Search Results (462)

AQP8-type water channels are expressed superficially in the plasma membrane or intracellularly in the inner mitochondrial membrane, where they respectively function in osmohomeostasis or as peroxiporins to alleviate oxidative stress. To date only single-copy AQP8 or AQP16 genes are known in tetrapods and two binary gene clusters composed of aqp8aa-aqp8ab and aqp8ba-aqp8bb in teleost fishes. Here, using phylogenomic and synteny analyses, we revise this view and show that bony fish aqp8aa, -ab, -ba and -bb genes are non-canonical co-orthologs that independently arose at chromosomal breakpoints. Conversely, canonical orthologs of tetrapod AQP8 are now detected in all vertebrate classes except hagfishes. In cartilaginous fishes, intact aqp8 orthologs and linked pseudogenes exist in squalomorph sharks and only fractionated aqp8-like pseudogenes in galeomorph sharks. Some isolated aqp8-like exons are detected in batoid ray genomes, while no aqp8-type coding sequences are currently found in holocephalan genomes. In the actinopterygian (ray-finned fish) lineage, the canonical ortholog of tetrapod AQP8 is estimated to have undergone gene translocation in their common ancestor ~400 million years ago but was subsequently inactivated or lost in many descendant lineages. In close temporal proximity to this gene translocation event, the actinopterygian aqp8aa-aqp8ab binary gene cluster was generated in the original syntenic locus, potentially as a result of meiotic recombination. Our data support a model of total chromosomal replication for the generation of AQP16 genes and the teleost aqp8ba-aqp8bb gene cluster. We further uncover additional duplicates in Strepsirrhini primates that provide an eminent example of the stochastic nature of neofunctionalization. The present data thus suggest that that common ancestral genome duplications combined with lineage-level chromosomal translocation, recombination and replication events contributed to the diversification of vertebrate AQP8-type genes. Full article

Background/Objectives: A central question in molecular genetics concerns how transcriptional regulatory sequences and de novo genes originate and reach evolutionary fixation. In this study, we utilize the human bicistronic gene SMIM45 as a model to analyze the evolutionary trajectories of gene development. This locus comprises several functional units: three enhancers (one featuring an embedded silencer), an exonic silencer that partially overlaps an ORF, a highly conserved ancestral sequence encoding a 68 aa microprotein, and a human-specific de novo gene encoding a 107 aa protein expressed spatiotemporally in embryonic brain tissues. Methods: The alignment of gene sequences from different species was used to determine the evolutionary development of enhancers and silencers, and the development of the exonic silencer was determined through application of the cultivator model and assessment of nearest-neighbor bases. Results: We identify significant disparities in formation mechanisms; for example, the LOC127896430 NANOG hESC enhancer originated simply via two Alu insertions that constitute the enhancer. In contrast, the exonic silencer (a segment of the LOC130067579 ATAC-STARR-seq lymphoblastoid silent region 13815)—a distinct, novel type of silencer—originated from a combination of diverse mechanisms, including a “cultivator gene” process of base pair fixation, consistent with the cultivator model proposed by Li Zhao and coworkers. Conclusions: SMIM45 exemplifies novel development mechanisms occurring over hundreds of millions of years, culminating in the birth of a human-specific, de novo 107 aa cistron. The associated complex of enhancers and silencers suggests intricate regulation of the 107 aa protein in fetal brain tissues. Full article

IgA nephropathy is the most common primary glomerulonephritis worldwide and a leading cause of chronic kidney disease and kidney failure, with geographic and ancestral variation and a course ranging from asymptomatic urinary abnormalities to progressive loss of kidney function. This narrative review links the multi-hit model to risk stratification, biomarkers, current management, and emerging therapies, and highlights implementation gaps. Risk assessment is longitudinal, prioritizing proteinuria and estimated glomerular filtration rate trajectories and integrating Oxford MEST-C, prediction tools, and biomarker and multi-omics approaches, while recognizing limitations in histologic reproducibility and model calibration. Current management is anchored in optimized supportive care aimed at sustained proteinuria reduction and kidney protection, including intensive blood pressure control with maximal tolerated renin–angiotensin system blockade, dietary sodium restriction and lifestyle measures, and sodium–glucose co-transporter 2 inhibitors for eligible patients. For selected higher-risk patients with persistent proteinuria despite optimized supportive care, immunomodulatory strategies are discussed, including systemic corticosteroids and targeted-release budesonide (Nefecon), emphasizing structured toxicity risk mitigation and cautioning against assuming interchangeability among alternative oral budesonide formulations. Emerging therapies are organized around mechanism-aligned targets across the BAFF/APRIL axis, complement pathways, and endothelin-based approaches, with growing interest in sequencing and combination regimens layered on supportive care. Key gaps include reliance on surrogate endpoints, limited long-term durability and safety data, and uneven evidence for special populations. Full article

