Impact of genetic background on wing morphology is greatest for alleles and allelic combinations of moderate effect.

<p>(A) Variation due to genetic background is greatest when mutational perturbation is of moderate phenotypic effect, whereas for mutant genotypes with mild or severe effects on fly wing morphology, genetic background has little influence on the phenotypic effects of the mutation. Each vertical line represents a mutant genotype (e.g., homozygous <i>sd</i>^<i>E3</i>, or trans-heterozygous <i>vg</i>^<i>1</i>/<i>vg</i>^<i>2a33</i>, etc.). The average effect of a genotype was estimated by computing the difference in wing area (WA) between wild-type flies and flies bearing that genotype (regardless of genetic background, i.e., WA_Mut—WA_WT). The range in genotypic effects across backgrounds was estimated using the difference between the effect in each background and the average effect. (B) Conceptual illustration of the "inverted hourglass" model suggested by this observation. Genetic background effects may be strongest for alleles of moderate effect, whereas genetic background variation is "swamped out" for alleles with very severe effects or for alleles with nearly wild-type function.