Abstract Many positive-sense RNA viruses, especially those infecting plants, are known to experience stringent, stochastic population bottlenecks inside the cells they invade, but exactly how and why these populations become bottlenecked are unclear. A model proposed ten years ago advocates that such bottlenecks are evolutionarily favored because they cause the isolation of individual viral variants in separate cells. Such isolation in turn allows the viral variants to manifest the phenotypic differences they encode. Recently published observations lend mechanistic support to this model and prompt us to refine the model with novel molecular details. The refined model, designated Bottleneck, Isolate, Amplify, Select (BIAS), postulates that these viruses impose population bottlenecks on themselves by encoding bottleneck-enforcing proteins (BNEPs) that function in a concentration-dependent manner. In cells simultaneously invaded by numerous virions of the same virus, BNEPs reach the bottleneck-ready concentration sufficiently early to arrest nearly all internalized viral genomes. As a result, very few (as few as one) viral genomes stochastically escape to initiate reproduction. Repetition of this process in successively infected cells isolates viral genomes with different mutations in separate cells. This isolation prevents mutant viruses encoding defective viral proteins from hitchhiking on sister genome-encoded products, leading to the swift purging of such mutants. Importantly, genome isolation also ensures viral genomes harboring beneficial mutations accrue the cognate benefit exclusively to themselves, leading to the fixation of such beneficial mutations. Further interrogation of the BIAS hypothesis promises to deepen our understanding of virus evolution and inspire new solutions to virus disease mitigation.

中文翻译：

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瓶颈、分离、扩增、选择 (BIAS) 作为正义 RNA 病毒细胞内种群动态的机制框架

摘要 众所周知，许多正链 RNA 病毒，尤其是那些感染植物的病毒，在它们侵入的细胞内会遇到严格的、随机的种群瓶颈，但这些种群究竟如何以及为什么会成为瓶颈尚不清楚。十年前提出的一个模型主张，这种瓶颈在进化上是有利的，因为它们会导致在单独的细胞中分离出单个病毒变体。这种分离反过来又允许病毒变体表现出它们编码的表型差异。最近发表的观察结果为该模型提供了机械支持，并促使我们用新的分子细节改进模型。改进后的模型，指定为瓶颈、隔离、放大、选择 (BIAS)，假设这些病毒通过编码以浓度依赖性方式起作用的瓶颈执行蛋白（BNEPs）来给自身施加种群瓶颈。在同时被同一病毒的多个病毒粒子侵入的细胞中，BNEPs 足够早地达到瓶颈就绪浓度以阻止几乎所有内化的病毒基因组。结果，很少（只有一个）病毒基因组随机逃逸以启动繁殖。在连续感染的细胞中重复这个过程会在不同的细胞中分离出具有不同突变的病毒基因组。这种隔离可防止编码有缺陷病毒蛋白的突变病毒搭便车使用姐妹基因组编码的产品，从而迅速清除此类突变体。重要的，基因组分离还确保含有有益突变的病毒基因组产​​生专门针对自身的同源益处，从而导致此类有益突变的固定。对 BIAS 假设的进一步询问有望加深我们对病毒进化的理解，并激发减轻病毒疾病的新解决方案。