4.6 Review

Mutation Rates, Mutation Frequencies, and Proofreading-Repair Activities in RNA Virus Genetics

Journal

VIRUSES-BASEL
Volume 13, Issue 9, Pages -

Publisher

MDPI
DOI: 10.3390/v13091882

Keywords

RNA virus; virus diversification; quasispecies; error catastrophe; exonuclease; SARS-CoV-2

Categories

Funding

  1. Ministerio de Ciencia, Innovacion y Universidades (MCIU) [SAF2014-52400-R, SAF2017-87846-R, BFU2017-91384]
  2. Instituto de Salud Carlos III [PI18/00210]
  3. Comunidad de Madrid/FEDER) [S2013/ABI-2906, S2018/BAA-4370]
  4. Miguel Servet program of the Instituto de Salud Carlos III [CPII19/00001]
  5. European Regional Development Fund (ERDF)
  6. CIBERehd (Centro de Investigacion en Red de Enfermedades Hepaticas y Digestivas) is - Instituto de Salud Carlos III
  7. Fundacion Ramon Areces and Banco Santander to the CBMSO
  8. MCIU [PRE2018-083422]
  9. Comunidad de Madrid [PEJD-2019-PRE/BMD-16414]

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The error rate during template copying for viral RNA progeny production is a biologically relevant parameter for virus replication complexes, with implications for virus-host interactions and virus diversification. Mutation rates for RNA viruses range from 10(-3) to 10(-6) copying errors per nucleotide incorporated into the new RNA product. Some viruses possess error correction mechanisms, like the proofreading-repair 3' to 5' exonuclease in coronaviruses, to decrease error rates during replication and maintain genetic stability.
The error rate displayed during template copying to produce viral RNA progeny is a biologically relevant parameter of the replication complexes of viruses. It has consequences for virus-host interactions, and it represents the first step in the diversification of viruses in nature. Measurements during infections and with purified viral polymerases indicate that mutation rates for RNA viruses are in the range of 10(-3) to 10(-6) copying errors per nucleotide incorporated into the nascent RNA product. Although viruses are thought to exploit high error rates for adaptation to changing environments, some of them possess misincorporation correcting activities. One of them is a proofreading-repair 3 ' to 5 ' exonuclease present in coronaviruses that may decrease the error rate during replication. Here we review experimental evidence and models of information maintenance that explain why elevated mutation rates have been preserved during the evolution of RNA (and some DNA) viruses. The models also offer an interpretation of why error correction mechanisms have evolved to maintain the stability of genetic information carried out by large viral RNA genomes such as the coronaviruses.

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