The cost of replication fidelity in an RNA virus

doi:10.1073/pnas.0501062102

The cost of replication fidelity in an RNA virus

Institut Cavanilles de Biodiversitat i Biologia Evolutiva, Universitat de València, P.O. Box 22085, 46071 València, Spain

Edited by Tomoko Ohta, National Institute of Genetics, Mishima, Japan (received for review February 8, 2005)

Abstract

It is often argued that high mutation rates are advantageous for RNA viruses, because they confer elevated rates of adaptation. However, there is no direct evidence showing a positive correlation between mutation and adaptation rates among RNA viruses. Moreover, theoretical work does not argue in favor of this prediction. We used a series of vesicular stomatitis virus clones harboring single amino acid substitutions in the RNA polymerase to demonstrate that changes inducing enhanced fidelity paid a fitness cost, but that there was no positive correlation between mutation an adaptation rates. We demonstrate that the observed mutation rate in vesicular stomatitis virus can be explained by a trade-off between replication rate and replication fidelity.

Footnotes

↵ * To whom correspondence should be addressed. E-mail: rafsaver{at}ibmcp.upv.es.
Author contributions: A.M. and R.S. designed research; V.F. performed research; V.F. and R.S. analyzed data; and R.S. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: hpi, hours postinoculation; pfu, plaque-forming units; ss l^-1·r^-1, substitutions per locus per replication cycle; VSV, vesicular stomatitis virus; BHK₂₁, baby hamster kidney; ML, maximum likelihood; CI, confidence interval.