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Research Article

Synonymous Substitution Rates Predict HIV Disease Progression as a Result of Underlying Replication Dynamics

  • Philippe Lemey mail,

    To whom correspondence should be addressed. E-mail: philippe.lemey@zoo.ox.ac.uk

    Affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom

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  • Sergei L Kosakovsky Pond,

    Affiliation: Department of Pathology, University of California San Diego, La Jolla, United States of America

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  • Alexei J Drummond,

    Affiliation: Department of Computer Science, University of Auckland, Auckland, New Zealand

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  • Oliver G Pybus,

    Affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom

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  • Beth Shapiro,

    Affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom

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  • Helena Barroso,

    Affiliations: Centro de Patogénese Molecular, Faculdade de Farmácia de Lisboa, Lisbon, Portugal, Instituto Superior de Ciências da Saúde Egas Moniz, Lisbon, Portugal

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  • Nuno Taveira,

    Affiliations: Centro de Patogénese Molecular, Faculdade de Farmácia de Lisboa, Lisbon, Portugal, Instituto Superior de Ciências da Saúde Egas Moniz, Lisbon, Portugal

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  • Andrew Rambaut

    Affiliation: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom

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  • Published: February 16, 2007
  • DOI: 10.1371/journal.pcbi.0030029

Reader Comments (1)

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Synonymous sites are not neutral

Posted by PLoS_CompBiol on 20 Feb 2008 at 19:40 GMT

Originally posted as a Reader Response on 18th February, 2007

The authors report a positive association between the "silent" (i.e., synonymous) evolutionary rate of HIV and the rate of disease progression, but their "reasoning assumes that synonymous substitutions are selectively neutral." To support this, they cite studies (Sanjuan et al. 2004) on another rapidly evolving RNA virus (vesicular stomatitis virus, VSV; ref. 39) that "clearly showed that synonymous changes were roughly neutral." However, Novella et al. have provided strong evidence for positive selection of synonymous mutations in VSV (Journal of Molecular Biology 2004;342:1415-1421). The numerous selective pressures on synonymous sites have been reviewed elsewhere (Forsdyke, DR. Trends in Parasitology 2002;18:411-418). For example, the potential for RNA secondary structure in HIV has been shown to be impaired when substitution rates are high (Forsdyke, DR. Journal of Molecular Evolution 1995;41:1022-1037). There are many reasons why there should be an association between disease progression and synonymous substitution rate apart from "underlying replication dynamics."

Submitted by: Donald Forsdyke
E-mail: forsdyke@post.queensu.ca
Occupation: Professor
Department of Biochemistry, Queen's University, Canada