Stop codons in bacteria are not selectively equivalent

Inna S Povolotskaya,Peter K Vlasov,Alice Ledda,Fyodor A Kondrashov

doi:10.1186/1745-6150-7-30

Inna S Povolotskaya, Peter K Vlasov + Show 2 more

Open Access

https://doi.org/10.1186/1745-6150-7-30

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Abstract

BackgroundThe evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids. Here we study the rate of evolution and frequency distribution of stop codons in bacterial genomes.ResultsWe show that in bacteria stop codons evolve slower than synonymous sites, suggesting the action of weak negative selection. However, the frequency of stop codons relative to genomic nucleotide content indicated that this selection regime is not straightforward. The frequency of TAA and TGA stop codons is GC-content dependent, with TAA decreasing and TGA increasing with GC-content, while TAG frequency is independent of GC-content. Applying a formal, analytical model to these data we found that the relationship between stop codon frequencies and nucleotide content cannot be explained by mutational biases or selection on nucleotide content. However, with weak nucleotide content-dependent selection on TAG, -0.5 < Nes < 1.5, the model fits all of the data and recapitulates the relationship between TAG and nucleotide content. For biologically plausible rates of mutations we show that, in bacteria, TAG stop codon is universally associated with lower fitness, with TAA being the optimal for G-content < 16% while for G-content > 16% TGA has a higher fitness than TAG.ConclusionsOur data indicate that TAG codon is universally suboptimal in the bacterial lineage, such that TAA is likely to be the preferred stop codon for low GC content while the TGA is the preferred stop codon for high GC content. The optimization of stop codon usage may therefore be useful in genome engineering or gene expression optimization applications.ReviewersThis article was reviewed by Michail Gelfand, Arcady Mushegian and Shamil Sunyaev. For the full reviews, please go to the Reviewers’ Comments section.

Highlights

The evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids
We compare rates of stop codon evolution to the rate of synonymous evolution and apply a simple population genetics model formulated by Bulmer [15] to stop codon frequency and nucleotide content in bacterial genomes
Stop codon evolution and frequency There are two predictions of the synonymous usage of stop codons: stop codon evolution should occur at a rate equivalent to that of synonymous evolution and stop codon frequency should mirror that of synonymous codons, such that AT-rich genomes should show a higher frequency of TAA

Summary

Introduction

The evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids. Translation termination is a crucial step in protein synthesis that, in most organisms, is triggered by three stop codons; TAA, TGA and TAG. These three stop codons are thought to be functionally equivalent in the broad sense of effective translation termination. Additional functions, such as coding for extra amino acids, effects only a tiny fraction of all codons [1], and these stop codons can be interchanged [2,3] or even lost [4,5,6,7,8] without obvious functional consequences. We compare rates of stop codon evolution to the rate of synonymous evolution and apply a simple population genetics model formulated by Bulmer [15] to stop codon frequency and nucleotide content in bacterial genomes

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