FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
J Am Chem Soc. 2010 Apr 28;132(16):5880-5. doi: 10.1021/ja100780p.
The frequency of errors during genome replication limits the amount of functionally important information that can be passed on from generation to generation. During the origin of life, mutation rates are thought to have been quite high, raising a classic chicken-and-egg paradox: could nonenzymatic replication propagate sequences accurately enough to allow for the emergence of heritable function? Here we show that the theoretical limit on genomic information content may increase substantially as a consequence of dramatically slowed polymerization after mismatches. As a result of postmismatch stalling, accurate copies of a template tend to be completed more rapidly than mutant copies and the accurate copies can therefore begin a second round of replication more quickly. To quantify this effect, we characterized an experimental model of nonenzymatic, template-directed nucleic acid polymerization. We found that most mismatches decrease the rate of primer extension by more than 2 orders of magnitude relative to a matched (Watson-Crick) control. A chemical replication system with this property would be able to propagate sequences long enough to have function. Our study suggests that the emergence of functional sequences during the origin of life would be possible even in the face of the high intrinsic error rates of chemical replication.
在基因组复制过程中,错误的频率限制了可以从上一代传递到下一代的功能重要信息的数量。在生命起源时,突变率被认为相当高,这就产生了一个经典的鸡与蛋的悖论:非酶复制能否足够准确地传播序列,从而允许遗传功能的出现?在这里,我们表明,由于错配后聚合作用显著减慢,基因组信息含量的理论限制可能会大大增加。由于错配后停顿,模板的准确拷贝往往比突变拷贝更快地完成,因此准确拷贝可以更快地开始第二轮复制。为了量化这种效果,我们对非酶、模板指导的核酸聚合的实验模型进行了表征。我们发现,与匹配(沃森-克里克)对照相比,大多数错配使引物延伸的速度降低了两个数量级以上。具有这种特性的化学复制系统将能够复制足够长的序列以发挥功能。我们的研究表明,即使在化学复制的固有高错误率的情况下,功能序列在生命起源时的出现也是可能的。