Ribosomal History Reveals Origins of Modern Protein Synthesis

The origin and evolution of the ribosome is central to our understanding of the cellular world. Most hypotheses posit that the ribosome originated in the peptidyl transferase center of the large ribosomal subunit. However, these proposals do not link protein synthesis to RNA recognition and do not use a phylogenetic comparative framework to study ribosomal evolution. Here we infer evolution of the structural components of the ribosome. Phylogenetic methods widely used in morphometrics are applied directly to RNA structures of thousands of molecules and to a census of protein structures in hundreds of genomes. We find that components of the small subunit involved in ribosomal processivity evolved earlier than the catalytic peptidyl transferase center responsible for protein synthesis. Remarkably, subunit RNA and proteins coevolved, starting with interactions between the oldest proteins (S12 and S17) and the oldest substructure (the ribosomal ratchet) in the small subunit and ending with the rise of a modern multi-subunit ribosome. Ancestral ribonucleoprotein components show similarities to in vitro evolved RNA replicase ribozymes and protein structures in extant replication machinery. Our study therefore provides important clues about the chicken-or-egg dilemma associated with the central dogma of molecular biology by showing that ribosomal history is driven by the gradual structural accretion of protein and RNA structures. Most importantly, results suggest that functionally important and conserved regions of the ribosome were recruited and could be relics of an ancient ribonucleoprotein world.

核糖体（ribosome）的起源与演化，是我们理解细胞生命世界的核心议题。多数假说认为，核糖体起源于大亚基（large ribosomal subunit）的肽基转移酶中心（peptidyl transferase center）。然而，这类假说并未将蛋白质合成与RNA识别相关联，也未采用系统发育比较框架来研究核糖体演化。本研究通过推演核糖体结构组分的演化历程，将形态计量学（morphometrics）中广泛使用的系统发育分析方法，直接应用于数千条RNA分子的结构数据，以及数百个基因组中蛋白质结构的普查结果。研究发现，参与核糖体过程持续性的小亚基（small ribosomal subunit）组分，其演化早于负责蛋白质合成的催化性肽基转移酶中心。值得注意的是，亚基RNA与蛋白质存在协同演化关系：其演化始于小亚基中最古老的蛋白质（S12与S17）与最古老的亚结构（核糖体棘轮结构 (ribosomal ratchet)）之间的相互作用，最终演化为现代多亚基核糖体。祖先状态的核糖核蛋白（ribonucleoprotein）组分，与体外演化获得的RNA聚合酶核酶（RNA replicase ribozymes），以及现存复制机器中的蛋白质结构存在相似性。因此，本研究揭示了与分子生物学中心法则（central dogma of molecular biology）相关的“先有鸡还是先有蛋”困境 (chicken-or-egg dilemma) 的重要线索：核糖体的演化历程由蛋白质与RNA结构的逐步积累所驱动。尤为关键的是，研究结果表明，核糖体中功能重要且保守的区域是被招募而来的，它们可能是古老核糖核蛋白世界的遗迹。