When new genes evolve through modification of existing genes, there are often tradeoffs between the new and original functions, making gene duplication and amplification necessary to buffer deleterious effects on the original function. We have used experimental evolution of a bacterial strain lacking peptide release factor 1 (RF1) in order to study how peptide release factor 2 (RF2) evolves to compensate the loss of RF1. As expected, amplification of the RF2-encoding gene prfB to high copy number was a rapid initial response, followed by the appearance of mutations in RF2 and other components of the translation machinery. Characterization of the evolved RF2 variants by their effects on bacterial growth rate, reporter gene expression, and in vitro translation termination reveals a complex picture of reduced discrimination between the cognate and near-cognate stop codons and highlights a functional tradeoff that we term “collateral toxicity.” We suggest that this type of tradeoff may be a more serious obstacle in new gene evolution than the more commonly discussed evolutionary tradeoffs between “old” and “new” functions of a gene, as it cannot be overcome by gene copy number changes. Further, we suggest a model for how RF2 autoregulation responds to alterations in the demand not only for RF2 activity but also for RF1 activity.

中文翻译：

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附带毒性限制了细菌释放因子2向全能的进化。

当新基因通过对现有基因的修饰而进化时，新功能和原始功能之间通常会进行权衡取舍，因此必须进行基因复制和扩增以缓冲对原始功能的有害影响。为了研究肽释放因子2（RF2）如何进化以补偿RF1的损失，我们使用了缺乏肽释放因子1（RF1）的细菌菌株的实验进化。不出所料，RF2编码基因prfB的扩增对高拷贝数的反应是快速的初始反应，随后在RF2和翻译机制的其他组件中出现了突变。通过其对细菌生长速率，报告基因表达和体外翻译终止的影响来表征进化的RF2变体，揭示了降低了同源和近同源终止密码子之间的区别的复杂图景，并强调了我们称之为“附带毒性”的功能折衷。” 我们建议这种类型的权衡可能是新基因进化中更严重的障碍，而不是在基因的“旧”和“新”功能之间进行更广泛讨论的进化权衡，因为不能通过基因拷贝数的变化来克服。进一步，