Natural Selection Promotes Antigenic Evolvability
Natural Selection Promotes Antigenic Evolvability
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DOI：
10.1371/journal.ppat.1003766
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发表时间：
2013-11-01
期刊：
影响因子：
6.7
通讯作者：
Brisson, Dustin
中科院分区：
文献类型：
--
作者：
Graves, Christopher J.;Ros, Vera I. D.;Brisson, Dustin
进化性--通过自然选择进化的能力--本身就是自然选择的对象这一假设非常有趣，但由于缺乏直接的实验证据，这一假设仍然存在争议。微生物病原体的抗原变异机制提供了一个实验上易于处理的系统，以测试自然选择是否有利于提高进化性的机制。许多抗原变异系统由重组到表达位点以快速改变表达蛋白的旁系同源未表达“盒”组成。重要的是，抗原性变化的程度是未表达盒之间遗传多样性的函数。因此，选择有利于基因盒多样性的证据是自然选择促进抗原进化性的直接证据。我们使用莱姆病细菌，伯氏疏螺旋体，作为模型来测试的预测，自然选择有利于未表达的vls盒之间的氨基酸多样性，从而促进在一个主要的表面抗原，VlsE的进化。在每个B中支持vls盒之间的多样性受到自然选择的青睐的假设。使用遗传序列数据的经典（dN/dS比率）和贝叶斯群体遗传分析来分析burgdorferi菌株。这一假设也得到了跨B的高度可变的串联重复结构的保守性的支持。尽管几乎完全不存在序列保守性，但仍然存在伯氏菌株。由于自然选择和可变重复结构，vls盒之间的多样性促进了VlsE的长期抗原进化性。这些发现提供了一个直接的证据，增强表面抗原的进化性的分子机制是一种进化适应。这里确定的分子进化过程可以作为一个模型，在许多病原体利用类似的策略来建立慢性感染的抗原进化性的演变。
The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.