The Fungus Candida albicans Tolerates Ambiguity at Multiple Codons

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Candida albicans, a common fungus, thrives in diverse environments.
• It possesses unique codon reassignment, notably the leucine CUG codon to serine.
• This genetic flexibility allows adaptation to environmental stressors.

Purpose of the Study:

• To investigate if codon ambiguity extends beyond CUG in Candida albicans.
• To assess the impact of mistranslating serine tRNAs on fungal fitness and adaptation.
• To identify genetic factors contributing to adaptation under codon ambiguity.

Main Methods:

• Construction and expression of serine tRNAs for non-cognate codons.
• Growth assays of engineered strains under various environmental conditions (temperature, pH, nutrients).
• Whole-genome sequencing of evolved strains to identify genetic mutations.

Main Results:

• Engineered mistranslating strains showed enhanced growth in altered conditions compared to wild type.
• Parallel evolution revealed strain-specific single nucleotide polymorphisms (SNPs).
• A conserved SNP in the JAB1 gene (deneddylase) was identified in all adapted strains.

Conclusions:

• Codon ambiguity and associated mistranslation contribute to Candida albicans adaptation.
• The deneddylase JAB1 and neddylation pathway are crucial for tolerance and adaptation to codon ambiguity.
• This highlights a novel mechanism for fungal adaptation and survival.