Curated Papers > Highly Cited Authoritative Literature on "Synthetic Biology"

Synonymous but not the same: the causes and consequences of codon bias.

Literature Information

DOI	10.1038/nrg2899
PMID	21102527
Journal	Nature reviews. Genetics
Impact Factor	52.0
JCR Quartile	Q1
Publication Year	2011
Times Cited	781
Keywords	synonymous mutations, codon bias, molecular evolution, biotechnology
Literature Type	Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review
ISSN	1471-0056
Pages	32-42
Issue	12(1)
Authors	Joshua B Plotkin, Grzegorz Kudla

TL;DR

This research highlights the significant impact of synonymous mutations on cellular processes, emphasizing the importance of understanding codon bias in both molecular evolution and biotechnology. The findings reveal new patterns in protein synthesis dynamics, suggesting that further exploration of initiation and elongation processes is crucial for both natural variation comprehension and transgene design.

Search for more papers on MaltSci.com

synonymous mutations · codon bias · molecular evolution · biotechnology

Abstract

Despite their name, synonymous mutations have significant consequences for cellular processes in all taxa. As a result, an understanding of codon bias is central to fields as diverse as molecular evolution and biotechnology. Although recent advances in sequencing and synthetic biology have helped to resolve longstanding questions about codon bias, they have also uncovered striking patterns that suggest new hypotheses about protein synthesis. Ongoing work to quantify the dynamics of initiation and elongation is as important for understanding natural synonymous variation as it is for designing transgenes in applied contexts.

MaltSci.com AI Research Service

Intelligent ReadingAnswer any question about the paper and explain complex charts and formulas

Locate StatementsFind traces of a specific claim within the paper

Add to KBasePerform data extraction, report drafting, and advanced knowledge mining

Primary Questions Addressed

1. How do synonymous mutations influence the efficiency of protein synthesis in different organisms?
2. What are the implications of codon bias for the design of synthetic genes in biotechnology?
3. In what ways can the understanding of codon bias contribute to advancements in molecular evolution studies?
4. How do recent sequencing technologies enhance our knowledge of the dynamics of codon bias?
5. What role does codon bias play in the adaptation of organisms to their environments?

Key Findings

Research Background and Purpose

The article "Synonymous but not the same: the causes and consequences of codon bias" by Joshua B. Plotkin and Grzegorz Kudla discusses the significant effects of synonymous mutations—mutations that do not change the encoded amino acid—on cellular processes across all taxa. The purpose of this review is to elucidate the mechanisms behind codon usage bias, its consequences for protein synthesis, and its implications for biotechnology and molecular evolution.

Main Methods/Materials/Experimental Design

The review synthesizes findings from recent advances in synthetic biology, mass spectrometry, and high-throughput sequencing to analyze codon usage patterns. It categorizes hypotheses into two main types: mutational and selective explanations. The review emphasizes the importance of understanding initiation and elongation dynamics in protein synthesis.

Key Results and Findings

1. Codon Usage Patterns: Codon usage varies significantly across species, with a strong correlation to genomic GC content. High GC content is linked to specific mutational processes.
2. Mechanisms of Codon Bias:
   • Mutational Bias: Arises from nucleotide composition and mutation rates.
   • Selective Pressure: Influences synonymous codon preference based on translational efficiency and accuracy, with evidence suggesting that highly expressed genes exhibit greater codon bias.
3. Endogenous vs. Heterologous Expression: The review highlights differences in codon optimization strategies for endogenous genes versus transgenes, emphasizing the complexity introduced by overexpression in biotechnological applications.

Main Conclusions/Significance/Innovativeness

The authors conclude that synonymous mutations are not neutral; they play a critical role in gene expression and cellular fitness. Understanding codon bias can enhance the design of transgenes for biotechnology applications, such as vaccine development and gene therapy. The review advocates for integrating evolutionary and biotechnological perspectives to improve transgene expression strategies.

Research Limitations and Future Directions

1. Limitations: The review acknowledges the complexity of codon bias mechanisms and the challenges in experimentally validating various hypotheses. Many findings are based on computational predictions or specific taxa, limiting generalizability.
2. Future Directions: The authors suggest that future research should focus on high-throughput experimental designs to systematically compare the effects of different codon usage patterns on protein expression. They also emphasize the need for better understanding of how codon bias can be manipulated in various contexts, especially in the design of synthetic genes.

