The Roles of Compensatory Evolution and Constraint in Aminoacyl tRNA Synthetase Evolution.

Jeffrey R Adrion,P Signe White,Kristi L Montooth

doi:10.1093/molbev/msv206

Jeffrey R Adrion, P Signe White + Show 1 more

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https://doi.org/10.1093/molbev/msv206

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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.

Highlights

Nonrecombining genomes are subject to the accumulation of deleterious mutations due to Muller’s ratchet (Muller 1964; Felsenstein 1974) and linked selection that reduces the efficacy of selection (Hill and Robertson 1966; Charlesworth et al 1993; Charlesworth 1994; Gillespie 2000)
It has been suggested that the effects of linked selection should be compounded in animal mitochondrial genomes, owing to the unique population genetics of mitochondrial DNA (Gabriel et al 1993; Lynch and Blanchard 1998; Neiman and Taylor 2009)
This model of compensatory evolution predicts that the ratio of nonsynonymous substitutions per nonsynonymous site to synonymous substitutions per synonymous site should be elevated in proteins that interact with mitochondrial-encoded versus nuclear-encoded factors, and that compensatory nuclear mutations should leave a signature of adaptive fixation

Summary

Introduction

Nonrecombining genomes are subject to the accumulation of deleterious mutations due to Muller’s ratchet (Muller 1964; Felsenstein 1974) and linked selection that reduces the efficacy of selection (Hill and Robertson 1966; Charlesworth et al 1993; Charlesworth 1994; Gillespie 2000). Relative to nuclear DNA (nDNA), animal mtDNA experiences an elevated mutation rate (Lynch et al 2006, 2008), does not generally recombine (Ballard 2000; Ingman et al 2000; but see Piganeau et al 2004; Gantenbein et al 2005), and is predominantly maternally inherited, subjecting it to the indirect effects of cytoplasmic elements, such as Wolbachia, that can sweep through populations (e.g., Shoemaker et al 2004) These unique dynamics have led to a well accepted model of mitochondrial-nuclear compensatory evolution, whereby mildly deleterious mitochondrial substitutions are compensated by the fixation of nDNA mutations that restore function (Lynch and Blanchard 1998; Rand et al 2004; Meiklejohn et al 2007; Dowling et al.2008; Oliveira et al 2008; Osada and Akashi 2012; Barreto and Burton 2013; Sloan et al 2014). Expressed genes have greater amino acid conservation (Pal et al 2001; Drummond et al 2005; Drummond and Wilke 2008; Nabholz et al 2013), and it is hypothesized that this is because highly expressed proteins should be more highly constrained to both fold appropriately (Drummond et al 2005; Drummond and Wilke 2008; Park et al 2013)

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