THE ORIGIN OF VARIATION 



Rate of Mutation. The rate at which mutation occurs has also been 

 the subject of many studies. Spencer has shown that the rate of mutation 

 in Drosophila diflFers from time to time. These differences were attributed 

 to environmental influences. Demerec found that the rate differed in dif- 

 ferent genetic strains of Drosophila, and hence proposed that the rate of 

 mutation is itself controlled by specific genes. He found that the rate of 

 lethal mutation varied from one in every 100 chromosomes to one in every 

 1000 chromosomes. Ives has identified such "mutator" genes in wild popu- 

 lations of Drosophila, genes which increase the mutation rate as much as 

 ten fold. Baur found that 5 to 7 per cent of the progeny of normal Antir- 

 rhinum majus showed at least one mutant, while none was observed in 

 A. siculum during twenty years of breeding. These data were explained 

 on the basis of a great difference in mutation rate in these two closely 

 related species. Stadler measured the frequency of the appearance of 

 eight mutants in maize. When expressed as the number of times each 

 occurred per million gametes, the following series was obtained: 492, 106, 

 11, 2.4, 2.3, 2.2, 1.2, and 0. It is clear, then, that different genes mutate at 

 different rates even within the same strain. This is supported by laboratory 

 studies of Drosophila. Some mutants have appeared many times in labora- 

 tory stocks, some rather rarely, and some are known only from single 

 records. 



The explanation of variations in mutation rates has been tentatively 

 considered in thermodynamic terms. Change from one allelic state to an- 

 other involves physicochemical change, and this must require free energy. 

 The amount of energy required depends upon the specific mutation. The 

 rate of any mutation, then, will generally be inversely proportional to the 

 amount of energy required. Thus in Stadler's study, 7 mutated to i 106 

 times per million gametes, while Pr mutated to pr only 11 times per mil- 

 lion, so it is probable that the latter mutation requires much more free 

 energy than the former. The same considerations apply to different muta- 

 tional steps in a series of multiple alleles. Thus in the eye color series in 

 Drosophila, W (red) mutates to its various alleles far more readily than 

 does w ( white ) . 



One may ask where mutator genes fit into this picture. They could act 

 by increasing the amount of available energy or by lowering the energy 

 threshold for mutation. No data are available which permit a choice be- 

 tween these hypotheses. Many data, however, show that mutation re- 

 quires time. Thus increased pressure reduces the mutagenic effects of 

 radiation (see below), even if the pressure is applied as much as 20 

 minutes after radiation. Hence it appears that the mutating gene first 

 passes to a labile state of some duration, from which it may go to a mutant 

 state or to its initial state. 



Direction of Mutation. It is commonly said that the direction of muta- 

 tion is random, meaning that chance alone determines in which of an 

 infinity of possible ways a particular gene will actually mutate. This is 

 true in the sense that the environment does not cause the appearance of 

 mutants which are appropriate to it. In all environments, both natural 

 and experimental, the majority of the mutants are disadvantageous: their 



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