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Related Experiment Videos

Evolution of phage with chemically ambiguous proteomes.

Jamie M Bacher1, James J Bull, Andrew D Ellington

  • 1Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA. jbacher@scripps.edu

BMC Evolutionary Biology
|December 12, 2003
PubMed
Summary

Directed evolution enabled bacteriophage Qbeta to incorporate unnatural amino acids, overcoming translation barriers. This study demonstrates a small number of mutations can adapt complex protein interactions for novel genetic codes.

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Area of Science:

  • Molecular Biology
  • Evolutionary Biology
  • Biochemistry

Background:

  • Natural evolution readily incorporates amino acid substitutions, but directed evolution faces challenges adapting translation machinery and proteomes.
  • Accommodating unnatural amino acids requires multiple mutations across proteins, posing a significant hurdle for directed evolution.
  • Studying bacteriophage proteome evolution offers insights into protein adaptability for incorporating novel amino acids.

Purpose of the Study:

  • To investigate the feasibility of adapting a bacteriophage proteome for the functional incorporation of an unnatural amino acid analogue.
  • To determine the number and types of mutations required for protein functionality during the adaptation process.
  • To explore the implications for the evolution of genetic codes.

Main Methods:

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  • Bacteriophage Qbeta was subjected to serial passages in the presence of the unnatural amino acid analogue 6-fluorotryptophan.
  • Fitness of the evolved phage was assessed on both the analogue and natural tryptophan.
  • Genetic analysis was performed to identify mutations fixed in the phage proteome.

Main Results:

  • Phage Qbeta exhibited poor initial growth on 6-fluorotryptophan but showed substantially increased fitness after 25 serial passages.
  • The evolved phage maintained fitness when passaged on natural tryptophan, indicating robust adaptation.
  • Seven mutations were fixed across the phage proteome in two independent evolutionary lines, with no mutations altering tryptophan residues.

Conclusions:

  • A limited number of mutations enabled the functional incorporation of an unnatural amino acid into a complex, interdependent protein set.
  • The findings support the 'ambiguous intermediate' hypothesis for divergent genetic code evolution.
  • This work suggests a potential pathway for directing the evolution of organisms with novel genetic codes.