Conservation of location of several specific inhibitory codon pairs in the Saccharomyces sensu stricto yeasts reveals translational selection.

Dalia H Ghoneim,Xiaoju Zhang,Christina E Brule,David H Mathews,Elizabeth J Grayhack

doi:10.1093/nar/gky1262

Abstract

Synonymous codons provide redundancy in the genetic code that influences translation rates in many organisms, in which overall codon use is driven by selection for optimal codons. It is unresolved if or to what extent translational selection drives use of suboptimal codons or codon pairs. In Saccharomyces cerevisiae, 17 specific inhibitory codon pairs, each comprised of adjacent suboptimal codons, inhibit translation efficiency in a manner distinct from their constituent codons, and many are translated slowly in native genes. We show here that selection operates within Saccharomyces sensu stricto yeasts to conserve nine of these codon pairs at defined positions in genes. Conservation of these inhibitory codon pairs is significantly greater than expected, relative to conservation of their constituent codons, with seven pairs more highly conserved than any other synonymous pair. Conservation is strongly correlated with slow translation of the pairs. Conservation of suboptimal codon pairs extends to two related Candida species, fungi that diverged from Saccharomyces ∼270 million years ago, with an enrichment for codons decoded by I•A and U•G wobble in both Candida and Saccharomyces. Thus, conservation of inhibitory codon pairs strongly implies selection for slow translation at particular gene locations, executed by suboptimal codon pairs.

Highlights

Synonymous codons specify insertion of the same amino acid into the nascent polypeptide, a redundancy in the genetic code that provides an opportunity for fine-tuned regulation of translation while preserving the resulting protein sequence [1]
Nine inhibitory codon pairs (ICPs) are highly conserved across Saccharomyces sensu stricto yeasts To examine conservation of codons and codon pairs in the Saccharomyces sensu stricto yeasts, we aligned 5161 S. cerevisiae open reading frames (ORFs) with their orthologs [45] across four other Saccharomyces sensu stricto yeast species: S. paradoxus, S. mikatae, S. kudriavzevii, and S. bayanus var. uvarum
One might expect that codon conservation rates would correlate with codon optimality, since optimal codon use is driven by translational selection and is enriched in highly expressed genes, which are themselves more conserved than poorly expressed genes

Summary

Introduction

Synonymous codons specify insertion of the same amino acid into the nascent polypeptide, a redundancy in the genetic code that provides an opportunity for fine-tuned regulation of translation while preserving the resulting protein sequence [1]. The prevailing idea is that translational selection operates more robustly on highly expressed genes than on poorly expressed genes, because alterations in translation of highly expressed genes will have a larger impact on the global rate of protein synthesis, which is limited by the pool of free ribosomes [6,10]. Consistent with this idea, highly expressed genes evolve at

Methods

Results

Conclusion