The frequency of mutations at specific loci and its relation to dosage of irradiation

Abstract

1. The data obtained from our experiment on the frequency of mutations at specif }c loci with two dosages of x -rays, of 1000 r and 4000 r, respectively, and involving the examination of 91726 F₁ females in all, are reported.

2. Included in our study were gross rearrangements of three types - (a) translocations of the fourth chromosome giving a cubitus "position effect", (b) rearrangements involving at least one break in some heterochromatic region and one in a very limited part of the "active" region, detectable by their influence on somatic variegation (in this case, by causing mottled alleles of white), (c) large deletions of the X-chromosome, giving exceptional F₁ males. Although all these of these types of changes have been reported by certain previous workers to occur in frequencies directly proportional to the dosage, like gene mutations, and unlike what has been reported by our colleagues for the commoner types of gross rearrangements, our data show clearly that the frequency of the gross rearrangements of these special classes varies at a rate that is definitely higher than the first power and lower than the second power of the dosage used, and that is most probably about the 1.5 power. Both the breakage 'and contact hypotheses are discussed, and it is pointed out that the power 1.5 is that to be expected on the breakage hypothesis, according to which the breakages involved in gross rearrangement occur first, as a result of separate individual ionizations, and union of the broken ends occurs later. Moreover, there is no theoretical reason to expect the three types of gross rearrangements here studied to follow a different rule from other gross rearrangements in this respect.

3. In the sane collection of flies in which we found the above exponential relationship for gross structural changes, the frequency of minute rearrangements - both of those (yellow in sc⁸) involving heterochromatic regions, and those (Notches and reverse Bar) involving euchromatic regions-proved to be linearly proportional to the dosage.

4. It was also found that the frequency of mutations involving recessive visible effects allelic to known mutations was linearly proportional to the dosage. As these mutations were found to include a high proportion of lethals, which must predominantly have been minute deletions, it nay be inferred that the latter minute rearrangements also, like gene mutations, have a linearly proportional frequency-dosage relation.

5. It is concluded that in the production of the minute rearrangements by radiation, breakage at two or more nearby points in the chromatin results from a spreading of the effect of one and the same ionization. It is conceivable (but not necessarily true) that in the production of gene mutations essentially the same process takes place, but on a still minuter scale, involving breakage and rearrangement within what have been considered single genes. Other methods will be needed to attack this latter question, however.

6. The data show clearly that the loci of different "visible" mutations differ in regard to the frequency with which surviving mutants, deviating in regard to visible characters, are produced from their normal alleles.