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Codon usage of HIV regulatory genes is not determined by nucleotide composition

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Abstract

Codon usage bias can be a result of either mutational bias or selection for translational efficiency and/or accuracy. Previous data has suggested that nucleotide composition constraint was the main determinant of HIV codon usage, and that nucleotide composition and codon usage were different between the regulatory genes, tat and rev, and other viral genes. It is not clear whether translational selection contributed to the codon usage difference and how nucleotide composition and translational selection interact to determine HIV codon usage. In this study, a model of codon bias due to GC composition with modification for the A-rich third codon position was used to calculate predicted HIV codon frequencies based on its nucleotide composition. The predicted codon usage of each gene was compared with the actual codon frequency. The predicted codon usage based on GC composition matched well with the actual codon frequencies for the structural genes (gag, pol and env). However, the codon usage of the regulatory genes (tat and rev) could not be predicted. Codon usage of the regulatory genes was also relatively unbiased showing the highest effective number of codons (ENC). Moreover, the codon adaptation index (CAI) of the regulatory genes showed better adaptation to human codons when compared to other HIV genes. Therefore, the early expressed genes responsible for regulation of the replication cycle, tat and rev, were more similar to humans in terms of codon usage and GC content than other HIV genes. This may help these genes to be expressed efficiently during the early stages of infection.

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Abbreviations

RSCU:

Relative synonymous codon usage

ENC:

Effective number of codon

CAI:

Codon adaptation index

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Acknowledgements

This work was financial supported by the Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (Grant No. PHD/0030/2556) and a research grant (Grant No. IRN60W0002) from Thailand Research Fund.

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Authors and Affiliations

  1. Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand

    Supinya Phakaratsakul, Thanyaporn Sirihongthong, Chompunuch Boonarkart & Prasert Auewarakul

  2. Research and International Relations Division, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, 10210, Thailand

    Ornpreya Suptawiwat

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  1. Supinya Phakaratsakul
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  2. Thanyaporn Sirihongthong
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Correspondence to Prasert Auewarakul.

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Handling editor: Li Wu.

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Phakaratsakul, S., Sirihongthong, T., Boonarkart, C. et al. Codon usage of HIV regulatory genes is not determined by nucleotide composition. Arch Virol 163, 337–348 (2018). https://doi.org/10.1007/s00705-017-3597-5

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  • DOI: https://doi.org/10.1007/s00705-017-3597-5

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