ANTIBODY SELECTION AND AMINO ACID REVERSIONS
Article first published online: 21 MAY 2012
© 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.
Volume 66, Issue 10, pages 3079–3087, October 2012
How to Cite
Silva, J. d. (2012), ANTIBODY SELECTION AND AMINO ACID REVERSIONS. Evolution, 66: 3079–3087. doi: 10.1111/j.1558-5646.2012.01686.x
- Issue published online: 1 OCT 2012
- Article first published online: 21 MAY 2012
- Accepted manuscript online: 9 MAY 2012 10:00PM EST
- Received July 31, 2010, Accepted April 22, 2012, Data Archived: Dryad doi:10.5061/dryad.69mk7
- Amino acid reversion;
- escape mutation;
Pathogens adapt to antibody surveillance through amino acid replacements in targeted protein regions, or epitopes, that interfere with antibody binding. However, such escape mutations may exact a fitness cost due to impaired protein function. Here, it is hypothesized that the recurring generation of specific neutralizing antibodies to an epitope region as it evolves in response to antibody selection will cause amino acid reversions by releasing early escape mutations from immune selection. The plausibility of this hypothesis was tested with stochastic simulation of adaptation at the molecular sequence level in finite populations. Under the conditions of strong selection and weak mutation, the rates of allele fixation and amino acid reversion increased with population size and selection coefficients. These rates decreased with population size, however, if mutation became strong, because clonal interference reduced the rate of adaptation. The model successfully predicts the rate of reversion per allele fixation for an important human immunodeficiency virus type 1 (HIV-1) antibody epitope region. Therefore, antibody selection may generate complex adaptive dynamics.