Article

Abstract

• The standard genetic code is robust to mutations during transcription and translation. Point mutations are likely to be synonymous or to preserve the chemical properties of the original amino acid. Saturation mutagenesis experiments suggest that in some cases the best-performing mutant requires replacement of more than a single nucleotide within a codon. These replacements are essentially inaccessible to common error-based laboratory engineering techniques that alter a single nucleotide per mutation event, due to the extreme rarity of adjacent mutations. In this theoretical study, we suggest a radical reordering of the genetic code that maximizes the mutagenic potential of single nucleotide replacements. We explore several possible genetic codes that allow a greater degree of accessibility to the mutational landscape and may result in a hyperevolvable organism that could serve as an ideal platform for directed evolution experiments. We then conclude by evaluating the challenges of constructing such recoded organisms and their potential applications within the field of synthetic biology.

Creator

• Pines, Assaf
• Gill, Ryan T
• Pines, Gur
• Winkler, James D

Date Issued

• 2017-11-14

Academic Affiliation

• Renewable & Sustainable Energy Institute

Journal Title

• MBio

Journal Issue/Number

• 6.0

Journal Volume

• 8.0

File Extent

• 622-622

Subject

• genome synthesis
• saturation mutagenesis
• evolution
• genetic code

Last Modified

• 2019-12-06

Identifier

• PubMed ID: 29138304

Resource Type

• Article

Rights Statement

• In Copyright

DOI

•  https://doi.org/10.1128/mBio.01654-17

ISSN

• 2150-7511

Language

• English [eng]

License

• Creative Commons BY Attribution 4.0 International

Relationships

Items

Thumbnail	Title	Date Uploaded	Visibility	Actions
	refactoringTheGeneticCodeForIncreasedEvolvability.pdf	2019-12-06	Public	Download