Multiple peaks and reciprocal sign epistasis in an empirically determined genotype-phenotype landscape
Multiple peaks and reciprocal sign epistasis in an empirically determined genotype-phenotype landscape
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DOI：
10.1063/1.3453602
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发表时间：
2010-06-01
期刊：
影响因子：
2.9
通讯作者：
Tans, Sander J.
中科院分区：
文献类型：
--
作者：
Dawid, Alexandre;Kiviet, Daniel J.;Tans, Sander J.
洞察适应性景观的崎岖性对于理解塑造进化过程的机制和约束至关重要。虽然有关适应性景观的经验数据仍然很少，但最近的一些研究揭示了基因型-表型和基因型-适应度景观看起来平滑且单峰。在这里，我们使用大肠杆菌中 lac 阻遏物和操纵基因突变体的现有体内测量来重建基因型-表型图，该图详细描述了该调节系统的抑制值作为两个关键阻遏物残基和四个关键操纵基因碱基对的函数。我们发现这个景观是多峰的，共有 19 个不同的最佳点。分析表明，峰之间的所有直接进化途径都涉及抑制值的显着下降。与早期的预测一致，我们发现两个峰之间最有利路径的抑制最小值处存在倒数上位相互作用。这些结果表明，多个峰的出现和相互上位相互作用可能是协同进化系统（如本文研究的阻遏物-操纵子对）的一般特征。 (C) 2010 年美国物理研究所。 [doi:10.1063/1.3453602]
Insight into the ruggedness of adaptive landscapes is central to understanding the mechanisms and constraints that shape the course of evolution. While empirical data on adaptive landscapes remain scarce, a handful of recent investigations have revealed genotype-phenotype and genotype-fitness landscapes that appeared smooth and single peaked. Here, we used existing in vivo measurements on lac repressor and operator mutants in Escherichia coli to reconstruct the genotype-phenotype map that details the repression value of this regulatory system as a function of two key repressor residues and four key operator base pairs. We found that this landscape is multipeaked, harboring in total 19 distinct optima. Analysis showed that all direct evolutionary pathways between peaks involve significant dips in the repression value. Consistent with earlier predictions, we found reciprocal sign epistatic interactions at the repression minimum of the most favorable paths between two peaks. These results suggest that the occurrence of multiple peaks and reciprocal epistatic interactions may be a general feature in coevolving systems like the repressor-operator pair studied here. (C) 2010 American Institute of Physics. [doi:10.1063/1.3453602]