Université Côte d'Azur, CNRS, Inserm, IRCAN, Nice, France.
Wellcome Trust Sanger Institute, Cambridge, United Kingdom.
Mol Biol Evol. 2019 Apr 1;36(4):691-708. doi: 10.1093/molbev/msz006.
Pre-existing and de novo genetic variants can both drive adaptation to environmental changes, but their relative contributions and interplay remain poorly understood. Here we investigated the evolutionary dynamics in drug-treated yeast populations with different levels of pre-existing variation by experimental evolution coupled with time-resolved sequencing and phenotyping. We found a doubling of pre-existing variation alone boosts the adaptation by 64.1% and 51.5% in hydroxyurea and rapamycin, respectively. The causative pre-existing and de novo variants were selected on shared targets: RNR4 in hydroxyurea and TOR1, TOR2 in rapamycin. Interestingly, the pre-existing and de novo TOR variants map to different functional domains and act via distinct mechanisms. The pre-existing TOR variants from two domesticated strains exhibited opposite rapamycin resistance effects, reflecting lineage-specific functional divergence. This study provides a dynamic view on how pre-existing and de novo variants interactively drive adaptation and deepens our understanding of clonally evolving populations.
预先存在的和新出现的遗传变异都可以推动对环境变化的适应，但它们的相对贡献和相互作用仍知之甚少。在这里，我们通过实验进化结合时间分辨测序和表型分析，研究了具有不同预先存在变异水平的药物处理酵母种群的进化动态。我们发现，预先存在变异的两倍增加分别使羟基脲和雷帕霉素的适应性提高了 64.1%和 51.5%。引起预先存在和新出现的变异的原因是在共享靶点上被选择：羟基脲中的 RNR4 和雷帕霉素中的 TOR1、TOR2。有趣的是，预先存在的和新出现的 TOR 变异体映射到不同的功能域，并通过不同的机制发挥作用。来自两个驯化菌株的预先存在的 TOR 变异体表现出相反的雷帕霉素抗性效应，反映了谱系特异性的功能分化。这项研究提供了一个动态的视角，展示了预先存在的和新出现的变异如何相互作用推动适应，并加深了我们对无性进化群体的理解。
