MANNER OF PRODUCTION OF MUTATIONS 497 



in which neither deletions nor any other structural rearrangements can be 

 detected, changes which are ordinarily considered to be gene mutations. 

 It is a priori conceivable that these changes Ukewise involve rearrange- 

 ments, such as deletions, inversions, and shifts, which occur on an ultra- 

 minute scale, within what is ordinarily referred to as one gene, and require 

 breaks and unions of broken ends like those which, on a larger scale, 

 result in the recognizable structural alterations. This view, however, 

 would come into conflict with the evidence on which the conclusion that 

 the genes are discrete segments was founded. For if this were true, such 

 "intragenic " breaks should be able to participate in gross rearrangements 

 also, and these gross rearrangements would be expected often to entail 

 the complete destruction of the normal functioning of the genes within 

 which the breakage points had been located. This is contrary to the 

 findings made concerning the breaks in the scute region and in some other 

 regions and to the finding that, in most kinds of organisms studied, struc- 

 tural changes have not been found to be associated with changes in gene 

 functioning, other than those rare ones definitely ascribable to position 

 effect. 



If, in view of these objections, the idea of the intragenic break as a 

 frequent phenomenon is abandoned, it is still conceivable that a break 

 between two genes is likely to be accompanied by an additional change, 

 within one or more of the genes in the neighborhood of the break. This 

 postulated intragenic mutation might be (1) a secondary effect somehow 

 resulting from the break itself, or (2) a separate effect of the same ioniza- 

 tion or activation as that which produced the break, caused by some 

 branching of the chain of reactions initiated by the given ionization or 

 activation, or (3) an effect of a different ionization or activation from 

 that which caused the break but belonging to the same physical cluster. 

 In any of these cases, even though the break later underwent restitution, 

 as most breaks do, the gene mutation might remain. It is almost cer- 

 tain that the third possibility, at least, would sometimes be realized. 

 Admitting this, the further question would present itself: what propor- 

 tion of all the gene mutations induced by radiation are in some such way 

 associated in their origination with breaks which later restitute, and, con- 

 versely, what proportion of breaks are associated with mutational changes 

 in nearby genes? 



Some light on this problem is cast by studies of the frequency of muta- 

 tions in ring chromosomes. As first shown in tests carried out under 

 Muller's direction by Offermann (see Muller, 1940), when Drosophila 

 spermatozoa containing X chromosomes of ring shape have been irradi- 

 ated with 4000-5000 r, the recovered offspring show about as high a 

 frequency of induced sex-linked lethals as in corresponding experiments 

 with rod-shaped X chromosomes. The same similarity of frequency for 

 rings and rods has been found in the case of visible mutations not associ- 



