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

The fungal genus Cryptococcus comprises of several diverse species. The pathogens forming Cryptococcus neoformans/ Cryptococcus gatti species complex are of immense clinical significance owing to the high frequency of infections and deaths globally. Three closely related non-pathogenic species namely, Cryptococcus amylolentus, Cryptococcus wingfieldii and Cryptococcus depauperatus are the non-pathogenic ancestral species from which pathogenic lineages have diverged. In the current study, a comprehensive analysis of factors influencing the codon and amino acid usage bias in six pathogenic and three non-pathogenic species was performed. Our results revealed that though compositional bias played a crucial role, translational selection and gene expression were the key determinants of codon usage variations. Analysis of relative dinucleotide abundance and codon context signatures revealed strict avoidance of TpA dinucleotide across genomes. Multivariate statistical analysis based on codon usage data resulted in discrete clustering of pathogens and non-pathogens which correlated with previous reports on their phylogenetic distribution.