Elucidating the Mechanisms Underlying Genetic Background Effects Utilizing Drosophila melanogaster Wing Tissue

Abstract

When investigating the developmental roles of genes on phenotypic expression it may seem reasonable to assume that a mutation would result in consistent phenotypic change. However, increasing evidence has shown this is not often the case, and the “wild-type” genetic background of an individual plays a large role in phenotypic expression of mutations and severity of genetic mediated diseases. Previous work has demonstrated that degree of genetic background effects shows a non-linear relationship with severity of mutational effects. This relationship is characterized by alleles of moderate phenotypic expressivity showing the relatively greatest degree of background dependence and between genotype variability in comparison with alleles of severe and modest phenotypic expressivity. Our previous work has shown this relationship for Drosophila melanogaster wing size through a scalloped (sd) allelic series crossed to naturally derived strains from the Drosophila Genetics Reference Panel (DGRP). I explored these effects with a miniature (m) allelic series where the results from our experiment suggest a vastly different response. m when compared to sd is characterized by a more linear relationship, whereby alleles of moderate phenotypic effect do not show increased background dependence nor increased variability within and between strains. Furthermore, our results suggest a strong correlation across DGRP strains with respect to m mutational severity and that the effect m has on wing shape is not largely due to wing size. Our working hypotheses for why this might be occurring is due to the increased interaction of sd with other aspects of wing development relative to that of m, the differences in when the genes are playing active roles in wing development, or the effects the mutations have on the wing to affect size. To add to our previous results employingutilizing sd, I am beginnings to elucidate the non-linear relationship of genetic background effects with severity of mutational effects at a gene expression level. I am accomplishing this through crossing autilizing a sd allelic series crossed to six naturally derived DGRP strains used in previous experiments involving wing size. Preliminary results agree with previous work on genetic background effects, displaying a non-linear relationship with the severity of mutational effect. I aim to continue to explore this relationship including more genotypes and investigating more genes to better elucidate the mechanistic causes of genetic background effects.