Highly Similar Average Collateral Effect of Synonymous Mutations Across Alternative Reading Frames: A Potential Role In Evolvability

Abstract Synonymous mutations in a protein coding gene lead to a remarkably similar average “collateral” mutation effect size across alternative reading frames (1). Here we quantify the rarity of this feature among possible block structure codes as 0.77%. Then we develop a simple model of evolutionary search with two types of mutation. Across different mutation step sizes and ratios of the two types, the fitness-maximizing region corresponds to using a single average mutation value. The analogous constant average collateral mutation effect observed for the standard genetic code may likewise facilitate evolutionary search in alternative frame sequences.