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Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/74502

Type: Journal article
Title: Antibody selection and amino acid reversions
Author: Da Silva, Jack
Citation: Evolution, 2012; 66(10):3079-3087
Publisher: Soc Study Evolution
Issue Date: 2012
ISSN: 0014-3820
School/Discipline: School of Molecular and Biomedical Science
Statement of
Responsibility: 
Jack da Silva
Abstract: 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.
Keywords: Amino acid reversion; antibody; epitope; escape mutation; HIV
Rights: © 2012 The Author(s). Evolution © 2012 The Society for the Study of Evolution.
RMID: 0020122387
DOI: 10.1111/j.1558-5646.2012.01686.x
Appears in Collections:Molecular and Biomedical Science Publications
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