Vela-Gallego Sonia, Pardo-Botero Zulay, Moya Cristian, de la Escosura Andrés
Department of Organic Chemistry, Universidad Autónoma de Madrid Campus de Cantoblanco 28049 Madrid Spain
IMDEA Nanociencia C/Faraday 7 28049 Madrid Spain.
Chem Sci. 2022 Aug 11;13(36):10715-10724. doi: 10.1039/d2sc02419e. eCollection 2022 Sep 21.
A major challenge for understanding the origins of life is to explore how replication networks can engage in an evolutionary process. Herein, we shed light on this problem by implementing a network constituted by two different types of extremely simple biological components: the amino acid cysteine and the canonical nucleobases adenine and thymine, connected through amide bonds to the cysteine amino group and oxidation of its thiol into three possible disulfides. Supramolecular and kinetic analyses revealed that both self- and mutual interactions between such dinucleobase compounds drive their assembly and replication pathways. Those pathways involving sequence complementarity led to enhanced replication rates, suggesting a potential bias for selection. The interplay of synergistic dynamics and competition between replicators was then simulated, under conditions that are not easily accessible with experiments, in an open reactor parametrized and constrained with the unprecedentedly complete experimental kinetic data obtained for our replicative network. Interestingly, the simulations show bistability, as a selective amplification of different species depending on the initial mixture composition. Overall, this network configuration can favor a collective adaptability to changes in the availability of feedstock molecules, with disulfide exchange reactions serving as 'wires' that connect the different individual auto- and cross-catalytic pathways.
理解生命起源的一个主要挑战是探索复制网络如何参与进化过程。在此,我们通过构建一个由两种极其简单的生物成分组成的网络来阐明这个问题:氨基酸半胱氨酸以及标准核碱基腺嘌呤和胸腺嘧啶,它们通过酰胺键与半胱氨酸氨基相连,并且其硫醇氧化为三种可能的二硫键。超分子和动力学分析表明,此类二核碱基化合物之间的自相互作用和相互作用驱动了它们的组装和复制途径。那些涉及序列互补性的途径导致复制速率提高,这表明存在选择的潜在偏向。然后,在一个开放反应器中,利用为我们的复制网络获得的前所未有的完整实验动力学数据进行参数化和约束,在实验难以实现的条件下模拟了复制子之间协同动力学和竞争的相互作用。有趣的是,模拟显示出双稳态,即根据初始混合物组成对不同物种进行选择性扩增。总体而言,这种网络配置有利于对原料分子可用性变化的集体适应性,二硫键交换反应充当连接不同个体自催化和交叉催化途径的“导线”。