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Molecular Biology and Evolution 17:942-950 (2000)
© 2000 Society for Molecular Biology and Evolution


Article

Big-Benefit Mutations in a Bacteriophage Inhibited with Heat

J. J. Bull2,*{dagger}, M. R. Badgett* and H. A. Wichman{dagger}

*Department of Integrative Biology and
{dagger}Institute of Cellular and Molecular Biology, University of Texas at Austin; and
{ddagger}Department of Biological Sciences, University of Idaho

High temperature inhibits the growth of the wild-type bacteriophage {phi}X174. 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 ß 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.


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