Data from: Antibody selection and amino acid reversions

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 hypothesised that the recurring generation of specific neutralising 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.病原体可通过靶向蛋白区域（亦称表位(epitope)）内的氨基酸替换逃避免疫抗体监视，此类替换会干扰抗体与抗原的结合。然而，这类逃逸突变可能因蛋白功能受损而产生适合度代价。本研究提出假说：当表位区域在抗体选择压力下持续演化时，针对该区域的特异性中和抗体的持续产生，会通过解除早期逃逸突变所承受的免疫选择压力，引发氨基酸回复突变。本研究通过有限种群下分子序列层面的适应性随机模拟，验证了该假说的合理性。在强选择、弱突变的条件下，等位基因固定速率与氨基酸回复突变速率均随种群规模与选择系数的增大而提升。但当突变强度较高时，此类速率反而随种群规模扩大而降低，这是因为克隆干扰会降低适应性演化速率。该模型成功预测了人类免疫缺陷病毒1型(HIV-1)重要抗体表位区域内，每单位等位基因固定所对应的回复突变速率。由此可见，抗体选择压力可催生复杂的适应性动力学过程。