Candida albicans is an opportunistic fungal pathogen of humans that is typically diploid yet has a highly labile genome tolerant of large-scale perturbations including chromosomal aneuploidy and loss-of-heterozygosity events. The ability to rapidly generate genetic variation is crucial for C. albicans to adapt to changing or stressful environments, like those encountered in the host. Genetic variation occurs via stress-induced mutagenesis or can be generated through its parasexual cycle, in which tetraploids arise via diploid mating or stress-induced mitotic defects and undergo nonmeiotic ploidy reduction. However, it remains largely unknown how genetic background contributes to C. albicans genome instability in vitro or in the host environment. Here, we tested how genetic background, ploidy, and the host environment impacts C. albicans genome stability. We found that host association induced both loss-of-heterozygosity events and genome size changes, regardless of genetic background or ploidy. However, the magnitude and types of genome changes varied across C. albicans strain background and ploidy state. We then assessed if host-induced genomic changes resulted in fitness consequences on growth rate and nonlethal virulence phenotypes and found that many host-derived isolates significantly changed relative to their parental strain. Interestingly, diploid host-associated C. albicans predominantly decreased host reproductive fitness, whereas tetraploid host-associated C. albicans increased host reproductive fitness. Together, these results are important for understanding how host-induced genomic changes in C. albicans alter its relationship with the host.

中文翻译：

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宿主诱导的基因组不稳定性会迅速在白色念珠菌菌株和倍性状态之间产生表型变异。

白色念珠菌是人的机会性真菌病原体，通常是二倍体，但对大规模扰动（包括染色体非整倍性和杂合丧失事件）的基因组耐受性很高。快速产生遗传变异的能力对于白色念珠菌适应不断变化或充满压力的环境（如宿主中遇到的环境）至关重要。遗传变异是通过应激诱导的诱变发生的，或者可以通过其双性恋周期产生，在这种情况下，四倍体通过二倍体交配或应激诱导的有丝分裂缺陷而发生，并发生非减数分裂倍性。然而，很大程度上尚不清楚遗传背景如何在体外导致白色念珠菌基因组不稳定。或在主机环境中。在这里，我们测试了遗传背景，倍性和宿主环境如何影响白色念珠菌基因组稳定性。我们发现，无论遗传背景或倍性如何，宿主协会均会引起杂合性丧失事件和基因组大小变化。然而，基因组变化的幅度和类型在白色念珠菌菌株背景和倍性状态之间变化。然后，我们评估了宿主诱导的基因组变化是否会对生长速率和非致命毒力表型产生适应性后果，并且发现许多宿主衍生的分离株相对于其亲本菌株而言有显着变化。有趣的是，与二倍体宿主相关的白色念珠菌主要降低了宿主的生殖适应能力，而与四倍体宿主相关的白色念珠菌增加宿主的生殖适应能力。总之，这些结果对于理解宿主诱导的白色念珠菌基因组变化如何改变其与宿主的关系非常重要。