Zaslaver Alon, Mayo Avi, Ronen Michal, Alon Uri
Department of Molecular Cell Biology and Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100, Israel.
Phys Biol. 2006 Sep 18;3(3):183-9. doi: 10.1088/1478-3975/3/3/003.
Gene arrangement into operons varies between bacterial species. Genes in a given system can be on one operon in some organisms and on several operons in other organisms. Existing theories explain why genes that work together should be on the same operon, since this allows for advantageous lateral gene transfer and accurate stoichiometry. But what causes the frequent separation into multiple operons of co-regulated genes that act together in a pathway? Here we suggest that separation is due to benefits made possible by differential regulation of each operon. We present a simple mathematical model for the optimal distribution of genes into operons based on a balance of the cost of operons and the benefit of regulation that provides 'just-when-needed' temporal order. The analysis predicts that genes are arranged such that genes on the same operon do not skip functional steps in the pathway. This prediction is supported by genomic data from 137 bacterial genomes. Our work suggests that gene arrangement is not only the result of random historical drift, genome re-arrangement and gene transfer, but has elements that are solutions of an evolutionary optimization problem. Thus gene functional order may be inferred by analyzing the operon structure across different genomes.
基因排列成操纵子的方式在不同细菌物种之间存在差异。在特定系统中的基因，在某些生物体中可能位于一个操纵子上，而在其他生物体中则可能位于几个操纵子上。现有理论解释了协同工作的基因为何应位于同一个操纵子上，因为这有利于进行有利的横向基因转移并实现精确的化学计量。但是，是什么导致在一条途径中共同起作用的共调控基因频繁分离成多个操纵子呢？在此，我们认为分离是由于每个操纵子的差异调节所带来的益处。我们基于操纵子的成本与提供“恰在需要时”时间顺序的调节益处之间的平衡，提出了一个将基因最优分配到操纵子的简单数学模型。分析预测，基因的排列方式是使得同一个操纵子上的基因不会跳过该途径中的功能步骤。这一预测得到了来自137个细菌基因组的基因组数据的支持。我们的研究表明，基因排列不仅是随机历史漂移、基因组重排和基因转移的结果，还具有作为进化优化问题解决方案的要素。因此，可以通过分析不同基因组的操纵子结构来推断基因的功能顺序。
