Fernando Chrisantha, Von Kiedrowski Günter, Szathmáry Eörs
School of Computer Science, University of Birmingham, Edgbaston, B15 2TT, UK.
J Mol Evol. 2007 May;64(5):572-85. doi: 10.1007/s00239-006-0218-4. Epub 2007 Apr 13.
The origin of nucleic acid template replication is a major unsolved problem in science. A novel stochastic model of nucleic acid chemistry was developed to allow rapid prototyping of chemical experiments designed to discover sufficient conditions for template replication. Experiments using the model brought to attention a robust property of nucleic acid template populations, the tendency for elongation to outcompete replication. Externally imposed denaturation-renaturation cycles did not reverse this tendency. For example, it has been proposed that fast tidal cycling could establish a TCR (tidal chain reaction) analogous to a PCR (polymerase chain reaction) acting on nucleic acid polymers, allowing their self-replication. However, elongating side-reactions that would have been prevented by the polymerase in the PCR still occurred in the simulation of the TCR. The same finding was found with temperature and monomer cycles. We propose that if cycling reactors are to allow template replication, oligonucleotide phenotypes that are capable of favorably altering the flux ratio between replication and elongation, for example, by facilitating sequence-specific cleavage within templates, are necessary; accordingly the minimal replicase ribozyme may have possessed restriction functionality.
核酸模板复制的起源是科学中一个主要未解决的问题。开发了一种新的核酸化学随机模型，以允许对旨在发现模板复制充分条件的化学实验进行快速原型设计。使用该模型进行的实验引起了人们对核酸模板群体一种强大特性的关注，即延伸胜过复制的趋势。外部施加的变性-复性循环并没有扭转这种趋势。例如，有人提出快速潮汐循环可以建立一种类似于作用于核酸聚合物的PCR（聚合酶链反应）的TCR（潮汐链反应），从而实现它们的自我复制。然而，在PCR中会被聚合酶阻止的延伸副反应在TCR模拟中仍然发生。在温度和单体循环实验中也发现了同样的结果。我们提出，如果循环反应器要实现模板复制，那么例如通过促进模板内序列特异性切割来有利地改变复制和延伸之间通量比的寡核苷酸表型是必要的；因此，最小复制酶核酶可能具有限制功能。
