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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. • Pathogenic species of the genus Cryptococcus diverged from non-pathogenic ancestral species. • Discrete clustering of pathogenic and non-pathogenic species resulted from multivariate statistical analysis. • Codon usage trends of the genus are predominately governed by translational selection and gene expression. [ABSTRACT FROM AUTHOR]

The genus Cryptococcus comprises of more than 30 species. It consists of clinically significant pathogenic Cryptococcus neoformans/Cryptococcus gattii species complex comprising of a minimum of seven species. These pathogens cost more than 200,000 lives annually by causing cryptococcal meningoencephalitis. The evolution of the pathogenic species from closely related non‐pathogenic species of the Cryptococcus amylolentus complex is of particular importance and several advances have been made to understand their phylogenetic and genomic relationships. The current review briefly describes the sexual reproduction process followed by an individual description of the members focusing on their key attributes and virulence mechanisms of the pathogenic species. A special section on phylogenetic studies is aimed at understanding the evolutionary divergence of pathogens from non‐pathogens. Recent findings from our group pertaining to parameters affecting codon usage bias in six pathogenic and three non‐pathogenic ancestral species and their corroboration with existing phylogenetic reports are also included in the current review. [ABSTRACT FROM AUTHOR]