Patterns of genomic variation in the opportunistic pathogen Candida glabrata suggest the existence of mating and a secondary association to the human host

Abstract

Candida glabrata is an opportunistic fungal pathogen that ranks as the second most common cause of systemic candidiasis. Despite its genus name, this yeast is more closely related to the model yeast Saccharomyces cerevisiae than to other Candida pathogens, and hence its ability to infect humans is thought to have emerged independently. Morover, C. glabrata has all the necessary genes to undergo a sexual cycle, but it is considered an asexual organism due to the lack of direct evidence of sexual reproduction. Here, we assessed genomic and phenotypic variation across 33 globally-distributed C. glabrata isolates. We cataloged extensive copy number variation, which particularly affects genes encoding cell-wall associated proteins, including adhesins. The observed level of genetic variation in C. glabrata is significantly larger than that found in Candida albicans. This variation is structured in seven deeply divergent clades, which show recent geographical dispersion and large within-clade genomic and phenotypic differences. We show compelling evidence of recent admixture between differentiated lineages, and of purifying selection on mating genes, which provide fist evidence for the existence of a sexual cycle in this yeast. Altogether, our data point to a recent global spread of previously genetically isolated populations and suggest that humans are only a secondary niche for this yeast.