The regulatory utilization of genetic redundancy through responsive backup circuits
The regulatory utilization of genetic redundancy through responsive backup circuits
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DOI：
10.1073/pnas.0604883103
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发表时间：
2006-08-01
影响因子：
11.1
通讯作者：
Pilpel, Yitzhak
中科院分区：
文献类型：
--
作者：
Kafri, Ran;Levy, Melissa;Pilpel, Yitzhak
由基因复制产生的功能冗余在所有已知的基因组中非常普遍。这些冗余的一个后果是生物体对突变和其他压力的鲁棒性大大增加。然而，这种鲁棒性也使得冗余在进化上不稳定，因此，预测它只有短暂的生命期。与此相反，许多报告描述的情况下，功能重叠已保存在整个延长的进化时期。更有趣的是，许多这样的备份基因被证明是转录响应于其冗余伴侣的完整性，如果后者突变失活，则上调。通过人工查阅文献，我们编制了一份清单，这样的“响应备份电路”在不同的物种名单。回顾这些响应备份电路，我们提取经常性的原则，其特点的监管。然后，我们应用建模方法来进一步探索其动态特性。我们的研究结果表明，响应备份电路可以作为理想的设备过滤非遗传噪声从转录途径和获得监管精度。因此，我们质疑这样的冗余只是古代复制的遗留物的观点，并建议它们是复杂的细胞调节机制的额外组成部分。在这方面，我们认为，基因丢失的补偿仅仅是一个复杂的设计原则，使用功能冗余的副作用。
Functional redundancies, generated by gene duplications, are highly widespread throughout all known genomes. One consequence of these redundancies is a tremendous increase to the robustness of organisms to mutations and other stresses. Yet, this very robustness also renders redundancy evolutionarily unstable, and it is, thus, predicted to have only a transient lifetime. In contrast, numerous reports describe instances of functional overlaps that have been conserved throughout extended evolutionary periods. More interestingly, many such backed-up genes were shown to be transcriptionally responsive to the intactness of their redundant partner and are up-regulated if the latter is mutationally inactivated. By manual inspection of the literature, we have compiled a list of such "responsive backup circuits" in a diverse list of species. Reviewing these responsive backup circuits, we extract recurring principles characterizing their regulation. We then apply modeling approaches to explore further their dynamic properties. Our results demonstrate that responsive backup circuits may function as ideal devices for filtering nongenetic noise from transcriptional pathways and obtaining regulatory precision. We thus challenge the view that such redundancies are simply leftovers of ancient duplications and suggest they are an additional component to the sophisticated machinery of cellular regulation. In this respect, we suggest that compensation for gene loss is merely a side effect of sophisticated design principles using functional redundancy.