itself with their degree of 

 dominance. It has not hitherto been widely realized that, although 

 most mutant genes produce far more than twice as much abnormality 

 when homozygous as when heterozygous, and are in this sense recessive, 

 nevertheless they usually produce some slight effect, at any rate, when 

 heterozygous, and that this effect is of major importance. Evidence for 

 this conclusion has long been in existence, but has been generally neg- 

 lected. This degree of dominance, occurring in man as well as in Dro- 

 sophila [Levit (36), Muller (52, 53, 54)], is usually so small as to be imper- 

 ceptible to ordinary observation. Nevertheless, it is highly significant 

 because it usually causes elimination of the gene to occur in a hetero- 

 zygous individual, before it ever gets a chance to show itself in homo- 

 zygous form. The realization of this situation is making necessary a 

 complete rereckoning of the mutant-gene frequencies to be expected in 

 populations at equilibrium, of the speed of approach to these equilibria, 

 of the prevalent mode of expression of mutant genes in populations, of 

 their extinction rates, etc. In all these respects the supposedly reces- 

 sive mutant genes are in effect, so far as their major action on the popu- 

 lation is concerned, to be reckoned with as dominants. As dominants, 

 however, most of them take their place in the category of mutations with 

 small effects (since the effect on the heterozygote is usually so small), 

 even in those cases in which, owing to their drastic action on the homo- 

 zygote, they had previously been classed as extreme "freaks" or lethals. 



Because of this slight dominance which most mutant genes exert, a 

 mutagenic agent must give rise to a biologically significant depression of 

 vigor and "viability" (survival rate) in the first generation after exposure. 



