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JOURNAL OF BIOLOGICAL CHEMISTRY · 2023 ·Vol. 299 ·期 11 · IF 4.8

Zymograph profiling reveals a divergent evolution of sirtuin that may originate from class III enzymes

Yujiao Yang,Siwei Zou,Kezhu Cai,Ningning Li,Zhongyue Li,Wei Tan,Wei Lin,Guo-Ping Zhao,Wei Zhao

Sirtuins are a group of NAD+-dependent deacylases that conserved in three domains of life and comprehensively involved in the regulation of gene transcription, chromosome segregation, RNA splicing, apoptosis, and aging. Previous studies in mammalian cells have revealed that sirtuins not only exist as multiple copies, but also show distinct deacylase activities in addition to deacetylation. However, the understanding of sirtuin zymographs in other organisms with respect to molecular evolution remains at an early stage. Here, we systematically analyze the sirtuin activities in representative species from archaea, bacteria, and eukaryotes, using both the HPLC assay and a 7-amino-4-methylcoumarin-based fluorogenic method. Global profiling suggests that the deacylase activities of sirtuins could be divided into three categories and reveals undifferentiated zymographs of class III sirtuins, especially for those from bacteria and archaea. Nevertheless, initial differentiation of enzymatic activity was also observed for the class III sirtuins at both paralog and ortholog levels. Further phylogenetic analyses support a divergent evolution of sirtuin that may originate from class III sirtuins. Together, this work demonstrates a comprehensive panorama of sirtuin zymographs and provides new insights into the cellular specific regulation and molecular evolution of sirtuins.

CAS / MDL: 76-05-1
研究领域: 生物化学 · 分子生物学 · 进化生物学
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DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY · 2023 · IF 2.9

Molecular evolution and gene expression of ferritin family involved in immune defense of lampreys

Junfu Guo,Shuangyu Lyu,Yanchen Qi,Xuanyi Chen,Lu Yang,Chunhui Zhao,Hao Wang

Ferritin, one of the key regulators of iron homeostasis, is widely present throughout almost all species. The vertebrate ferritin family, which originates from a single gene in the ancestral invertebrates, contains the widest variety of ferritin subtypes among all animal species. However, the evolutionary history of the vertebrate ferritin family remains to be further clarified. In this study, genome-wide identification of the ferritin homologs is performed in lampreys, which are the extant representatives of jawless vertebrates that diverged from the future jawed vertebrates more than 500 million years ago. Molecular evolutionary analyses show that four members of the lamprey ferritin family, L-FT1–4, are derived from a common ancestor with jawed vertebrate ferritins prior to the divergence of the jawed vertebrate ferritin subtypes. The lamprey ferritin family shares evolutionarily conserved characteristics of the ferritin H subunit with higher vertebrates, but certain members such as L-FT1 additionally accumulate some features of the M or L subunits. Expression profiling reveals that lamprey ferritins are highly expressed in the liver. The transcription of L-FT1 is significantly induced in the liver and heart during lipopolysaccharide stimulation, indicating that L-FTs may play a role in the innate immune response to bacterial infection in lampreys. Furthermore, the transcriptional expression of L-FT1 in quiescent and LPS-activated leukocytes is up- and down-regulated by the lamprey TGF-β2, an essential regulator of the inflammatory response, respectively. Our results provide new insights into the origin and evolution of the vertebrate ferritin family and reveal that lamprey ferritins may be involved in immune regulation as target genes of the TGF-β signaling pathway.

研究领域: 分子进化 · 免疫学 · 基因组学 · 生物化学
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IMMUNOGENETICS · 2025 ·Vol. 77 ·期 1 ·1-16 · IF 2.9

Molecular evolution of the transcription factor PRDM genes and expression profiles in response to stimulations and spinal cord injury repair in lamprey (Lethenteron reissneri)

