Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro-ku, Tokyo, Japan.
Research Center for Complex Systems Biology, Universal Biology Institute, The University of Tokyo, Komaba, Meguro-ku, Tokyo, Japan.
PLoS Comput Biol. 2019 Jun 6;15(6):e1007094. doi: 10.1371/journal.pcbi.1007094. eCollection 2019 Jun.
The emergence of replicases that can replicate themselves is a central issue in the origin of life. Recent experiments suggest that such replicases can be realized if an RNA polymerase ribozyme is divided into fragments short enough to be replicable by the ribozyme and if these fragments self-assemble into a functional ribozyme. However, the continued self-replication of such replicases requires that the production of every essential fragment be balanced and sustained. Here, we use mathematical modeling to investigate whether and under what conditions fragmented replicases achieve continued self-replication. We first show that under a simple batch condition, the replicases fail to display continued self-replication owing to positive feedback inherent in these replicases. This positive feedback inevitably biases replication toward a subset of fragments, so that the replicases eventually fail to sustain the production of all essential fragments. We then show that this inherent instability can be resolved by small rates of random content exchange between loose compartments (i.e., horizontal transfer). In this case, the balanced production of all fragments is achieved through negative frequency-dependent selection operating in the population dynamics of compartments. The horizontal transfer also ensures the presence of all essential fragments in each compartment, sustaining self-replication. Taken together, our results underline compartmentalization and horizontal transfer in the origin of the first self-replicating replicases.
复制酶能够自我复制是生命起源的核心问题。最近的实验表明，如果 RNA 聚合酶核酶被分割成足够短的片段，这些片段可以被核酶复制，并且这些片段自我组装成有功能的核酶，那么这样的复制酶就可以实现。然而，这种复制酶的持续自我复制需要平衡和维持每个必需片段的产生。在这里，我们使用数学建模来研究分裂的复制酶是否能够以及在什么条件下实现持续的自我复制。我们首先表明，在简单的批量条件下，由于这些复制酶中固有的正反馈，复制酶无法显示持续的自我复制。这种正反馈不可避免地会使复制偏向于片段的子集，因此复制酶最终无法维持所有必需片段的产生。然后我们表明，这种内在的不稳定性可以通过在松散隔间（即水平转移）之间进行小的随机内容交换率来解决。在这种情况下，通过在隔间的种群动力学中操作负频率依赖性选择，实现了所有片段的平衡产生。水平转移还确保了每个隔间中都存在所有必需的片段，从而维持自我复制。总之，我们的结果强调了在第一个自我复制的复制酶起源中的分隔和水平转移。
