Carothers James M, Oestreich Stephanie C, Davis Jonathan H, Szostak Jack W
Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, 02114 USA.
J Am Chem Soc. 2004 Apr 28;126(16):5130-7. doi: 10.1021/ja031504a.
Very little is known about the distribution of functional DNA, RNA, and protein molecules in sequence space. The question of how the number and complexity of distinct solutions to a particular biochemical problem varies with activity is an important aspect of this general problem. Here we present a comparison of the structures and activities of eleven distinct GTP-binding RNAs (aptamers). By experimentally measuring the amount of information required to specify each optimal binding structure, we show that defining a structure capable of 10-fold tighter binding requires approximately 10 additional bits of information. This increase in information content is equivalent to specifying the identity of five additional nucleotide positions and corresponds to an approximately 1000-fold decrease in abundance in a sample of random sequences. We observe a similar relationship between structural complexity and activity in a comparison of two catalytic RNAs (ribozyme ligases), raising the possibility of a general relationship between the complexity of RNA structures and their functional activity. Describing how information varies with activity in other heteropolymers, both biological and synthetic, may lead to an objective means of comparing their functional properties. This approach could be useful in predicting the functional utility of novel heteropolymers.
关于功能性DNA、RNA和蛋白质分子在序列空间中的分布，我们所知甚少。特定生化问题的不同解决方案的数量和复杂性如何随活性变化，这一问题是该一般问题的重要方面。在此，我们对11种不同的GTP结合RNA（适体）的结构和活性进行了比较。通过实验测量确定每个最佳结合结构所需的信息量，我们发现定义一个结合力强10倍的结构需要大约额外10比特的信息。信息含量的这种增加等同于确定另外五个核苷酸位置的身份，并且在随机序列样本中丰度相应降低约1000倍。在比较两种催化RNA（核酶连接酶）时，我们观察到结构复杂性与活性之间存在类似关系，这增加了RNA结构复杂性与其功能活性之间存在普遍关系的可能性。描述信息在其他生物和合成杂聚物中如何随活性变化，可能会产生一种比较其功能特性的客观方法。这种方法可能有助于预测新型杂聚物的功能效用。
