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      Pacing a small cage: mutation and RNA viruses

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          Abstract

          RNA viruses have an extremely high mutation rate, and we argue that the most plausible explanation for this is a trade-off with replication speed. We suggest that research into further increasing this mutation rate artificially as an antiviral treatment requires a theoretical reevaluation, especially relating to the so-called error threshold. The main evolutionary consequence of a high mutation rate appears to have been to restrict RNA viruses to a small genome; they thus rapidly exploit a limited array of possibilities. Investigating this constraint to their evolution, and how it is occasionally overcome, promises to be fruitful. We explain the many terms used in investigating RNA viral evolution and highlight the specific experimental and comparative work that needs to be done.

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          Most cited references42

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          Rates of spontaneous mutation.

          Rates of spontaneous mutation per genome as measured in the laboratory are remarkably similar within broad groups of organisms but differ strikingly among groups. Mutation rates in RNA viruses, whose genomes contain ca. 10(4) bases, are roughly 1 per genome per replication for lytic viruses and roughly 0.1 per genome per replication for retroviruses and a retrotransposon. Mutation rates in microbes with DNA-based chromosomes are close to 1/300 per genome per replication; in this group, therefore, rates per base pair vary inversely and hugely as genome sizes vary from 6 x 10(3) to 4 x 10(7) bases or base pairs. Mutation rates in higher eukaryotes are roughly 0.1-100 per genome per sexual generation but are currently indistinguishable from 1/300 per cell division per effective genome (which excludes the fraction of the genome in which most mutations are neutral). It is now possible to specify some of the evolutionary forces that shape these diverse mutation rates.
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            Deleterious mutations and the evolution of sexual reproduction.

            The origin and maintenance of sexual reproduction continues to be an important problem in evolutionary biology. If the deleterious mutation rate per genome per generation is greater than 1, then the greater efficiency of selection against these mutations in sexual populations may be responsible for the evolution of sex and related phenomena. In modern human populations detrimental mutations with small individual effects are probably accumulating faster than they are being eliminated by selection.
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              The distribution of fitness effects caused by single-nucleotide substitutions in an RNA virus.

              Little is known about the mutational fitness effects associated with single-nucleotide substitutions on RNA viral genomes. Here, we used site-directed mutagenesis to create 91 single mutant clones of vesicular stomatitis virus derived from a common ancestral cDNA and performed competition experiments to measure the relative fitness of each mutant. The distribution of nonlethal deleterious effects was highly skewed and had a long, flat tail. As expected, fitness effects depended on whether mutations were chosen at random or reproduced previously described ones. The effect of random deleterious mutations was well described by a log-normal distribution, with -19% reduction of average fitness; the effects distribution of preobserved deleterious mutations was better explained by a beta model. The fit of both models was improved when combined with a uniform distribution. Up to 40% of random mutations were lethal. The proportion of beneficial mutations was unexpectedly high. Beneficial effects followed a gamma distribution, with expected fitness increases of 1% for random mutations and 5% for preobserved mutations.
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                Author and article information

                Contributors
                Journal
                Trends Ecol Evol
                Trends Ecol. Evol. (Amst.)
                Trends in Ecology & Evolution
                Elsevier Ltd.
                0169-5347
                1872-8383
                4 March 2008
                April 2008
                4 March 2008
                : 23
                : 4
                : 188-193
                Affiliations
                [1 ]Department of Zoology, University of Oxford, Oxford OX1 3PS, UK
                [2 ]Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK
                [3 ]St John's College, University of Oxford, Oxford OX1 3JP, UK
                Article
                S0169-5347(08)00055-4
                10.1016/j.tree.2007.11.010
                7125972
                18295930
                93884c07-ea88-4c51-ab43-d8886331dbeb
                Copyright © 2007 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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                Ecology
                Ecology

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