The roles of compensatory evolution and constraint in aminoacyl trna synthetase evolution

Abstract

Mitochondrial protein translation requires interactions between transfer RNAs encoded by the mitochondrial genome (mt- TRNAs) and mitochondrial aminoacyl tRNA synthetase proteins (mt- AaRS) encoded by the nuclear genome. It has been argued that animal mt- TRNAs have higher deleterious substitution rates relative to their nuclear-encoded counterparts, the cytoplasmic tRNAs (cyt- TRNAs). This dynamic predicts elevated rates of compensatory evolution of mt- AaRS that interact with mt- TRNAs, relative to aaRS that interact with cyt- TRNAs (cyt- AaRS).We find that mt- AaRS do evolve at significantly higher rates (exemplified by higher dN and dN/dS) relative to cyt- AaRS, across mammals, birds, and Drosophila. While this pattern supports a model of compensatory evolution, the level at which a gene is expressed is a more general predictor of protein evolutionary rate.We find that gene expression level explains 10-56% of the variance in aaRS dN/dS, and that cyt- AaRS are more highly expressed in addition to having lower dN/dS values relative to mt- AaRS, consistent with more highly expressed genes being more evolutionarily constrained. Furthermore, we find no evidence of positive selection acting on either class of aaRS protein, as would be expected under a model of compensatory evolution. Nevertheless, the signature of faster mt- AaRS evolution persists in mammalian, but not bird or Drosophila, lineages after controlling for gene expression, suggesting some additional effect of compensatory evolution for mammalian mt- AaRS. We conclude that gene expression is the strongest factor governing differential amino acid substitution rates in proteins interacting with mitochondrial versus cytoplasmic factors, with important differences in mt- AaRS molecular evolution among taxonomic groups.