Point Mutations 



195 



indicated by -f . The horizontal axis refers 

 to the dosage of either the normal gene or 

 a hypomorphic mutant. Notice that a sin- 

 gle + gene itself produces almost the full 

 normal phenotypic effect (and often the dif- 

 ference between its effect and the normal 

 effect is not readily detected) . Two -f genes 

 reach the wild-type phenotypic level. In the 

 case of the hypomorphic mutant, however, 

 even three doses may not reach the pheno- 

 typic level produced by one -(- gene (recall 

 the discussion oibb). Note also that genetic 

 modifiers or environmental factors, which 

 can shift the position of the genes on the 

 horizontal axis and thereby shift the pheno- 

 typic effect, have a decreasing influence as 

 one proceeds from individuals carrying only 

 one dose of mutant toward individuals carry- 

 ing two + genes. Natural selection would 

 clearly favor alleles that result in phenotypic 

 effects close to wild-type — that is, near the 

 curve's plateau — for such alleles assure 

 phenotypic stability. Any mutant which 

 produced such a phenotypic effect would, 

 in the course of time, become the normal 

 gene in the population and would automat- 

 ically be dominant when heterozygous with 

 a hypomorphic gene alternative. This model 

 illustrates how the heterozygote with one + 

 and one mutant gene has practically the same 

 effect as the normal homozygote, and it 

 seems to best explain most cases of com- 

 plete or almost complete dominance. Since 

 the normal gene alternative already pro- 

 duces a near-optimum phenotypic effect, this 

 scheme also illustrates why, other things be- 

 ing equal, so few mutants are beneficial. 



Although it is understandable from the 

 preceding discussion that hypomorphic and 

 amorphic mutants are usually detrimental 

 when pure, one may still wonder what effects 

 these mutants have when heterozygous with 

 the normal gene. If the mutant is an 

 amorph, the mutant heterozygote can fall 

 short of producing the wild-type phenotypic 

 effect and, therefore, such mutants are ex- 



pected to be sJightly detrimental when het- 

 erozygous. Hypomorphs are expected to be 

 less or not at all detrimental when hetero- 

 zygous, at least with respect to the trait for 

 which they are classified as hypomorphic. 

 But since each gene affects many different 

 biochemical processes, a mutant hypo- 

 morphic in respect to one trait may be 

 amorphic in respect to another. In Dro- 

 sophila, for example, the normal allele apr+ 

 which results in dull-red eye color also pig- 

 ments the Malpighian tubules. One of its 

 alleles, apr, causes a lighter eye color (being 

 hypomorphic in this respect) but no color 

 in the Malpighian tubules (being amorphic 

 in this respect). 



Experience confirms the expectation that 

 most "recessive" lethal point mutants — these 

 are lethal when homozygous — also have 

 some detrimental effect on reproductive po- 

 tential when heterozygous. Such mutants 

 are not completely recessive, therefore, and 

 when heterozygous in Drosophila cause 

 death before adulthood in about two per 

 cent of individuals. Usually mutants which 

 are detrimental but not lethal when pure also 

 show a detrimental effect when heterozy- 

 gous; this effect is somewhat less than that 

 produced by heterozygous recessive lethal 

 point mutants. The principles of phenotypic 

 action discussed here are expected to apply 

 both to spontaneous and to induced point 

 mutants. 



Detection of Point Mutants in Drosophila 



We have already mentioned the existence of 

 genetic methods for collecting point mutants. 

 Let us now consider in some detail one ele- 

 gant procedure ;; employed in Drosophila 

 melanogaster for this and other purposes. 



The commonly-used technique for detect- 

 ing recessive lethals is called "Base" (see 

 Figure 14-2) and was designed 4 to discover 

 such mutants arising in the male germ line, 



:i Invented by H. J. Muller. 



4 To replace the old "C1B" method. 



