We hypothesize prebiotic evolution of self-replicating macro-molecules (Alberts, Molecular biology of the cell, 2015; Orgel, Crit Rev Biochem Mol Biol 39:99-123, 2004; Hud, Nat Commun 9:5171) favoured the constituent nucleotides and biophysical properties observed in the RNA and DNA of modern organisms. Assumed initial conditions are a shallow tide pool, containing a racemic mix of diverse nucleotide monomers (Barks et al., Chembiochem 11:1240-1243, 2010; Krishnamurthy, Nat Commun 9:5175, 2018; Hirao, Curr Opin Chem Biol 10:622-627), subject to day/night thermal fluctuations (Piccirilli et al., Nature 343:33-37, 1990). Self-replication, like Polymerase Chain Reactions, followed as higher daytime thermal energy “melted” inter-strand hydrogen bonds causing strand separation while solar UV radiation increased prebiotic nucleobase formation (Szathmary, Proc Biol Sci 245:91-99, 1991; Materese et al., Astrobiology 17:761-770, 2017; Bera et al., Astrobiology 17:771-785, 2017). Lower night energies allowed free monomers to form hydrogen bonds with their template counterparts leading to daughter strand synthesis (Hirao, Biotechniques 40:711, 2006). Evolutionary selection favoured increasing strand length to maximize auto-catalytic function in RNA and polymer stability in double stranded DNA (Krishnamurthy, Chemistry 24:16708-16715, 2018; Szathmary, Nat Rev Genet 4:995-1001, 2003). However, synthesis of the full daughter strand before daytime temperatures produced strand separation, longer polymer length required increased speed of self-replication. Computer simulations demonstrate optimal polynucleotide autocatalytic speed is achieved when the constituent nucleotides possess a left-right asymmetry that decreases the hydrogen bond kinetic barrier for the free nucleotide attachment to the template on one side and increases bond barrier on the other side preventing it from releasing prior to covalent bond formation. This phenomenon is similar to asymmetric kinetics observed during polymerization of the front and the back ends of linear cytoskeletal proteins such as actin and microtubules (Orgel, Nature 343:18-20, 1990; Henry, Curr Opin Chem Biol 7:727-733, 2003; Walker et al., J Cell Biol 108:931-937, 1989; Crevenna et al., J Biol Chem 288:12102-12113, 2013). Since rotation of the nucleotide would disrupt the asymmetry, the optimal nucleotides must form two or more hydrogen bonds with their counterpart on the template strand. All nucleotides in modern RNA and DNA have these predicted properties. Our models demonstrate these constraints on the properties of constituent monomers result in biophysical properties found in modern DNA and RNA including strand directionality, anti-parallel strand orientation, homochirality, quadruplet alphabet, and complementary base pairing. Furthermore, competition between RNA and DNA auto-replicators for 3 nucleotides in common permit states coexistence and possible cooperative interactions that could be incorporated into nascent living systems. Our findings demonstrate the molecular properties of DNA/RNA could have emerged from Darwinian competition among macromolecular replicators that selected nucleotide monomers that maximized the speed of autocatalysis.

中文翻译：

---

自我复制多核苷酸的益生元竞争和进化可以解释现代生命系统中 DNA/RNA 的特性。

我们假设自我复制大分子的益生元进化（Alberts, Molecular Biology of the cell, 2015; Orgel, Crit Rev Biochem Mol Biol 39:99-123, 2004; Hud, Nat Commun 9:5171）有利于组成核苷酸和在现代生物的 RNA 和 DNA 中观察到的生物物理特性。假设的初始条件是一个浅潮池，包含多种核苷酸单体的外消旋混合物（Barks 等人，Chembiochem 11:1240-1243, 2010；Krishnamurthy, Nat Commun 9:5175, 2018；Hirao, Curr Opin Chem Biol 10： 622-627)，受昼夜热波动影响 (Piccirilli 等人，Nature 343:33-37, 1990)。自我复制，如聚合酶链式反应，随后是较高的白天热能“熔化”链间氢键导致链分离，而太阳紫外线辐射增加了益生元核碱基的形成（Szathmary，Proc Biol Sci 245:91-99, 1991; Materese 等人，天体生物学 17:761-770，2017；Bera 等人，Astrobiology 17:771-785, 2017)。较低的夜间能量允许游离单体与其模板对应物形成氢键，从而导致子链合成（Hirao, Biotechniques 40:711, 2006）。进化选择有利于增加链长度以最大化 RNA 中的自催化功能和双链 DNA 中的聚合物稳定性（Krishnamurthy, Chemistry 24:16708-16715, 2018; Szathmary, Nat Rev Genet 4:995-1001, 2003）。然而，在白天温度之前合成完整的子链会产生链分离，更长的聚合物长度需要增加的自我复制速度。计算机模拟表明，当组成核苷酸具有左右不对称性时，可以实现最佳多核苷酸自催化速度，这会降低游离核苷酸与模板连接的氢键动力学屏障，并增加另一侧的键屏障，防止其释放先前的以形成共价键。这种现象类似于在线性细胞骨架蛋白（例如肌动蛋白和微管）的前端和后端聚合期间观察到的不对称动力学（Orgel, Nature 343:18-20, 1990；Henry, Curr Opin Chem Biol 7:727-733， 2003；Walker 等人，J Cell Biol 108：931-937，1989；Crevenna 等人，J Biol Chem 288：12102-12113，2013)。由于核苷酸的旋转会破坏不对称性，最佳核苷酸必须与模板链上的对应物形成两个或多个氢键。现代 RNA 和 DNA 中的所有核苷酸都具有这些预测的特性。我们的模型证明了对组成单体特性的这些限制导致现代 DNA 和 RNA 中发现的生物物理特性，包括链方向性、反平行链方向、单手性、四联体字母和互补碱基配对。此外，RNA 和 DNA 自动复制器之间对共同的 3 个核苷酸的竞争允许状态共存和可能的合作相互作用，这些相互作用可以整合到新生的生命系统中。