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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
Occupation: Professor
Department of Biochemistry, Queen's University, Canada