A speed-fidelity trade-off determines the mutation rate and virulence of an RNA virus

William Fitzsimmons; Robert J. Woods; John T. McCrone; Andrew Woodman; Jamie J. Arnold; Madhumita Yennawar; Richard Evans; Craig E. Cameron; Adam S. Lauring

Trade-offs are essentially constraints that force one parameter to change with another. In this 263 case, viral mutation rate changes with replicative speed [53] . Similar trade-offs are central to the 264 kinetic proofreading hypothesis, which posits a close relationship between the error rates of 265 biosynthetic processes and the kinetics of their component reactions [54] . Interestingly, studies 266 of DNA replication and protein translation suggest that these systems optimize speed over 267 accuracy, so long as the error rates are within a tolerable range [55, 56] . We find a similar 268 phenomenon in viral RdRp, where the WT generates an extraordinary amount of mutational 269 load, largely because of the benefit in replicative speed.