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      Quasispecies theory in the context of population genetics

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      1 , 2 ,
      BMC Evolutionary Biology
      BioMed Central

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          Abstract

          Background

          A number of recent papers have cast doubt on the applicability of the quasispecies concept to virus evolution, and have argued that population genetics is a more appropriate framework to describe virus evolution than quasispecies theory.

          Results

          I review the pertinent literature, and demonstrate for a number of cases that the quasispecies concept is equivalent to the concept of mutation-selection balance developed in population genetics, and that there is no disagreement between the population genetics of haploid, asexually-replicating organisms and quasispecies theory.

          Conclusion

          Since quasispecies theory and mutation-selection balance are two sides of the same medal, the discussion about which is more appropriate to describe virus evolution is moot. In future work on virus evolution, we would do good to focus on the important questions, such as whether we can develop accurate, quantitative models of virus evolution, and to leave aside discussions about the relative merits of perfectly equivalent concepts.

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          Most cited references80

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          Rapid evolution of RNA genomes.

          RNA viruses show high mutation frequencies partly because of a lack of the proofreading enzymes that assure fidelity of DNA replication. This high mutation frequency is coupled with high rates of replication reflected in rates of RNA genome evolution which can be more than a millionfold greater than the rates of the DNA chromosome evolution of their hosts. There are some disease implications for the DNA-based biosphere of this rapidly evolving RNA biosphere.
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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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              Evolution of digital organisms at high mutation rates leads to survival of the flattest.

              Darwinian evolution favours genotypes with high replication rates, a process called 'survival of the fittest'. However, knowing the replication rate of each individual genotype may not suffice to predict the eventual survivor, even in an asexual population. According to quasi-species theory, selection favours the cloud of genotypes, interconnected by mutation, whose average replication rate is highest. Here we confirm this prediction using digital organisms that self-replicate, mutate and evolve. Forty pairs of populations were derived from 40 different ancestors in identical selective environments, except that one of each pair experienced a 4-fold higher mutation rate. In 12 cases, the dominant genotype that evolved at the lower mutation rate achieved a replication rate >1.5-fold faster than its counterpart. We allowed each of these disparate pairs to compete across a range of mutation rates. In each case, as mutation rate was increased, the outcome of competition switched to favour the genotype with the lower replication rate. These genotypes, although they occupied lower fitness peaks, were located in flatter regions of the fitness surface and were therefore more robust with respect to mutations.
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                Author and article information

                Journal
                BMC Evol Biol
                BMC Evolutionary Biology
                BioMed Central (London )
                1471-2148
                2005
                17 August 2005
                : 5
                : 44
                Affiliations
                [1 ]Keck Graduate Institute of Applied Life Sciences, 535 WatsonDrive, Claremont, California 91711, USA
                [2 ]Digital Life Laboratory, California Institute of Technology, Mail Code 136-93, Pasadena, California 91125, USA
                Article
                1471-2148-5-44
                10.1186/1471-2148-5-44
                1208876
                16107214
                18522783-8628-4707-8301-32483b9189ee
                Copyright © 2005 Wilke; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 February 2005
                : 17 August 2005
                Categories
                Correspondence

                Evolutionary Biology
                Evolutionary Biology

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