Sex-linked Recessive Lethals Research Articles

Further evidence for differential effects of mutagens inDrosophila Melanogaster

A sample of X-ray sex-linked recessive lethals has been localized by the same marker chromosome, and under identical experimental conditions, as prevailed in the placing of the same mutations induced by the alkylating compounds, so as to insure homogeneity of localization. The distribution of this sample of X-ray lethals along the X-chromosome varied significantly from that for the chemically induced mutations.

Cytogenetic analysis of the action of carcinogens and tumour inhibitors inDrosophila melanogaster V. Differential genetic response to the alkylating mutagens and x-radiation

1. Chemical mutagens have been shown to act on gene loci which are apparently stable to X-radiation. By the use of a group of alkylating compounds it was possible to induce nearly 200 ‘new’ sex-linked recessive visibles (ranks 1 and 2), different in phenotype and genetic position from those induced by the physical agent. 2. The ratio of sex-linked recessive visibles/lethals in the same sample of treated chromosornes is exceptionally high for a particular amino-acid mustard (p-N-di(chloroethyl)phenylalanine); which mutates 2–3 times as many morphogenesis loci (relative to lethals) as X-rays or any other alkylating compound. 3. The distribution of the loci of recessive lethals along the X-chromosome is the same for three representative alkylating mutagens, and is significantly different from that for X-rays. A significant difference also occurs in the distribution of theF 1 viable breaks induced by an imine (tri(ethyleneimino)triazine) as compared to X-radiation. 4. The rate of induction of small deficiencies by the alkylating compounds is nearly twice that produced by mutagenically equivalent doses of X-rays. Evidence is available that chemically induced deficiencies result from errors in gene reproduction rather than chromosome breaks. 5. There is a shortage in major structural rearrangements in viable sperm, as well as among the sex-linked recessive lethals, under the effect of the alkylating agents compared with mutagenically equivalent doses of X-rays. This shortage, in the case of the tri(ethyleneimino)triazine rearrangement lethals, has been shown to be due to differences in the properties of the chromosome breaks induced by the imine and X-rays, rather than a lower efficiency in the induction of the primary chromosome breaks by the chemical agent. 6. The dose effects as regards the induction of sex-linked recessive lethals, dominant lethals and viable chromosome breaks, are identical for tri(ethyleneirnmo)triazne and X-rays. This suggests that the hypothesis of direct action of radiations on the genetic material is not conclusively proved by evidence based solely on dose relations. 7. Among the sex-linked recessive lethals induced by various closes of tri(ethyleneimiao)triazine there is a fixed proportion showing cytoiogically detectable chromosome aberrations: major rearrangements and deficiencies. Within this fixed proportion, the fraction with rearrangements increases and that with deficiencies decreases with increase in dose. The bearing of this observation on the mechanism of induction of chromosome breaks by chemical means has been outlined.

"Natural Implantation" of a Lethal Mutation in Drosophila melanogaster

A method is described for the production of mosaic flies with tissues hemizygous for sex-linked recessive lethals. Our investigation deals with the mutant, lethal(1) melanoma-like (lml, 1-1.0). Individuals with patches hemizygous for this sex-linked lethal are viable, but it was observed that these areas were much smaller than mosaic parts in gynanders of the control class. It therefore appears that lml does not act as a cell-lethal but that its deleterious effects prevent the animal from reaching the imaginal stage if sizeable areas are under the influence of this gene.

Cytogenetic analysis of the action of carcinogens and tumour inhibitors in Drosophila melanogaster. I. 1:2, 3:4-diepoxybutane.

