Doctoral Dissertations

Date of Award

8-1955

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Zoology

Major Professor

Gordon Carlson

Abstract

One of the fundamental problems confronting geneticists today is the determination of the mechanism by which spontaneous and induced mutations arise. In order to obtain quantitative information on the induction of mutations by radiation in Drosophila, sex-linked recessive lethals have been utilized by many investigators because of the high frequency of their occurrence and the relative ease with which they can be detected.

It has been demonstrated that recessive lethals are not composed of intragenic changes (point mutations) alone, but arise partly as the result of chromosome deficiencies (Slizynski, 1938) and in association with gross structural changes (Oliver, 1932; Demerec, 1937; Dubinin, Khvostova, and Mansurova, 1941; Fano, 1944; Herskowitz, 1946; and Ives, Levine, and Yost, 1954). It has also been shown that, in the majority of cases in which the lethal is associated with a chromosome rearrangement, the lethal cannot be separated from the aberration by crossing over (Demerec, 1937), which suggests that such lethals either are located at, or near, the breakage points, or are position effects. Although the frequency of lethals associated with gross rearrangements increases with increasing dose (Oliver, 1932; Demerec, 1937; Dubinin, Khvostova, and Mansurova, 1941; Herskowitz, 1946; and Ives, Levine, and Yost, 1954), that proportion of the total lethals which are associated with rearrangements remains constant (Ives, Levine, and Yost, 1954).

Since the frequency of induced chromosome aberrations such as translocations and inversions increases as a power of the dose greater than one, it would seem logical to assume that the total frequency of recessive lethals associated with such aberrations might be expected to increase exponentially with respect to dose. Since it has been demonstrated that primary chromosome breaks increase linearly with dose (Sax, 1940, 1941; Carlson, 1941; and others), lethals which are associated with chromosome breaks will also increase linearly with respect to dose. If the lethals are the result of position effect, they should increase exponentially with respect to dose. This, however, is not the case, since it has been adequately demonstrated by Oliver, 1930, 1932; Demerec, 1933; Timoféeff- Ressovsky, 1939, and others that the total frequency of recessive lethals increases linearly.

On the basis of the available frequency-dose data for the various cytological and genetical effects studied, Lea and Catcheside (1945) and Herskowitz (1946) independently postulated that the induction of recessive lethals in Drosophila was associated with chromosome breakage per se with few, if any, lethals arising as the result of chromosome rearrangement (position effect) or point mutation. Muller (1940, 1950, 1954), however, argues that some recessive lethals are position effects and that the remainder are point mutations and deficiencies. Since Muller (1950, 1954), Catcheside (1948), Fano (1947), and Herskowitz (1946) discuss these hypotheses in more detail, the reader is referred to their papers. With the above-mentioned hypotheses in mind, it should be possible to obtain evidence on the composition of recessive lethals by use of radiations of different ion densities. For example, early reports in the literature concerning the relative biological effectiveness (RBE) of radiations of different ion densities indicated that fast neutrons were 1.5 to 2.0 times more effective in producing dominant lethals and viable rearrangements (Dempster, 1941, and Fano, 1943, 1944) than less densely ionizing X rays but less effective (0.7) in producing recessive lethals (Timoféeff-Ressovsky and Zimmer, 1938; Zimmer and Timoféeff-Ressovsky, 1938, 1942; Dempster, 1941; Giles, 1943; and Fano, 1944).

Recently, however, it has become established that fast neutrons from both the cyclotron and nuclear detonations are 5 to 6 times more efficient than X rays in producing translocations (Lewis, 1954; Stone, Alexander, Clayton, and Dudgeon, 1954) and 4 to 7 times as effective in producing dominant lethals (Baker and Von Halle, 1954) in Drosophila. In contrast to the high RBE values reported for the above effects, the RBE for sex-linked recessive lethals induced by fast neutrons, as compared to X rays, has been reported to be about 2 to 3.5 (Mickey, 1954; Ives, Levine, and Yost, 1954), instead of 0.7 as found earlier.

The striking difference between the RBE for symmetrical exchanges and dominant lethals on the one hand and for recessive lethals on the other is unexpected if one assumes that a large number of these recessive lethals are associated with rearrangements. Since neutron dosimetry at the present is much more reliable than in the past, it was considered appropriate to make a detailed comparison between the effects of X rays, gamma rays, and fast neutrons on the induction of recessive lethals in Drosophila in an effort to gain further information concerning the mechanism involved in the induction of mutations.

Another method which will yield information concerning the composition of recessive lethals is one in which the frequency of induced lethals in a ring-X chromosome is compared to the frequency induced in a rod-X chromosome. Since a ring chromosome can be lost after chromosome breakage as a result of torsional restitution or sister union of the broken chromosome ends and a rod chromosome can be lost only after sister union, one would expect to observe a decrease in the frequency of recessive lethals induced in a ring-X as compared to a rod-X chromosome, if one assumes that lethals occur as the result of chromosome breakage. The occurrence of interchromosomal rearrangements involving a ring-X will tend to accentuate this effect since the probability that such a rearrangement is viable is much less for the ring than the rod.

The results of this study show that, whereas the recessive lethals induced by X rays are predominantly point mutations, a portion of those produced by fast neutrons are associated with chromosome breakage.

Download
Files over 3MB may be slow to open. For best results, right-click and select "save as..."

Share

COinS