High Sequence Similarity Research Articles

Novel cycloviruses identified by mining human blood metagenomic data show close relationship to those from animals

The family Circoviridae includes the genera Circovirus and Cyclovirus. Cycloviruses have been found in serum samples from chronic HBV, HCV, or HIV-infected individuals as well as asymptomatic blood donors. However, research on cycloviruses is relatively limited. We used viral metagenomics to mine, analyze, and visualize the human blood virome, successfully identifying three new genomes, each encoding Rep and Capsid proteins. These proteins are crucial for viral replication and host-cell interaction: the Rep protein is involved in initiating viral genome replication, while the Capsid protein plays a key role in the assembly of new virions and the virus's ability to interact with host immune systems. Distance matrix and phylogenetic analyses show that these cycloviruses share high sequence similarity with viruses found in both humans and animals across different regions of Africa. This finding not only confirms the presence of previously uncharacterized cycloviruses in human blood, but also provides insight into their potential role in host transmission and their ecological significance. Further research is needed to explore the functional roles of these cycloviruses in viral pathogenesis, particularly how they may influence host immunity and contribute to chronic infections. Additionally, studies investigating the host range and mechanisms of cross-species transmission will be essential to understanding the broader implications of cycloviruses in human and animal health.

Comparison and Classification of LMW-GS Genes at Glu-3 Loci of Common Wheat.

The low molecular weight glutenin subunits (LMW-GS) of wheat have great effects on food processing quality, but the resolution of LMW-GS and the scoring of their alleles by direct analysis of proteins are difficult due to the larger number of expressed subunits and high similarity of DNA sequences. It is important to identify and classify the LMW-GS genes in order to recognize the LMW-GS alleles clearly and develop the functional markers. The LMW-GS genes registered in GenBank were searched at NCBI, and 593 Glu-3 genes with complete coding sequences were obtained, including 146 Glu-A3, 136 Glu-B3, and 311 Glu-D3. Sequence analysis and characterization of DNA and deduced amino acids were performed using the software DNAman. The alignment and classification showed that there were at least 9 genes with 69 allelic variants at the Glu-A3 locus, 11 genes with 64 allelic variants at the Glu-B3 locus, and 10 genes with 96 variants at the Glu-D3 locus, respectively. Furthermore, the specificity of some Glu-3 genes and their variations was analyzed. The results were beneficial to understanding the LMW-GS genes fully and to developing the functional markers and will provide a theoretical reference for the quality improvement of wheat variety.

Functional characterization of GAPDH2 through overexpression and dsRNA-mediated RNA interference in Synechocystis.

Glyceraldehyde-3-phosphate dehydrogenase 2 (GAPDH2) plays a vital role in cell growth, stress responses, and various cellular processes in organisms. However, its functional characterization in cyanobacteria, particularly in Synechocystis sp. PCC 6803, remains largely unexplored, especially concerning its overexpression and RNA interference (RNAi) via double-stranded RNA (dsRNA). This study aimed to investigate the biological role of GAPDH2 in Synechocystis sp. PCC 6803 by cloning its complete coding sequence (SyGAPDH2). The SyGAPDH2 protein comprises 350 amino acids with a molecular weight of 86.480 kDa and an isoelectric point of 5.03. The sequence alignment analysis revealed two conserved domains: NADH (Nicotinamide Adenine Dinucleotide)-quinone oxidoreductase subunit NuoI and NADH-ubiquinone/plastoquinone oxidoreductase chain 6. Similarly, Phylogenetic analysis demonstrated high sequence similarity of 96 % and 94 % with Coliform (Gammaproteobacteria bacterium), respectively. We further explored the functional significance of SyGAPDH2 through overexpression using the PpsbAII+SyGAPDH2 vector and double stranded RNA (dsRNA)-mediated silencing with dsGAPDH2. Overexpression significantly enhanced cell growth, while dsRNA-mediated suppression resulted in reduced cell proliferation, with effects observed 12 h post-treatment and persisting up to 36 h. These findings emphasize the essential regulatory role of SyGAPDH2 in cellular development and stress response. This study contributes to our understanding of GAPDH2 functional importance in cyanobacteria, providing a foundation for future investigations into its subcellular localization, additional functional roles, and broader regulatory mechanisms within cyanobacterial cellular processes.

