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CHAPTER 24 



phenotype when heterozygous with the reces- 

 sive allele, and provided it is not a dominant 

 lethal. Once such mutants are obtained, 

 they can be screened for point mutants. 



The study of recessive lethals on the X 

 chromosome and on the autosomes shows 

 that there are hundreds of loci whose point 

 mutations may be recessively lethal. It 

 should be noted that the recessive lethals de- 

 tected by Base, and the visibles detected by 

 Maxy, are not mutually exclusive types of 

 mutants, for some Maxy-detected visibles are 

 lethal when hemizygous, and about 10 per 

 cent of Base-detected hemizygous lethals 

 show some morphological effect when het- 

 erozygous. It can be stated, in general, that 

 any mutant in homo- or hemizygous condi- 

 tion which is a "visible" will be found to pro- 

 duce some change in viability, and, con- 

 versely, that any mutant which affects vi- 

 ability will be found to produce a "visible" 

 effect, "visible" at least at the biochemical 

 level. 



What, in general, is the nature of the pheno- 

 typic effect of point mutants when homozy- 

 gous or hemizygous? A mutant's biological 

 activity is best described in terms of its effect 

 upon reproductive potential, i.e., the capacity 

 to produce surviving offspring. These terms 

 include the mutant individual's capacity to 

 reach the reproductive stage, its fertility and 

 fecundity during this period, as well as the 

 viability of its offspring until sexual ma- 

 turity. We already know that each mutant 

 has manifold effects due to a pedigree of 

 causes (Chapter 10). It has been found that 

 point mutants with small phenotypic effects 

 are much more frequent than those with large 

 effects. For instance, using the Base tech- 

 nique, it is found that recessive mutants, 

 which lower the viability of males without 

 being lethal, are at least three to five times 

 more frequent than those that are lethal 

 (Figure 24-3). 



The vast majority of point mutants pro- 

 duce a detrimental effect on the reproductive 



potential, those that are beneficial being ex- 

 tremely rare. For example, the great ma- 

 jority of mutations affecting a trait or organ 

 cause its degeneration. This is understand- 

 able in terms of the past evolutionary his- 

 tory of a species. All the genotypes in a 

 species have been subjected to selection for 

 many generations, and those which produced 

 the greatest reproductive potential were re- 

 tained. Although point mutation at any 

 locus is a rare event, many of the alterna- 

 tives possible for each gene must have oc- 

 curred at least several times in the past his- 

 tory of the species. Of these alternatives 

 only the more advantageous alleles were re- 

 tained, and these are the ones found in pres- 

 ent populations. So, when point mutation 

 occurs today, it is likely to produce one of 

 the genetic alternatives which had already 

 occurred in the past and had been elimi- 

 nated because it produced a lower biological 

 fitness, that is, a lower reproductive poten- 

 tial. It should be realized, moreover, that 

 reproductive potential is the result of coordi- 

 nated action of the whole genotype. The 

 genotype may be likened to the machinery 

 that makes modern automobiles, the en- 

 vironment furnishing the raw materials for 

 this process, with the automobile represent- 

 ing the phenotype. Just as it is true for 

 present genotypes, the machinery that manu- 

 factures automobiles is complex and has 

 had a long evolutionary development. The 

 chance that a random local change in the 

 present machinery will result in a better 

 automobile is just as small as the chance that 

 a newly occurring point mutation will in- 

 crease reproductive potential. 



In what way does the phenotypic effect of 

 a point mutant differ from that of its normal 

 alternative? This can be studied by examin- 

 ing the effect of increasing the relative num- 

 ber of doses of the mutant present in the 

 genotype. In Drosop/ii/a, for example, the 

 normal fly has long bristles when the domi- 

 nant gene Z?/j+ is present. There is a mutant 



