Ribosome assembly is an essential and carefully choreographed cellular process. In eukaryotes, several 100 proteins, distributed across the nucleolus, nucleus, and cytoplasm, co-ordinate the step-wise assembly of four ribosomal RNAs (rRNAs) and approximately 80 ribosomal proteins (RPs) into the mature ribosomal subunits. Due to the inherent complexity of the assembly process, functional studies identifying ribosome biogenesis factors and, more importantly, their precise functions and interplay are confined to a few and very well-established model organisms. Although best characterized in yeast (Saccharomyces cerevisiae), emerging links to disease and the discovery of additional layers of regulation have recently encouraged deeper analysis of the pathway in human cells. In archaea, ribosome biogenesis is less well-understood. However, their simpler sub-cellular structure should allow a less elaborated assembly procedure, potentially providing insights into the functional essentials of ribosome biogenesis that evolved long before the diversification of archaea and eukaryotes. Here, we use a comprehensive phylogenetic profiling setup, integrating targeted ortholog searches with automated scoring of protein domain architecture similarities and an assessment of when search sensitivity becomes limiting, to trace 301 curated eukaryotic ribosome biogenesis factors across 982 taxa spanning the tree of life and including 727 archaea. We show that both factor loss and lineage-specific modifications of factor function modulate ribosome biogenesis, and we highlight that limited sensitivity of the ortholog search can confound evolutionary conclusions. Projecting into the archaeal domain, we find that only few factors are consistently present across the analyzed taxa, and lineage-specific loss is common. While members of the Asgard group are not special with respect to their inventory of ribosome biogenesis factors (RBFs), they unite the highest number of orthologs to eukaryotic RBFs in one taxon. Using large ribosomal subunit maturation as an example, we demonstrate that archaea pursue a simplified version of the corresponding steps in eukaryotes. Much of the complexity of this process evolved on the eukaryotic lineage by the duplication of ribosomal proteins and their subsequent functional diversification into ribosome biogenesis factors. This highlights that studying ribosome biogenesis in archaea provides fundamental information also for understanding the process in eukaryotes.

核糖体组装是必不可少且精心编排的细胞过程。在真核生物中，分布在核仁、细胞核和细胞质中的 100 种蛋白质协调四个核糖体 RNA (rRNA) 和大约 80 个核糖体蛋白质 (RP) 逐步组装成成熟核糖体亚基。由于组装过程固有的复杂性，识别核糖体生物发生因子的功能研究，更重要的是，它们的精确功能和相互作用仅限于少数非常完善的模式生物。虽然最好的特点是酵母（酿酒酵母)，与疾病的新联系和额外调控层的发现最近鼓励对人类细胞中的途径进行更深入的分析。在古细菌中，核糖体的生物发生不太清楚。然而，它们更简单的亚细胞结构应该允许一个不太复杂的组装过程，有可能提供对核糖体生物发生的功能要素的见解，这些要素在古细菌和真核生物多样化之前很久就已经进化了。在这里，我们使用全面的系统发育分析设置，将靶向直系同源搜索与蛋白质结构域相似性的自动评分以及搜索灵敏度何时变得有限的评估相结合，以追踪跨越生命之树的 982 个分类群中的 301 个精选的真核生物核糖体生物发生因子，包括727 古细菌。我们表明因子丢失和因子功能的谱系特异性修饰都会调节核糖体的生物发生，并且我们强调直向同源物搜索的有限敏感性可能会混淆进化结论。投射到古菌领域，我们发现在所分析的分类群中只有少数因素始终存在，并且谱系特定的损失很常见。虽然 Asgard 组的成员在核糖体生物发生因子 (RBF) 的清单方面并不特殊，但他们在一个分类单元中将最多数量的直系同源物与真核生物 RBF 结合在一起。以大核糖体亚基成熟为例，我们证明古细菌追求真核生物中相应步骤的简化版本。这个过程的大部分复杂性是通过核糖体蛋白的复制及其随后的功能多样化在真核细胞谱系上进化成核糖体生物发生因子的。这突出表明，研究古细菌中的核糖体生物发生也为理解真核生物的过程提供了基础信息。