Feder Alison F, Rhee Soo-Yon, Holmes Susan P, Shafer Robert W, Petrov Dmitri A, Pennings Pleuni S
Department of Biology, Stanford University, Stanford, United States.
Department of Medicine, Stanford University, Stanford, United States.
Elife. 2016 Feb 15;5:e10670. doi: 10.7554/eLife.10670.
In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here, we use 6717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely.
在艾滋病病毒治疗的早期，所有患者都会迅速且可预测地出现耐药性，但在现代治疗方法下，耐药性即便出现，也是缓慢产生的。耐药性的概率应由耐药性突变的产生速率来控制。如果许多适应性突变同时出现，那么适应过程就会通过软选择性清除发生，即多个适应性突变会同时传播，但如果适应性突变在群体中很少出现，那么单个适应性突变就会通过硬选择性清除单独传播。在此，我们使用了1989年至2013年间接受一线治疗的患者的6717个HIV-1共识序列，以证实耐药性从快速进化到缓慢进化的转变确实伴随着从软选择性清除到硬选择性清除的预期转变。这更普遍地表明，如果耐药性不太可能出现，进化就会通过硬清除进行；如果耐药性很可能出现，进化就会通过软清除进行。
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