Department of Biology, College of Arts and Sciences, Saint Louis University, St. Louis, MO 63103, USA.
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Genome Biol Evol. 2024 Aug 5;16(8). doi: 10.1093/gbe/evae171.
Cytoplasmic incompatibility (CI), a non-Mendelian genetic phenomenon, involves the manipulation of host reproduction by Wolbachia, a maternally transmitted alphaproteobacterium. The underlying mechanism is centered around the CI Factor (CIF) system governed by two genes, cifA and cifB, where cifB induces embryonic lethality, and cifA counteracts it. Recent investigations have unveiled intriguing facets of this system, including diverse cifB variants, prophage association in specific strains, copy number variation, and rapid component divergence, hinting at a complex evolutionary history. We utilized comparative genomics to systematically classify CIF systems, analyze their locus structure and domain architectures, and reconstruct their diversification and evolutionary trajectories. Our new classification identifies ten distinct CIF types, featuring not just versions present in Wolbachia, but also other intracellular bacteria, and eukaryotic hosts. Significantly, our analysis of CIF loci reveals remarkable variability in gene composition and organization, encompassing an array of diverse endonucleases, variable toxin domains, deubiquitinating peptidases (DUBs), prophages, and transposons. We present compelling evidence that the components within the loci have been diversifying their sequences and domain architectures through extensive, independent lateral transfers and interlocus recombination involving gene conversion. The association with diverse transposons and prophages, coupled with selective pressures from host immunity, likely underpins the emergence of CIF loci as recombination hotspots. Our investigation also posits the origin of CifB-REase domains from mobile elements akin to CR (Crinkler-RHS-type) effectors and Tribolium Medea1 factor, which is linked to another non-Mendelian genetic phenomenon. This comprehensive genomic analysis offers novel insights into the molecular evolution and genomic foundations of Wolbachia-mediated host reproductive control.
细胞质不兼容（CI）是一种非孟德尔遗传现象，涉及到沃尔巴克氏体（一种母系传递的α-变形菌）对宿主生殖的操纵。其潜在机制围绕着由两个基因 cifA 和 cifB 控制的 CI 因子（CIF）系统，其中 cifB 诱导胚胎致死，而 cifA 则拮抗它。最近的研究揭示了这个系统的一些有趣方面，包括多样化的 cifB 变体、特定菌株中的原噬菌体关联、拷贝数变异和快速成分分化，暗示了一个复杂的进化历史。我们利用比较基因组学系统地对 CIF 系统进行分类，分析它们的基因座结构和结构域架构，并重建它们的多样化和进化轨迹。我们的新分类方法确定了十种不同的 CIF 类型，不仅包括沃尔巴克氏体中存在的版本，还包括其他细胞内细菌和真核宿主中的版本。重要的是，我们对 CIF 基因座的分析揭示了基因组成和组织的显著可变性，包括一系列不同的内切核酸酶、可变毒素结构域、去泛素化肽酶（DUB）、原噬菌体和转座子。我们提供了令人信服的证据表明，这些基因座中的元件通过广泛的、独立的横向转移和涉及基因转换的基因座内重组，使序列和结构域架构多样化。与多样化的转座子和原噬菌体的关联，加上宿主免疫的选择压力，可能是 CIF 基因座作为重组热点出现的原因。我们的研究还提出了 CifB-REase 结构域起源于类似于 CR（Crinkler-RHS 型）效应物和 Tribolium Medea1 因子的移动元件，这与另一种非孟德尔遗传现象有关。这项全面的基因组分析为沃尔巴克氏体介导的宿主生殖控制的分子进化和基因组基础提供了新的见解。
