Amoros Julien, Buysse Marie, Floriano Anna Maria, Moumen Bouziane, Vavre Fabrice, Bouchon Didier, Duron Olivier
MIVEGEC, University of Montpellier, CNRS, IRD, Montpellier, France.
LBBE, Université Lyon 1, CNRS, VetAgroSup, Villeurbanne, France.
PLoS Genet. 2025 Sep 9;21(9):e1011856. doi: 10.1371/journal.pgen.1011856. eCollection 2025 Sep.
Cytoplasmic Incompatibility (CI) causes embryonic lethality in arthropods, resulting in a significant reduction in reproductive success. In most cases, this reproductive failure is driven by Wolbachia endosymbionts through their cifA-cifB gene pair, whose products disrupts arthropod DNA replication during embryogenesis. While a cif pair has been considered a hallmark of Wolbachia, its presence and functional significance in other bacterial lineages remains poorly investigated. Here, we conducted a comprehensive survey of 762 genomes spanning non-Wolbachia endosymbionts and their close relatives, revealing that the cif pair is far more widespread than previously recognized. We identified cif loci in 8.4% of the surveyed genomes, with a striking incidence of 17.4% in facultative symbionts. Beyond Wolbachia, cif pair occurs across eight bacterial genera spanning α-Proteobacteria, γ-Proteobacteria, Mollicutes, and Bacteroidota. Notably, cif pair has been identified in several intracellular pathogens of mammals showing high rate of transovarial transmission in their arthropod hosts, suggesting a potential role of cif pair and CI in vector-borne disease dynamics. Structural analyses further reveal that the PD(D/E)-XK nucleases and AAA-ATPase-like motifs are consistently conserved across cif pairs in all bacterial taxa. Moreover, cif pairs are frequently integrated within diverse mobile genetic elements, from transposons to large intact WO prophages in Wolbachia and RAGEs in Rickettsiaceae. Phylogenetic analyses reveal recent and potentially ongoing horizontal transfers of cif pair between distantly related bacterial lineages, a process potentially facilitated by mobile genetic elements. Indeed, the PDDEXK2 transposase exhibits a phylogenetic pattern consistent with the co-transmission of cif genes, suggesting that it may facilitate horizontal transfers of cif across bacterial lineages. Furthermore, the detection of endosymbionts harboring cif pair in arthropod groups where Wolbachia is scarce, such as ticks, suggests that CI may be more widespread than previously known, with significant implications for arthropod symbiosis, reproductive manipulation, and future biocontrol strategies.
细胞质不相容性（CI）会导致节肢动物胚胎致死，从而使繁殖成功率大幅降低。在大多数情况下，这种繁殖失败是由沃尔巴克氏体共生菌通过其cifA - cifB基因对驱动的，其产物在胚胎发育过程中破坏节肢动物的DNA复制。虽然cif基因对一直被认为是沃尔巴克氏体的标志，但其在其他细菌谱系中的存在及其功能意义仍未得到充分研究。在此，我们对762个基因组进行了全面调查，这些基因组涵盖了非沃尔巴克氏体共生菌及其近亲，结果表明cif基因对比之前认为的更为广泛存在。我们在8.4%的被调查基因组中鉴定出了cif基因座，在兼性共生菌中的发生率高达17.4%，令人惊讶。除了沃尔巴克氏体外，cif基因对存在于跨越α - 变形菌门、γ - 变形菌门、柔膜菌纲和拟杆菌门的八个细菌属中。值得注意的是，在几种哺乳动物细胞内病原体中发现了cif基因对，这些病原体在其节肢动物宿主中显示出高频率的经卵传递，这表明cif基因对和CI在媒介传播疾病动态中可能具有潜在作用。结构分析进一步表明，PD(D/E)-XK核酸酶和AAA - ATP酶样基序在所有细菌类群的cif基因对中始终保持保守。此外，cif基因对经常整合到各种移动遗传元件中，从转座子到沃尔巴克氏体中的大型完整WO原噬菌体以及立克次氏体科中的RAGEs。系统发育分析揭示了cif基因对在远缘细菌谱系之间近期且可能仍在进行的水平转移，这一过程可能由移动遗传元件促进。事实上，PDDEXK2转座酶呈现出与cif基因共传递一致的系统发育模式，表明它可能促进cif基因在细菌谱系间的水平转移。此外，在蜱等沃尔巴克氏体稀少的节肢动物群体中检测到携带cif基因对的共生菌，这表明CI可能比之前所知的更为广泛，对节肢动物共生、繁殖操纵及未来生物防治策略具有重要意义。