Evaluation of 16S rRNA genes sequences and genome-based analysis for identification of non-pathogenic Yersinia.

16S rRNA genes sequencing has been used for routine species identification and phylogenetic studies of bacteria. However, the high sequence similarity between some species and heterogeneity within copies at the intragenomic level could be a limiting factor of discriminatory ability. In this study, we aimed to compare 16S rRNA genes sequences and genome-based analysis (core SNPs and ANI) for identification of non-pathogenic Yersinia. We used complete and draft genomes of 373 Yersinia strains from the NCBI Genome database. The taxonomic affiliations of 34 genomes based on core SNPs and the ANI results did not match those specified in the GenBank database (NCBI). The intragenic homology of the 16S rRNA gene copies exceeded 99.5% in complete genomes, but above 50% of genomes have four or more variants of the 16S rRNA gene. Among 327 draft genomes of non-pathogenic Yersinia, 11% did not have a full-length 16S rRNA gene. Most of draft genomes has one copy of gene and it is not possible to define the intragenomic heterogenicity. The average homology of 16S rRNA gene was 98.76%, and the maximum variability was 2.85%. The low degree of genetic heterogenicity of the gene (0.36%) was determined in group Y. pekkanenii/Y. proxima/Y. aldovae/Y. intermedia/Y. kristensenii/Y. rochesterensis. The identical gene sequences were found in the genomes of the Y. intermedia and Y. rochesterensis strains identified using ANI and core SNPs analyses. The phylogenetic tree based on 16S rRNA genes differed from the tree based on core SNPs of the genomes and did not represent phylogenetic relationship between the Yersinia species. These findings will help to fill the data gaps in genome characteristics of deficiently studied non-pathogenic Yersinia.

Quantitative Analysis of Pseudogene-Associated Errors During Germline Variant Calling.

A pseudogene is a non-functional copy of a protein-coding gene. Processed pseudogenes, which are created by the reverse transcription of mRNA and subsequent integration of the resulting cDNA into the genome, being a major pseudogene class, represent a significant challenge in genome analysis due to their high sequence similarity to the parent genes and their frequent absence in the reference genome. This homology can lead to errors in variant identification, as sequences derived from processed pseudogenes can be incorrectly assigned to parental genes, complicating correct variant calling. In this study, we quantified the occurrence of variant calling errors associated with pseudogenes, generated by the most popular germline variant callers, namely GATK-HC, DRAGEN, and DeepVariant, when analysing 30x human whole-genome sequencing data (n = 13,307). The results show that the presence of pseudogenes can interfere with variant calling, leading to false positive identifications of potentially clinically relevant variants. Compared to other approaches, DeepVariant was the most effective in correcting these errors.

Label-free miRNA fluorescent biosensors based on duplex-specific nucleases and silver nanoclusters.

MicroRNAs (miRNAs) are considered reliable biomarkers for a variety of diseases. However, their low abundance in organisms and high sequence similarity of homologous miRNAs make their accurate detection challenging. Here, we constructed a novel fluorescent biosensor for the detection of miRNA-155, a potential biomarker of neuroinflammation, based on duplex-specific nuclease (DSN) assisted amplification and DNA-templated silver nanoclusters (DNA-AgNCs) as fluorescence signal probes. DSN-assisted amplification can transform unstable miRNA into stable DNA and amplify the miRNA signal at the same time. Using DNA-AgNCs as fluorescence signal probes for biosensors can avoid complex labeling processes and reduce costs. The biosensor shows excellent selectivity, reproducibility, a wide linear range (1-600 nM) with a detection limit of 0.86 nM, and potentiality for real sample detection. This work provides a potential universal biosensing platform for miRNA detection.

Development of pyrimidone derivatives as nonpeptidic and noncovalent 3-chymotrypsin-like protease (3CLpro) inhibitors with anti-coronavirus activities.

