Department of Microbiology, The Ohio State University, Columbus, Ohio, USA.
The Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA.
mBio. 2020 Oct 27;11(5):e02717-20. doi: 10.1128/mBio.02717-20.
The only universally conserved family of transcription factors comprises housekeeping regulators and their specialized paralogs, represented by well-studied NusG and RfaH. Despite their ubiquity, little information is available on the evolutionary origins, functions, and gene targets of the NusG family members. We built a hidden Markov model profile of RfaH and identified its homologs in sequenced genomes. While NusG is widespread among bacterial phyla and coresides with genes encoding RNA polymerase and ribosome in all except extremely reduced genomes, RfaH is mostly limited to and lacks common gene neighbors. RfaH activates only a few xenogeneic operons that are otherwise silenced by NusG and Rho. Phylogenetic reconstructions reveal extensive duplications and horizontal transfer of genes, including those borne by plasmids, and the molecular evolution pathway of RfaH, from "early" exclusion of the Rho terminator and tightened RNA polymerase binding to "late" interactions with the DNA element and autoinhibition, which together define the RfaH regulon. Remarkably, NusG is not only ubiquitous in but also common in plants, where it likely modulates the transcription of plastid genes. In all domains of life, NusG-like proteins make contacts similar to those of RNA polymerase and promote pause-free transcription yet may play different roles, defined by their divergent interactions with nucleic acids and accessory proteins, in the same cell. This duality is illustrated by NusG and RfaH, which silence and activate xenogenes, respectively. We combined sequence analysis and recent functional and structural insights to envision the evolutionary transformation of NusG, a core regulator that we show is present in all cells using bacterial RNA polymerase, into a virulence factor, RfaH. Our results suggest a stepwise conversion of a NusG duplicate copy into a sequence-specific regulator which excludes NusG from its targets but does not compromise the regulation of housekeeping genes. We find that gene duplication and lateral transfer give rise to a surprising diversity within the only ubiquitous family of transcription factors.
唯一普遍保守的转录因子家族包括管家调节剂及其专门的旁系同源物，以研究充分的 NusG 和 RfaH 为代表。尽管它们无处不在，但关于 NusG 家族成员的进化起源、功能和基因靶标知之甚少。我们构建了 RfaH 的隐马尔可夫模型轮廓，并在已测序的基因组中识别出了它的同源物。虽然 NusG 在细菌门中广泛存在，并且除了极度简化的基因组外，与编码 RNA 聚合酶和核糖体的基因共存，但 RfaH 主要局限于 ，并且缺乏常见的基因邻居。RfaH 仅激活少数异种操纵子，否则这些操纵子会被 NusG 和 Rho 沉默。系统发育重建揭示了广泛的基因重复和水平转移，包括那些由质粒携带的基因，以及 RfaH 的分子进化途径，从早期排除 Rho 终止子和紧密结合 RNA 聚合酶到晚期与 DNA 元件相互作用和自动抑制，这些共同定义了 RfaH 的调控物。值得注意的是，NusG 不仅在 中普遍存在，而且在植物中也很常见，在植物中，它可能调节质体基因的转录。在所有生命领域中，NusG 样蛋白与 RNA 聚合酶的接触相似，并促进无暂停转录，但可能在同一细胞中发挥不同的作用，这取决于它们与核酸和辅助蛋白的不同相互作用。这种二元性通过分别沉默和激活异种基因的 NusG 和 RfaH 来说明。我们将序列分析与最近的功能和结构见解相结合，设想了 NusG 的进化转变，NusG 是一种核心调节剂，我们使用细菌 RNA 聚合酶表明它存在于所有细胞中，变成了一种毒力因子 RfaH。我们的结果表明，NusG 重复副本的逐步转化为序列特异性调节剂，将 NusG 从其靶标中排除，但不影响管家基因的调节。我们发现基因复制和横向转移在唯一普遍存在的转录因子家族中产生了惊人的多样性。
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