Driving change: the evolution of alternative genetic codes

doi:10.1016/j.tig.2003.12.009

Trends in Genetics

Volume 20, Issue 2, February 2004, Pages 95-102

https://doi.org/10.1016/j.tig.2003.12.009 Get rights and content

Abstract

Pioneering studies in the 1960s that elucidated the genetic code suggested that all extant forms of life use the same genetic code. This early presumption has subsequently been challenged by the discovery of deviations of the universal genetic code in prokaryotes, eukaryotic nuclear genomes and mitochondrial genomes. These studies have revealed that the genetic code is still evolving despite strong negative forces working against the fixation of mutations that result in codon reassignment. Recent data from in vitro, in vivo and in silico comparative genomics studies are revealing significant, previously overlooked links between modified nucleosides in tRNAs, genetic code ambiguity, genome base composition, codon usage and codon reassignment.

Section snippets

Genetic code ambiguity: from codon usage to reassignment

An important consideration arising from evolutionary models based on translational ambiguity of a codon undergoing reassignment is the link between codon reassignment, codon usage and ambiguous decoding, particularly where two-or-more different tRNAs are competing for the same codon (Figure 2). Does tRNA selection affect codon usage in a way that might lead to reassignment? In this respect, there are two key parameters to consider: tRNA abundance and the strength of the codon–anticodon

Genetic code ambiguity as a modulator of genome GC content

As mentioned earlier, some (if not all) genetic code changes are best explained by a synergistic effect between the evolutionary forces postulated by the codon capture and Ambiguous Intermediary theories. However, these processes rely on two distinct cellular machineries: DNA replication and/or repair machinery, which changes coding sequence, and the ribosome. This raises the following question: what is the link between these two apparently unconnected molecular mechanisms? Three experimental

Is there a selective advantage introduced by genetic code ambiguity?

The main caveat with the ambiguous intermediate theory is the potential negative impact of the ambiguous decoding of mRNA, because this would lead to significant alterations in the proteome, and generate potentially growth-inhibiting levels of protein malfunction and misfolding. This, in turn, would impact both cell physiology and adaptation. For example, in the leucine CUG codon reassignment in Candida spp., the chemical properties of serine and leucine are different and can not be considered

Concluding remarks

The diversity of the genetic code and its expansion to incorporate new amino acids has weakened the concept of a universal and frozen genetic code. Additional findings are uncovering surprising flexibility of the genetic code, especially within microorganisms and mitochondria, further raising the possibility of engineering microorganisms that are capable of using non-natural amino acids 42, 43, 44, 45. Moreover, the study of genetic code variation will probably provide important new insights

Acknowledgements

The research reported here was supported by project grants from the Portuguese Foundation for Science and Technology (FCT; Projects POCTI BME/32938, 32942/99 and BME/39030/01 to M.A.S.S.), and by funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust (to M.F.T., S.E.M.). G.M. is supported by a postdoctoral research fellowship (SFRH/BPD/7195/2001) from FCT, and M.A.S.S. is supported by the EMBO Young Investigator Programme.

Glossary

Ambiguous decoding.: Aberrant translation of a specific codon by two different isoacceptor tRNAs leading to the potential to insert one of two different amino acids into a growing polypeptide chain in response to that codon. One tRNA usually predominates over the other.
Codon reassignment.: A change in the meaning of a sense codon as defined by which amino acid is inserted into a growing polypeptide chain in response to that codon. It can also refer to situations in which an amino acid is inserted

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Trends in Genetics

Driving change: the evolution of alternative genetic codes

Abstract

Section snippets

Genetic code ambiguity: from codon usage to reassignment

Genetic code ambiguity as a modulator of genome GC content

Is there a selective advantage introduced by genetic code ambiguity?

Concluding remarks

Acknowledgements

Glossary

Glossary

J. Mol. Biol.

J. Mol. Biol.

Cell

Curr. Biol.

Gene

J. Biol. Chem.

J. Biol. Chem.

Biochim. Biophys. Acta

J. Biol. Chem.

Ageing Res. Rev.

J. Biol. Chem.

Adv. Protein Chem.

J. Biol. Chem.

A different genetic code in human mitochondria

Nature

Rewiring the keyboard: evolvability of the genetic code

Nat. Rev. Genet.

Genetic code variations in mitochondria: tRNA as a major determinant of genetic code plasticity

J. Mol. Evol.

Codon reassignment (codon capture) in evolution

J. Mol. Evol.

CGG: an unassigned or nonsense codon in Mycoplasma capricolum

Proc. Natl. Acad. Sci. U. S. A.

Recent evidence for the evolution of the genetic code

Microbiol. Rev.

Role of GC-biased mutation pressure on synonymous codon choice in Micrococcus luteus, a bacterium with a high genomic GC-content

Nucleic Acids Res.

Misreading of termination codons in eukaryotes by natural nonsense suppressor tRNAs

Nucleic Acids Res.

The polysemous codon – a codon with multiple amino acid assignment caused by dual specificity of tRNA identity

EMBO J.

Comparative evolutionary genomics unveils the molecular mechanisms of reassignment of the CTG codon in Candida spp

Genome Res.

Codon usage and tRNA content in unicellular and multicellular organisms

Mol. Biol. Evol.

Evolution of the Genetic Code