Author: William Fitzsimmons; Robert J. Woods; John T. McCrone; Andrew Woodman; Jamie J. Arnold; Madhumita Yennawar; Richard Evans; Craig E. Cameron; Adam S. Lauring
Title: A speed-fidelity trade-off determines the mutation rate and virulence of an RNA virus Document date: 2018_4_27
ID: 8p24gszj_27
Snippet: We also examined the impact of the r-selected mutations on virulence. The 2C V127L mutation, 238 which conferred a fitness of 1.11 in the 3D G64S background and does not appear to affect fidelity 239 ( Fig. S3) , restored virulence to nearly WT levels (p=0.0012, log rank test, compare 3D G64S to 240 3D G64S ;2C V127L in Fig. 4E ). In contrast, the triple mutant, 3D G64S;I92T;K276R , which replicates with a 241 wild type mutation rate and a margin.....
Document: We also examined the impact of the r-selected mutations on virulence. The 2C V127L mutation, 238 which conferred a fitness of 1.11 in the 3D G64S background and does not appear to affect fidelity 239 ( Fig. S3) , restored virulence to nearly WT levels (p=0.0012, log rank test, compare 3D G64S to 240 3D G64S ;2C V127L in Fig. 4E ). In contrast, the triple mutant, 3D G64S;I92T;K276R , which replicates with a 241 wild type mutation rate and a marginally increased fitness of 0.7637, was only slightly more 242 virulent than the high fidelity variant 3D G64S (p=0.0411, log rank test, compare 3D G64S to 243 3D G64S;I92T;K276R in Fig. 4F ). Therefore, restoration of replicative speed restored virulence in 244 3D G64S , but compensation of the fidelity phenotype did not.
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