Projects per year
Abstract / Description of output
Many organisms are subject to selective pressure that gives rise to unequal usage of synonymous codons, known as codon bias. To experimentally dissect the mechanisms of selection on synonymous sites, we expressed several hundred synonymous variants of the GFP gene in Escherichia coli, and used quantitative growth and viability assays to estimate bacterial fitness. Unexpectedly, we found many synonymous variants whose expression was toxic to E. coli. Unlike previously studied effects of synonymous mutations, the effect that we discovered is independent of translation, but it depends on the production of toxic mRNA molecules. We identified RNA sequence determinants of toxicity and evolved suppressor strains that can tolerate the expression of toxic GFP variants. Genome sequencing of these suppressor strains revealed a cluster of promoter mutations that prevented toxicity by reducing mRNA levels. We conclude that translation-independent RNA toxicity is a previously unrecognized obstacle in bacterial gene expression.
|Number of pages
|Proceedings of the National Academy of Sciences (PNAS)
|Early online date
|6 Aug 2018
|Published - 21 Aug 2018
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- Deanery of Molecular, Genetic and Population Health Sciences - Personal Chair of Genetic Engineering
- MRC Human Genetics Unit
Person: Academic: Research Active , Academic: Research Active (Research Assistant)