TY - JOUR T1 - Selection-driven cost-efficiency optimisation of transcript sequences determines the rate of gene sequence evolution in bacteria JF - bioRxiv DO - 10.1101/136861 SP - 136861 AU - Emily A. Seward AU - Steven Kelly Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/05/11/136861.abstract N2 - Due to genetic redundancy, multiple synonymous codons can code for the same amino acid. However synonymous codons are not used equally and this biased codon use varies between different organisms. Through analysis of 1,320 bacterial genomes we show that bacteria are under genome-wide selection to reduce resource allocation to mRNA production. This is achieved by simultaneously decreasing transcript biosynthetic cost and increasing transcript translational efficiency, with highly expressed genes under the greatest selection. We show that tRNA gene copy number alters the cost-efficiency trade-off of synonymous codons such that for many species it is difficult to both minimise transcript cost and maximise transcript translational efficiency to an equal extent. Finally, we show that genes highly optimised to reduce cost and increase efficiency show reduced rates of synonymous and non-synonymous mutation. This provides a simple mechanistic explanation for variation in evolutionary rate between genes that depends on selection-driven cost-efficiency optimisation of the transcript. These findings reveal how optimisation of resource allocation to mRNA synthesis is a critical factor that determines both the evolution and composition of genes.Significance statement Resource limitation limits cell growth. In this work, we show that the simple economic principles of minimising cost and maximising efficiency of gene production are key drivers of molecular sequence evolution in bacteria. We demonstrate that natural selection has optimised the cost and efficiency of transcript sequences directly in proportion to their production demand. Furthermore, we show that selection-driven optimisation of the economics of gene production is a simple unifying mechanism that explains variation in the evolution and composition of genes as well as the correlation between synonymous and non-synonymous mutation rates. ER -