Guo Jinyang,Du Xinyu,Wu Jiaqi,Lan Boting,Yang Ning,Su Peng

Positive regulatory domain member (PRDM) family proteins play important roles in nervous system development, neural stem cell proliferation and differentiation, and central nervous system inflammation. The unique evolutionary position of the lamprey ( Lethenteron reissneri ) as one of the oldest jawless vertebrates makes it an ideal animal model for understanding vertebrate evolution. Nevertheless, the evolutionary characteristics of PRDM genes have not yet been demonstrated in lampreys. In this study, we identified PRDM1 , 4 , 5 , 8 , 12 , 14 , and 15 genes in the lamprey genomes and also investigated their evolutionary relationships through phylogenetic analysis. The characterization of PRDM genes appears to be conserved among vertebrates, as indicated by protein structural domain, motif, and 3D structure analysis. Genomic synteny analysis revealed that lamprey PRDM neighbor genes are significantly different from those of jawed vertebrates. Real-time quantitative results demonstrate that the PRDM gene family may be involved in immune defense and spinal cord injury (SCI) repair. This study not only enriches the understanding of PRDM gene evolution but also provides new clues for the Lr-PRDMs’ roles in immune defense and SCI .

CAS / MDL: 886-86-2
研究领域: 进化生物学 · 分子遗传学 · 神经生物学 · 比较基因组学 · 发育生物学
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ACS Earth and Space Chemistry · 2024 · IF 2.9

Demonstrating Prebiotic Peptide Evolution by Nitrogen Isotope Discrimination in an Autocatalytic Chemical Reaction Network

Peng Bao,Xiao-Tong Wu,Yu-Qin He,Yao-Chen Yang,Guo-Xiang Li,Hui-En Zhang

Nitrogen isotope discrimination may be closely related to the prebiotic evolution of peptides that occurred in the origin of life from chemical reaction networks (CRNs). We deduce that autocatalytic Sammox (sulfurous reduction coupled to anaerobic ammonium oxidation)-driven CRN is a feasible scenario for life origin. To demonstrate prebiotic peptide evolution, we investigated N isotope discrimination in proteinogenic amino acids and peptide synthesis in Sammox-driven CRNs, combining mathematical and physical models. The species and amounts of proteinogenic amino acids generated in Sammox-driven CRNs with 14NH4+ as the N source were all significantly higher than those in Sammox-driven CRNs with 15NH4+ as the N source for both hydrothermal and microaerobic eutectic freezing conditions. The low yield of 15N-amino acids, both species and amounts, will lead to the formation of 15N-peptides with poor structure and function and slow peptide dynamics; these peptides might be preferentially degraded in Sammox-driven CRNs. We then explored the nitrogen isotopic effects during the synthesis process from ammonia to glycine, from glycine to glycine-containing peptides, and during the process of glycine-containing peptide hydrolysis. 15N are eliminated in competition with 14N during the process of glycine synthesis, glycine-containing peptide synthesis, and glycine-containing peptide hydrolysis under hydrothermal conditions as determined by the maximum entropy production principle, which is a prebiotic evolution process. In addition, pyrrole as the building block of the prosthetic group, which is generated from Sammox-driven CRNs under hydrothermal conditions, may provide a more evolutionary possibility of prebiotic peptides.

研究领域: 生物化学 · 起源化学 · 分子进化
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ACS Catalysis · 2019 · IF 12.221

Structural Insights into the Dual-Substrate Recognition and Catalytic Mechanisms of a Bifunctional Acetyl Ester–Xyloside Hydrolase from Caldicellulosiruptor lactoaceticus

Hao Cao,Lichao Sun,Ying Huang,Xin Liu,Dong Yang,Tengfei Liu,Xiaojing Jia,Boting Wen,Tianyi Gu,Fengzhong Wang,Fengjiao Xin

Enzymes are usually characterized by their evolutionarily conserved catalytic domains; however, this work presents the incidental gain-of-function of an enzyme in a loop region by natural evolution of its amino acids. A bifunctional acetyl ester–xyloside hydrolase (CLH10) was heterologously expressed, purified, and characterized. The primary sequence of CLH10 contains the fragments of the conserved sequence of esterase and glycosidase, which distribute in a mixed type. The crystal structure revealed that the primary sequence folded into two independent structural regions to undertake both acetyl esterase and β-1,4-xylanase hydrolase functions. CLH10 is capable of cleaving both the β-1,4-xylosidic bond-linked main chain and the ester bond-linked acetylated side chain of xylan, which renders it valuable because it can degrade acetylated xylan within one enzyme. Significantly, the β-1,4-xylanase activity of CLH10 appears to have been fortuitously obtained because of the variable Asp10 and Glu139 located in its loop region, which suggested that the exposed loop region might act as a potential hot-spot for the design and generation of promising enzyme function in both directed evolution and rational protein design.

