Parallel Evolution of HIV-1 in a Long-Term Experiment.

Area of Science:

• Evolutionary Biology
• Virology
• Genetics

Background:

• The repeatability of evolution is a fundamental question in biology.
• Investigating parallel evolution in clinically relevant viruses like HIV-1 is crucial but underexplored.

Purpose of the Study:

• To investigate the extent of parallel evolution in Human Immunodeficiency Virus type 1 (HIV-1).
• To assess the impact of parallel evolution on phylogenetic reconstruction.
• To determine if initial viral genetic diversity predicts evolutionary outcomes.

Main Methods:

• Passaging HIV-1 populations for nearly one year in human T-cell lines.
• Deep sequencing the entire viral genome at multiple time points across four independent evolution lines.
• Analyzing both majority and minority mutations to understand viral population dynamics.

Main Results:

• Significant parallel evolution was observed, with many mutations arising independently in multiple HIV-1 populations.
• 62% of majority mutations in one line also appeared in another, indicating extreme repeatability.
• Phylogenetic reconstruction was hindered by parallel evolution, but including minority mutations improved accuracy.
• Initial viral genetic diversity was predictive of the frequency of majority mutations at the experiment's conclusion.

Conclusions:

• HIV-1 evolution exhibits a high degree of parallelism, challenging traditional phylogenetic methods.
• Incorporating minority mutations is essential for accurate evolutionary history reconstruction of rapidly evolving viruses.
• Early viral genetic diversity is a significant predictor of long-term evolutionary trajectories in HIV-1.