Molecular Cell Biology, Taiwan International Graduate Program, Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
PLoS Genet. 2013;9(1):e1003232. doi: 10.1371/journal.pgen.1003232. Epub 2013 Jan 24.
Large-scale genome rearrangements have been observed in cells adapting to various selective conditions during laboratory evolution experiments. However, it remains unclear whether these types of mutations can be stably maintained in populations and how they impact the evolutionary trajectories. Here we show that chromosomal rearrangements contribute to extremely high copper tolerance in a set of natural yeast strains isolated from Evolution Canyon (EC), Israel. The chromosomal rearrangements in EC strains result in segmental duplications in chromosomes 7 and 8, which increase the copy number of genes involved in copper regulation, including the crucial transcriptional activator CUP2 and the metallothionein CUP1. The copy number of CUP2 is correlated with the level of copper tolerance, indicating that increasing dosages of a single transcriptional activator by chromosomal rearrangements has a profound effect on a regulatory pathway. By gene expression analysis and functional assays, we identified three previously unknown downstream targets of CUP2: PHO84, SCM4, and CIN2, all of which contributed to copper tolerance in EC strains. Finally, we conducted an evolution experiment to examine how cells maintained these changes in a fluctuating environment. Interestingly, the rearranged chromosomes were reverted back to the wild-type configuration at a high frequency and the recovered chromosome became fixed in less selective conditions. Our results suggest that transposon-mediated chromosomal rearrangements can be highly dynamic and can serve as a reversible mechanism during early stages of adaptive evolution.
在实验室进化实验中，细胞适应各种选择条件时会观察到大规模的基因组重排。然而，这些类型的突变是否可以在种群中稳定维持，以及它们如何影响进化轨迹，目前仍不清楚。在这里，我们展示了染色体重排在一组从以色列进化峡谷（EC）中分离出来的天然酵母菌株中对极高铜耐受性的贡献。EC 菌株中的染色体重排导致染色体 7 和 8 的片段重复，从而增加了参与铜调节的基因的拷贝数，包括关键的转录激活因子 CUP2 和金属硫蛋白 CUP1。CUP2 的拷贝数与铜耐受性水平相关，表明通过染色体重排增加单个转录激活因子的剂量对调控途径有深远的影响。通过基因表达分析和功能测定，我们鉴定了 CUP2 的三个以前未知的下游靶标：PHO84、SCM4 和 CIN2，它们都有助于 EC 菌株的铜耐受性。最后，我们进行了一项进化实验，以检验细胞如何在波动的环境中维持这些变化。有趣的是，重排的染色体以高频率恢复为野生型构型，而恢复的染色体在选择性较低的条件下固定下来。我们的结果表明，转座子介导的染色体重排可能具有高度的动态性，并可作为适应性进化早期的一种可逆机制。
