The relation between recessive lethals,dominant lethals,and chromosome aberrations inDrosophila

Journal of Genetics - The suggestion is put forward that radiation-induced recessive lethals, or a large proportion of them, are due to chromosome breaks. About one-third of all the chromosome...     

The population genetics of synthetic lethals.

Synthetic lethals are variants at different loci that have little or no effect on viability singly but cause lethality in combination. The importance of synthetic lethals and, more generally, of synthetic deleterious loci (SDL) has been controversial. Here, we derive the expected frequencies for SDL under a mutation-selection balance for the complete haploid model and selected cases of the diploid model. We have also obtained simple approximations that demonstrate good fit to exact solutions based on numerical iterations. In the haploid case, equilibrium frequencies of carrier haplotypes (individuals with only a single mutation) are comparable to analogous single-locus results, after allowing for the effects of linkage. Frequencies in the diploid case, however, are much higher and more comparable to the square root of the single-locus results. In particular, when selection operates only on the double-mutant homozygote and linkage is not too tight, the expected frequency of the carriers is approximately the quartic root of the ratio between the mutation rate and the selection coefficient of the synthetics. For a reasonably wide set of models, the frequencies of carriers can be on the order of a few percent. The equilibrium frequencies of these deleterious alleles can be relatively high because, with SDL, both dominance and epistasis act to shield carriers from exposure to selection. We also discuss the possible role of SDL in maintaining genetic variation and in hybrid breakdown.     

Test of recessive lethals in the mouse

The presence of spontaneous lethal mutations in inbred strains is discussed with special reference to their variation and influence on estimates to induced mutations.A model is presented that will facilitate classification of lethal-free and lethal heterozygotes.The model is used in classification of sons to lethal heterozygous males carrying a spontaneous mutation.The observed results are in good agreement with the model.From experience it is concluded that the most efficient way to use the facilities in lethal tests is to examine 10 or more full brothers to the P parents. By doing so pre-existing spontaneous lethals can be excludde by eliminating families in which any of the P parents were lethal heterozygous. The observed total rate of recessive lethals gives slight over-estimation of the induced rate of mutations, as spontaneous mutations in the gametes forming the F₁ cannot be excluded.     

The population genetics of X-autosome synthetic lethals and steriles

Epistatic interactions are widespread, and many of these interactions involve combinations of alleles at different loci that are deleterious when present in the same individual. The average genetic environment of sex-linked genes differs from that of autosomal genes, suggesting that the population genetics of interacting X-linked and autosomal alleles may be complex. Using both analytical theory and computer simulations, we analyzed the evolutionary trajectories and mutation-selection balance conditions for X-autosome synthetic lethals and steriles. Allele frequencies follow a set of fundamental trajectories, and incompatible alleles are able to segregate at much higher frequencies than single-locus expectations. Equilibria exist, and they can involve fixation of either autosomal or X-linked alleles. The exact equilibrium depends on whether synthetic alleles are dominant or recessive and whether fitness effects are seen in males, females, or both sexes. When single-locus fitness effects and synthetic incompatibilities are both present, population dynamics depend on the dominance of alleles and historical contingency (i.e., whether X-linked or autosomal mutations occur first). Recessive synthetic lethality can result in high-frequency X-linked alleles, and dominant synthetic lethality can result in high-frequency autosomal alleles. Many X-autosome incompatibilities in natural populations may be cryptic, appearing to be single-locus effects because one locus is fixed. We also discuss the implications of these findings with respect to standing genetic variation and the origins of Haldane's rule.     

The sheltering of lethals on metatherian sex chromosomes

The accumulation of non-functional (especially lethal) genes on sex-chromosomes will be slower in metatherians than in eutherians, in eases where the sex-determining system is other than XY/XX.     

Effects of reproductive compensation and genetic drift on X-linked lethals

A revival of interest in Haldane's equilibrium theory for X-linked lethals has been stimulated by the introduction of accurate tests for the detection of female heterozygotes in Lesch-Nyhan disease. Application of these tests appears to indicate an excess of familial cases. This excess can be attributed to ascertainment bias, a difference in female and male mutation rates, genetic drift, and reproductive compensation. Reproductive compensation will be particularly effective in increasing the proportion of familial cases if (1) birth control is widespread; (2) selection against affected males acts in utero; (3) affected sons show symptoms at an early age; and (4) sons are more highly valued than daughters. We demonstrate how only a few generations of reproductive compensation are sufficient to achieve an approximate equilibrium between selection and mutation showing a high proportion of familial cases. We also discuss the random fluctuations around equilibrium caused by genetic drift.     

Analysis of lethals in selected lines of Drosophila melanogaster

Summary Five lines of Drosophila melanogaster that reached an extreme phenotype after long-term selection for increased dorsocentral bristle number, were analysed for the presence of lethals. Seven chromosome II and three chromosome III lethal types were detected in four of the lines, at frequencies ranging from between 6% and 36%. No lethal had any demonstrable effect over the selected trait. In one line, where almost every chromosome II was a lethal carrier, it was shown that the main lethal (at a frequency of 36%) was associated with the transmission ratio distortion in males. The processes which could lead to the accumulation of this lethal and others linked in disequilibrium to it is discussed. Some results suggest similar mechanisms for the accumulation of lethals in the other lines. These findings show that causes other than the direct effect of artificial selection must be taken into account when trying to explain the accumulation of lethals in selected lines.