Shifting Fitness and Epistatic Landscapes Reflect Trade-offs along an Evolutionary Pathway.
Shifting Fitness and Epistatic Landscapes Reflect Trade-offs along an Evolutionary Pathway.
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DOI：
10.1016/j.jmb.2016.04.033
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发表时间：
2016-07
影响因子：
5.6
通讯作者：
Barrett E Steinberg;M. Ostermeier
中科院分区：
文献类型：
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作者：
Barrett E Steinberg;M. Ostermeier
大自然通过进化过程重新利用蛋白质。这种适应可能以牺牲原始蛋白质的功能为代价，这是适应的一种权衡。我们试图研究其他潜在的适应性权衡。我们测量了TEM-1、TEM-17、TEM-19和TEM-15 β-内酰胺酶等位基因的约12，500个独特的单氨基酸突变体对氨苄青霉素耐药性的影响，这些突变体构成了头孢噻肟耐药性进化的适应性途径。比较这些蛋白质适应度景观，并用于计算这些突变与途径中的两个突变（E104 K和G238 S）之间的上位相互作用。这一系列的蛋白质健身景观提供了一个系统的，定量的描述成对/三级基因内上位性涉及适应性突变。我们发现，显示上位性的突变频率随着进化途径的沿着增加。适应移动的蛋白质的健身景观的特点是减少突变的鲁棒性和增加的坚固性，如TEM-1的原始功能的突变和上位相互作用的健身效果测量的区域。这种向这种“适应领域”的移动具有进化的后果，是一种重要的适应性权衡和适应成本。我们的系统研究提供了详细的洞察突变，蛋白质结构，蛋白质稳定性和上位性之间的关系，并定量描述了新功能进化中固有的不同成本。
Nature repurposes proteins via evolutionary processes. Such adaptation can come at the expense of the original protein's function, which is a trade-off of adaptation. We sought to examine other potential adaptive trade-offs. We measured the effect on ampicillin resistance of ~ 12,500 unique single amino acid mutants of theTEM-1,TEM-17,TEM-19, andTEM-15 β-lactamase alleles, which constitute an adaptive path in the evolution of cefotaxime resistance. These protein fitness landscapes were compared and used to calculate epistatic interactions between these mutations and the two mutations in the pathway (E104K and G238S). This series of protein fitness landscapes provides a systematic, quantitative description of pairwise/tertiary intragenic epistasis involving adaptive mutations. We find that the frequency of mutations exhibiting epistasis increases along the evolutionary pathway. Adaptation moves the protein to a region in the fitness landscape characterized by decreased mutational robustness and increased ruggedness, as measured by fitness effects of mutations and epistatic interactions for TEM-1's original function. This movement to such a “fitness territory” has evolutionary consequences and is an important adaptive trade-off and cost of adaptation. Our systematic study provides detailed insight into the relationships between mutation, protein structure, protein stability, and epistasis and quantitatively depicts the different costs inherent in the evolution of new functions.