A genetic code alteration is a phenotype diversity generator in the human pathogen Candida albicans.
BACKGROUND
The discovery of genetic code alterations and expansions in both prokaryotes and eukaryotes abolished the hypothesis of a frozen and universal genetic code and exposed unanticipated flexibility in codon and amino acid assignments. It is now clear that codon identity alterations involve sense and non-sense codons and can occur in organisms with complex genomes and proteomes. However, the biological functions, the molecular mechanisms of evolution and the diversity of genetic code alterations remain largely unknown. In various species of the genus Candida, the leucine CUG codon is decoded as serine by a unique serine tRNA that contains a leucine 5'-CAG-3'anticodon (tRNA(CAG)(Ser)). We are using this codon identity redefinition as a model system to elucidate the evolution of genetic code alterations.


RESULTS
We have reconstructed the early stages of the Candida genetic code alteration by engineering tRNAs that partially reverted the identity of serine CUG codons back to their standard leucine meaning. Such genetic code manipulation had profound cellular consequences as it exposed important morphological variation, altered gene expression, re-arranged the karyotype, increased cell-cell adhesion and secretion of hydrolytic enzymes.


CONCLUSIONS
Our 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.
Miranda
Isabel
I
Department of Biology, Centro de Estudos do Ambiente e do Mar, University of Aveiro, Aveiro, Portugal.
Rocha
Rita
R
Santos
Maria C
MC
Mateus
Denisa D
DD
Moura
Gabriela R
GR
Carreto
Laura
L
Santos
Manuel A S
MA
D044822:Biodiversity; D002176:Candida albicans / Q000235:genetics* / Q000502:physiology*; D003062:Codon; D005786:Gene Expression Regulation; D005815:Genetic Code; D014644:Genetic Variation; D016681:Genome, Fungal; D023281:Genomics; D007621:Karyotyping; D008957:Models, Genetic; D010641:Phenotype; D011003:Ploidies; D040901:Proteomics / Q000379:methods; D012343:RNA, Transfer / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000235:genetics
D003062:Codon; D012343:RNA, Transfer