Ribulose 1,5‐bisphosphate (RuBP) carboxylase/oxygenase (RuBisCO, or Rubisco) catalyzes a key reaction by which inorganic carbon is converted into organic carbon in the metabolism of many aerobic and anaerobic organisms. Across the broader Rubisco protein family, homologs exhibit diverse biochemical characteristics and metabolic functions, but the evolutionary origins of this diversity are unclear. Evidence of the timing of Rubisco family emergence and diversification of its different forms has been obscured by a meager paleontological record of early Earth biota, their subcellular physiology and metabolic components. Here, we use computational models to reconstruct a Rubisco family phylogenetic tree, ancestral amino acid sequences at branching points on the tree, and protein structures for several key ancestors. Analysis of historic substitutions with respect to their structural locations shows that there were distinct periods of amino acid substitution enrichment above background levels near and within its oxygen‐sensitive active site and subunit interfaces over the divergence between Form III (associated with anoxia) and Form I (associated with oxia) groups in its evolutionary history. One possible interpretation is that these periods of substitutional enrichment are coincident with oxidative stress exerted by the rise of oxygenic photosynthesis in the Precambrian era. Our interpretation implies that the periods of Rubisco substitutional enrichment inferred near the transition from anaerobic Form III to aerobic Form I ancestral sequences predate the acquisition of Rubisco by fully derived cyanobacterial (i.e., dual photosystem‐bearing, oxygen‐evolving) clades. The partitioning of extant lineages at high clade levels within our Rubisco phylogeny indicates that horizontal transfer of Rubisco is a relatively infrequent event. Therefore, it is possible that the mutational enrichment periods between the Form III and Form I common ancestral sequences correspond to the adaptation of key oxygen‐sensitive components of Rubisco prior to, or coincident with, the Great Oxidation Event.

中文翻译：

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限制Rubisco系统发生树内大氧化事件的时间。

核糖1,5-二磷酸（RuBP）羧化酶/加氧酶（RuBisCO或Rubisco）催化一种关键反应，在许多好氧和厌氧生物的代谢中，无机碳都转化为有机碳。在更广泛的Rubisco蛋白家族中，同源物表现出多种生化特征和代谢功能，但这种多样性的进化起源尚不清楚。Rubisco家族出现时间和其不同形式多样化的证据已被早期地球生物，其亚细胞生理学和代谢成分的微薄的古生物学记录所掩盖。在这里，我们使用计算模型来重构Rubisco家族系统树，在树的分支点上的祖先氨基酸序列，以及几个关键祖先的蛋白质结构。对历史性取代物的结构位置进行的分析表明，在其氧敏感活性位点和亚单位界面附近和内部以及在形式III（与缺氧有关）和形式I之间的分歧处，高于背景水平的氨基酸取代存在明显的富集期（与oxia相关）群体在其进化史中。一种可能的解释是，这些替代富集时期与前寒武纪时期氧光合作用的兴起所施加的氧化应激同时发生。我们的解释暗示，在从厌氧形式III到有氧形式I祖先序列的过渡附近推断Rubisco替代富集的时期早于完全衍生的蓝细菌（即，带有双光系统，放氧）进化枝。在我们的Rubisco系统发生系统中，在高进化枝水平上现存谱系的划分表明，Rubisco的水平转移是相对罕见的事件。因此，有可能III型和I型共同祖先序列之间的突变富集期对应于Rubisco重要氧化事件之前或同时发生的Rubisco关键氧敏感成分的适应。