Selective pressure causes an RNA virus to trade reproductive fitness for increased structural and thermal stability of a viral enzyme.
Selective pressure causes an RNA virus to trade reproductive fitness for increased structural and thermal stability of a viral enzyme.
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DOI：
10.1371/journal.pgen.1003102
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Modis Y
中科院分区：
文献类型：
--
作者：
Dessau M;Goldhill D;McBride R;Turner PE;Modis Y
在环境变化过程中，通过单个突变替换来调节适应性是自然选择最基本的结果。因此，在不断变化的环境中，可以选择的多效性突变的拮抗权衡是进化生物学的基础。然而，适应性权衡的分子基础很少确定这些多效性突变如何影响蛋白质结构。在这里，我们使用一个跨学科的方法来研究如何拮抗多效性和蛋白质功能决定健身权衡。我们挑战了RNA病毒噬菌体Φ6的种群，使其在一种新的温度环境中进化，在这种环境中，热休克会导致极端的病毒死亡率。病毒溶素蛋白P5（V207 F）中的单个氨基酸取代有利于改善稳定性，因此有利于挑战病毒的存活，尽管伴随着降低病毒繁殖的权衡。该突变增加了P5的热稳定性。野生型，突变体和配体结合的P5的晶体结构揭示了这种热稳定性的分子基础-Phe 207侧链填充了野生型中未被占据的疏水空腔-并将P5鉴定为裂解性转糖基酶。该突变没有降低P5的酶活性，这表明繁殖权衡源于其他因素，如低效的衣壳组装或拆卸。我们的研究展示了如何结合实验进化，生物化学和结构生物学可以确定在生存和繁殖之间的经典进化拔河中驱动单个点突变的拮抗性多效性表型的机制。在不断变化的环境中，自然选择最基本的机制是通过突变来调节适应性。正是这些突变提供的权衡推动了进化。然而，在分子水平上很少了解适应性权衡，即所选突变如何影响蛋白质结构和功能。在这里，我们将实验进化和结构生物学相结合，研究生存和繁殖之间的基本权衡。我们挑战RNA病毒种群在一种新的温度环境中进化，在这种环境中，热休克会导致极端的病毒死亡率。特定病毒蛋白中的单一突变增加了稳定性，因此增加了受挑战病毒的存活，尽管伴随着降低病毒繁殖的权衡。该突变增加了突变蛋白的热稳定性。野生型和突变蛋白的原子结构揭示了这种稳定的分子基础。这种突变并没有降低蛋白质的酶活性，这表明繁殖的权衡源于其他因素，如无效的病毒组装或拆卸。我们的研究揭示了在生存和繁殖之间的经典进化拔河中驱动单个点突变的拮抗作用的机制。
The modulation of fitness by single mutational substitutions during environmental change is the most fundamental consequence of natural selection. The antagonistic tradeoffs of pleiotropic mutations that can be selected under changing environments therefore lie at the foundation of evolutionary biology. However, the molecular basis of fitness tradeoffs is rarely determined in terms of how these pleiotropic mutations affect protein structure. Here we use an interdisciplinary approach to study how antagonistic pleiotropy and protein function dictate a fitness tradeoff. We challenged populations of an RNA virus, bacteriophage Φ6, to evolve in a novel temperature environment where heat shock imposed extreme virus mortality. A single amino acid substitution in the viral lysin protein P5 (V207F) favored improved stability, and hence survival of challenged viruses, despite a concomitant tradeoff that decreased viral reproduction. This mutation increased the thermostability of P5. Crystal structures of wild-type, mutant, and ligand-bound P5 reveal the molecular basis of this thermostabilization—the Phe207 side chain fills a hydrophobic cavity that is unoccupied in the wild-type—and identify P5 as a lytic transglycosylase. The mutation did not reduce the enzymatic activity of P5, suggesting that the reproduction tradeoff stems from other factors such as inefficient capsid assembly or disassembly. Our study demonstrates how combining experimental evolution, biochemistry, and structural biology can identify the mechanisms that drive the antagonistic pleiotropic phenotypes of an individual point mutation in the classic evolutionary tug-of-war between survival and reproduction. The most fundamental mechanism of natural selection in a changing environment is the modulation of fitness by mutations. It is the tradeoffs offered by these mutations that drive evolution. However, fitness tradeoffs are rarely understood at the molecular level, in terms of how the selected mutations affect protein structure and function. Here, we merge experimental evolution and structural biology to study the fundamental tradeoff between survival and reproduction. We challenged populations of an RNA virus to evolve in a novel temperature environment where heat shock imposed extreme virus mortality. A single mutation in a specific viral protein increased the stability, and hence survival of challenged viruses, despite a concomitant tradeoff that decreased viral reproduction. This mutation increased the thermal stability of the mutant protein. Atomic structures of the wild-type and mutant protein reveal the molecular basis of this stabilization. The mutation did not reduce the enzymatic activity of the protein, suggesting that the reproduction tradeoff stems from other factors, such as inefficient virus assembly or disassembly. Our study uncovers the mechanism that drives the antagonistic effects of an individual point mutation in the classic evolutionary tug-of-war between survival and reproduction.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1016/0167-4838(92)90073-m
发表时间：
1992-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
CALDENTEY, J;BAMFORD, DH
通讯作者：
BAMFORD, DH
影响因子：
2
作者：
HAMILTON, WD
通讯作者：
HAMILTON, WD
影响因子：
64.8
作者：
BLAKE, CCF;KOENIG, DF;SARMA, VR
通讯作者：
SARMA, VR
影响因子：
1.9
作者：
Alto, Barry W.;Turner, Paul E.
通讯作者：
Turner, Paul E.