THE SYNTHESIS OF NEW SUBSTANCES 375 



probable that the different alleles differed only quantitatively, in efficiency 

 or even perhaps in quantity of substance (cf. Goldschmidt 1938). More 

 recently, several cases have been described in which the differences must 

 be qualitative. For instance, Stem and Schaeffer (1943) showed that there 

 must be two aspects to the activity of the gene cubitus interruptus in 

 Drosophila, an abihty to combine with a substrate, and power of reacting 

 with the combined substrate; and they demonstrated that in the various 

 alleles of this locus these two properties vary independently, some alleles 

 having a high combining ability and low reactivity, others the reverse. 

 Similarly, Waddington and Clayton (1952) found that the various alleles 

 of the gene aristopedia in Drosophila vary independently in their effective- 

 ness in altering the legs and the antenna of the animal, and cannot be 

 arranged in any single quantitative series. 



Recent work has, however, gone much further than such demonstra- 

 tions that mutation may produce quahtative, and not merely quantitative, 

 changes in genes, hi the last few years, an increasing number of cases 

 have been found in which crossing-over takes place between two genetic 

 factors which according to all other evidence would seem to be alleles of a 

 single locus (Review: Lewis 195 1). The existence of such 'pseudo-alleles' 

 is beginning to appear so widespread that one is bound to suspect that all 

 apparent alleles may really be of this nature, that is to say, that the quanti- 

 tatively or quahtatively altered action of each type of mutated gene is 

 correlated with the particular stretch of chromosome which has become 

 changed. If this is so, we shall have to envisage the genetic unit of activity 

 as something which is considerably larger than was previously thought, 

 a point of view which has been strongly urged for some years by Gold- 

 schmidt (1938). It remains very difficult to form a picture of the chemical 

 nature of such active units, which would be much larger than normal 

 protein molecules and perhaps similar in size to some of the viruses. 



There is another category of position effects which also suggests some 

 rather specific conclusions about the action of genes. It is quite commonly 

 found that when a chromosome is broken and rearranged in a way which 

 brings the heterochromatin into an abnormal position, the functioning of 

 the genes which are now near to it becomes unstable, so that in some cells 

 the genes function with full activity, while in others they are more or less 

 inhibited (cf Lewis 1950). This gives rise to a variegated or mottled effect, 

 the degree of motthng varying somewhat from tissue to tissue or even in 

 different parts of the same organ. Since many different genes show the 

 same kind of behaviour in such rearrangements, it seems that the hetero- 

 chromatin must exert some general influence on the activity of most or all 

 genes; the nature of its action remains obscure, but is probably connected 



