The misfolding avoidance hypothesis postulates that sequence mutations render proteins cytotoxic and therefore the higher the gene expression, the stronger the operation of selection against substitutions. This translates into prediction that relative toxicity of extant proteins is higher for those evolving faster. In the present experiment, we selected pairs of yeast genes which were paralogous but evolving at different rates. We expressed them artificially to high levels. We expected that toxicity would be higher for ones bearing more mutations, especially that overcrowding should rather exacerbate than reverse the already existing differences in misfolding rates. We did find that the applied mode of overexpression caused a considerable decrease in fitness and that the decrease was proportional to the amount of excessive protein. However, it was not higher for proteins which are normally expressed at lower levels (and have less conserved sequence). This result was obtained consistently, regardless whether the rate of growth or ability to compete in common cultures was used as a proxy for fitness. In additional experiments, we applied factors that reduce accuracy of translation or enhance structural instability of proteins. It did not change a consistent pattern of independence between the fitness cost caused by overexpression of a protein and the rate of its sequence evolution.

中文翻译：

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过表达实验不支持避免毒性决定蛋白质进化速率的假说。

避免错误折叠的假设假设序列突变使蛋白质具有细胞毒性，因此基因表达越高，针对取代的选择操作越强。这转化为预测，即对于那些进化较快的蛋白质，现存蛋白质的相对毒性更高。在本实验中，我们选择了成对的酵母基因对，但是它们以不同的速率进化。我们以高水平人为地表达了他们。我们预期，对于携带更多突变的突变体，毒性会更高，尤其是过度拥挤会加剧而不是扭转错折叠率已经存在的差异。我们确实发现，过度表达的应用模式会导致健康状况显着下降，并且下降与过量蛋白质的数量成正比。然而，对于通常以较低水平表达（且保守性较低的序列）的蛋白质，它的含量并不高。无论是否将生长速度或在普通文化中的竞争能力用作适应性指标，均能始终如一地获得该结果。在其他实验中，我们应用了降低翻译准确性或增强蛋白质结构不稳定性的因素。它并没有改变蛋白质过度表达引起的适应性成本与其序列进化速率之间的一致独立模式。我们应用了降低翻译准确性或增强蛋白质结构不稳定性的因素。它并没有改变蛋白质过度表达引起的适应性成本与其序列进化速率之间的一致独立模式。我们应用了降低翻译准确性或增强蛋白质结构不稳定性的因素。它并没有改变蛋白质过度表达引起的适应性成本与其序列进化速率之间的一致独立模式。