SUBCLONAL COMPONENTS OF CONSENSUS FITNESS IN AM RNA VIRUS CLONE
SUBCLONAL COMPONENTS OF CONSENSUS FITNESS IN AM RNA VIRUS CLONE
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DOI：
10.1128/jvi.68.7.4295-4301.1994
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发表时间：
1994-07-01
影响因子：
5.4
通讯作者：
HOLLAND, JJ
中科院分区：
文献类型：
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作者：
DUARTE, EA;NOVELLA, IS;HOLLAND, JJ
大多数RNA病毒群体表现出极高的突变频率，产生复杂的，遗传异质性的群体称为准种。以前的研究表明，当大量准种被转移时，自然选择就会发生作用，导致非竞争性（劣势）基因组的淘汰和适应性的快速提高。然而，每当人口不断减少到一个单一的病毒粒子，可变下降的健身发生的预测穆勒的棘轮假说。在这里，我们定量的健身98个亚克隆分离的RNA病毒克隆群体。我们发现了一个正常的分布在一个较低的健身，平均亚克隆不适合比父母克隆人口。这一发现证明了RNA病毒群体中的表型多样性，并表明，正如预期的那样，在病毒复制过程中产生的大部分突变是有害的。这阐明了穆勒棘轮的操作，并说明了为什么必须转移大量病毒体才能发生快速适应性增益。我们还发现，重复的遗传瓶颈通道可以导致不规则的随机下降的健身，再次强调存在于RNA病毒种群的表型异质性。最后，我们发现，仅经过60小时的选择（15次传代，4小时后收获病毒产量），RNA病毒群体的适应性平均增加了250%，即使在它们已经很好适应的宿主细胞类型上也是如此。这是一种非凡的能力;在种群生物学中，即使是低得多的适应性增益（例如，1 - 2%）可以代表非常显著的生殖优势。我们讨论了这些研究结果的自然传播和RNA病毒的发病机制的生物学意义。
Most RNA virus populations exhibit extremely high mutation frequencies which generate complex, genetically heterogeneous populations referred to as quasispecies. Previous work has shown that when a large spectrum of the quasispecies is transferred, natural selection operates, leading to elimination of noncompetitive (inferior) genomes and rapid gains in fitness. However, whenever the population is repeatedly reduced to a single virion, variable declines in fitness occur as predicted by the Muller's ratchet hypothesis. Here, we quantitated the fitness of 98 subclones isolated from an RNA virus clonal population. We found a normal distribution around a lower fitness, with the average subclone being less fit than the parental clonal population. This finding demonstrates the phenotypic diversity in RNA virus populations and shows that, as expected, a large fraction of mutations generated during virus replication is deleterious, This clarifies the operation of Muller's ratchet and illustrates why a large number of virions must be transferred for rapid fitness gains to occur. We also found that repeated genetic bottleneck passages can cause irregular stochastic declines in fitness, emphasizing again the phenotypic heterogeneity present in RNA virus populations. Finally, we found that following only 60 h of selection (15 passages in which virus yields were harvested after 4 h), RNA virus populations can undergo a 250% average increase in fitness, even on a host cell type to which they were already well adapted. This is a remarkable ability; in population biology, even a much lower fitness gain (e.g., 1 to 2%) can represent a highly significant reproductive advantage. We discuss the biological implications of these findings for the natural transmission and pathogenesis of RNA viruses.