Refactoring the Genetic Code for Increased Evolvability

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 requ...

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Autores principales:	Gur Pines, James D. Winkler, Assaf Pines, Ryan T. Gill
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	evolution genetic code genome synthesis saturation mutagenesis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2254fccf94434b5795fa8d1833abadee
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spelling	oai:doaj.org-article:2254fccf94434b5795fa8d1833abadee2021-11-15T15:51:55ZRefactoring the Genetic Code for Increased Evolvability10.1128/mBio.01654-172150-7511https://doaj.org/article/2254fccf94434b5795fa8d1833abadee2017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01654-17https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE The conservative nature of the genetic code prevents bioengineers from efficiently accessing the full mutational landscape of a gene via common error-prone methods. Here, we present two computational approaches to generate alternative genetic codes with increased accessibility. These new codes allow mutational transitions to a larger pool of amino acids and with a greater extent of chemical differences, based on a single nucleotide replacement within the codon, thus increasing evolvability both at the single-gene and at the genome levels. Given the widespread use of these techniques for strain and protein improvement, along with more fundamental evolutionary biology questions, the use of recoded organisms that maximize evolvability should significantly improve the efficiency of directed evolution, library generation, and fitness maximization.Gur PinesJames D. WinklerAssaf PinesRyan T. GillAmerican Society for Microbiologyarticleevolutiongenetic codegenome synthesissaturation mutagenesisMicrobiologyQR1-502ENmBio, Vol 8, Iss 6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	evolution genetic code genome synthesis saturation mutagenesis Microbiology QR1-502
spellingShingle	evolution genetic code genome synthesis saturation mutagenesis Microbiology QR1-502 Gur Pines James D. Winkler Assaf Pines Ryan T. Gill Refactoring the Genetic Code for Increased Evolvability
description	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. IMPORTANCE The conservative nature of the genetic code prevents bioengineers from efficiently accessing the full mutational landscape of a gene via common error-prone methods. Here, we present two computational approaches to generate alternative genetic codes with increased accessibility. These new codes allow mutational transitions to a larger pool of amino acids and with a greater extent of chemical differences, based on a single nucleotide replacement within the codon, thus increasing evolvability both at the single-gene and at the genome levels. Given the widespread use of these techniques for strain and protein improvement, along with more fundamental evolutionary biology questions, the use of recoded organisms that maximize evolvability should significantly improve the efficiency of directed evolution, library generation, and fitness maximization.
format	article
author	Gur Pines James D. Winkler Assaf Pines Ryan T. Gill
author_facet	Gur Pines James D. Winkler Assaf Pines Ryan T. Gill
author_sort	Gur Pines
title	Refactoring the Genetic Code for Increased Evolvability
title_short	Refactoring the Genetic Code for Increased Evolvability
title_full	Refactoring the Genetic Code for Increased Evolvability
title_fullStr	Refactoring the Genetic Code for Increased Evolvability
title_full_unstemmed	Refactoring the Genetic Code for Increased Evolvability
title_sort	refactoring the genetic code for increased evolvability
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/2254fccf94434b5795fa8d1833abadee
work_keys_str_mv	AT gurpines refactoringthegeneticcodeforincreasedevolvability AT jamesdwinkler refactoringthegeneticcodeforincreasedevolvability AT assafpines refactoringthegeneticcodeforincreasedevolvability AT ryantgill refactoringthegeneticcodeforincreasedevolvability
_version_	1718427322856505344

Refactoring the Genetic Code for Increased Evolvability

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