3CLPro is crucial to the life cycle of SARS-CoV-2 and exhibits high sequence similarity with other coronaviruses, while being absent in human proteases. This makes it an ideal target for developing broad-spectrum antiviral drugs. Ensitrelvir (S-217622) is the only launched non-covalent, non-peptidomimetic 3CLPro inhibitor, offering certain advantages in terms of dosage and metabolism. Using S-217622 as the lead, we designed and synthesized 43 pyrimidone derivatives and conducted a systematic evaluation of their structure-activity relationships. Among them, A36 exhibited strong inhibitory activity against several β-coronaviruses and demonstrated low cytotoxicity. A36 also displayed moderate stability in mouse liver microsomes. Co-crystal structure analysis of 3CLPro in complex with A36 revealed the similar binding mode with S-217622. A36 shows strong potential as a promising lead for broad-spectrum anti-coronavirus therapy, warranting further investigation.

Carbapenem-induced β-lactamase-isoform expression trends in Acinetobacter baumannii

Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent bacterial threat to public health, with only a few treatment options and a > 50% fatality rate. Although several resistance mechanisms are understood, it is still impossible to predict which mutations are most likely to occur. Here, we demonstrate that independent samples of Ab, exposed to different carbapenems with escalating concentrations, show concentration- and carbapenem-dependent trends in β-lactamase-isoform expression. This result, based on the isoforms identified through label-free-quantification LC-MS/MS measurements of cell-free, gel-separated β-lactamases, suggests that the appearance of antibiotic resistance may be have some predictability based on structural factors. Additionally, the identified minor isoforms also have high sequence similarity to major expressed isoforms, indicating a potential path over which resistance occurred in independent samples. Antibiotic resistance maybe therefore somewhat predictable based on specific structural properties and further investigation may lead to new strategies for mitigating antibiotic resistance.

Identification and Bioactivity Analysis of a Novel Bacillus Species, B. maqinnsis sp. nov. Bos-x6-28, Isolated from Feces of the Yak (Bos grunniens).

Background: The identification of novel bacterial species from the intestines of yaks residing on the Qinghai-Tibet Plateau is pivotal in advancing our understanding of host-microbiome interactions and represents a promising avenue for microbial drug discovery. Methods: In this study, we conducted a polyphasic taxonomic analysis and bioactive assays on a Bacillus strain, designated Bos-x6-28, isolated from yak feces. Results: The findings revealed that strain Bos-x6-28 shares a high 16S rRNA gene sequence similarity (98.91%) with B. xiamenensis HYC-10T and B. zhangzhouensis DW5-4T, suggesting close phylogenetic affinity. Physiological and biochemical characterizations demonstrated that Bos-x6-28 could utilize nine carbon sources, including D-galactose, inositol, and fructose, alongside nine nitrogen sources, such as threonine, alanine, and proline. Analysis of biochemical markers indicated that Bos-x6-28's cell wall hydrolysates contained mannose, glucose, and meso-2,6-diaminopimelic acid, while menaquinone-7 (MK-7), phosphatidylethanolamine (PE), phosphatidylcholine (PC), and phosphatidylglycerol (DPG) were found in the cell membrane. The primary cellular fatty acids included C16:0 (28.00%), cyclo-C17:0 (19.97%), C14:0 (8.75%), cyclo-C19:0 (8.52%), iso-C15:0 (5.49%), anteiso-C15:0 (4.61%), and C12:0 (3.15%). Whole-genome sequencing identified a genome size of 3.33 Mbp with 3353 coding genes. Digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) analyses confirmed Bos-x6-28 as a novel species, hereby named B. maqinnsis Bos-x6-28 (MCCC 1K09379). Further genomic analysis unveiled biosynthetic gene clusters encoding bioactive natural compounds, including β-lactones, sactipeptides, fengycin, and lichenysin analogs. Additionally, in vitro assays demonstrated that this strain exhibits antibacterial and cytotoxic activities. Conclusions: These findings collectively indicate the novel Bacillus species B. maqinnsis Bos-x6-28 as a promising source for novel antibiotic and antitumor agents.

Excessive Extracellular Ammonium Production by a Free-Living Nitrogen-Fixing Soil Clostridium sp. Strain.

