Phenotypic dominance emerges from activity-fitness functions and molecular interactions

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 molecular activity onto fitness. For homomeric proteins, physical interactions between alleles provide a mechanism by which one allele can have a dominant effect on the activity of the other. Here, we refer to the effect of these interactions as molecular dominance and examine how they determine total protein activity and contribute to phenotypic dominance. The relative impact of such molecular dominance effects depends on the proportion of subunits that heteromerize relative to those that form homomers. In turn, we show how the effect of physical interactions on phenotypic dominance depends on the function linking protein activity to fitness. Our results show the complex relationships between molecular and phenotypic dominance and highlight the fundamental difference in dominance landscapes for monomeric and homomeric proteins.