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Widespread adaptive evolution in the human immunodeficiency virus type 1 genome
Wa Yang1, Joseph P Bielawski, Ziheng Yang
1Department of Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Journal of Molecular Evolution
|October 18, 2003
Summary
HIV-1 evolution is driven by diversifying selection pressures acting on amino acid sites across its genome. These pressures, particularly evident in the env gene, highlight key sites for potential therapeutic targeting.
Area of Science:
- Evolutionary biology
- Virology
- Genomics
Background:
- HIV-1 exhibits rapid evolution, necessitating an understanding of the selective pressures shaping its genome.
- Amino acid site variability is crucial for viral adaptation and immune evasion.
Purpose of the Study:
- To investigate variable selective pressures at amino acid sites within HIV-1 genes.
- To identify specific sites under positive selection and analyze their properties.
Main Methods:
- Analysis of genomic sequences from 26 HIV-1 lineages using maximum likelihood models.
- Calculation of the nonsynonymous/synonymous substitution rate ratio (omega = dN/dS) to detect positive selection (omega > 1).
- Mapping of selected sites onto protein structures and immunogenic epitopes.
Main Results:
- Positive selection was detected across major HIV-1 genes (env, gag, pol, vif, vpr, nef, tat, vpu), with a concentration in gp160.
- Amino acid sites under positive selection exhibited greater physicochemical diversity, especially at exposed sites.
- Averaging omega across all sites lacked the power to detect these localized selection pressures.
Conclusions:
- Genomewide diversifying selection actively shapes the HIV-1 proteome.
- Understanding site-specific selection is critical for comprehending viral adaptation and developing interventions.