Phenotypic heterogeneity can enhance rare-cell survival in 'stress-sensitive' yeast populations
Phenotypic heterogeneity can enhance rare-cell survival in 'stress-sensitive' yeast populations
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DOI：
10.1111/j.1365-2958.2006.05504.x
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发表时间：
2007-01-01
影响因子：
3.6
通讯作者：
Avery, Simon V.
中科院分区：
文献类型：
--
作者：
Bishop, Amy L.;Rab, Faiza A.;Avery, Simon V.
同基因微生物培养物中的单个细胞表现出表型异质性，这是一个吸引人们强烈兴趣的问题。杂合可以带来好处，在产生变异的亚群，可能更好地装备在扰动持续。我们通过比较野生型酿酒酵母与被认为是应力敏感的突变体的存活率来验证这一假设，但我们证明，这些突变体也具有增加的异质性。突变体（如vma 3，ctr 1，sod 1）表现出预期的敏感性，中等剂量的镍，铜，碱性pH值，甲萘醌或百草枯。然而，增强的异质性意味着单个突变细胞的抗性跨越了很宽的范围，并且在高应力下，这些种群中的大多数细胞的存活率超过了野生型。绿色荧光蛋白（GFP）报告研究表明，这种异质性依赖的优势是不相关的缓冲基因表达的扰动。缺失菌株筛选结合其他方法表明，液泡碱化Vma依赖的液泡H+-ATP酶活性的损失所造成的vma突变体的净应力敏感性的原因。另一种Vma依赖的电阻机制被发现抑制可变液泡pH值对单个野生型细胞的金属电阻的影响。除了揭示异质性产生的新机制外，这些结果还通过实验证明了在异质性引起的不利条件下以及在传统上被认为处于不利地位的人群中的益处。
Individual cells within isogenic microbial cultures exhibit phenotypic heterogeneity, an issue that is attracting intense interest. Heterogeneity could confer benefits, in generating variant subpopulations that may be better equipped to persist during perturbation. We tested this hypothesis by comparing the survival of wild-type Saccharomyces cerevisiae with that of mutants which are considered stress-sensitive but which, we demonstrate, also have increased heterogeneity. The mutants (e.g. vma3, ctr1, sod1) exhibited the anticipated sensitivities to intermediate doses of nickel, copper, alkaline pH, menadione or paraquat. However, enhanced heterogeneity meant that the resistances of individual mutant cells spanned a broad range, and at high stress occasional-cell survival in most of these populations overtook that of the wild type. Green fluorescent protein (GFP) reporter studies showed that this heterogeneity-dependent advantage was not related to perturbation of buffered gene expression. Deletion strain screens combined with other approaches revealed that vacuolar alkalinization resulting from loss of Vma-dependent vacuolar H+-ATPase activity was not the cause of vma mutants' net stress sensitivities. An alternative Vma-dependent resistance mechanism was found to suppress an influence of variable vacuolar pH on the metal resistances of individual wild-type cells. In addition to revealing new mechanisms of heterogeneity generation, the results demonstrate experimentally a benefit under adverse conditions that arises specifically from heterogeneity, and in populations conventionally considered to be disadvantaged.