Functional Divergence for Every Paralog

Because genes can be constrained by selection at more than one phenotypic level, the relaxation of constraints following gene duplication allows for functional divergence (FD) along multiple phenotypic axes. Many studies have generated individual measures of FD, but the profile of FD between paralogs across levels of phenotypic space remains largely uncharted. We evaluate paralog pairs that originated via the yeast whole-genome duplication (ohnolog pairs) at three distinct phenotypic levels (properties of proteins, gene expression, and overall organismal growth) using eight complementary measures of FD (protein: evolutionary rates, radical amino acid substitutions, and domain architecture; gene expression: expression differences in a single species and condition, across species in a single condition, and in a single species across conditions; and organismal: genetic interaction profiles and growth profiles in multiple conditions). We find that the majority of ohnolog pairs show FD by multiple phenotypic measures. Within each phenotypic level, measures of FD are strongly correlated but are generally weakly correlated between levels, suggesting that functional constraints exerted on genes from distinct phenotypic levels are largely decoupled. Our results suggest that redundancy is a rare functional fate for retained paralogs and that FD cannot be fully captured by measures at any single phenotypic level.