This analysis is part of an investigation designed for the elucidation of the correlation between mutagenesis and carcinogenesis. Diepoxybutane was found to be a strong mutagen when injected into the haemocoel of adultDrosophilamales, producing lethal, semi-lethal and ‘visible’ mutations. One of the ‘visible’ mutations produced resulted in the appearance of neoplastic melanotic ‘tumours’ in the offspring of the treated flies. This is most significant in relation to the mutation theory of cancer causation. The successive stages of the male germ line manifest a varied susceptibility to mutagenic action, there being a certain stage among the earlier germ cells which is the most sensitive. The proportion of major structural rearrangements among the sex-linked recessive lethals produced by chemical agents (diepoxybutane and mustard gas) is far lower than that produced by mutagenically equivalent doses of X-rays. Small deficiencies, on the other hand, are twice as frequent among diepoxybutane lethals as among the same type of mutation induced by mustard gas or X -rays. The quality of the bands involved in the deficiencies is also different, diepoxybutane affecting the darker bands of the salivary glandX-chromosome preferentially, mustard gas the lighter ones. This might indicate that diepoxybutane has a preferential action on the gene loci with a higher charge of nucleic acid. A ‘coarse’ specificity for chromosome segments, however, does not seem to occur. The distributions of recessive lethals and loci of damage, induced by the diepoxide and mustard gas in the successive segments of theX-chromosome, are not significantly different. Mosaics for visible mutations and chromosomal changes occur more frequently after treatment with chemical mutagens than after X-radiation. This mosaicism has been explained on the basis of the multiple-strand structure of the mitotic chromosome and partial damage to some of its subunits.

Reduction in Productivity and Recessive Lethal Mutation Following X-Irradiation CF Female Drosophila melanogaster

Sex-linked recessive lethals were recovered from successive batches of eggs laid by female Drosophila melanogaster irradiated with 4,000 r of X-rays. While the initial frequency of lethals (10 per cent.) is similar to that of males treated in an identical manner, there is an immediate linear decline in lethal frequency which reaches a value only 60 per cent. the initial frequency in eggs laid 7-12 days after irradiation. The decline in frequency is taken to represent the elimination in immature germ cells of induced lethal effects belonging to the class of chromosome aberrations. The fecundity and/or fertility of irradiated females is greatly reduced for the first four days after treatment. A rise in female productivity occurs between days 4 and 5. After a week has passed the productivity of treated females is almost normal, although the eggs produced by the females contain 60 per cent. as many sex-linked lethals as the eggs produced immediately after irradiation. The rise in productivity of females from four to five days after treatment is explained by assuming that the eggs laid at this time were 16-cell cysts at the time of irradiation and were resistant to irradiation in much the same fashion as is polyploid tissue.

Genetical and Cytological Studies of Lethals induced by Chemical Treatment inDrosophila melanogaster.

Thepresent paper forms a continuation of studies of recessive sex-linked lethals inDrosophila melanogasterpublished previously (1938, 1941). In these, lethals occurring spontaneously, induced by X-ray treatment and by ultra-violet light were examined cytologically in the salivary gland chromosomes.The genetic factors which stop or change the development of an individual in such a way that its death ensues under normal conditions are termed lethals. A lethal effect may be connected with a mutation of a gene or with its absence from the chromosome: those which cannot be proved to be associated with the absence of a cytologically detectable part of the chromosome are considered as due to “point” mutations.The absence of a microscopically identifiable section of a chromosome with all its genetical and structural elements is called a deficiency. With few exceptions (Muller, 1935; Demerec and Hoover, 1936) the deficiencies in the X-chromosome, whatever their size and whatever loci they involve, are lethal for males. In females heterozygous for them deficiencies of small or even moderate size usually do not produce any visible phenotypical effect, although some cases are known (Mohr, 1923; Slizynska, 1938) in which a heterozygous deficiency for a particular band is always associated with a definite phenotype. Thus a lethal effect may or may not be the result of a deficiency, while a deficiency in the X-chromosome almost always has a lethal effect in the males.In 1941 Auerbach (1943, 1946 in press) succeeded in producing “visible” and lethal mutations and chromosomal rearrangements by chemical treatment in which adult males were exposed to vapours of (C1CH2CH2)2S in a specially designed apparatus. The object of this paper is to show what proportion of sex-linked recessive lethals produced inDrosophila melanogasterby these new agents is connected with detectable deficiencies. Besides finding out whether chemically produced lethals are associated with detectable deficiencies, the problem of the relation between lethals and “visible” mutations is discussed on the basis of their respective distributions along the chromosome. It should be stated that the lethals connected with gross structural changes represent probably only a small fraction of such lethals actually produced since many of them were eliminated by zygotic lethality.