A Gram-positive, rod-shaped, and obligate anaerobic bacterial strain OS1-26 was isolated from apple orchard soil in Iksan, South Korea. Interestingly, strain OS1-26 was observed to possess the functional genes involved in biological nitrogen fixation (BNF), including nifH, which was actively transcribed during the anaerobic cultivation with excessive production of extracellular NH4+ despite of presence of other fixed N nutrients. The BNF of strain OS1-26 was distinguished from the other well-known Clostridium diazotrophs, such as C. pasteurianum and C. acetobutylicum. The altruistic N-fixing ability of the strain may play a pivotal role in providing N nutrients to the microbial community and plants in the soil ecosystem. The microorganism grew at 25-35 °C (optimum 30-35 °C) and pH 5.0-8.0 (optimum 6.0-8.0) but was not able to grow in the presence of >0.5% NaCl. The major cellular fatty acids of strain OS1-26 were C16:0, C14:0, and the summed feature consisted of C16:1 ω7c and C16:1 ω6c (35.63%, 25.29%, and 18.84%, respectively). The 16S rRNA phylogeny indicated that strain OS1-26 is a member of the genus Clostridium, and the closest species are C. aciditolerans, C. nitrophenolicum, and C. thailandense, with 16S rRNA sequence similarities such as 99.71%, 98.52%, and 98.45%, respectively. In spite of the high 16S rRNA sequence similarity, strain OS1-26 showed overall genomic relatedness, such as the average nucleotide identity (ANI), and phenotypical features distinctly different from Clostridium aciditolerans. Although the species taxonomy of strain OS1-26 is undetermined within the genus Clostridium based on overall genomic and phenotypic properties, further studies on the soil bacterial strain would enhance our understanding of its taxonomic identity, ecological roles for the terrestrial soil N cycle, and the potential to be developed as a biological N fertilizer.

Genome Studies in Amaranthus cruentus L. and A. hypochondriacus L. Based on Repeatomic and Cytogenetic Data.

Amaranthus cruentus L. and Amaranthus hypochondriacus L. are valuable and promising food crops for multi-purpose use that are distributed worldwide in temperate, subtropical, and tropical zones. However, their karyotypes and genomic relationships still remain insufficiently studied. For the first time, a comparative repeatome analysis of A. cruentus and A. hypochondriacus was performed based on the available NGS data; bioinformatic analyses using RepeatExplorer/TAREAN pipelines; and chromosome FISH mapping of 45S rDNA, 5S rDNA, and the most abundant satellite DNAs. In the repeatomes of these species, interspecific variations in the amount of Ty3/Gypsy and Ty1/Copia retroelements, DNA transposons, ribosomal, and satellite DNA were detected. In the repeatomes of both species, shared satDNAs with high sequence similarity were identified. The chromosome distribution patterns of four effective molecular markers, 45S rDNA, 5S rDNA, AmC4, and AmC9, allowed us to identify all chromosome pairs in the species karyotypes, construct unique karyograms of A. cruentus and A. hypochondriacus, and confirm the close relationship between their genomes. These results are important for comparative karyotypic studies within the genus Amaranthus. Our findings demonstrated that cytogenomic analyses might provide important data on genomic relationships within Amaranthus and increase knowledge on genome organization in these valuable crops.

NgLst8 Coactivates TOR Signaling to Activate Photosynthetic Growth in Nannochloropsis gaditana.

The target of rapamycin (TOR) serves as a central regulator of cell growth, coordinating anabolic and catabolic processes in response to nutrient availability, growth factors, and energy supply. Activation of TOR has been shown to promote photosynthesis, growth, and development in yeast, animals, and plants. In this study, the complete cDNA sequence of the Lst8 gene was obtained from Nannochloropsis gaditana. The structure of N. gaditana LST8 comprises a typical WD40 repeat sequence, exhibiting high sequence similarity to several known LST8 proteins. By overexpressing the Lst8 gene in N. gaditana, we constructed the NgLst8 transgenic algal strain and measured its photosynthetic activity and growth. We observed that an increase in LST8 abundance promotes the expression of TOR-related kinase, thereby enhancing photosynthetic growth. Transcriptome analysis further elucidated the response mechanism of elevated Lst8 abundance in relation to photosynthesis. Our findings indicate that increased Lst8 expression activates ABC transporter proteins and the MAPK signaling pathway, which regulate the transmembrane transport of sugars and other metabolites, integrate photosynthesis, sugar metabolism, and energy signaling, and modulate energy metabolism in algal cells through interactions with the TOR signaling pathway.

