Coding-Sequence Determinants of Gene Expression in
            <i>Escherichia coli</i>

Kudla, Grzegorz; Murray, Andrew W.; Tollervey, David; Plotkin, Joshua B.

doi:10.1126/science.1170160

Cited by 1,340 publications

(1,849 citation statements)

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“…Pervasive variation in the frequencies of synonymous codons across genes and genomes (codon usage bias) 1 suggests that selection may favour some synonymous codons over others. Moreover, direct measures of the impact of synonymous mutations from nucleotide replacement studies demonstrate that they can impact gene expression 2,3 , presumably through changes to the rate or accuracy of transcription and/or translation 4 , mRNA stability and folding 5 , protein secondary structure 6,7 and even fitness 3,[8][9][10][11] . Taken together, these results suggest that the frequency of at least some synonymous mutations is governed by selection.…”

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confidence: 99%

Adaptive synonymous mutations in an experimentally evolved Pseudomonas fluorescens population

2014

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Conventional wisdom holds that synonymous mutations, nucleotide changes that do not alter the encoded amino acid, have no detectable effect on phenotype or fitness. However, a growing body of evidence from both comparative and experimental studies suggests otherwise. Synonymous mutations have been shown to impact gene expression, protein folding and fitness, however, direct evidence that they can be positively selected, and so contribute to adaptation, is lacking. Here we report the recovery of two beneficial synonymous single base pair changes that arose spontaneously and independently in an experimentally evolved population of Pseudomonas fluorescens. We show experimentally that these mutations increase fitness by an amount comparable to non-synonymous mutations and that the fitness increases stem from increased gene expression. These results provide unequivocal evidence that synonymous mutations can drive adaptive evolution and suggest that this class of mutation may be underappreciated as a cause of adaptation and evolutionary dynamics.

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confidence: 99%

Adaptive synonymous mutations in an experimentally evolved Pseudomonas fluorescens population

2014

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“…However, at least some understanding of the dynamical regime in real organisms is now forthcoming. The assumption that translation initiation is the main limiting factor (Aitken, 2012) seems to be corroborated by Kudla et al (2009) who found that for E. coli the ribosome affinity to be the main determinant of gene expression, whereas local codon substitutions have a small effect only. This is interesting because an affinity limited regime would be inefficient in that it would leave ribosomes, which are expensive to make, unused.…”

Section: Discussionmentioning

confidence: 60%

“…Using Escherichia coli as a host Kudla et al (2009) measured the translation rates of an extensive library of synonymous sequences with widely varying speeds. The authors reported no correlation between codon adaptedness and translation rate.…”

Section: Introductionmentioning

confidence: 99%

Charting the dynamics of translation

2014

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a b s t r a c tCodon usage bias (CUB) is the well-known phenomenon that the frequency of synonymous codons is unequal. This is presumably the result of adaptive pressures favouring some codons over others. The underlying reason for this pressure is unknown, although a large number of possible driver mechanisms have been proposed. According to one hypothesis, the decoding time could be such a driver. A tacit assumption of this hypothesis is that faster codons lead to a higher translation rate which in turn is more resource efficient. While it is generally assumed that there is such a link, there are no rigorous studies to establish under which conditions the link between translation speed and rate actually exists. Using a computational simulation model and explicitly calculated codon decoding times, this contribution maps the entire range of dynamical regimes of translation. These simulations make it possible to understand precisely under which conditions translation speed and rate are linked.

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“…In this regard, it is interesting to note that, among the several different ways by which translation can be regulated, the secondary structure of the 59 UTR is known to have a profound influence on translation efficiency [28]. Indeed, it has been previously shown that loose structures at the 59 end promotes whereas tight structures inhibits translation [29,30]. In support of such a model for translation of the Gata4 transcripts, E1a and E1b mRNAs precisely differ only by the extremity of their 59 UTR and this appears to be enough for generating mRNA variants with different predicted secondary structures [13].…”

Section: Discussionmentioning

confidence: 99%

An E-Box Element in the Proximal GATA4 Promoter Is Required for Gata4 Expression In Vivo.

Boulende¹,

Béland²,

Bouchard³

et al. 2010

Biology of Reproduction

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GATA4 is an essential transcription factor required for the development and function of multiple tissues, including a major role in gonadogenesis. Despite its crucial role, the molecular mechanisms that regulate Gata4 expression in vivo remain poorly understood. We recently found that the Gata4 gene is expressed as multiple transcripts with distinct 59 origins. These co-expressed alternative transcripts are generated by different non-coding first exons with transcripts E1a and E1b being the most prominent. Moreover, we previously showed that an Ebox element, located in Gata4 59 flanking sequences upstream of exon 1a, is important for the promoter activity of these sequences in cell lines. To confirm the importance of this element in vivo, we generated and characterized Gata4 Ebox knockout mice. Quantitative PCR analyses realized on gonads, heart and liver at three developmental stages (embryonic, pre-pubertal and adult) revealed that the Ebox mutation leads to a robust and specific decrease (up to 89%) of Gata4 E1a transcript expression in all tissues and stages examined. However, a detailed characterization of the gonads revealed normal morphology and GATA4 protein levels in these mutants. Our qPCR data further indicate that this outcome is most likely due to the presence of Gata4 E1b mRNA, whose expression levels were not decreased by the Ebox mutation. In conclusion, our work clearly confirms the importance of the proximal Ebox element and suggests that adequate GATA4 protein expression is likely protected by a compensation mechanism between Gata4 E1a and E1b transcripts operating at the translational level.

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Coding-Sequence Determinants of Gene Expression in Escherichia coli

Cited by 1,340 publications

References 35 publications

Adaptive synonymous mutations in an experimentally evolved Pseudomonas fluorescens population

Adaptive synonymous mutations in an experimentally evolved Pseudomonas fluorescens population

Charting the dynamics of translation

An E-Box Element in the Proximal GATA4 Promoter Is Required for Gata4 Expression In Vivo.

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