The Journal of Heredity 



ic methods, adapted to the recognition 



of mutations that ordinarily escape de- 

 tection — (1) lethals, (2) changes with 

 but small visible effects, and (3) changes 

 without any externally visible effects 

 but influencing the viability more or less 

 unfavorably. It would take us too far 

 afield to explain these techniques here. 

 Suffice it to say that they made use of 

 the principle according to which a chro- 

 mosome is, as we say, "marked," by hav- 

 ing had inserted into it to begin with 

 one or more known mutant genes with 

 conspicuous visible effects, to differenti- 

 ate it from the homologous chromosome. 

 An individual with two such differenti- 

 ated chromosomes, when appropriately 

 bred, will then be expected to give two 

 groups of visibly different offspring, 

 holding certain expected ratios to one 

 another. If, however, a lethal mutation 

 has occurred in one of the two chromo- 

 somes, its existence will be made evident 

 by the absence of the corresponding ex- 

 pected group of offspring. Similarly, a 

 mutated gene with invisible but some- 

 what detrimental action, though not fully 

 lethal, will be recognized by the fact that 

 the corresponding group of offspring 

 are found in smaller numbers than ex- 

 pected. And a gene with a very small 

 visible effect, that might be overlooked 

 in a single individual, will have a great- 

 ly increased chance of being seen because 

 the given group of offspring as a whole 

 will tend to be distinguished in this re- 

 gard from the corresponding group de- 

 rived from a non-mutant. 



In this way, it was possible in the 

 first tests of this kind, which Alten- 

 burg and the writer conducted, part- 

 lv in collaboration, in 1918-19, to get 

 definite evidence in Drosophila that the 

 lethal mutations greatly outnumbered 

 those with visible effects, and that among 

 the latter the types having an obscure 

 manifestation were more numerous than 

 the definite conspicuous ones used in 

 ordinary genetic work. Visible or not, 

 the great majority had lowered viability. 

 Tests of their genetic basis, using the 

 newly found facts of linkage, showed 

 them to be most varied in their locus in 

 the chromosomes, and it could be calcu- 



lated by a simple extrapolative process 

 that there must he at least hundreds, and 

 probably thousands, of different kinds 

 arising in the course of spontaneous mu- 

 tation. In work done much later, employ- 

 ing induced mutations, it was also shown 

 (in independent experiments both of 

 the present writer and Kerkis, and of 

 Timofeeff and his co-workers, done in 

 1934) that "invisible" mutations, which 

 by reason of one or another physiologi- 

 cal change lower viability without being 

 fully lethal, form the most abundant 

 group of any detected thus far, being at 

 least two to three times as numerous as 

 the complete lethals. No doubt there are 

 in addition very many, perhaps even 

 more, with effects too small to have been 

 detected at all by our rather crude meth- 

 ods. It is among these that we should 

 be most apt to find those rare accidents 

 which, under given conditions or in 

 given combinations with others, may 

 happen to have some adaptive value. 

 Tests of Timofeeff, however, have shown 

 that even a few of the more conspicuous 

 visible mutations do in certain combina- 

 tions give an advantage in laboratory 

 breeding. 



Because of the nature of the test 

 whereby it is detected — the absence of 

 an entire group of offspring bearing cer- 

 tain conspicuous expected characters — 

 a lethal is surer of being detected, and 

 detected by any observer, than is the 

 inconspicuous or invisible, merely detri- 

 mental, mutation. Fortunately, there are 

 relatively few borderline cases, of nearly 

 but not quite completely lethal genes. It 

 was this objectivity of recognition, com- 

 bined with the fact that they were so 

 much more numerous than conspicuous 

 visible mutations, that made it feasible 

 for lethals to be used as an index of 

 mutation frequency, even though they 

 suffer from the disadvantage of requir- 

 ing the breeding of an individual, rather 

 than its mere inspection, for the recogni- 

 tion that it carries a lethal. In the earli- 

 est published work, we (Altenburg and 

 the author) attempted not only to find a 

 quantitative value for the "normal" mu- 

 tation frequency, but also to determine 

 whether a certain condition, which we 



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