<i>Candida albicans</i> isolates contain frequent heterozygous structural variants and transposable elements within genes and centromeres

The human fungal pathogen <i>Candida albicans</i> poses a significant burden on global health, causing high rates of mortality and antifungal drug resistance. <i>C. albicans</i> is a heterozygous diploid organism that reproduces asexually. Structural variants (SVs) are an important source of genomic rearrangement, particularly in species that lack sexual recombination. To comprehensively investigate SVs across clinical isolates of <i>C. albicans</i>, we conducted long-read sequencing and genome-wide SV analysis in three distantly related clinical isolates. Our work includes a new, comprehensive analysis of transposable element (TE) composition, location, and diversity. SVs and TEs are frequently close to coding sequences and many SVs are heterozygous, suggesting that SVs might impact gene and allele-specific expression. Most SVs are uniquely present in only one clinical isolate, indicating that SVs represent a significant source of intraspecies genetic variation. We identify multiple, distinct SVs at the centromeres of Chromosome 4 and Chromosome 5, including inversions and transposon polymorphisms. These two chromosomes are often aneuploid in drug-resistant clinical isolates and can form isochromosome structures with breakpoints near the centromere. Further screening of 100 clinical isolates confirms the widespread presence of centromeric SVs in <i>C. albicans</i>, often appearing in a heterozygous state, indicating that SVs are contributing to centromere evolution in <i>C. albicans</i> Together, these findings highlight that SVs and TEs are common across diverse clinical isolates of <i>C. albicans</i> and that the centromeres of this organism are important sites of genome rearrangement.