Clonal interference can cause wavelet-like oscillations of multilocus linkage disequilibrium

Area of Science:

• Evolutionary biology
• Population genetics
• Virology

Background:

• Pathogen adaptation, such as within-host evolution of human immunodeficiency virus (HIV), frequently involves multiple genetic loci.
• The simultaneous emergence of beneficial mutations on different genetic backgrounds can lead to interference, impacting their evolutionary trajectories.

Purpose of the Study:

• To investigate the relationship between evolutionary dynamics of within-host pathogen adaptation and multilocus linkage disequilibrium (MLD).
• To determine if MLD can serve as a signature for interference among multiple advantageous mutations during pathogen evolution.

Main Methods:

• Utilized deterministic early infection models to simulate pathogen evolution.
• Analyzed multilocus linkage disequilibrium (MLD) as a measure of multi-way allele associations.
• Explored parameter regimes relevant to human immunodeficiency virus (HIV) evolution.

Main Results:

• Deterministic models simulating HIV evolution induced oscillating MLD patterns over time, resembling wavelets.
• The frequency of these MLD oscillations was found to be directly proportional to the rate of adaptation.
• This oscillatory signature demonstrated robustness to genetic drift but could be diminished by significant variation in the fitness effects of beneficial mutations.

Conclusions:

• MLD oscillations can serve as a detectable signature of interference among multiple, equally advantageous mutations during within-host pathogen adaptation.
• Interpreting MLD patterns, particularly oscillations, can provide insights into the evolutionary dynamics and adaptation rates of pathogens like HIV.