The human fungal pathogen Candida albicans poses a significant burden on global health, causing high rates of mortality and antifungal drug resistance. C. albicans 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 C. albicans, we conducted long read sequencing and genome-wide SV analysis in three distantly related clinical isolates. Our work included 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 intra-species genetic variation. We identified 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 confirmed the widespread presence of centromeric SVs in C. albicans, often appearing in a heterozygous state, indicating that SVs are contributing to centromere evolution in C. albicans. Together, these findings highlight that SVs and TEs are common across diverse clinical isolates of C. albicans and that the centromeres of this organism are important sites of genome rearrangement.

中文翻译：

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白色念珠菌分离株在基因和着丝粒内包含频繁的杂合结构变异和转座因子


人类真菌病原体白色念珠菌对全球健康构成重大负担，导致高死亡率和抗真菌药物耐药性。C. albicans 是一种无性繁殖的杂合二倍体生物。结构变异 （SVs） 是基因组重排的重要来源，尤其是在缺乏性重组的物种中。为了全面研究白色念珠菌临床分离株中的 SV，我们对三个远亲临床分离株进行了长读长测序和全基因组 SV 分析。我们的工作包括对转座因子 （TE） 组成、位置和多样性进行新的全面分析。SVs 和 TEs 通常接近编码序列，并且许多 SVs 是杂合子，这表明 SVs 可能影响基因和等位基因特异性表达。大多数 SVs 仅独特存在于一种临床分离株中，表明 SVs 代表了种内遗传变异的重要来源。我们在 4 号染色体和 5 号染色体的着丝粒处鉴定了多个不同的 SV，包括倒位和转座子多态性。这两条染色体在耐药临床分离株中通常是非整倍体，并且可以形成等染色体结构，在着丝粒附近有断点。对 100 个临床分离株的进一步筛选证实，白色念珠菌中广泛存在着丝粒 SV，通常以杂合状态出现，表明 SV 有助于白色念珠菌着丝粒的进化。总之，这些发现强调 SVs 和 TEs 在白色念珠菌的不同临床分离株中很常见，并且该生物体的着丝粒是基因组重排的重要位点。