Pressman Abe, Moretti Janina E, Campbell Gregory W, Müller Ulrich F, Chen Irene A
Department of Chemistry and Biochemistry 9510, University of California, Santa Barbara, CA 93106, USA.
Program in Chemical Engineering, University of California, Santa Barbara, CA 93106, USA.
Nucleic Acids Res. 2017 Aug 21;45(14):8167-8179. doi: 10.1093/nar/gkx540.
The emergence of catalytic RNA is believed to have been a key event during the origin of life. Understanding how catalytic activity is distributed across random sequences is fundamental to estimating the probability that catalytic sequences would emerge. Here, we analyze the in vitro evolution of triphosphorylating ribozymes and translate their fitnesses into absolute estimates of catalytic activity for hundreds of ribozyme families. The analysis efficiently identified highly active ribozymes and estimated catalytic activity with good accuracy. The evolutionary dynamics follow Fisher's Fundamental Theorem of Natural Selection and a corollary, permitting retrospective inference of the distribution of fitness and activity in the random sequence pool for the first time. The frequency distribution of rate constants appears to be log-normal, with a surprisingly steep dropoff at higher activity, consistent with a mechanism for the emergence of activity as the product of many independent contributions.
催化RNA的出现被认为是生命起源过程中的一个关键事件。了解催化活性如何分布在随机序列中，对于估计催化序列出现的概率至关重要。在这里，我们分析了三磷酸化核酶的体外进化，并将它们的适应性转化为数百个核酶家族催化活性的绝对估计值。该分析有效地识别出高活性核酶，并以良好的准确性估计催化活性。进化动力学遵循费希尔自然选择基本定理及其一个推论，首次允许对随机序列库中的适应性和活性分布进行回顾性推断。速率常数的频率分布似乎呈对数正态分布，在较高活性时下降得惊人地陡峭，这与活性作为许多独立贡献的产物而出现的机制一致。
