NATURE OF THE GENETIC EFFECTS 449 



Cases involving subtraction of pieces, "deficiency," further showed 

 that there are only a limited number of individual genes — probably 

 several score altogether, scattered along the chromosomes — the reduction 

 of which from two doses to one results in full lethality or in a definite, 

 readily observable morphological effect. Moreover, a considerable pro- 

 portion of the morphological effects in these cases consists in a given, 

 regularly appearing syndrome (the "Minute bristle" complex of char- 

 acteristics). But, apart from these marked effects of a few genes, it is 

 in general true that the larger the deficiency, in any chromosome region, 

 the lower the viability and fertility, until a size of deficiency is reached 

 which cannot be tolerated. This maximum size varies with the region 

 but is never greater in Drosophila than a few per cent of a total chromo- 

 some-set (as in the case of the loss of an entire fourth chromosome), and 

 is usually less than 1 per cent. This result is necessarily due to the 

 cumulative action of very many individually small effects, i.e., to the 

 collective weight of numberless fractional genetic loads, each caused by 

 the heterozygous (single dose) state of a normal gene (compare discussion 

 in Sect. 20). 



It was observations of the consequences of changing the dosage of indi- 

 vidual mutant genes of known morphological expression, effected by the 

 addition or subtraction of small chromosome fragments produced by radi- 

 ation and chosen so as to contain these genes, which gave the most sig- 

 nificant results concerning the phenomena of genie balance. This was 

 the work which provided the evidence for the classification of mutant 

 genes presented in Sect. 13, and for the finding that the majority of 

 detected mutants are hypomorphs, with amorphs second in freciuency. 

 It was this work which at the same time showed that for most genes the 

 phenotypic effect at first (for hypomorphs) rises steeply with increase of 

 gene activity or dose, and that the curve of effect (Fig. 7-(3) then becomes 

 convex, approaching a saturation level, which, however (as the studies on 

 dosage compensation showed), is never fully attained. This furnished a 

 simultaneous, common interpretation based on evolutionary and bio- 

 chemical considerations for (1) the phenotypic variability of most 

 mutants, (2) the phenotypic stabiUty of the normal type, (3) the fact that 

 most normal genes appear to have the same expression when present in 

 two doses as when present in one, and (4) the dominance, in most cases 

 appearing complete when judged by ordinary inspection, of most normal 

 genes over their mutant alleles. 



Through the same tests, the facts of dosage compensation also came to 

 light, and this phenomenon was further investigated by studies utilizing 

 a systematic series of radiation-induced chromosome fragments. There- 

 by cogent evidence, quite apart from that already mentioned, was 

 obtained that despite the seemingly complete dominance of normal genes 

 there must usually be enough difference between individuals with two and 



