Codon usage signatures in the genus Cryptococcus: A complex interplay of gene expression, translational selection and...

Area of Science:

• Mycology
• Genomics
• Molecular Biology

Background:

• The fungal genus Cryptococcus includes clinically significant pathogenic species like Cryptococcus neoformans and Cryptococcus gatti.
• Pathogenic Cryptococcus lineages evolved from non-pathogenic ancestors such as Cryptococcus amylolentus, Cryptococcus wingfieldii, and Cryptococcus depauperatus.
• Understanding genetic variations in Cryptococcus is crucial for disease management and evolutionary studies.

Purpose of the Study:

• To comprehensively analyze codon and amino acid usage bias in six pathogenic and three non-pathogenic Cryptococcus species.
• To identify the key factors driving codon usage variations within the Cryptococcus genus.
• To investigate the genomic features, such as dinucleotide abundance, associated with pathogenicity.

Main Methods:

• Comparative genomic analysis of codon usage patterns across selected Cryptococcus species.
• Assessment of compositional bias, translational selection, and gene expression's role in codon usage.
• Analysis of relative dinucleotide abundance and codon context signatures.
• Multivariate statistical analysis of codon usage data for species clustering.

Main Results:

• Compositional bias, translational selection, and gene expression were identified as major determinants of codon usage variations.
• A strict avoidance of the TpA dinucleotide was observed across all analyzed Cryptococcus genomes.
• Multivariate statistical analysis clearly separated pathogenic and non-pathogenic species based on codon usage, aligning with phylogenetic data.

Conclusions:

• Codon usage bias in Cryptococcus is primarily driven by translational selection and gene expression, not solely by base composition.
• Genomic signatures, including dinucleotide avoidance, differentiate pathogenic from non-pathogenic Cryptococcus species.
• These findings provide insights into the molecular evolution of Cryptococcus pathogenicity and can aid in phylogenetic classification.