Antibody selection and amino acid reversions

Area of Science:

• Evolutionary biology
• Immunology
• Molecular biology

Background:

• Pathogens evade antibody surveillance via mutations in epitopes, which can incur a fitness cost.
• Antibody selection drives pathogen evolution, but the long-term consequences of this evolutionary pressure are complex.

Purpose of the Study:

• To investigate the hypothesis that evolving antibody responses can lead to the reversion of early escape mutations.
• To model the dynamics of molecular adaptation in pathogen populations under immune selection.

Main Methods:

• Stochastic simulation of molecular sequence evolution in finite populations.
• Analysis of allele fixation and reversion rates under varying selection and mutation pressures.
• Model validation using data from a human immunodeficiency virus type 1 (HIV-1) epitope.

Main Results:

• Allele fixation and amino acid reversion rates increased with population size and selection strength under strong selection and weak mutation.
• Increased mutation strength led to decreased adaptation rates due to clonal interference.
• The model accurately predicted reversion rates for an HIV-1 antibody epitope.

Conclusions:

• Antibody selection can drive complex adaptive evolutionary dynamics in pathogens.
• The interplay between immune selection, mutation, and population size shapes pathogen evolution.
• Understanding these dynamics is crucial for predicting pathogen adaptation and designing effective interventions.