Adaptation to the dietary sugar D-tagatose via genome instability in polyploid Candida albicans cells.
Adaptation to the dietary sugar D-tagatose via genome instability in polyploid Candida albicans cells.
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DOI：
10.1093/g3journal/jkab110
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发表时间：
2021-07-14
期刊：
影响因子：
--
通讯作者：
Bennett RJ
中科院分区：
文献类型：
--
作者：
Thomson GJ;Kakade P;Hirakawa MP;Ene IV;Bennett RJ
机会性真菌病原体白色念珠菌经历了一个不同寻常的无性繁殖周期，在这个周期中，二倍体细胞交配形成四倍体细胞，这些细胞可以通过染色体丢失的非减数分裂程序产生遗传多样性的后代。白念珠菌的基因多样性影响着包括耐药性和毒力在内的临床相关特征，然而影响白念珠菌基因组不稳定的因素还没有很好地确定。为了了解环境因素如何影响基因组的不稳定性，我们监测了四倍体细胞在一组不同碳源中生长后的倍性变化。我们发现，在一种碳源D-塔格糖中生长会导致四倍体细胞基因组高度不稳定和染色体丢失。这种糖是L-山梨糖的立体异构体，以前曾被证明可以促进白色念珠菌的核型变化。然而，虽然SOU1基因的表达促进了对L山梨糖的利用，但该基因的过度表达并没有促进D-塔格糖的生长，这表明两种糖的同化存在差异。此外，对从D-塔格糖培养中恢复的多个后代的基因组测序显示，4号染色体的相对拷贝数增加，提示D-塔格糖代谢在染色体水平上的调节。总之，这些研究确定了一个新的环境线索，导致白色念珠菌基因组不稳定，并进一步暗示染色体变化支持该物种的代谢适应。
The opportunistic fungal pathogen Candida albicans undergoes an unusual parasexual cycle wherein diploid cells mate to form tetraploid cells that can generate genetically diverse progeny via a nonmeiotic program of chromosome loss. The genetic diversity afforded by parasex impacts clinically relevant features including drug resistance and virulence, and yet the factors influencing genome instability in C. albicans are not well defined. To understand how environmental cues impact genome instability, we monitored ploidy change following tetraploid cell growth in a panel of different carbon sources. We found that growth in one carbon source, D-tagatose, led to high levels of genomic instability and chromosome loss in tetraploid cells. This sugar is a stereoisomer of L-sorbose which was previously shown to promote karyotypic changes in C. albicans. However, while expression of the SOU1 gene enabled utilization of L-sorbose, overexpression of this gene did not promote growth in D-tagatose, indicating differences in assimilation of the two sugars. In addition, genome sequencing of multiple progenies recovered from D-tagatose cultures revealed increased relative copy numbers of chromosome 4, suggestive of chromosome-level regulation of D-tagatose metabolism. Together, these studies identify a novel environmental cue that induces genome instability in C. albicans, and further implicate chromosomal changes in supporting metabolic adaptation in this species.
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