Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
Elife. 2020 Feb 11;9:e51963. doi: 10.7554/eLife.51963.
Many biological features are conserved and thus considered to be resistant to evolutionary change. While rapid genetic adaptation following the removal of conserved genes has been observed, we often lack a mechanistic understanding of how adaptation happens. We used the budding yeast, , to investigate the evolutionary plasticity of chromosome metabolism, a network of evolutionary conserved modules. We experimentally evolved cells constitutively experiencing DNA replication stress caused by the absence of Ctf4, a protein that coordinates the enzymatic activities at replication forks. Parallel populations adapted to replication stress, over 1000 generations, by acquiring multiple, concerted mutations. These mutations altered conserved features of two chromosome metabolism modules, DNA replication and sister chromatid cohesion, and inactivated a third, the DNA damage checkpoint. The selected mutations define a functionally reproducible evolutionary trajectory. We suggest that the evolutionary plasticity of chromosome metabolism has implications for genome evolution in natural populations and cancer.
许多生物特征是保守的，因此被认为不易发生进化改变。虽然在去除保守基因后，快速的遗传适应已经被观察到，但我们通常缺乏对适应发生机制的理解。我们利用 budding yeast （酿酒酵母）来研究染色体代谢的进化可塑性，这是一个进化保守模块的网络。我们通过实验使细胞持续经历 DNA 复制应激，这种应激是由 Ctf4 蛋白缺失引起的，Ctf4 蛋白协调复制叉处的酶活性。在超过 1000 代的时间里，平行的种群通过获得多个协调的突变来适应复制应激。这些突变改变了两个染色体代谢模块（DNA 复制和姐妹染色单体黏合）的保守特征，并使第三个模块（DNA 损伤检查点）失活。选择的突变定义了一个功能上可重复的进化轨迹。我们认为，染色体代谢的进化可塑性对自然种群和癌症中的基因组进化具有重要意义。
