Department of Biology, Stanford University, 371 Serra Mall, Stanford, CA 94305, USA
Department of Biology, Stanford University, 371 Serra Mall, Stanford, CA 94305, USA.
J R Soc Interface. 2018 Mar;15(140). doi: 10.1098/rsif.2017.0921.
Within-host adaptation of pathogens such as human immunodeficiency virus (HIV) often occurs at more than two loci. Multiple beneficial mutations may arise simultaneously on different genetic backgrounds and interfere, affecting each other's fixation trajectories. Here, we explore how these evolutionary dynamics are mirrored in multilocus linkage disequilibrium (MLD), a measure of multi-way associations between alleles. In the parameter regime corresponding to HIV, we show that deterministic early infection models induce MLD to oscillate over time in a wavelet-like fashion. We find that the frequency of these oscillations is proportional to the rate of adaptation. This signature is robust to drift, but can be eroded by high variation in fitness effects of beneficial mutations. Our findings suggest that MLD oscillations could be used as a signature of interference among multiple equally advantageous mutations and may aid the interpretation of MLD in data.
病原体(如人类免疫缺陷病毒 (HIV))在宿主内的适应通常发生在两个以上的位点。多个有益突变可能会在不同的遗传背景下同时出现,并相互干扰,影响彼此的固定轨迹。在这里,我们探讨了这些进化动态如何在多基因座连锁不平衡(MLD)中得到反映,MLD 是衡量等位基因之间多向关联的一种方法。在对应于 HIV 的参数范围内,我们表明,确定性早期感染模型会导致 MLD 以类似小波的方式随时间波动。我们发现,这些波动的频率与适应速度成正比。这种特征对漂变具有鲁棒性,但会被有益突变的适应度效应的高变异性所侵蚀。我们的研究结果表明,MLD 波动可以作为多个同等有利突变相互干扰的标志,并可能有助于对数据中 MLD 的解释。