Genetics 45 



When rates per cell division are measured by tissue-culture studies 

 of bone marrow cells, they average about lO"*'. 



Mutation rate appears to be under genetic control and is therefore 

 subject to change in the course of evolution. Genes whose major 

 effect seems to be affecting the mutation rate of other genes are 

 known. One would expect that in most organisms selection would 

 have resulted in the genotype that maintains an optimum level of 

 mutations in the population. This is difficult to study, and few data 

 are available. The problem is closely connected with that concerning 

 the effects of heterozygosity in developmental buffering or homeo- 

 stasis and in genetic homeostasis and is discussed in later chapters. 



EVOLUTION OF DOMINANCE 



There are several other interesting aspects of mutation about which 

 little is known. Most mutant alleles occurring in the organisms that 

 have been studied in detail are recessive to the wild-type gene. This 

 raises the problem of how dominance-recessiveness arose. It is clear 

 that most mutations that take place will be deleterious to the organ- 

 ism, since they alter a functional system. If they have a major effect, 

 almost certainly the complexly interrelated developmental pathways 

 will be grossly upset and the organism will die. Even if the gene has 

 only a relatively minor effect, however, the integration of the geno- 

 type is such that the mutant organism will be less fit than its parents, 

 provided that there is no environmental change. (The chances of 

 improving the operation of a radio receiver by making a small ran- 

 dom change in its circuits are slim indeed.) Recessive mutations, 

 when they occur in a diploid organism, are stored in the organism's 

 reservoir of variability. When they are (rarely) combined in the 

 homozygous state, they will be eliminated unless the environment 

 (in the broadest sense) has changed sufficiently to give them posi- 

 tive selective value. 



How then does recessiveness arise? There are several hypotheses 

 among which it is difficult to discriminate at present, although all 

 probably have elements of truth. Fisher has suggested that muta- 

 tions will not necessarily be completely recessive on their first occur- 

 rence. They will thus, in general, be disadvantageous unless other 

 modifying genes at different loci reduce the deleterious effects of 

 their expression. Since the homozygous condition for the mutation 

 will rarely occur, selection will operate on the more common hctero- 

 zygotes to build up systems of modifiers that will result in the hctero- 

 zygote resembling the homozygous dominant. 



Wright and Haldane have discussed the problem of the origin of 