In silico design and discovery of pan coronavirus small molecule anti-virals targeting 3CLPRO protease

Coronaviruses (CoV), belonging to the family Coronaviridae, were not considered dangerous pathogens until the outbreaks of SARS, MERS, and more recently, COVID-19. The coronaviruses causing these respective diseases/syndromes, SARS, MERS, and SARS-CoV2, share high sequence and structural similarities. COVID-19 continues to have a global impact on human health and the economy. Human-to-human transmission is at the center of COVID-19’s ability to stall the entire world and force lockdowns across the globe. The corona viruses’ positive sense RNA genome is ∼30 kb long and encodes non-structural (ORF1ab) and structural (Spike, Envelope, Membrane, and Nucleo-capsid) proteins. The main viral protease (NSP5) is a Chymotrypsin-like protease (3CLpro) that cleaves on the carboxy side of the glutamine (Q) of the polypeptide sequence motif x-(L/F/M)-Q-(G/A/S)-x. 3CLPRO is highly conserved among coronaviruses and is critical in the replication and viral life cycle. Therefore, 3CLPRO is considered a promising drug target. We have recently reported three natural compounds, flavonoid derivatives, to target the cysteine 145 of the catalytic dyad covalently. Here, we have screened for small molecules with pan coronavirus activity to target 3CLpro. Our rigid body docking studies have identified 30 small molecules with comparable binding affinities to all the beta coronaviruses. Of these, five molecules have showed the possibility of covalently attacking the C145 of the catalytic dyad. MD simulations have revealed compounds 22 and 23 to be the most ideal lead compounds. Interestingly, one of the compounds, 22, identified in the current study has already shown to be an ideal lead compound against SARS-CoV2 3CLPRO.

Rational engineering of a highly active and resilient α-carbonic anhydrase from the hydrothermal vent speciesPersephonella hydrogeniphila.

Carbonic anhydrases (CAs) are ideal catalysts for carbon dioxide sequestration in efforts to alleviate climate change. Here, we report the characterisation of three α-CAs that originate from the thermophilic bacteria Persephonella hydrogeniphila (PhyCA), Persephonella atlantica (PaCA), and Persephonella sp. KM09-Lau-8 (PlauCA) isolated from hydrothermal vents. The three α-Cas, showing high sequence similarities, were produced in Escherichia coli, purified and characterised. Surprisingly, they revealed very different behaviours with regards to their thermostability profiles. PhyCA presented a more stable thermostability profile amongst the three, thus we chose it for rational engineering to improve it further. PhyCA's residue K88, a proton transfer residue in α-CAs, was mutated to His, Ala, Gln and Tyr. A 4-fold activity improvement was noted for variants K88H and K88Q at 30 °C, owing to the higher proton transfer efficiency of the replacement proton transfer residues. K88Q also proved more stable than PhyCA. K88Y did not increase activity, but notably increased thermal stability, with this enzyme variant retaining 50% of its initial activity after incubation for 1 h at 90 °C. Removal of the two main proton shuttles (variant H85A_K88A) resulted in diminished activity of the enzyme. Molecular dynamics simulations performed for PhyCA and all its variants revealed differences in residue fluctuations, with K88A resulting in a general reduction in root mean square fluctuation (RMSF) of active site residues as well as most of the CA's residues. Its specific activity and stability in turn increased compared to the wild type.

How to handle high subgenome sequence similarity in allopolyploid Fragaria x ananassa: linkage disequilibrium based variant filtering

BackgroundThe allo-octoploid Fragaria x ananassa follows disomic inheritance, yet the high sequence similarity among its subgenomes can lead to misalignment of short sequencing reads (150 bp). This misalignment results in an increased number of erroneous variants during variant calling. To accurately associate traits with the appropriate subgenome, it is essential to filter out these erroneous variants. By classifying variants into correct (type 1) and erroneous types (homoeologous variants—type 2, and multi-locus variants—type 3), we can improve the reliability of downstream analyses.ResultsOur analysis reveals that while erroneous variant types often display skewed average allele balances (AAB) for heterozygous calls, this measure alone is insufficient. To mitigate the erroneous variants further, we employed a Linkage Disequilibrium (LD) based filtering method that correlates highly (99%) with an approach that utilizes a genetic map from a biparental population. This combined filtering strategy—using both LD-based and average allele balance methods—resulted in the lowest switch error rate (0.037). Notably, our best filtering approach decreased phasing switch error rates by 44% and preserved 72% of the original dataset.ConclusionsThe results indicate that identifying erroneous variants due to subgenome similarity can be effectively achieved without extensive genotyping of mapping populations. By implementing the LD-based filtering method, the phasing accuracy improved which improves the tracability of important alleles in the germplasm, paving the way for better understanding of trait associations in F. x ananassa.

