Department of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Nature. 2013 Feb 7;494(7435):55-9. doi: 10.1038/nature11865. Epub 2013 Jan 30.
Candida albicans, the most prevalent human fungal pathogen, is considered to be an obligate diploid that carries recessive lethal mutations throughout the genome. Here we demonstrate that C. albicans has a viable haploid state that can be derived from diploid cells under in vitro and in vivo conditions, and that seems to arise through a concerted chromosome loss mechanism. Haploids undergo morphogenetic changes like those of diploids, including the yeast-hyphal transition, chlamydospore formation and a white-opaque switch that facilitates mating. Haploid opaque cells of opposite mating type mate efficiently to regenerate the diploid form, restoring heterozygosity and fitness. Homozygous diploids arise spontaneously by auto-diploidization, and both haploids and auto-diploids show a similar reduction in fitness, in vitro and in vivo, relative to heterozygous diploids, indicating that homozygous cell types are transient in mixed populations. Finally, we constructed stable haploid strains with multiple auxotrophies that will facilitate molecular and genetic analyses of this important pathogen.
白色念珠菌是最常见的人类真菌病原体，被认为是一种必需的二倍体，其基因组中携带隐性致死突变。在这里，我们证明了白色念珠菌具有可行的单倍体状态，可以在体外和体内条件下从二倍体细胞中衍生出来，并且似乎是通过协同染色体丢失机制产生的。单倍体经历与二倍体相似的形态发生变化，包括酵母-菌丝过渡、厚垣孢子形成和白色-不透明转换，这有助于交配。相反交配型的单倍体不透明细胞有效地交配，以再生二倍体形式，恢复杂合性和适应性。同型二倍体自发地通过自身二倍化产生，单倍体和自身二倍体在体外和体内的适应性相对于杂合二倍体都有类似的降低，表明同型细胞类型在混合群体中是短暂的。最后，我们构建了具有多种营养缺陷型的稳定单倍体菌株，这将有助于对这种重要病原体进行分子和遗传分析。
