Molecular clock-like evolution of human immunodeficiency virus type 1

Area of Science:

• Molecular evolution
• Virology
• Population genetics

Background:

• The molecular clock hypothesis posits a constant rate of nucleotide substitution per generation.
• Noncontemporaneous sampling can lead to misinterpretations of substitution rates, potentially invalidating the molecular clock hypothesis.
• A recent study questioned the clock-like evolution of HIV-1 based on noncontemporaneous samples.

Purpose of the Study:

• To re-evaluate the molecular clock hypothesis for HIV-1 evolution.
• To investigate the impact of noncontemporaneous sampling on perceived substitution rates.
• To differentiate the effects of sampling time, recombination, and natural selection on HIV-1 molecular evolution.

Main Methods:

• Analysis of HIV-1 molecular sequences from within-individual data.
• Stratification of data based on sampling time to account for generation differences.
• Assessment of contributions from noncontemporaneous sampling, recombination, and natural selection.

Main Results:

• Apparent nonclock-like evolution in HIV-1 was largely explained by noncontemporaneous sampling.
• Recombination was identified as a secondary factor contributing to rate variation.
• Natural selection did not significantly obscure the underlying clock-like evolutionary pattern.

Conclusions:

• The molecular clock hypothesis remains largely valid for HIV-1 when sampling time is adequately considered.
• Noncontemporaneous sampling is a critical confounder in molecular clock studies.
• Recombination influences HIV-1 evolution, but does not negate clock-like substitution rates.