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Bacteriophages use an expanded genetic code on evolutionary paths to higher fitness

Nature Chemical Biology volume 10, pages 178–180 (2014)Cite this article

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Abstract

Bioengineering advances have made it possible to fundamentally alter the genetic codes of organisms. However, the evolutionary consequences of expanding an organism's genetic code with a noncanonical amino acid are poorly understood. Here we show that bacteriophages evolved on a host that incorporates 3-iodotyrosine at the amber stop codon acquire neutral and beneficial mutations to this new amino acid in their proteins, demonstrating that an expanded genetic code increases evolvability.

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Figure 1: Genome evolution of a bacterial virus with a newly expanded genetic code.
Figure 2: Beneficial amber mutation in the T7 holin II protein.

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Sequence Read Archive

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NCBI Reference Sequence

Protein Data Bank

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Acknowledgements

We thank J. Bull, I. Molineux, R. Hughes, C. Barnhart, D. Deatherage, R. Alnahhas, M. Schmerer, A. Miklos, A. Meyer and A. Maranhão (all at the University of Texas at Austin) for plasmids, strains, advice and technical assistance. The RF0 IodoY strain was provided by RIKEN and by the Targeted Proteins Research Program, the Ministry of Education, Culture, Sports, Science and Technology, Japan. We acknowledge the Texas Advanced Computing Center (TACC) at The University of Texas at Austin for providing HPC resources. This research was supported by the US National Institutes of Health (NIH) (R00-GM087550 to J.E.B.), the US National Science Foundation (NSF) BEACON Center for the Study of Evolution in Action (DBI-0939454 to J.E.B.), the US Army Research Office (W911NF-12-1-0390 to J.E.B. and E.M.M.), the US National Security Science and Engineering Faculty (FA9550-10-1-01-69 to A.D.E.), the US Defense Advanced Research Project Agency (HR-0011-12-C-0066 to A.D.E.) and the NSF (MCB-0943383 to A.D.E.). E.M.M. also acknowledges funding from the NIH, the NSF, the Cancer Prevention Research Institute of Texas and the Welch Foundation (F1515).

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Authors and Affiliations

  1. Department of Molecular Biosciences, Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, USA

    Michael J Hammerling, Jared W Ellefson, Daniel R Boutz, Edward M Marcotte, Andrew D Ellington & Jeffrey E Barrick

Authors
  1. Michael J Hammerling
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  2. Jared W Ellefson
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  3. Daniel R Boutz
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  4. Edward M Marcotte
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  5. Andrew D Ellington
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  6. Jeffrey E Barrick
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Contributions

M.J.H., J.W.E., J.E.B. and A.D.E. conceived the study. M.J.H. performed evolution experiments. J.E.B. and M.J.H. analyzed sequencing data. M.J.H. and J.W.E. created RF0 Tyr and characterized phage lysis times. D.R.B and E.M.M. analyzed proteomics data. J.E.B. performed statistical analyses. J.E.B., M.J.H., J.W.E. and D.R.B. created figures and wrote the manuscript. All of the authors designed experiments and edited the manuscript.

Corresponding author

Correspondence to Jeffrey E Barrick.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Results, Supplementary Figures 1–10 and Supplementary Tables 1 and 2. (PDF 5289 kb)

Supplementary Data Set 1

Mutations in bacteriophage samples. (XLSX 99 kb)

Supplementary Data Set 2

Informative peptide-spectrum matches. (XLSX 22 kb)

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Hammerling, M., Ellefson, J., Boutz, D. et al. Bacteriophages use an expanded genetic code on evolutionary paths to higher fitness. Nat Chem Biol 10, 178–180 (2014). https://doi.org/10.1038/nchembio.1450

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