Directionality of Epistasis in a Murine Intercross Population

Directional epistasis describes a situation in which epistasis consistently increases or decreases the effect of allele substitutions, thereby affecting the amount of additive genetic variance available for selection in a given direction. This study applies a recent parameterization of directionality of epistasis to empirical data. Data stems from a QTL mapping study on an intercross between inbred mouse (Mus musculus) strains LG/J and SM/J, originally selected for large and small body mass, respectively. Results show a negative average directionality of epistasis for body-composition traits, predicting a reduction in additive allelic effects and in the response to selection for increased size. Focusing on average modification of additive effect of single loci, we find a more complex picture, whereby the effects of some loci are enhanced consistently across backgrounds, while effects of other loci are decreased, potentially contributing to either enhancement or reduction of allelic effects when selection acts at single loci. We demonstrate and discuss how the interpretation of the overall measurement of directionality depends on the complexity of the genotype-phenotype map. The measure of directionality changes with the power of scale in a predictable way; however, its expected effect with respect to the modification of additive genetic effects remains constant.