The effect of allelic molecular interactions on phenotypic dominance

Mendelian genetics provides us with a framework for studying allelic dominance relationships at a locus at the phenotypic level. These dominance relationships result from different molecular factors, including the mapping of fitness onto molecular activity. For homomeric proteins, physical interactions between alleles could affect protein activity, providing a mechanism for dominance. Here, we examine the molecular underpinnings of dominance using a model in which fitness is determined by the activities of monomeric and dimeric proteins. Our model recapitulates previous observations that monomeric proteins can show phenotypic dominance due to the underlying fitness function in the absence of molecular dominance. In turn, the landscape of phenotypic dominance for the dimer system results from the interplay of the fitness function, molecular dominance, and the selective homo- or heteromerization of the two alleles. Our results show the complex relationships between molecular and phenotypic dominance and highlight the fundamental difference in dominance landscapes for monomeric and homomeric proteins.