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The Selective Advantage of Synonymous Codon Usage Bias in Salmonella
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
2016 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 12, no 3, e1005926Article in journal (Refereed) Published
Abstract [en]

The genetic code in mRNA is redundant, with 61 sense codons translated into 20 different amino acids. Individual amino acids are encoded by up to six different codons but within codon families some are used more frequently than others. This phenomenon is referred to as synonymous codon usage bias. The genomes of free-living unicellular organisms such as bacteria have an extreme codon usage bias and the degree of bias differs between genes within the same genome. The strong positive correlation between codon usage bias and gene expression levels in many microorganisms is attributed to selection for translational efficiency. However, this putative selective advantage has never been measured in bacteria and theoretical estimates vary widely. By systematically exchanging optimal codons for synonymous codons in the tuf genes we quantified the selective advantage of biased codon usage in highly expressed genes to be in the range 0.2–4.2 x 10−4 per codon per generation. These data quantify for the first time the potential for selection on synonymous codon choice to drive genome-wide sequence evolution in bacteria, and in particular to optimize the sequences of highly expressed genes. This quantification may have predictive applications in the design of synthetic genes and for heterologous gene expression in biotechnology.

Place, publisher, year, edition, pages
2016. Vol. 12, no 3, e1005926
Keyword [en]
EF-Tu, Synonymous codon usage bias
National Category
Evolutionary Biology Microbiology Genetics
Research subject
Biology with specialization in Microbiology
URN: urn:nbn:se:uu:diva-276274DOI: 10.1371/journal.pgen.1005926ISI: 000373268900033OAI: oai:DiVA.org:uu-276274DiVA: diva2:902159
Swedish Research Council, 521-2013-2904Swedish Research Council, 621-2012-2188Swedish Foundation for Strategic Research , RBa08-0063Knut and Alice Wallenberg Foundation
Available from: 2016-02-10 Created: 2016-02-10 Last updated: 2016-08-12Bibliographically approved
In thesis
1. Biased Evolution: Causes and Consequences
Open this publication in new window or tab >>Biased Evolution: Causes and Consequences
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In evolution alternative genetic trajectories can potentially lead to similar phenotypic outcomes. However, certain trajectories are preferred over others. These preferences bias the genomes of living organisms and the underlying processes can be observed in ongoing evolution.

We have studied a variety of biases that can be found in bacterial chromosomes and determined the selective causes and functional consequences for the cell. We have quantified codon usage bias in highly expressed genes and shown that it is selected to optimise translational speed. We further demonstrated that the resulting differences in decoding speed can be used to regulate gene expression, and that the use of ‘non-optimal’ codons can be detrimental to reading frame maintenance. Biased gene location on the chromosome favours recombination between genes within gene families and leads to co-evolution. We have shown that such recombinational events can protect these gene families from inactivation by mobile genetic elements, and that chromosome organization can be selectively maintained because inversions can lead to the formation of unstable hybrid operons.

We have used the development of antibiotic resistance to study how different bacterial lifestyles influence evolutionary trajectories. For this we used two distinct pairs of antibiotics and disease-causing bacteria, namely (i) Mycobacterium tuberculosis that is treated with rifampicin and (ii) Escherichia coli that is treated with ciprofloxacin. We have shown that in the slow-growing Mycobacterium tuberculosis, resistance mutations are selected for high-level resistance. Fitness is initially less important, and over time fitness costs can be ameliorated by compensatory mutations. The need for rapid growth causes the selection of ciprofloxacin resistance in Escherichia coli not only to be selected on the basis of high-level resistance but also on high fitness. Compensatory evolution is therefore not required and is not observed.

Taken together, our results show that the evolution of a phenotype is the product of multiple steps and that many factors influence which trajectory is the most likely to occur and be most beneficial. Over time, selection will favour this particular trajectory and lead to biased evolution, affecting genome sequence and organization.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 48 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1198
Evolution, Codon usage bias, Post-transcriptional regulation, Recombination, Inversion, EF-Tu, Frameshift suppression, Antibiotic resistance, Rifampicin, Ciprofloxacin, Compensatory evolution, Drug efflux, RNA polymerase, DNA gyrase
National Category
Research subject
urn:nbn:se:uu:diva-276456 (URN)978-91-554-9518-3 (ISBN)
Public defence
2016-05-09, A1:107a, BMC, Husargatan 3, Uppsala, 09:00 (English)
Available from: 2016-04-13 Created: 2016-02-13 Last updated: 2016-04-21

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