Lost in translation: Implications of HIV-1 codon usage for immune escape and drug resistance

Gustavo H. Kijak*, Jeffrey R. Currier, Sodsai Tovanabutra, Josephine H. Cox, Nelson L. Michael, Scott A. Wegner, Deborah L. Birx, Francine E. McCutchan

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations


Synonymous nucleotide substitutions in protein-coding sequences are often regarded as evolutionarily neutral and not subject to selective pressure. However, synonymous codons can sometimes lead to different patterns of amino acid substitutions by single nucleotide changes. Based on the deconstruction of the standard genetic code, we propose the term 'quasi-synonymous' to describe codons that specify the same amino acid, but lie on different mutational pathways, and we show that in at least one rapidly evolving organism, HIV-1, quasi-synonymy plays a role in its evolution. We present concrete examples that demonstrate the relevance of codon usage in the development of antiretroviral-drug resistance. In the case of the host immune response, the data indicates that viral evasion is achieved through use of codons that lie on the direct path to escape mutants, and equally, permit rapid reversion to wild-type in the absence of these selective pressures. Quasi-synonymy conditions HIV-1 and, potentially, other rapidly evolving organisms in their exploration of the mutational space.

Original languageEnglish
Pages (from-to)54-60
Number of pages7
JournalAIDS Reviews
Issue number1
StatePublished - Jan 2004
Externally publishedYes


  • Condon usage
  • Drug resistance
  • HIV evolution
  • Immune escape


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