Department of Biology, University of Florence, Florence, Italy.
Department of Biosciences, Biotechnology and Environment (DBBA), University of Bari Aldo Moro, Bari, Italy.
mSystems. 2024 Nov 19;9(11):e0096024. doi: 10.1128/msystems.00960-24. Epub 2024 Oct 28.
The evolution of operons has puzzled evolutionary biologists since their discovery, and many theories exist to explain their emergence, spreading, and evolutionary conservation. In this work, we suggest that DNA replication introduces a selective force for the clustering of functionally related genes on chromosomes, which we interpret as a preliminary and necessary step in operon formation. Our reasoning starts from the observation that DNA replication produces copy number variations of genomic regions, and we propose that such changes perturb metabolism. The formalization of this effect by exploiting concepts from metabolic control analysis suggests that the minimization of such perturbations during evolution could be achieved through the formation of gene clusters and operons. We support our theoretical derivations with simulations based on a realistic metabolic network, and we confirm that present-day genomes have a degree of compaction of functionally related genes, which is significantly correlated to the proposed perturbations introduced by replication. The formation of clusters of functionally related genes in microbial genomes has puzzled microbiologists since their first discovery. Here, we suggest that replication, and the copy number variations due to the replisome passage, might play a role in the process through a perturbation in metabolite homeostasis. We provide theoretical support to this hypothesis, and we found that both simulations and genomic analysis support our hypothesis.
The formation of clusters of functionally related genes in microbial genomes has puzzled microbiologists since their discovery. Here, we suggest that replication, and the copy number variations due to the replisome passage, might play a role in the process through a perturbation in metabolite homeostasis. We provide theoretical support to this hypothesis, and we found that both simulations and genomic analysis support our hypothesis.
自从操纵子被发现以来，其进化一直令进化生物学家感到困惑，并且存在许多理论来解释它们的出现、传播和进化保守性。在这项工作中，我们提出，DNA 复制为在染色体上聚类功能相关的基因引入了一种选择力，我们将其解释为操纵子形成的初步且必要的步骤。我们的推理始于观察到 DNA 复制会产生基因组区域的拷贝数变化，并且我们提出这种变化会扰乱新陈代谢。通过利用代谢控制分析的概念来形式化这种效应，我们提出在进化过程中，通过形成基因簇和操纵子，可以最小化这种变化的干扰。我们使用基于真实代谢网络的模拟来支持我们的理论推导，并证实当今的基因组具有与复制引入的建议扰动相关的功能相关基因的紧密度。微生物基因组中功能相关基因簇的形成一直令微生物学家感到困惑，自从它们的首次发现以来。在这里，我们提出复制以及由于复制体通过而导致的拷贝数变化可能通过代谢物动态平衡的扰动在该过程中起作用。我们为该假设提供了理论支持，并且发现模拟和基因组分析都支持我们的假设。
自从操纵子被发现以来，其进化一直令进化生物学家感到困惑，并且存在许多理论来解释它们的出现、传播和进化保守性。在这项工作中，我们提出，DNA 复制为在染色体上聚类功能相关的基因引入了一种选择力，我们将其解释为操纵子形成的初步且必要的步骤。我们的推理始于观察到 DNA 复制会产生基因组区域的拷贝数变化，并且我们提出这种变化会扰乱新陈代谢。通过利用代谢控制分析的概念来形式化这种效应，我们提出在进化过程中，通过形成基因簇和操纵子，可以最小化这种变化的干扰。我们使用基于真实代谢网络的模拟来支持我们的理论推导，并证实当今的基因组具有与复制引入的建议扰动相关的功能相关基因的紧密度。微生物基因组中功能相关基因簇的形成一直令微生物学家感到困惑，自从它们的首次发现以来。在这里，我们提出复制以及由于复制体通过而导致的拷贝数变化可能通过代谢物动态平衡的扰动在该过程中起作用。我们为该假设提供了理论支持，并且发现模拟和基因组分析都支持我们的假设。
