Muller: Production of Mutations 



Induced and Natural Mutations 



Inasmuch as the changes brought 

 about in the genes by radiation must 

 certainly be of an accidental nature, un- 

 premeditated, ateleological, without ref- 

 erence to the value of the end result for 

 the organism or its descendants, it is of 

 interest to compare them with the so- 

 called spontaneous or natural mutations. 

 For in the radiation mutations we have 

 a yardstick of what really random 

 changes should be. Now it is found in 

 Drosophila that the radiation-induced 

 mutations of the genes (we exclude here 

 the demonstrable chromosome rear- 

 rangements) are in every respect which 

 has been investigated of the same es- 

 sential nature as those arising naturally 

 in the laboratory or field. They usually 

 occur in one gene without affecting an 

 identical one nearby. They are distrib- 

 uted similarly in the chromosomes. The 

 effects, similarly, may be large or small 

 and there is a similar ratio of fully lethal 

 to so-called visible gene mutations. That 

 is, the radiation mutations of the genes 

 do not give evidence of being more dele- 

 terious. And when one concentrates at- 

 tention upon given genes one finds that 

 a whole series of different forms, or al- 

 leles, may be produced, of a similar and 

 in many cases sensibly identical nature 

 in the two cases. In fact, every natural 

 mutation, when searched for long 

 enough, is found to be producible also 

 by radiation. Moreover, under any given 

 condition of living tried, without radia- 

 tion, the effects appear as scattered as 

 when radiation is applied, even though 

 of much lower frequency. All this sure- 

 ly means then, does it not, that the natu- 

 ral mutations have in truth no innate 

 tendency to be adaptive, nor even to be 

 different, as a whole group, under some 

 natural conditions than under others? 

 In other words, they cannot be determi- 

 nate in a molar sense, but must them- 

 selves be caused by the ultramicroscopic 

 accidents of the molecular and submolec- 

 ular motions, i.e. by the individual quan- 

 tum exchanges of thermal agitation, tak- 

 ing this word in a broad sense. The only 

 escape from this would be to suppose 



that they are caused by the radiation 

 present in nature, resulting from natural 

 radioactive substances and cosmic rays, 

 but a little calculation (by Mott-Smith 

 and the writer, corroborated by others) 

 has shown that this radiation is quite 

 inadequate in amount to account for the 

 majority of mutations occurring in most 

 organisms. 



But to say that most natural muta- 

 tions are the results of the quantum ex- 

 changes of thermal agitation, and, fur- 

 ther, that a given energy level must be 

 reached to produce them, does not, as 

 some authors have seemed to imply, 

 mean that the physicochemical condi- 

 tions in and around the organism, other 

 than temperature, have no influence 

 upon their chance of occurrence. That 

 such circumstances may play a decided 

 role was early evident from the studies 

 of spontaneous mutation frequency, 

 when it was found (1921, reported 

 1928) that the frequency in one ex- 

 periment, with one genetic stock, might 

 be ten times as high as in another, with 

 another stock. And more recently we 

 have found that, in different portions 

 of the natural life cycle of the same in- 

 dividual, the mutation frequency may be 

 very dift'erent. Finally, in the work of 

 Auerbach and Robson, with mustard 

 gas and related substances, it has been 

 proved that these chemicals may induce 

 mutations at as high a frequency as a 

 heavy dose of X-rays. In all these cases, 

 however, the effects are similarly scat- 

 tered at random, individually uncon- 

 trolled, and similarly non-adaptive. 



It should also be noted in this con- 

 nection that the genes are not under all 

 conditions equally vulnerable to the 

 mutating effects of X-rays themselves. 

 Genes in the condensed chromosomes of 

 spermatozoa, for example, appear to be 

 changed more easily than those in the 

 more usual "resting" stages. W'e have 

 mentioned that, as Swanson has shown, 

 ultraviolet exerts besides its own mutat- 

 ing effect an inhibition on the pro-cess of 

 chromosome breakage, or at any rate on 

 that of reunion of the broken parts in a 

 new viable order, while infrared, in Hol- 

 laender's and Kaufmann's recent experi- 



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