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Evolution of relative synonymous codon usage in Human Immunodeficiency Virus type-1
Peter L Meintjes1, Allen G Rodrigo
1Bioinformatics Institute and Computational and Evolutionary Biology Lab, School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand. p.meintjes@auckland.ac.nz
Journal of Bioinformatics and Computational Biology
|March 8, 2005
Summary
Human Immunodeficiency Virus type-1 (HIV-1) evolves rapidly due to its reverse transcription. This study investigated if HIV-1 codon usage shifts towards human patterns over time, but found mutation pressure, not host adaptation, drives this change.
Area of Science:
- Virology
- Molecular Biology
- Evolutionary Biology
Background:
- Human Immunodeficiency Virus type-1 (HIV-1) exhibits rapid mutation rates, approximately 1% per year in its envelope gene, due to low-fidelity reverse transcription.
- HIV-1's relative synonymous codon usage (RSCU) differs from its human host, yet reengineering HIV-1 to match human RSCU significantly increases protein expression.
- This suggests a potential selective pressure for HIV-1's RSCU to adapt towards that of the human host during prolonged infection.
Purpose of the Study:
- To investigate the hypothesis that HIV-1's RSCU evolves towards human patterns within a host over time.
- To determine if observed changes in codon usage are driven by host adaptation or other evolutionary pressures.
Main Methods:
- Analysis of serially sampled HIV-1 partial envelope sequences from eight patients.
- Construction of RSCU tables for early and late stage sequences within each patient.
- Application of Principal Components Analysis (PCA) to discriminate between early and late sequences based on RSCU values.
- Correlation analysis of viral RSCU with human RSCU for both early and late sequence groups.
Main Results:
- Principal Components Analysis clearly distinguished between early and late HIV-1 sequences based on RSCU.
- While late viral RSCUs showed a tendency towards higher correlation with human RSCU, statistical significance was observed.
- Closer examination revealed that this trend was primarily caused by mutation pressure homogenizing codon usage, rather than active host adaptation.
Conclusions:
- The observed shift in HIV-1 RSCU towards human patterns over time is not driven by host adaptation.
- Mutation pressure plays a significant role in homogenizing codon usage in HIV-1, mimicking a trend towards host patterns.
- Understanding these evolutionary dynamics is crucial for developing effective antiviral strategies and therapies.