从核糖复制体——生命的终极RNA机器——视角看早期进化路径

中文摘要 AI 辅助

遗传密码向蛋白质的翻译在所有生命形式中是普遍存在的，核糖体作为实现这一信息转化的古老分子机器。我们提出，早期复制和蛋白质生物合成是不可分割的功能，由一种单一的古老RNA分子执行：核糖复制体。这一假说解决了RNA世界、蛋白质世界以及RNA-蛋白质协同进化理论面临的基本挑战——特别是非达尔文主义起点的问题以及复制和翻译机器的相互依赖性。我们提出了一个从简单RNA复制酶到原始核糖体的12步进化路径，并通过定量建模证明，仅有两步需要非达尔文主义转变，其余十步通过标准选择进行。单分子核糖复制体架构相比多组分“RNA汤”场景提供了约6倍的进化优势，主要通过维持遗传连锁并将催化产物保留在复制基因组附近（抵抗扩散损失）；对寄生性“作弊者”分子的结构抗性作为推论随之而来。核糖复制体框架解释了核糖体RNA、转移RNA和信使RNA作为单一祖先分子衍生物的起源，同时为细胞区室化提供了驱动力。尽管原始核糖复制体可能已深埋于远古时代，分子残留物可能仍存在于现存生物RNA中。识别或重建类核糖复制体分子可以推进生命起源研究和合成生物学应用。

英文摘要

Translation of the genetic code into proteins is universal across life, with ribosomes serving as the ancient molecular machines enabling this information transformation. We propose that early replication and protein biosynthesis were inseparable functions performed by a single ancient RNA molecule: the riboreplisome. This hypothesis addresses fundamental challenges facing RNA world, protein world, and RNA-protein co-evolution theories -- particularly the problem of non-Darwinian starting points and the interdependence of replication and translation machineries. We present a 12-step evolutionary pathway from simple RNA replicase to proto-ribosome, supported by quantitative modelling demonstrating that only two steps require non-Darwinian transitions while the remaining ten proceed through standard selection. The single-molecule riboreplisome architecture provides an approximately 6-fold evolutionary advantage over multi-component "RNA soup" scenarios, principally by maintaining genetic linkage and retaining catalytic products close to the replicating genome (resisting diffusion loss); structural resistance to parasitic "cheater" molecules follows as a corollary. The riboreplisome framework explains the origins of ribosomal, transfer, and messenger RNA as derivatives of a single ancestral molecule, while providing a driving force for cellular compartmentalisation. Although the original riboreplisome is likely lost to deep time, molecular remnants may persist in extant biological RNA. Identification or reconstruction of riboreplisome-like molecules could advance both origin-of-life research and synthetic biology applications.

发表机构

• University of Montpellier（蒙彼利埃大学）
• CNRS（法国国家科学研究中心）
• Australian National University（澳大利亚国立大学）
• Australian Centre for RNA Therapeutics in Cancer（癌症RNA治疗澳大利亚中心）
• School of Human Sciences, University of Western Australia（西澳大学人文科学学院）

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