Data from: Unraveling the causes of adaptive benefits of synonymous mutations in TEM-1 β-lactamase

  • Mark Zwart (Maker)
  • Martijn F. Schenk University of Cologne, Germany. (Maker)
  • Sungmin Hwang (Maker)
  • A Bertha Koopmanschap (Maker)
  • Niek de Lange Wageningen University (Maker)
  • Lion van de Pol Wageningen University (Maker)
  • Tran Thi Thuy Nga Wageningen University (Maker)
  • Ivan G. Szendro (Maker)
  • Joachim Krug (Maker)
  • Johannes de Visser (Maker)

Dataset

Beschrijving

While synonymous mutations were long thought to be without phenotypic consequences, there is growing evidence they can affect gene expression, protein folding and ultimately the fitness of an organism. In only a few cases have the mechanisms by which synonymous mutations affect the phenotype been elucidated. We previously identified 48 mutations in TEM-1 β-lactamase that increased resistance of Escherichia coli to cefotaxime, 10 of which were synonymous. To better understand the molecular mechanisms underlying the beneficial effect of synonymous mutations, we made a series of measurements for a panel containing the 10 synonymous together with 10 non-synonymous mutations as a reference. Whereas messenger levels were unaffected, we found that total and functional TEM protein levels were higher for 5 out of 10 synonymous mutations. These observations suggest that some of these mutations act on translation or a downstream process. Similar effects were observed for some small-benefit non-synonymous mutations, suggesting a similar causal mechanism. For the synonymous mutations, we found that the cost of resistance scales with TEM protein levels. A resistance landscape for four synonymous mutations revealed strong epistasis: None of the combinations of mutations exceeded the resistance of the largest-effect mutation and there were synthetically neutral combinations. By considering combined effects of these mutations, we could infer that functional TEM protein level is a multi-dimensional phenotype. These results suggest that synonymous mutations may have beneficial effects by increasing the expression of an enzyme with low substrate activity, which may be realized via multiple, yet unknown, post-transcriptional mechanisms.
Datum van beschikbaarheid30 mei 2018
UitgeverDryad

Onderzoekersoutput

Unraveling the causes of adaptive benefits of synonymous mutations in TEM-1 β-lactamase

Zwart, M., Schenk, M. F., Hwang, S., Koopmanschap, A. B., de Lange, N., van de Pol, L., Nga, T. T. T., Szendro, I. G., Krug, J. & de Visser, A., 2018, In : Heredity. 121, blz. 406-421 16 blz.

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

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    Zwart, M. (Maker), Schenk, M. F. (Maker), Hwang, S. (Maker), Koopmanschap, A. B. (Maker), de Lange, N. (Maker), van de Pol, L. (Maker), Nga, T. T. T. (Maker), Szendro, I. G. (Maker), Krug, J. (Maker), de Visser, J. (Maker) (30 mei 2018). Data from: Unraveling the causes of adaptive benefits of synonymous mutations in TEM-1 β-lactamase. Dryad. 10.5061/dryad.hp370m2