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质区域（即抗原表位（epitope））中的氨基酸替换来适应抗体监视，此类替换会干扰抗体结合。不过这类逃逸突变可能因蛋白质功能受损而带来适合度代价。本研究提出假说：当抗原表位区域因应对抗体选择压力而发生演化时，若持续产生针对该区域的特异性中和抗体，将通过解除早期逃逸突变所面临的免疫选择压力，引发氨基酸回复突变。本研究通过对有限种群中分子序列层面的适应性演化进行随机模拟，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及选择系数的增大而提升。但若突变强度较高，这些速率则会随种群规模扩大而下降，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1型人类免疫缺陷病毒（HIV-1）的重要抗体抗原表位区域中，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演化动力学。