Physics of Living Systems, Department of Physics, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Nat Commun. 2018 Apr 18;9(1):1530. doi: 10.1038/s41467-018-04026-w.
How new functions arise de novo is a fundamental question in evolution. We studied de novo evolution of promoters in Escherichia coli by replacing the lac promoter with various random sequences of the same size (~100 bp) and evolving the cells in the presence of lactose. We find that ~60% of random sequences can evolve expression comparable to the wild-type with only one mutation, and that ~10% of random sequences can serve as active promoters even without evolution. Such a short mutational distance between random sequences and active promoters may improve the evolvability, yet may also lead to accidental promoters inside genes that interfere with normal expression. Indeed, our bioinformatic analyses indicate that E. coli was under selection to reduce accidental promoters inside genes by avoiding promoter-like sequences. We suggest that a low threshold for functionality balanced by selection against undesired targets can increase the evolvability by making new beneficial features more accessible.
新功能是如何全新出现的是进化中的一个基本问题。我们通过用各种大小相同（约 100bp）的随机序列替换 lac 启动子，并在乳糖存在的情况下使细胞进化，来研究大肠杆菌中启动子的全新进化。我们发现，大约 60%的随机序列只需一个突变即可进化出与野生型相当的表达水平，而大约 10%的随机序列甚至无需进化即可作为活性启动子。随机序列和活性启动子之间如此短的突变距离可能会提高可进化性，但也可能导致基因内的意外启动子干扰正常表达。事实上，我们的生物信息学分析表明，大肠杆菌受到选择，通过避免启动子样序列来减少基因内的意外启动子。我们认为，通过降低功能的门槛，并针对不需要的目标进行选择，可以通过使新的有益特征更容易获得来提高可进化性。
