Diversification of AID/APOBEC-like deaminases in metazoa: multiplicity of clades and widespread roles in immunity

AID/APOBEC deaminases (AADs) convert cytidine to uridine in single-stranded nucleic acids. They are involved in numerous mutagenic processes, including those underpinning vertebrate innate and adaptive immunity. Using a multipronged sequence analysis strategy, we uncover several AADs across metazoa, dictyosteliida, and algae, including multiple previously unreported vertebrate clades, and versions from urochordates, nematodes, echinoderms, arthropods, lophotrochozoans, cnidarians, and porifera. Evolutionary analysis suggests a fundamental division of AADs early in metazoan evolution into secreted deaminases (SNADs) and classical AADs, followed by diversification into several clades driven by rapid-sequence evolution, gene loss, lineage-specific expansions, and lateral transfer to various algae. Most vertebrate AADs, including AID and APOBECs1–3, diversified in the vertebrates, whereas the APOBEC4-like clade has a deeper origin in metazoa. Positional entropy analysis suggests that several AAD clades are diversifying rapidly, especially in the positions predicted to interact with the nucleic acid target motif, and with potential viral inhibitors. Further, several AADs have evolved neomorphic metal-binding inserts, especially within loops predicted to interact with the target nucleic acid. We also observe polymorphisms, driven by alternative splicing, gene loss, and possibly intergenic recombination between paralogs. We propose that biological conflicts of AADs with viruses and genomic retroelements are drivers of rapid AAD evolution, suggesting a widespread presence of mutagenesis-based immune-defense systems. Deaminases like AID represent versions “institutionalized” from the broader array of AADs pitted in such arms races for mutagenesis of self-DNA, and similar recruitment might have independently occurred elsewhere in metazoa.

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Faculty Opinions recommendation of EST analysis of the cnidarian Acropora millepora reveals extensive gene loss and rapid sequence divergence in the model invertebrates.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1016867.201716 ◽

2004 ◽

Author(s):

Patricia Simpson

Keyword(s):

Gene Loss ◽

Sequence Divergence ◽

Acropora Millepora ◽

Est Analysis ◽

Rapid Sequence

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Faculty Opinions recommendation of Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13622956.15029056 ◽

2012 ◽

Author(s):

Howard Chang ◽

Pedro Batista

Keyword(s):

Embryonic Development ◽

Sequence Evolution ◽

Rapid Sequence

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Evolutionary Analysis of Plastid Genomes of Seven Lonicera L. Species: Implications for Sequence Divergence and Phylogenetic Relationships

International Journal of Molecular Sciences ◽

10.3390/ijms19124039 ◽

2018 ◽

Vol 19 (12) ◽

pp. 4039 ◽

Cited By ~ 5

Author(s):

Mi-Li Liu ◽

Wei-Bing Fan ◽

Ning Wang ◽

Peng-Bin Dong ◽

Ting-Ting Zhang ◽

...

Keyword(s):

Molecular Genetic ◽

Phylogenetic Reconstruction ◽

Sequence Divergence ◽

Genomic Analysis ◽

Repeat Sequence ◽

Biological Research ◽

Comparative Genomic ◽

Sequence Evolution ◽

Evolutionary Analysis ◽

Plastid Genomes

Plant plastomes play crucial roles in species evolution and phylogenetic reconstruction studies due to being maternally inherited and due to the moderate evolutionary rate of genomes. However, patterns of sequence divergence and molecular evolution of the plastid genomes in the horticulturally- and economically-important Lonicera L. species are poorly understood. In this study, we collected the complete plastomes of seven Lonicera species and determined the various repeat sequence variations and protein sequence evolution by comparative genomic analysis. A total of 498 repeats were identified in plastid genomes, which included tandem (130), dispersed (277), and palindromic (91) types of repeat variations. Simple sequence repeat (SSR) elements analysis indicated the enriched SSRs in seven genomes to be mononucleotides, followed by tetra-nucleotides, dinucleotides, tri-nucleotides, hex-nucleotides, and penta-nucleotides. We identified 18 divergence hotspot regions (rps15, rps16, rps18, rpl23, psaJ, infA, ycf1, trnN-GUU-ndhF, rpoC2-rpoC1, rbcL-psaI, trnI-CAU-ycf2, psbZ-trnG-UCC, trnK-UUU-rps16, infA-rps8, rpl14-rpl16, trnV-GAC-rrn16, trnL-UAA intron, and rps12-clpP) that could be used as the potential molecular genetic markers for the further study of population genetics and phylogenetic evolution of Lonicera species. We found that a large number of repeat sequences were distributed in the divergence hotspots of plastid genomes. Interestingly, 16 genes were determined under positive selection, which included four genes for the subunits of ribosome proteins (rps7, rpl2, rpl16, and rpl22), three genes for the subunits of photosystem proteins (psaJ, psbC, and ycf4), three NADH oxidoreductase genes (ndhB, ndhH, and ndhK), two subunits of ATP genes (atpA and atpB), and four other genes (infA, rbcL, ycf1, and ycf2). Phylogenetic analysis based on the whole plastome demonstrated that the seven Lonicera species form a highly-supported monophyletic clade. The availability of these plastid genomes provides important genetic information for further species identification and biological research on Lonicera.

