GENETIC BOTTLENECKS AND POPULATION PASSAGES CAUSE PROFOUND FITNESS DIFFERENCES IN RNA VIRUSES
GENETIC BOTTLENECKS AND POPULATION PASSAGES CAUSE PROFOUND FITNESS DIFFERENCES IN RNA VIRUSES
复制标题
DOI：
10.1128/jvi.67.1.222-228.1993
复制
发表时间：
1993-01-01
影响因子：
5.4
通讯作者：
HOLLAND, J
中科院分区：
文献类型：
--
作者：
CLARKE, DK;DUARTE, EA;HOLLAND, J
RNA噬菌体和水泡性口炎病毒的重复克隆（遗传瓶颈）传代先前已被证明会导致穆勒棘轮引起的适应性丧失。我们现在证明，当基因瓶颈传代在37摄氏度而不是32摄氏度下进行时，穆勒棘轮也会起作用。因此，这些适应性损失并不取决于温度敏感（ts）突变体在较低温度下的生长。我们还证明，在重复的遗传瓶颈传代中，有害突变的积累确实以Muller最初提出的循序渐进（棘轮状）的方式发生。在克隆-克隆系列中，选择一个仅经过20个遗传瓶颈传代后适应度损失显著的无性系进行再传代。在9个独立的瓶颈序列中，有5个观察到额外的大适应度损失；其他四个系列的相对适合度保持接近于初始适合度。与此形成鲜明对比的是，当同一选择的克隆作为大群体转移20次以上(每次传递10（5)至10(6)个PFU）时，在所有8个传代系列中都观察到适应度的显著增加。最后，我们选择了几个在20个瓶颈传代中适应度损失最大的无性系。当这些低适应度的克隆作为大病毒群体传代多次时，它们总是恢复到非常高的相对适应度。我们得出结论，RNA病毒大群体的转移通常会选择准种群体中相对适应度最高的基因组，而瓶颈转移则很可能通过随机分离携带衰弱突变的基因组而导致适应度丧失。这两种现象都源于并强调了RNA病毒的极端易变性和可变性。
Repeated clone-to-clone (genetic bottleneck) passages of an RNA phage and vesicular stomatitis virus have been shown previously to result in loss of fitness due to Muller's ratchet. We now demonstrate that Muller's ratchet also operates when genetic bottleneck passages are carried out at 37 rather than 32-degrees-C. Thus, these fitness losses do not depend on growth of temperature-sensitive (ts) mutants at lowered temperatures. We also demonstrate that during repeated genetic bottleneck passages, accumulation of deleterious mutations does occur in a stepwise (ratchet-like) manner as originally proposed by Muller. One selected clone which had undergone significant loss of fitness after only 20 genetic bottleneck passages was passaged again in clone-to-clone series. Additional large losses of fitness were observed in five of nine independent bottleneck series; the relative fitnesses of the other four series remained close to the starting fitness. In sharp contrast, when the same selected clone was transferred 20 more times as large populations (10(5) to 10(6) PFU transferred at each passage), significant increases in fitness were observed in all eight passage series. Finally, we selected several clones which had undergone extreme losses of fitness during 20 bottleneck passages. When these low-fitness clones were passaged many times as large virus populations, they always regained very high relative fitness. We conclude that transfer of large populations of RNA viruses regularly selects those genomes within the quasispecies population which have the highest relative fitness, whereas bottleneck transfers have a high probability of leading to loss of fitness by random isolation of genomes carrying debilitating mutations. Both phenomena arise from, and underscore, the extreme mutability and variability of RNA viruses.