Summary Table

Aspect	Details
Codon Usage Bias	Variation across species, linked to genomic GC content.
Mutational Explanations	Arise from nucleotide composition and mutation rates.
Selective Explanations	Influence from translational efficiency and accuracy; correlated with gene expression levels.
Endogenous vs. Heterologous	Different optimization strategies needed for natural versus artificially expressed genes.
Research Implications	Insights into codon bias can enhance transgene design in biotechnology.
Future Research	Focus on high-throughput studies to explore codon usage impacts on expression dynamics.

This structured summary encapsulates the essential findings and implications of the review on codon bias, highlighting its relevance in both evolutionary biology and biotechnology.

References

1. Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution. - D Allan Drummond;Claus O Wilke - Cell (2008)
2. The signature of selection mediated by expression on human genes. - Araxi O Urrutia;Laurence D Hurst - Genome research (2003)
3. Evidence of selection upon genomic GC-content in bacteria. - Falk Hildebrand;Axel Meyer;Adam Eyre-Walker - PLoS genetics (2010)
4. What drives codon choices in human genes? - S Karlin;J Mrázek - Journal of molecular biology (1996)
5. Synonymous codon usage in Drosophila melanogaster: natural selection and translational accuracy. - H Akashi - Genetics (1994)
6. A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. - M Kimura - Journal of molecular evolution (1980)
7. Codon usage in bacteria: correlation with gene expressivity. - M Gouy;C Gautier - Nucleic acids research (1982)
8. Global analysis of protein localization in budding yeast. - Won-Ki Huh;James V Falvo;Luke C Gerke;Adam S Carroll;Russell W Howson;Jonathan S Weissman;Erin K O'Shea - Nature (2003)
9. A sampling of the yeast proteome. - B Futcher;G I Latter;P Monardo;C S McLaughlin;J I Garrels - Molecular and cellular biology (1999)
10. Post-transcriptional control of bacteriophage T4 gene 25 expression: mRNA secondary structure that enhances translational initiation. - R Nivinskas;N Malys;V Klausa;R Vaiskunaite;E Gineikiene - Journal of molecular biology (1999)

Literatures Citing This Work

1. Evolution of synonymous codon usage in Neurospora tetrasperma and Neurospora discreta. - C A Whittle;Y Sun;H Johannesson - Genome biology and evolution (2011)
2. Molecular genetics: The sound of silence. - Laurence D Hurst - Nature (2011)
3. Genome-wide survey of natural selection on functional, structural, and network properties of polymorphic sites in Saccharomyces paradoxus. - Anchal Vishnoi;Praveen Sethupathy;Daniel Simola;Joshua B Plotkin;Sridhar Hannenhalli - Molecular biology and evolution (2011)
4. Codon usage: nature's roadmap to expression and folding of proteins. - Evelina Angov - Biotechnology journal (2011)
5. Explaining complex codon usage patterns with selection for translational efficiency, mutation bias, and genetic drift. - Premal Shah;Michael A Gilchrist - Proceedings of the National Academy of Sciences of the United States of America (2011)
6. A ribosomal misincorporation of Lys for Arg in human triosephosphate isomerase expressed in Escherichia coli gives rise to two protein populations. - Beatriz Aguirre;Miguel Costas;Nallely Cabrera;Guillermo Mendoza-Hernández;Donald L Helseth;Paulette Fernández;Marietta Tuena de Gómez-Puyou;Ruy Pérez-Montfort;Alfredo Torres-Larios;Armando Gómez Puyou - PloS one (2011)
7. The 3-base periodicity and codon usage of coding sequences are correlated with gene expression at the level of transcription elongation. - Edoardo Trotta - PloS one (2011)
8. Novel SNPs in the PRDM16 gene and their associations with performance traits in chickens. - Ruili Han;Yang Wei;Xiangtao Kang;Hong Chen;Guirong Sun;Guoxi Li;Yichun Bai;Yadong Tian;Yanqun Huang - Molecular biology reports (2012)
9. Complex interplay of evolutionary forces in the ladybird homeobox genes of Drosophila melanogaster. - Evgeniy S Balakirev;Maria Anisimova;Francisco J Ayala - PloS one (2011)
10. Selection for translation efficiency on synonymous polymorphisms in recent human evolution. - Yedael Y Waldman;Tamir Tuller;Alon Keinan;Eytan Ruppin - Genome biology and evolution (2011)

... (771 more literatures)

---

© 2025 MaltSci - We reshape scientific research with AI technology