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Homogeneous detection of a target nucleic acid sequence by combination of the intercalation activating fluorescence DNA probe and the isothermal sequence amplification

Nucleic Acids Symposium Series ◽

10.1093/nass/42.1.51 ◽

1999 ◽

Vol 42 (1) ◽

pp. 51-52 ◽

Cited By ~ 1

Author(s):

T. Taya ◽

J. Saitoh ◽

T. Ishizuka ◽

K. Matsubayashi ◽

T. Ishiguro

Keyword(s):

Nucleic Acid ◽

Dna Probe ◽

Nucleic Acid Sequence ◽

Target Nucleic Acid

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Scanning single-molecule counting system for Eprobe with highly simple and effective approach

PLoS ONE ◽

10.1371/journal.pone.0243319 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0243319

Author(s):

Takeshi Hanami ◽

Tetsuya Tanabe ◽

Takuya Hanashi ◽

Mitsushiro Yamaguchi ◽

Hidetaka Nakata ◽

...

Keyword(s):

Nucleic Acid ◽

Single Molecule ◽

Detection System ◽

Signal To Noise Ratio ◽

High Sensitivity ◽

Nucleic Acid Detection ◽

Digital Measurement ◽

Excitation Light ◽

Target Nucleic Acid ◽

Fluorescent Molecules

Here, we report a rapid and ultra-sensitive detection technique for fluorescent molecules called scanning single molecular counting (SSMC). The method uses a fluorescence-based digital measurement system to count single molecules in a solution. In this technique, noise is reduced by conforming the signal shape to the intensity distribution of the excitation light via a circular scan of the confocal region. This simple technique allows the fluorescent molecules to freely diffuse into the solution through the confocal region and be counted one by one and does not require statistical analysis. Using this technique, 28 to 62 aM fluorescent dye was detected through measurement for 600 s. Furthermore, we achieved a good signal-to-noise ratio (S/N = 2326) under the condition of 100 pM target nucleic acid by only mixing a hybridization-sensitive fluorescent probe, called Eprobe, into the target oligonucleotide solution. Combination of SSMC and Eprobe provides a simple, rapid, amplification-free, and high-sensitive target nucleic acid detection system. This method is promising for future applications to detect particularly difficult to design primers for amplification as miRNAs and other short oligo nucleotide biomarkers by only hybridization with high sensitivity.

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Distinguishing L from M photopigment coding sequences by hybridization to novel locked nucleic acid (LNA) oligonucleotide probes

Visual Neuroscience ◽

10.1017/s0952523808080607 ◽

2008 ◽

Vol 25 (3) ◽

pp. 283-287

Author(s):

CHRISTINA PETTAN-BREWER ◽

LI FU ◽

SAMIR S. DEEB

Keyword(s):

Nucleic Acid ◽

Locked Nucleic Acid ◽

Macaca Nemestrina ◽

Oligonucleotide Probes ◽

Coding Sequences ◽

Cone Mosaic ◽

Target Nucleic Acid ◽

High Degree

Many attempts have been made over the years to distinguish human and primate L (long-wavelength sensitive) from M (middle-wavelength sensitive) cone photoreceptors using either immunohistochemistry or in situ hybridization. These attempts have been unsuccessful due to the very high degree of identity between the sequences of the L and M proteins and encoding mRNAs. The recent development of chemically modified oligonucleotide probes, referred to as locked nucleic acid (LNA) probes, has shown that they hybridize with much greater affinity and specificity to the target nucleic acid. This has greatly increased the potential for differentiating L from M cones by in situ hybridization. We have designed LNA oligonucleotide probes that are complementary to either the L or M coding sequences located in exon 5 of the Macaca nemestrina L and M pigment genes. We have shown that the LNA-M and LNA-L probes hybridize specifically to their respective target nucleic acid sequences in vitro. This result strongly suggests that these probes would be instrumental in rapidly distinguishing L from M cone in the entire retina, and in defining the cone mosaic during development and in adults.

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Detection of Microbial Infections Through Innate Immune Sensing of Nucleic Acids

Annual Review of Microbiology ◽

10.1146/annurev-micro-102215-095605 ◽

2018 ◽

Vol 72 (1) ◽

pp. 447-478 ◽

Cited By ~ 100

Author(s):

Xiaojun Tan ◽

Lijun Sun ◽

Jueqi Chen ◽

Zhijian J. Chen

Keyword(s):

Nucleic Acid ◽

Nucleic Acids ◽

Immune Defense ◽

Innate Immune ◽

Type I Interferons ◽

Microbial Pathogens ◽

Type I ◽

Immune Recognition ◽

Microbial Infection ◽

Microbial Infections

Microbial infections are recognized by the innate immune system through germline-encoded pattern recognition receptors (PRRs). As most microbial pathogens contain DNA and/or RNA during their life cycle, nucleic acid sensing has evolved as an essential strategy for host innate immune defense. Pathogen-derived nucleic acids with distinct features are recognized by specific host PRRs localized in endolysosomes and the cytosol. Activation of these PRRs triggers signaling cascades that culminate in the production of type I interferons and proinflammatory cytokines, leading to induction of an antimicrobial state, activation of adaptive immunity, and eventual clearance of the infection. Here, we review recent progress in innate immune recognition of nucleic acids upon microbial infection, including pathways involving endosomal Toll-like receptors, cytosolic RNA sensors, and cytosolic DNA sensors. We also discuss the mechanisms by which infectious microbes counteract host nucleic acid sensing to evade immune surveillance.

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