Bull J J, Badgett M R, Wichman H A
Department of Integrative Biology and Institute of Cellular and Molecular Biology, University of Texas at Austin, 78712-1023, USA.
Mol Biol Evol. 2000 Jun;17(6):942-50. doi: 10.1093/oxfordjournals.molbev.a026375.
High temperature inhibits the growth of the wild-type bacteriophage phiX174. Three different point mutations were identified that each recovered growth at high temperature. Two affected the major capsid protein (residues F188 and F242), and one affected the internal scaffolding protein (B114). One of the major capsid mutations (F242) is located in a beta strand that contacts B114 in the procapsid during viral maturation, whereas the other capsid mutation (F188) is involved in subunit interactions at the threefold axis of symmetry. Selective coefficients of these mutations ranged from 13.9 to 3.8 in the inhibitory, hot environment, but all mutations reduced fitness at normal temperature. The selective effect of one of the mutations (F242) was evaluated at high temperature in four different genetic backgrounds and exhibited epistasis of diminishing returns: as log fitness of the background genotype increased from -0.1 to 4.1, the fitness boost provided by the F242 mutation decreased from 3.9 to 0. 8. These results support a model in which viral fitness is bounded by an upper limit and the benefit of a mutation is scaled according to the remaining opportunity for fitness improvement in the genome.
高温会抑制野生型噬菌体phiX174的生长。已鉴定出三种不同的点突变，每种突变都能在高温下恢复生长。其中两种突变影响主要衣壳蛋白（第188位和第242位氨基酸），一种突变影响内部支架蛋白（第114位氨基酸）。主要衣壳突变之一（F242）位于病毒成熟过程中前衣壳内与B114接触的一条β链中，而另一个衣壳突变（F188）则参与了对称三重轴处的亚基相互作用。在抑制性的高温环境中，这些突变的选择系数范围为13.9至3.8，但所有突变在正常温度下都会降低适应性。其中一个突变（F242）在四种不同遗传背景下的高温环境中进行了评估，结果显示出收益递减的上位性：随着背景基因型的对数适应性从-0.1增加到4.1，F242突变带来的适应性提升从3.9降至0.8。这些结果支持了一种模型，即病毒适应性存在上限，并且突变的益处会根据基因组中剩余的适应性提升机会进行缩放。