研究领域: 生物化学 · 酶学 · 结构生物学 · 分子进化
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CHEMICAL COMMUNICATIONS · 2024 ·Vol. 61 ·期 8 ·1701-1704 · IF 4.3

A selective non-enzymatic synthesis of ribose simply from formaldehyde, metal salts and clays

Hao-Xing Xu,Ze-Run Zhao,Xiao Wang

This study demonstrates that metal-doped-clay (MDC) can be a selective platform for ribose produced from formaldehyde under abiotic conditions. Ribose exhibits superior retention compared with other carbohydrates on naturally occurring minerals on the early Earth in the presence of divalent cations. This finding offers an insight into the necessity of the emergence of ribose as the backbone of extant RNA.

研究领域: 化学生物学 · 分子进化 · 前生命化学 · 地球生物学 · 生物无机化学
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Frontiers of Environmental Science & Engineering · 2025 ·Vol. 19 ·期 12 ·1-16 · IF 6.4

Substrate competition over 320 days maintains extracellular electron transfer and parallel genomic evolution in Shewanella oneidensis MR-1

Zhao Biyi,Chen Wei,Chen Geng,Zhao Feng,Xiao Yong

Electroactive microorganisms are integral to biogeochemical cycles through extracellular electron transfer and have potential applications in environmental remediation. However, their long-term competitive interactions and evolutionary dynamics with non-electroactive microorganisms remain poorly understood. In this study, we conducted a 320-day cultivation experiment in which monocultures of the electroactive Shewanella oneidensis MR-1, the non-electroactive Citrobacter freundii An1, and their cocultures were compared under three single electron acceptor conditions: anaerobic (no exogenous electron acceptor), ferrihydrite, or oxygen. After 320 d, S. oneidensis MR-1 presented the highest relative abundance of 30.94% ± 0.74% in the ferrihydrite cocultures. S. oneidensis MR-1 maintained ferrihydrite reduction capacity after cultivation under all three conditions, indicating the long-term stability of its extracellular electron transfer. Moreover, no other phenotypic evolution was observed in S. oneidensis MR-1 after ferrihydrite or anaerobic cultivation. In contrast, both monocultured and cocultured S. oneidensis MR-1 exhibited enhanced adaptation to oxygen, characterized by increased growth rates, metabolic activity, and reduced cell aggregation. Notably, substrate consumption increased in monocultures but decreased in cocultures, suggesting an optimization of metabolic efficiency in the latter. Genome sequencing revealed mutations in genes associated with cell division, adenosine triphosphate synthesis, lactate metabolism, and flagellar/pilus expression in S. oneidensis MR-1. Interestingly, the ferrihydrite-adapted groups also exhibited enhanced adaptation to oxygen. 83.96% of mutations were shared across all culture systems and enriched in environmental signal-sensing pathways, indicating that parallel genomic evolution facilitated cross-environmental adaptation. Our findings reveal the ecological evolution of electroactive microorganisms in diverse redox environments and establish a foundation for engineering electroactive communities.

研究领域: 微生物生态学 · 环境微生物学 · 分子进化 · 生物地球化学 · 合成生物学
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ACS Synthetic Biology · 2022 · IF 5.249

A Nucleic Acid Sequence That is Catalytically Active in Both RNA and TNA Backbones

Dongying Wei,Yueyao Wang,Dongfan Song,Ze Zhang,Juan Wang,Jia-Yu Chen,Zhe Li,Hanyang Yu

Threose nucleic acid (TNA) is considered a potential RNA progenitor due to its chemical simplicity, base pairing property, and capability of folding into a functional tertiary structure. However, it is unknown whether the functional property can be maintained during transition from TNA to RNA. Here, we use a toggle in vitro selection to identify nucleic acid catalyst sequences that are active in both TNA and RNA backbones. One such nucleic acid enzyme with exchangeable backbone (CAMELEON) catalyzes an RNA cleavage reaction when prepared as TNA (T) and RNA (R). Further biochemical characterization reveals that CAMELEON R and T exhibit different catalytic behaviors such as rate enhancement and magnesium dependence. Structural probing and mutagenesis experiments suggest that they likely fold into distinct tertiary structures. This work demonstrates that the catalytic activity can be preserved during backbone transition from TNA to RNA and provides further experimental support for TNA as an RNA precursor in evolution.

研究领域: 生物化学 · 分子进化 · 核酸化学
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