Whole genome sequencing of 48 Candida glabrata strains isolated from clinical conditions. Abundant genetic variations were identified in these strains, including single nucleotide polymorphisms (SNPs), small insertion/deletions (indels) and copy number variations (CNVs).

The yeast Candida glabrata, an opportunistic human fungal pathogen, is the second most prevalent cause of candidiasis worldwide, with incidence of its infection keeping increasing in the past decades. The releasing of the C. glabrata reference genome has made fundamental contribution to understand the molecular basis for its pathogenic phenotypes. However, the knowledge of genome-wide genetic variations among C. glabrata strains is limited. In this study, we presented the first population genomics study of C. glabrata based on whole genome re-sequencing of 48 clinical isolates to an average of ~63X coverage. Abundant genetic variations were identified in these strains, including single nucleotide polymorphisms (SNPs), small insertion/deletions (indels) and copy number variations (CNVs). The SNP distribution revealed clear population structure of these strains. Using population genetic test, we detected some genes involved in C. glabrata adherence ability, such as EPA9 and EPA10, show adaptive evolution. We also located genome structural variations, including aneuploidies and large fragment CNVs, in regions that are functionally related to virulence. Genome wide copy number variations showed that subtelometric regions were CNV hotspots, which might contribute to another virulence factor, i.e., adhesin gene expression variation. We further conducted genome-wide association studies, and found two SNPs in CTS6 5'UTR region that were associated with fluconazole susceptibility. These observations revealed highly dynamic nature of the C. glabrata genomes with potential adaptive evolution to clinical environments, and provided rich resources for investigating the mechanisms underlying drug resistance and virulence in this fungal pathogen.