Department of Microbiology and Immunology, University of Toledo Health Science Campus, Mail Stop 1210, Toledo, OH 43614, USA.
J Virol. 2010 May;84(10):4960-8. doi: 10.1128/JVI.00710-09. Epub 2010 Feb 24.
Virus strains with a history of repeated genetic bottlenecks frequently show a diminished ability to adapt compared to strains that do not have such a history. These differences in adaptability suggest differences in either the rate at which beneficial mutations are produced, the effects of beneficial mutations, or both. We tested these possibilities by subjecting four populations (two controls and two mutants with lower adaptabilities) to multiple replicas of a regimen of positive selection and then determining the fitnesses of the progeny through time and the changes in the consensus, full-length sequences of 56 genomes. We observed that at a given number of passages, the overall fitness gains observed for control populations were larger than fitness gains in mutant populations. However, these changes did not correlate with differences in the numbers of mutations accumulated in the two types of genomes. This result is consistent with beneficial mutations having a lower beneficial effect on mutant strains. Despite the overall fitness differences, some replicas of one mutant strain at passage 50 showed fitness increases similar to those observed for the wild type. We hypothesized that these evolved, high-fitness mutants may have a lower robustness than evolved, high-fitness controls. Robustness is the ability of a virus to avoid phenotypic changes in the face of mutation. We confirmed our hypothesis in mutation-accumulation experiments that showed a normalized fitness loss that was significantly larger in mutant bottlenecked populations than in control populations.
具有多次遗传瓶颈历史的病毒株与没有这种历史的病毒株相比，适应能力常常减弱。这些适应性差异表明，有益突变的产生速度、有益突变的影响或两者都存在差异。我们通过将四个群体（两个对照群体和两个适应能力较低的突变体群体）置于多次正选择方案的重复中，然后通过时间确定后代的适应性，并确定 56 个全基因组序列共识的变化，来检验这些可能性。我们观察到，在给定的传代次数下，对照群体的总体适应性增益大于突变体群体的适应性增益。然而，这些变化与两种基因组中积累的突变数量的差异无关。这一结果与有益突变对突变株的有益影响较低相一致。尽管存在整体适应性差异，但在传代 50 时，一个突变体菌株的一些复制品显示出与野生型相似的适应性增加。我们假设这些进化后的高适应性突变体可能比进化后的高适应性对照体的稳健性更低。稳健性是指病毒在面对突变时避免表型变化的能力。我们在突变积累实验中证实了我们的假设，该实验显示，在突变瓶颈化群体中，归一化适应性损失明显大于对照群体。
