Selection-driven cost-efficiency optimization of transcripts modulates gene evolutionary rate in bacteria

Emily A Seward,Steven Kelly

doi:10.1186/s13059-018-1480-7

Abstract

BackgroundMost amino acids are encoded by multiple synonymous codons. However, synonymous codons are not used equally, and this biased codon use varies between different organisms. It has previously been shown that both selection acting to increase codon translational efficiency and selection acting to decrease codon biosynthetic cost contribute to differences in codon bias. However, it is unknown how these two factors interact or how they affect molecular sequence evolution.ResultsThrough analysis of 1320 bacterial genomes, we show that bacterial genes are subject to multi-objective selection-driven optimization of codon use. Here, selection acts to simultaneously decrease transcript biosynthetic cost and increase transcript translational efficiency, with highly expressed genes under the greatest selection. This optimization is not simply a consequence of the more translationally efficient codons being less expensive to synthesize. Instead, we show that transfer RNA gene copy number alters the cost-efficiency trade-off of synonymous codons such that, for many species, selection acting on transcript biosynthetic cost and translational efficiency act in opposition. Finally, we show that genes highly optimized to reduce cost and increase efficiency show reduced rates of synonymous and non-synonymous mutation.ConclusionsThis analysis provides a simple mechanistic explanation for variation in evolutionary rate between genes that depends on selection-driven cost-efficiency optimization of the transcript. These findings reveal how optimization of resource allocation to messenger RNA synthesis is a critical factor that determines both the evolution and composition of genes.

Highlights

Most amino acids are encoded by multiple synonymous codons
Selection acts to reduce biosynthetic cost and increase translational efficiency of transcript sequences selection has been shown to reduce resource allocation to messenger RNA (mRNA) production by reducing the biosynthetic cost of a codon of RNA or increasing translational efficiency independently [2,3,4,5,6,7,8,9,10], it is unknown how these two factors interact or whether optimization of one factor inherently results in optimization of the other
An analysis was conducted on 1320 bacterial species (Additional file 1) representing 730 different genera to establish if they were either under selection to increase codon translational efficiency, reduce codon biosynthetic cost or a combination of the two

Summary

Introduction

Most amino acids are encoded by multiple synonymous codons. synonymous codons are not used and this biased codon use varies between different organisms. It has previously been shown that both selection acting to increase codon translational efficiency and selection acting to decrease codon biosynthetic cost contribute to differences in codon bias It is unknown how these two factors interact or how they affect molecular sequence evolution. Since the biosynthetic cost and translational efficiency of synonymous codons vary, biased use of synonymous codons makes it possible to reduce the expenditure of cellular resources on messenger RNA (mRNA) production without altering the encoded protein sequence. It is possible to reduce resource allocation to protein synthesis without altering the encoded protein or affecting protein abundance This is done by reducing transcript sequence cost or by increasing the efficiency with which those transcripts can be translated into protein. Though selection has been shown to act on codon biosynthetic cost and translational efficiency independently, it is unknown how these two factors interact or whether

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