Selective advantages created by codon ambiguity allowed for the evolution of an alternative genetic code in Candida spp.

  title={Selective advantages created by codon ambiguity allowed for the evolution of an alternative genetic code in Candida spp.},
  author={Manuel A. S. Santos and Caroline Cheesman and V{\'i}tor Costa and Pedro Moradas‐Ferreira and Mick F. Tuite},
  journal={Molecular Microbiology},
Several species of the genus Candida decode the standard leucine CUG codon as serine. This and other deviations from the standard genetic code in both nuclear and mitochondrial genomes invalidate the notion that the genetic code is frozen and universal and prompt the questions ‘why alternative genetic codes evolved and, more importantly, how can an organism survive a genetic code change?’ To address these two questions, we have attempted to reconstruct the early stages of Candida albicans CUG… 
Critical roles for a genetic code alteration in the evolution of the genus Candida
This study reconstructed a Candida genetic code alteration in Saccharomyces cerevisiae and used a combination of DNA microarrays, proteomics and genetics approaches to evaluate its impact on gene expression, adaptation and sexual reproduction, and suggests that genetic code alterations create genetic barriers that speed up speciation.
A Genetic Code Alteration Is a Phenotype Diversity Generator in the Human Pathogen Candida albicans
This study provides the first experimental evidence for an important role of genetic code alterations as generators of phenotypic diversity of high selective potential and supports the hypothesis that they speed up evolution of new phenotypes.
Yeast as a model organism for studying the evolution of non-standard genetic codes.
An experimental framework based on forced evolution, molecular genetics and comparative and functional genomics methodologies is put forward for the study of non-standard genetic codes and genetic code ambiguity in general and the importance of using Saccharomyces cerevisiae as a model organism for elucidating the evolutionary pathway of the Candida and other genetic code changes is emphasised.
Evolution of the genetic code in yeasts
A unique genetic code change involving the decoding of the leucine CUG codon as serine was discovered in the cytoplasm of Candida and Debaryomyces species, indicating that the genetic code of yeasts may be under specific evolutionary pressures whose molecular nature is not yet fully understood.
A genetic code alteration generates a proteome of high diversity in the human pathogen Candida albicans
It is shown that C. albicans decodes CUG codons ambiguously and tolerates partial reversion of their identity from serine back to leucine on a genome-wide scale, which expands the proteome of this human pathogen exponentially and is used to generate important phenotypic diversity.
Molecular reconstruction of a fungal genetic code alteration
It is demonstrated here that such low level CUG ambiguity is advantageous in specific ecological niches and it is proposed that misreading tRNAs are targeted for degradation by an unidentified tRNA quality control pathway.
Reversion of a fungal genetic code alteration links proteome instability with genomic and phenotypic diversification
The data unveil unanticipated links between gene translational fidelity, proteome instability and variability, genome diversification, and adaptive phenotypic diversity and explain the high heterozygosity of the C. albicans genome.
Mitochondrial Genetic Codes Evolve to Match Amino Acid Requirements of Proteins
An analysis of 24 phylogenetically independent codon reassignments in mitochondria strongly suggests that mitochondrial genetic codes evolve to match the amino acid requirements of proteins.
Nuclear codon reassignments in the genomics era and mechanisms behind their evolution.
This hypothesis comprehensively explains the CTG codon translation as alanine in Pachysolen yeast together with the long known translation of the same codon as serine in Candida albicans and related species, and can also be applied to most other known reassignments.
Properties of the Standard Genetic Code and Its Alternatives Measured by Codon Usage from Corresponding Genomes
A new measure involving codon usage as an additional parameter, which allowed us to assess the quality of a given genetic code, and indicates that the alternative variants of the SGC evolved in specific conditions.


Transfer RNA structural change is a key element in the reassignment of the CUG codon in Candida albicans.
Ser‐tRNA(CAG) anticodon loop is a key structural element in the reassignment of the CUG codon from leucine to serine in that it decreases the decoding efficiency of the tRNA, thereby allowing cells to survive low level serine CUG translation.
The non‐standard genetic code of Candida spp.: an evolving genetic code or a novel mechanism for adaptation?
It is proposed that G‐33 has two important functions: lowering the decoding efficiency of the ser‐tRNACAG and preventing binding of the leucyl‐tRNA synthetase, which implicates this nucleotide as a key player in the evolutionary reassignment of the CUG codon.
Evolutionary origin of nonuniversal CUGSer codon in some Candida species as inferred from a molecular phylogeny.
It is demonstrated that the group of Candida showing the genetic code deviation is monophyletic and that this deviation could have originated more than 150 million years ago and described how phylogenetic analysis can be used for genetic code predictions.
Evolution of the genetic code.
  • B. K. Davis
  • Biology
    Progress in biophysics and molecular biology
  • 1999
The 'polysemous' codon--a codon with multiple amino acid assignment caused by dual specificity of tRNA identity.
These findings provide the first evidence that two distinct amino acids are assigned by a single codon, which occurs naturally in the translation process of certain Candida species, and are term this novel type of codon a ‘polysemous codon’.
Recent evidence for evolution of the genetic code.
It is proposed that the changes are typically preceded by loss of a codon from all coding sequences in an organism or organelle, often as a result of directional mutation pressure, accompanied by Loss of the tRNA that translates the codon.
Transfer RNA mutation and the malleability of the genetic code.
It is proposed that evolutionary reassignment of codons is facilitated by a translationally ambiguous intermediate, and characterized codon reassignments are strikingly non-random, and half can be immediately explained by unusual tRNA activities already demonstrated.
New heterologous modules for classical or PCR‐based gene disruptions in Saccharomyces cerevisiae
A dominant resistance module, for selection of S. cerevisiae transformants, which entirely consists of heterologous DNA is constructed and tested, and some kanMX modules are flanked by 470 bp direct repeats, promoting in vivo excision with frequencies of 10–3–10–4.
Suppression in the Yeast Saccharomyces cerevisiae
The conceptual framework for the work on yeast suppressors has been based on the earlier and more extensive work on bacterial suppressors, and the properties of the suppressors of the yeast S. cerevisiae are tabulated, and their properties are summarized.
Unassigned or nonsense codons in Micrococcus luteus.
Investigation of whether AGA and AUA, universal Arg and Ile codons, respectively, are really unassigned codons by using a cell-free extract prepared from M. luteus and synthetic messenger RNAs suggests that at least some of them are unassignment (nonsense) codons.