A Candida albicans population genomics study

Candida albicans is a diploid yeast species responsible for life-threatening infections in hospitalized patients and also the most frequent fungal commensal of humans. Previous population studies using Multi-Locus Sequence Typing (MLST) have revealed a strong genetic differentiation between strains, showing at least 18 well-differentiated clusters. Each clade comprises strains that have evolved independently from those in other clades, possibly through past association to a geographic locale. While a parasexual cycle, involving mating between two diploid individuals carrying opposite mating types followed by random chromosome loss without meiosis has been described, no direct evidence for its occurrence in humans has been provided.

We have now sequenced the diploid genomes of 182 C. albicans isolates from healthy carriers, and superficial and invasive infections. Population structures defined using different molecular markers (SNPs, indels, CNVs) recapitulate that inferred from MLST, indicating predominantly clonal reproduction. Yet, events of introgression are observed, consistent with (rare) parasexuality events in the human host. As expected in a clonal diploid population, strain-specific recessive lethal and deleterious alleles were shown to accumulate. Interestingly, we have observed that a specific clade grouping C. albicans isolates with a number of distinctive phenotypic features and niche restriction shows reduced genetic diversity despite worldwide dissemination. Our analysis indicates that reduced virulence in these isolates is likely to result from the accumulation of homozygous nonsense mutations in several genes with known contribution to C. albicans pathogenicity.