Holder K K, Bull J J
Section of Integrative Biology, Institute of Cellular and Molecular Biology, University of Texas, Austin, Texas 78712-1023, USA.
Genetics. 2001 Dec;159(4):1393-404. doi: 10.1093/genetics/159.4.1393.
The related bacteriophages phiX174 and G4 were adapted to the inhibitory temperature of 44 degrees and monitored for nucleotide changes throughout the genome. Phage were evolved by serial transfer at low multiplicity of infection on rapidly dividing bacteria to select genotypes with the fastest rates of reproduction. Both phage showed overall greater fitness effects per substitution during the early stages of adaptation. The fitness of phiX174 improved from -0.7 to 5.6 doublings of phage concentration per generation. Five missense mutations were observed. The earliest two mutations accounted for 85% of the ultimate fitness gain. In contrast, G4 required adaptation to the intermediate temperature of 41.5 degrees before it could be maintained at 44 degrees. Its fitness at 44 degrees increased from -2.7 to 3.2, nearly the same net gain as in phiX174, but with three times the opportunity for adaptation. Seventeen mutations were observed in G4: 14 missense, 2 silent, and 1 intergenic. The first 3 missense substitutions accounted for over half the ultimate fitness increase. Although the expected pattern of periodic selective sweeps was the most common one for both phage, some mutations were lost after becoming frequent, and long-term polymorphism was observed. This study provides the greatest detail yet in combining fitness profiles with the underlying pattern of genetic changes, and the results support recent theories on the range of fitness effects of substitutions fixed during adaptation.
将相关噬菌体φX174和G4适应44摄氏度的抑制温度，并监测整个基因组的核苷酸变化。通过在快速分裂的细菌上以低感染复数进行连续传代来进化噬菌体，以选择繁殖速度最快的基因型。在适应的早期阶段，两种噬菌体每发生一次替换总体上都表现出更大的适应性效应。φX174的适应性从每代噬菌体浓度增加-0.7倍提高到5.6倍。观察到五个错义突变。最早的两个突变占最终适应性增加的85%。相比之下，G4需要先适应41.5摄氏度的中间温度，才能在44摄氏度下维持。它在44摄氏度时的适应性从-2.7提高到3.2，净增加量与φX174几乎相同，但有三倍的适应机会。在G4中观察到17个突变：14个错义突变, 2个沉默突变和1个基因间突变。前3个错义替换占最终适应性增加的一半以上。尽管周期性选择性清除的预期模式是两种噬菌体最常见的模式，但一些突变在变得频繁后消失了，并观察到了长期多态性。这项研究在将适应性概况与潜在的遗传变化模式相结合方面提供了迄今为止最详细的信息，结果支持了最近关于适应过程中固定替换的适应性效应范围的理论。
