Molecular Cell Biology, Taiwan International Graduate Program, Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
PLoS Genet. 2011 Mar;7(3):e1002034. doi: 10.1371/journal.pgen.1002034. Epub 2011 Mar 31.
Various types of genetic modification and selective forces have been implicated in the process of adaptation to novel or adverse environments. However, the underlying molecular mechanisms are not well understood in most natural populations. Here we report that a set of yeast strains collected from Evolution Canyon (EC), Israel, exhibit an extremely high tolerance to the heavy metal cadmium. We found that cadmium resistance is primarily caused by an enhanced function of a metal efflux pump, PCA1. Molecular analyses demonstrate that this enhancement can be largely attributed to mutations in the promoter sequence, while mutations in the coding region have a minor effect. Reconstruction experiments show that three single nucleotide substitutions in the PCA1 promoter quantitatively increase its activity and thus enhance the cells' cadmium resistance. Comparison among different yeast species shows that the critical nucleotides found in EC strains are conserved and functionally important for cadmium resistance in other species, suggesting that they represent an ancestral type. However, these nucleotides had diverged in most Saccharomyces cerevisiae populations, which gave cells growth advantages under conditions where cadmium is low or absent. Our results provide a rare example of a selective sweep in yeast populations driven by a tradeoff in metal resistance.
各种类型的基因改造和选择压力都可能参与到适应新环境或不利环境的过程中。然而，在大多数自然种群中，其潜在的分子机制还不是很清楚。在这里，我们报告说，从以色列的进化峡谷（EC）收集的一组酵母菌株对重金属镉表现出极高的耐受性。我们发现，镉抗性主要是由金属外排泵 PCA1 的增强功能引起的。分子分析表明，这种增强在很大程度上归因于启动子序列中的突变，而编码区中的突变则影响较小。重建实验表明，PCA1 启动子中的三个单核苷酸替换可定量增加其活性，从而增强细胞的镉抗性。不同酵母物种之间的比较表明，在 EC 菌株中发现的关键核苷酸是保守的，并且对其他物种的镉抗性具有重要的功能作用，表明它们代表了一种原始类型。然而，这些核苷酸在大多数酿酒酵母种群中已经分化，这使得细胞在镉含量低或不存在的情况下具有生长优势。我们的研究结果提供了一个罕见的酵母种群中由金属抗性权衡驱动的选择清扫的例子。