Taken to extremes: Loss of plastid rpl32 in Streptophyta and Cuscuta’s unconventional solution for its replacement

The evolution of plant genomes is riddled with exchanges of genetic material within one plant (endosymbiotic gene transfer/EGT) and between unrelated plants (horizontal gene transfer/HGT). These exchanges have left their marks on plant genomes. Parasitic plants with their special evolutionary niche provide ample examples for these processes because they are under a reduced evolutionary pressure to maintain autotrophy and thus to conserve their plastid genomes. On the other hand, the close physical connections with different hosts enabled them to acquire genetic material from other plants. Based on an analysis of an extensive dataset including the parasite Cuscuta campestris and other parasitic plant species, we identified a unique evolutionary history of rpl32 genes coding for an essential plastid ribosomal subunit in Cuscuta. Our analysis suggests that the gene was most likely sequestered by HGT from a member of the Oxalidales order serving as host to an ancestor of the Cuscuta subgenus Grammica. Oxalidales had suffered an ancestral EGT of rpl32 predating the evolution of the genus Cuscuta. The HGT subsequently relieved the plastid rpl32 from its evolutionary constraint and led to its loss from the plastid genome. The HGT-based acquisition in Cuscuta is supported by a high sequence similarity of the mature L32 protein between species of the subgenus Grammica and representatives of the Oxalidales, and by a surprisingly conserved transit peptide, whose functionality in Cuscuta was experimentally verified. The findings are discussed in view of an overall pattern of EGT events for plastid ribosomal subunits in Streptophyta.

Peptide Toxins from Marine Conus Snails with Activity on Potassium Channels and/or Currents.

Toxins from Conus snails are peptides characterized by a great structural and functional diversity. They have a high affinity for a wide range of membrane proteins such as ion channels, neurotransmitter transporters, and G protein-coupled receptors. Potassium ion channels are integral proteins of cell membranes that play vital roles in physiological processes in muscle and neuron cells, among others, and reports in the literature indicate that perturbation in their function (by mutations or ectopic expression) may result in the development and progression of different ailments in humans. This review aims to gather as much information as possible about Conus toxins (conotoxins) with an effect on potassium channels and/or currents, with a perspective of exploring the possibility of finding or developing a possible drug candidate from these toxins. The research indicates that, among the more than 900 species described for this genus, in only 14 species of the >100 studied to date have such toxins been found (classified according to the most specific evidence for each case), as follows: 17 toxins with activity on two groups of potassium channels (Kv and KCa), 4 toxins with activity on potassium currents, and 5 toxins that are thought to inhibit potassium channels by symptomatology and/or a high sequence similarity.

Aberrant expression of histone H2B variants reshape chromatin and alter oncogenic gene expression programs.

Chromatin architecture governs DNA accessibility and gene expression. Thus, any perturbations to chromatin can significantly alter gene expression programs and promote disease. Prior studies demonstrate that every amino acid in a histone is functionally significant, and that even a single amino acid substitution can drive specific cancers. We previously observed that naturally occurring H2B variants are dysregulated during the epithelial to mesenchymal transition (EMT) in bronchial epithelial cells. Naturally occurring H2B variants differ from canonical H2B by only a few amino acids, yet single amino acid changes in other histone variants (e.g., H3.3) can drive cancer. We therefore hypothesized that H2B variants might function like oncohistones, and investigated how they modify chromatin architecture, dynamics, and function. We find that H2B variants are frequently dysregulated in many cancers, and correlate with patient prognosis. Despite high sequence similarity, mutations in each H2B variant tend to occur at specific "hotspots" in cancer. Some H2B variants cause tighter DNA wrapping around nucleosomes, leading to more compact chromatin structures and reduced transcription factor accessibility to nucleosomal DNA. They also altered genome-wide accessibility to oncogenic regulatory elements and genes, with concomitant changes in oncogenic gene expression programs. Although we did not observe changes in cell proliferation or migration in vitro , our Gene Ontology (GO) analyses of ATAC-seq peaks and RNA-seq data indicated significant changes in oncogenic pathways. These findings suggest that H2B variants may influence early-stage, cancer-associated regulatory mechanisms, potentially setting the stage for oncogenesis later on. Thus, H2B variant expression could serve as an early cancer biomarker, and H2B variants might be novel therapeutic targets.

