Institute of Evolutionary Biology and Environmental Studies, University of Zurich, CH-8057 Zurich, Switzerland;
The Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):7075-7080. doi: 10.1073/pnas.1717243115. Epub 2018 Jun 18.
Large-scale DNA deletions and gene loss are pervasive in bacterial genomes. This observation raises the possibility that evolutionary adaptation has altered bacterial genome organization to increase its robustness to large-scale tandem gene deletions. To find out, we systematically analyzed 55 bacterial genome-scale metabolisms and showed that metabolic gene ordering renders an organism's viability in multiple nutrient environments significantly more robust against tandem multigene deletions than expected by chance. This excess robustness is caused by multiple factors, which include the clustering of essential metabolic genes, a greater-than-expected distance of synthetically lethal metabolic gene pairs, and the clustering of nonessential metabolic genes. By computationally creating minimal genomes, we show that a nonadaptive origin of such clustering could in principle arise as a passive byproduct of bacterial genome growth. However, because genome randomization forces such as translocation and inversion would eventually erode such clustering, adaptive processes are necessary to sustain it. We provide evidence suggesting that this organization might result from adaptation to ongoing gene deletions, and from selective advantages associated with coregulating functionally related genes. Horizontal gene transfer in the presence of gene deletions contributes to sustaining the clustering of essential genes. In sum, our observations suggest that the genome organization of bacteria is driven by adaptive processes that provide phenotypic robustness in response to large-scale gene deletions. This robustness may be especially important for bacterial populations that take advantage of gene loss to adapt to new environments.
大规模的 DNA 缺失和基因丢失在细菌基因组中普遍存在。这一观察结果提出了一种可能性，即进化适应已经改变了细菌基因组的组织，以增加其对大规模串联基因缺失的稳健性。为了找出答案，我们系统地分析了 55 个细菌基因组规模的新陈代谢，并表明代谢基因的排序使生物体在多种营养环境下的生存能力对串联多基因缺失的稳健性明显高于随机预期。这种额外的稳健性是由多种因素引起的，包括必需代谢基因的聚类、合成致死代谢基因对的距离大于预期，以及非必需代谢基因的聚类。通过计算创建最小基因组，我们表明，这种聚类的非适应性起源原则上可以作为细菌基因组生长的被动副产品出现。然而，由于易位和倒位等基因组随机化因素最终会侵蚀这种聚类，因此需要适应过程来维持它。我们提供的证据表明，这种组织可能是由于对持续基因缺失的适应以及与功能相关基因的共同调控相关的选择优势而产生的。基因缺失存在时的水平基因转移有助于维持必需基因的聚类。总之，我们的观察结果表明，细菌的基因组组织是由适应过程驱动的，这些过程为应对大规模基因缺失提供了表型稳健性。这种稳健性对于利用基因丢失来适应新环境的细菌种群可能尤为重要。
