The parasexual cycle in Candida albicans provides an alternative pathway to meiosis for the formation of recombinant strains.
The parasexual cycle in Candida albicans provides an alternative pathway to meiosis for the formation of recombinant strains.
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DOI：
10.1371/journal.pbio.0060110
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发表时间：
2008-05-06
期刊：
影响因子：
9.8
通讯作者：
Bennett RJ
中科院分区：
文献类型：
--
作者：
Forche A;Alby K;Schaefer D;Johnson AD;Berman J;Bennett RJ
白色念珠菌有一个复杂而有效的交配系统，促进二倍体a和α菌株之间的接合。交配的产物是一个四倍体的a/α细胞，它必须经历减数分裂才能返回到二倍体状态。尽管在白念珠菌基因组中存在几个“减数分裂特有的”基因，但尚未观察到减数分裂程序。相反，交配的四倍体产物可以被诱导经历有效的、随机的染色体丢失，通常产生倍性为二倍体或接近二倍体的菌株。利用SNP和比较基因组杂交阵列，我们现在已经分析了白念珠菌准性周期产物的基因类型。我们发现，无性繁殖周期产生的后代菌株具有8条白色念珠菌染色体的改组组合。此外，几个分离株在同源染色体之间进行了广泛的基因重组，包括多次基因转换事件。子代菌株在实验室培养基上表现出改变的菌落形态，证明了准性周期产生了白色念珠菌的表型变异。在一些真菌中，包括酿酒酵母和裂殖酵母，保守的Spo11蛋白是减数分裂重组所必需的，在那里它是形成DNA双链断裂所必需的。我们发现，在白念珠菌的无性繁殖周期中，SPO11的缺失阻止了同源染色体之间的基因重组。这些发现表明，至少有一个减数分裂特异基因已经被重新编程，以在白念珠菌的另类无性生命周期中介导基因重组。鉴于白色念珠菌与温血动物的长期联系，我们讨论了与常规性周期相比，准性周期的潜在优势。白色念珠菌是一种重要的人类真菌病原体，具有非常规性周期。有效的交配需要相反交配型的二倍体细胞首先从更常见的“白色”相切换到“不透明”相，然后进行细胞融合。由此产生的四倍体菌株可以通过协调的染色体丢失的非减数分裂副性程序返回到二倍体状态。我们使用SNP和比较基因组杂交来分析这种准性周期产生的后代，发现了一系列表型发生变化的遗传多样性菌株。此外，在这些菌株的一个子集中，发现在同源染色体之间发生了基因重组。这种重组依赖于Spo11，这是一种保守的蛋白质，在经历常规减数分裂的真核生物的染色体中引入DNA双链断裂所必需的。因此，在白念珠菌的无性繁殖周期中，Spo11是基因重组和增加遗传多样性所必需的。条件致病菌白色念珠菌有一个隐蔽的准性交配周期，涉及表观遗传转换和染色体丢失。这项研究表明，基因重组发生在交配周期，这需要Spo11的活性，Spo11是其他真核生物减数分裂重组所必需的蛋白质。
Candida albicans has an elaborate, yet efficient, mating system that promotes conjugation between diploid a and α strains. The product of mating is a tetraploid a/α cell that must undergo a reductional division to return to the diploid state. Despite the presence of several “meiosis-specific” genes in the C. albicans genome, a meiotic program has not been observed. Instead, tetraploid products of mating can be induced to undergo efficient, random chromosome loss, often producing strains that are diploid, or close to diploid, in ploidy. Using SNP and comparative genome hybridization arrays we have now analyzed the genotypes of products from the C. albicans parasexual cycle. We show that the parasexual cycle generates progeny strains with shuffled combinations of the eight C. albicans chromosomes. In addition, several isolates had undergone extensive genetic recombination between homologous chromosomes, including multiple gene conversion events. Progeny strains exhibited altered colony morphologies on laboratory media, demonstrating that the parasexual cycle generates phenotypic variants of C. albicans. In several fungi, including Saccharomyces cerevisiae and Schizosaccharomyces pombe, the conserved Spo11 protein is integral to meiotic recombination, where it is required for the formation of DNA double-strand breaks. We show that deletion of SPO11 prevented genetic recombination between homologous chromosomes during the C. albicans parasexual cycle. These findings suggest that at least one meiosis-specific gene has been re-programmed to mediate genetic recombination during the alternative parasexual life cycle of C. albicans. We discuss, in light of the long association of C. albicans with warm-blooded animals, the potential advantages of a parasexual cycle over a conventional sexual cycle. Candida albicans is an important human fungal pathogen that has an unconventional sexual cycle. Efficient mating requires that diploid cells of opposite mating type first switch from the more common “white” phase to the “opaque” phase and then undergo cell fusion. The resulting tetraploid strains can return to the diploid state via a non-meiotic parasexual program of concerted chromosome loss. We used SNP and comparative genome hybridization to analyze the progeny resulting from this parasexual cycle and found a range of genetically diverse strains with altered phenotypes. In addition, in a subset of these strains, genetic recombination was found to have taken place between homologous chromosomes. This recombination was dependent on Spo11, a conserved protein required for the introduction of DNA double-strand breaks in the chromosomes of eukaryotes that undergo conventional meiosis. Thus, Spo11 is required for genetic recombination and the generation of increased genetic diversity during the C. albicans parasexual cycle. The opportunistic pathogen Candida albicans has a cryptic parasexual mating cycle involving epigenetic switching and chromosome loss. This study demonstrates that genetic recombination occurs during the mating cycle and that this requires the activity of Spo11, a protein necessary for meiotic recombination in other eukaryotes.
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影响因子：
4.5
作者：
Gerstein AC;Chun HJ;Grant A;Otto SP
通讯作者：
Otto SP
影响因子：
11.8
作者：
Edmond, MB;Wallace, SE;Wenzel, RP
通讯作者：
Wenzel, RP
影响因子：
3.2
作者：
Anderson, JB;Wickens, C;Kohn, LM
通讯作者：
Kohn, LM
DOI：
10.1007/bf00383330
发表时间：
1985-01-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
HILTON, C;MARKIE, D;POULTER, R
通讯作者：
POULTER, R
影响因子：
11.4
作者：
Bennett, RJ;Johnson, AD
通讯作者：
Johnson, AD