Relative contributions of structural designability and functional diversity in molecular evolution of duplicates.

Analysis of increasingly saturated sequence databases have shown that gene family sizes are highly skewed with many families being small and few containing many, far-diverged homologs. Additionally, recently published results have identified a structural determinant of mutational plasticity: designability that correlates strongly with gene family size. In this paper, we explore the possible links between the two observations, exploring the possible effect of designability on duplication and divergence. We show that designability has an inverse of expected relationship with strength of selection. More designable domains that should have more mutational plasticity evolve slower. However, we also present evidence that recently duplicated genes have variable probability of locus fixation correlated with strength of selection. As expected, paralogs under stronger evolutionary pressure have a lower failure rate. Finally, we show that probability of pseudogene formation from gene duplication can be directly tied to designability and functional flexibility of the family. We present evidence that gene families with higher designability have diverged farther because of lower probability of pseudogenization. Additionally, mutational plasticity may play an integral role by influencing pseudogenization rate. Either way, we show that considering the failure rate of duplications is integral in understanding the determinants and dynamics of molecular evolution.