Bacteriophages use an expanded genetic code on evolutionary paths to higher fitness (original) (raw)
- Brief Communication
- Published: 02 February 2014
- Jared W Ellefson1,
- Daniel R Boutz1,
- Edward M Marcotte1,
- Andrew D Ellington1 &
- …
- Jeffrey E Barrick1
Nature Chemical Biology volume 10, pages 178–180 (2014)Cite this article
- 6193 Accesses
- 49 Citations
- 23 Altmetric
- Metrics details
Subjects
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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to the full article PDF.
USD 39.95
Prices may be subject to local taxes which are calculated during checkout
Additional access options:
Figure 1: Genome evolution of a bacterial virus with a newly expanded genetic code.

The alternative text for this image may have been generated using AI.
Figure 2: Beneficial amber mutation in the T7 holin II protein.

The alternative text for this image may have been generated using AI.
Similar content being viewed by others
Accession codes
Primary accessions
Sequence Read Archive
Referenced accessions
NCBI Reference Sequence
Protein Data Bank
References
- Crick, F.H.C. J. Mol. Biol. 38, 367–379 (1968).
Article CAS Google Scholar - Knight, R.D., Freeland, S.J. & Landweber, L.F. Nat. Rev. Genet. 2, 49–58 (2001).
Article CAS Google Scholar - Ambrogelly, A., Palioura, S. & Söll, D. Nat. Chem. Biol. 3, 29–35 (2007).
Article CAS Google Scholar - Freeland, S.J. & Hurst, L.D. J. Mol. Evol. 47, 238–248 (1998).
Article CAS Google Scholar - Itzkovitz, S. & Alon, U. Genome Res. 17, 405–412 (2007).
Article CAS Google Scholar - Liu, C.C. & Schultz, P.G. Annu. Rev. Biochem. 79, 413–444 (2010).
Article CAS Google Scholar - Davis, L. & Chin, J.W. Nat. Rev. Mol. Cell Biol. 13, 168–182 (2012).
Article CAS Google Scholar - Brustad, E.M. & Arnold, F.H. Curr. Opin. Chem. Biol. 15, 201–210 (2011).
Article CAS Google Scholar - Wang, K., Neumann, H., Peak-Chew, S.Y. & Chin, J.W. Nat. Biotechnol. 25, 770–777 (2007).
Article Google Scholar - Bacher, J.M., Hughes, R.A., Tze-Fei Wong, J. & Ellington, A.D. Trends Ecol. Evol. 19, 69–75 (2004).
Article Google Scholar - Ohtake, K. et al. J. Bacteriol. 194, 2606–2613 (2012).
Article CAS Google Scholar - Dunn, J.J. & Studier, F.W. J. Mol. Biol. 166, 477–535 (1983).
Article CAS Google Scholar - Molineux, I.J. The Bacteriophages 277–301 (Oxford UP, 2006).
- Bull, J.J. et al. Genetics 147, 1497–1507 (1997).
CAS PubMed PubMed Central Google Scholar - Bull, J.J., Badgett, M.R., Rokyta, D. & Molineux, I.J. J. Mol. Evol. 57, 241–248 (2003).
Article CAS Google Scholar - Chan, L.Y., Kosuri, S. & Endy, D. Mol. Syst. Biol. 1, 2005.0018 (2005).
Article Google Scholar - Sakamoto, K. et al. Structure 17, 335–344 (2009).
Article CAS Google Scholar - Mukai, T. et al. Biochem. Biophys. Res. Commun. 411, 757–761 (2011).
Article CAS Google Scholar - Tabor, S. & Richardson, C.C. J. Biol. Chem. 264, 6447–6458 (1989).
CAS PubMed Google Scholar - Cheetham, G.M. & Steitz, T.A. Science 286, 2305–2309 (1999).
Article CAS Google Scholar - Wang, I.N., Smith, D.L. & Young, R. Annu. Rev. Microbiol. 54, 799–825 (2000).
Article CAS Google Scholar - Wang, N., Dykhuizen, D. & Slobodkin, L. Evol. Ecol. 10, 545–558 (1996).
Article Google Scholar - Heineman, R.H., Bull, J.J. & Molineux, I.J. Mol. Biol. Evol. 26, 1289–1298 (2009).
Article CAS Google Scholar - Lajoie, M.J. et al. Science 342, 357–360 (2013).
Article CAS Google Scholar - Moe-Behrens, G.H.G., Davis, R. & Haynes, K.A. Front. Microbiol. 4, 5 (2013).
Article Google Scholar - Dodt, M., Roehr, J., Ahmed, R. & Dieterich, C. Biology 1, 895–905 (2012).
Article Google Scholar - Gfeller, D., Michielin, O. & Zoete, V. Nucleic Acids Res. 41, D327–D332 (2013).
Article CAS Google Scholar - Young, D.D., Jockush, S., Turro, N.J. & Schultz, P.G. Bioorg. Med. Chem. Lett. 21, 7502–7504 (2011).
Article CAS Google Scholar - Shevchenko, A., Tomas, H., Havlis, J. & Olsen, J. Nat. Protoc. 1, 2856–2860 (2006).
Article CAS Google Scholar
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).
Author information
Authors and Affiliations
- 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
- Michael J Hammerling
- Jared W Ellefson
- Daniel R Boutz
- Edward M Marcotte
- Andrew D Ellington
- Jeffrey E Barrick
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 toJeffrey E Barrick.
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Rights and permissions
About this article
Cite this article
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
- Received: 11 August 2013
- Accepted: 19 December 2013
- Published: 02 February 2014
- Issue date: March 2014
- DOI: https://doi.org/10.1038/nchembio.1450
This article is cited by
The developing toolkit of continuous directed evolution
- Mary S. Morrison
- Christopher J. Podracky
- David R. Liu
Nature Chemical Biology (2020)
Evolving Bacterial Fitness with an Expanded Genetic Code
- Drew S. Tack
- Austin C. Cole
- Andrew D. Ellington
Scientific Reports (2018)
Expanding and reprogramming the genetic code
- Jason W. Chin
Nature (2017)
- Jason W. Chin
Crystal structures reveal an elusive functional domain of pyrrolysyl-tRNA synthetase
- Tateki Suzuki
- Corwin Miller
- Dieter Söll
Nature Chemical Biology (2017)
Addicting diverse bacteria to a noncanonical amino acid
- Drew S Tack
- Jared W Ellefson
- Andrew D Ellington
Nature Chemical Biology (2016)