The Two Sides of Indoleamine 2,3-Dioxygenase 2 (IDO2).

Indoleamine 2,3-dioxygenase 1 (IDO1) and IDO2 originated from gene duplication before vertebrate divergence. While IDO1 has a well-defined role in immune regulation, the biological role of IDO2 remains unclear. Discovered in 2007, IDO2 is located near the IDO1 gene. Because of their high sequence similarity, IDO2 was initially thought to be a tryptophan (Trp)-degrading enzyme like IDO1. Differently from what expected, IDO2 displays extremely low catalytic activity toward Trp. Nevertheless, many studies, often contradictory, have tried to demonstrate that IDO2 modulates immune responses by catabolizing Trp into kynurenine, an unconvincing hypothesis linked to an incomplete understanding of IDO2's activity. In this study, we review IDO2's functional role beyond Trp metabolism. IDO2's evolutionary persistence across species, despite being almost inactive as an enzyme, suggests it has some relevant biological importance. IDO2 expression in human normal cells is poor, but significant in various cancers, with two prevalent SNPs. Overall, the comparison of IDO2 to IDO1 as a Trp-degrading enzyme may have led to misunderstandings about IDO2's true physiological and pathological roles. New insights suggest that IDO2 might function more as a signaling molecule, particularly in cancer contexts, and further studies could reveal its potential as a target for cancer therapy.

The complete mitochondrial genome assembly of Capsicum pubescens reveals key evolutionary characteristics of mitochondrial genes of two Capsicum subspecies

BackgroundPepper (Capsicum pubescens), one of five domesticated pepper species, has unique characteristics, such as numerous hairs on the epidermis of its leaves and stems, black seeds, and vibrant purple flowers. To date, no studies have reported on the complete assembly of the mitochondrial genome (mitogenome) of C. pubescens. Understanding the mitogenome is crucial for further research on C. pubescens.ResultsIn our study, we successfully assembled the first mitogenome of C. pubescens, which was assigned the GenBank accession number OP957066. This mitogenome has a length of 454,165 bp and exhibits the typical circular structure observed in most mitogenomes. We annotated a total of 70 genes, including 35 protein-coding genes (PCGs), 30 tRNA genes, 3 rRNA genes, and 2 pseudogenes. Compared to the other three pepper mitogenomes (KJ865409, KJ865410, and MN196478), C. pubescens OP957066 exhibited four unique PCGs (atp4, atp8, mttB, and rps1), while two PCGs (rpl10 and rps3) were absent. Notably, each of the three pepper mitogenomes from C. annuum (KJ865409, KJ865410, and MN196478) experienced the loss of four PCGs (atp4, atp8, mttB, and rps1). To further explore the evolutionary relationships, we reconstructed a phylogenetic tree using the mitogenomes of C. pubescens and fourteen other species. Structural comparison and synteny analysis of the above four pepper mitogenomes revealed that C. pubescens shares high sequence similarity with KJ865409 and that C. pubescens has rearranged with the other three pepper mitogenomes. Interestingly, we observed 72 similar sequences between the mitochondrial and chloroplast genomes, which accounted for 12.60% of the mitogenome, with a total length of 57,207 bp. These sequences encompassed 12 tRNA genes and the rRNA gene (rrn18). Remarkably, selective pressure analysis suggested that the nad5 gene underwent obvious positive selection. Furthermore, a single-base mutation in three genes (nad1, nad2, and nad4) resulted in an amino acid change.ConclusionThis study provides a high-quality mitogenome of pepper, providing valuable molecular data for future investigations into the exchange of genetic information between pepper organelle genomes.