Muller: Production of Mutationi 



One of the most interesting findings 

 which has come out of the study of Dro- 

 sophila chromosomes that underwent re- 

 arrangement of parts as a result of ir- 

 radiation has been the generalization of 

 the existence of the phenomenon known 

 as "position effect. " This effect was 

 first found by Sturtevant in the case 

 of the spontaneous mutant known as 

 Bar eye, but it was not known to what 

 extent the effect might be a special one 

 until numerous rearrangements could be 

 studied. The term position effect im- 

 plies that the functioning of a gene is to 

 a certain extent at least dependent upon 

 what other genes lie in its neighborhood. 

 There is now adequate evidence that this 

 is a general principle, applying to very 

 many if not all the genes in Droso- 

 phila, and that their functioning can be 

 qualitatively as well as quantitatively 

 conditioned by the character of the genes 

 in their vicinity, some of the genes hav- 

 ing much more effect than others and 

 different genes working in different ways 

 and to different extents. 



It is possible that, as Sturtevant sug- 

 gested, the position effect is caused by 

 the interaction between gene products in 

 the vicinity of the genes producing them, 

 assuming that such products are more 

 concentrated there and under such cir- 

 cumstances tend to react more with one 

 another than when dispersed. However, 

 the interpretation which we favor is that 

 the functioning of the gene is affected 

 by its shape and that this, in turn, varies 

 with the strength and nature of synaptic 

 forces acting on the region of the chro- 

 mosome in which it lies. These might 

 consist of forces directly exerted on the 

 gene by other genes, whether allelic or 

 not (Muller), or they might be resul- 

 tants of the state of spiralization, etc., of 

 the chromosome region, circumstances 

 which in their turn are in part dependent 

 on synaptic forces (Ephrussi and Sut- 

 ton). This interpretation, in either of 

 its variants, would explain why position 

 effects are so much more general in 

 Drosophila, an organism in which the 

 synaptic forces are known to operate 

 strongly even in somatic cells, than in 

 other organisms tested, in which such 



forces are much weaker or absent in 

 somatic 'cells. It would also fit in with 

 the author's findings that the hetero- 

 chromatic regions tend to have especial- 

 ly strong, extensive, and distinctive 

 kinds of position effects, effects varying 

 in degree with the total amount of heter- 

 ochromatin present in a cell, as well as 

 with vacillating embryological factors. 

 For these genetic findings are in con- 

 formity with the cytological effects of 

 heterochromatin, observed first by Pro- 

 kofyeva, on the degree of extension, 

 synaptic properties, etc., of euchromatin 

 in its neighborhood, effects which she 

 showed to be subject to similar vacilla- 

 tions, that are correlated with the varia- 

 tions in the phenotypically observed po- 

 sition effects. Recent observations, both 

 by Ephrussi and by Sutton, following 

 suggestions :>f the author, and by Stern, 

 also seem to point in this direction, for 

 they show an influence, on the position 

 effects exhibited by given parts, of the 

 arrangement of homologous chromosome 

 parts. If this interpretation based on 

 gene shape should hold, it would open 

 up a new angle of attack on the struc- 

 ture and method of functioning of the 

 gene, perhaps ultimately relating it to 

 nucleoprotein composition and proper- 

 ties. 



Another use to which the process of 

 breakage and rearrangement of chromo- 

 some parts by irradiation has been put is 

 for the study of the effects of adding 

 and of subtracting small pieces of chro- 

 mosomes, in order to determine the re- 

 lation of gene dosage to gene expression. 

 In this way, it has been found out (1) 

 that most normal genes are, even in sin- 

 gle dose, near the upper limit of their 

 effectiveness, and (2) that most mutant 

 genes have a final effect qualitatively 

 similar to but Quantitatively less than 

 that of their allelic normal gene. The 

 dominance of normal genes over their 

 mutant alleles, then, turns out in most 

 instances to be a special ca=e of the prin- 

 ciple that one dose of a normal gene usu- 

 ally produces nearly though not quite 

 as much effect as two doses. This in 

 turn is best understood as resulting from 

 a long course of selection of the normal 



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