Department of Biology, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
BMC Genomics. 2022 Dec 16;23(1):834. doi: 10.1186/s12864-022-09072-9.
Bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) is a bacterial second messenger that affects diverse processes in different bacteria, including the cell cycle, motility, and biofilm formation. Its cellular levels are controlled by the opposing activities of two types of enzymes, with synthesis by diguanylate cyclases containing a GGDEF domain and degradation by phosphodiesterases containing either an HD-GYP or an EAL domain. These enzymes are ubiquitous in bacteria with up to 50 encoded in some genomes, the specific functions of which are mostly unknown.
We used comparative analyses to identify genomic patterns among genes encoding proteins with GGDEF, EAL, and HD-GYP domains in five orders of the class Alphaproteobacteria. GGDEF-containing sequences and GGDEF-EAL hybrids were the most abundant and had the highest diversity of co-occurring auxiliary domains while EAL and HD-GYP containing sequences were less abundant and less diverse with respect to auxiliary domains. There were striking patterns in the chromosomal localizations of the genes found in two of the orders. The Rhodobacterales' EAL-encoding genes and Rhizobiales' GGDEF-EAL-encoding genes showed opposing patterns of distribution compared to the GGDEF-encoding genes. In the Rhodobacterales, the GGDEF-encoding genes showed a tri-modal distribution with peaks mid-way between the origin (ori) and terminus (ter) of replication and at ter while the EAL-encoding genes peaked near ori. The patterns were more complex in the Rhizobiales, but the GGDEF-encoding genes were biased for localization near ter.
The observed patterns in the chromosomal localizations of these genes suggest a coupling of synthesis and hydrolysis of c-di-GMP with the cell cycle. Moreover, the higher proportions and diversities of auxiliary domains associated with GGDEF domains and GGDEF-EAL hybrids compared to EAL or HD-GYP domains could indicate that more stimuli affect synthesis compared to hydrolysis of c-di-GMP.
双-(3'-5')-环二鸟苷酸（c-di-GMP）是一种细菌第二信使，影响不同细菌的多种过程，包括细胞周期、运动和生物膜形成。其细胞水平受两种类型酶的拮抗活性控制，含有 GGDEF 结构域的二鸟苷酸环化酶合成 c-di-GMP，含有 HD-GYP 或 EAL 结构域的磷酸二酯酶降解 c-di-GMP。这些酶在细菌中普遍存在，有些基因组中多达 50 种，但其具体功能大多未知。
我们使用比较分析鉴定了五个α变形菌目订单中编码具有 GGDEF、EAL 和 HD-GYP 结构域的蛋白质的基因的基因组模式。含有 GGDEF 的序列和 GGDEF-EAL 杂种最为丰富，共存辅助结构域的多样性最高，而含有 EAL 和 HD-GYP 的序列在辅助结构域方面则不太丰富且多样性较低。在两个订单中发现的基因的染色体定位存在显著模式。红杆菌目中的 EAL 编码基因和根瘤菌目中的 GGDEF-EAL 编码基因与 GGDEF 编码基因的分布模式相反。在红杆菌目中，GGDEF 编码基因的分布呈三峰模式，峰值在复制起点（ori）和终点（ter）之间的中间位置和 ter 处，而 EAL 编码基因的峰值靠近 ori。在根瘤菌目中，模式更加复杂，但 GGDEF 编码基因偏向于靠近 ter 的定位。
这些基因在染色体上的定位模式表明 c-di-GMP 的合成和水解与细胞周期偶联。此外，与 EAL 或 HD-GYP 结构域相比，与 GGDEF 结构域和 GGDEF-EAL 杂种相关的辅助结构域的比例和多样性更高，这可能表明影响 c-di-GMP 合成的刺激因素比水解的更多。