In Africa, hares (Lepus spp.) show a high variability in external phenotypes. Species identification, delimitation, and distinction are difficult, due to the generally shallow evolutionary divergence of species, high intraspecific phenotypic variability, potentially complex reticulate evolutionary scenarios, and absence of relevant data across large areas. Our microsatellite and mitochondrial (mt) CR1 sequence data of hares from Tunisia with four different coat color morphs revealed high levels of gene flow both in nuclear and mt gene pools but no relevant partitioning of genetic variability parallel to the four coat color types. Nuclear and mt gene pool correspondence was at a very low level, and no phylogenetic gaps were observed in the mtDNA. Our results indicate only one hare species with different coat colors in Tunisia that shows no signals of reticulate evolution or incipient speciation. Because of potential reticulate evolutionary signals, especially in the mtDNA and the probably high adaptive significance of coat colors and patterns, external phenotypes combined with mtDNA alone may not serve as good proxies for species delimitation in hares from wide ranges in Africa. Combined nuclear and mtDNA population genetic and phylogenetic data allow more complex inferences on current and ancestral evolutionary processes for species identification and delimitation. Full article

(1) Background: The “Bider” marking refers to the symmetrical black stripes distributed on the shoulder blades of Dun Mongolian horses, representing an ancestral trait of significant genetic value. However, the molecular mechanisms underlying its formation remain unclear. This study aims to elucidate the molecular basis of these markings by comparing transcriptomic differences in skin tissues from variously pigmented areas of Mongolian horses’ “Bider” patterns. (2) Methods: Using three Dun Mongolian horses as subjects, skin tissue samples were collected from their shoulders (dark-marked and light-marked areas), dorsal midline, and croup regions for transcriptome sequencing. Differentially expressed genes were identified based on sequencing data, followed by Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Key findings were validated through quantitative reverse transcription polymerase chain reaction (qRT-PCR). (3) Results: The sequencing yielded approximately 893 million high-quality clean reads, with an overall alignment rate exceeding 96%. A total of 140 to 775 differentially expressed genes were identified. GO enrichment analysis revealed that these genes were significantly enriched in biological processes related to pigment metabolism, skin and hair follicle development, signal transduction (including calcium and cyclic guanosine monophosphate (cGMP) signaling), and immune regulation. KEGG analysis further indicated that multiple pathways closely associated with pigment regulation, including the calcium signaling pathway, tyrosine metabolism, cyclic adenosine monophosphate (cAMP) signaling pathway, and melanoma pathway, were significantly enriched across different tissue comparison groups, suggesting their potential key roles in coat color phenotype formation. The reliability of the sequencing data was corroborated by the results of qRT-PCR validation. (4) Conclusions: This study conducted a transcriptome analysis of skin samples from various pigmented regions of the Dun Mongolian horse’s Bider marking, revealing that the formation of this marking is associated with the differential expression of numerous genes and is co-regulated by multiple pigment-related signaling pathways. Full article

Water scavenger beetles (Coleoptera: Hydrophiloidea) exhibit remarkable adaptations to both aquatic and terrestrial habitats and play irreplaceable ecological roles, yet their higher-level phylogeny and the molecular basis of their adaptive evolution remain unresolved. Here, we sequenced four complete mitogenomes of C. unipunctatus from the Qinghai–Tibetan Plateau (QTP) and conducted a comprehensive mitogenomic analysis by integrating these new data with 22 publicly available Hydrophiloidea mitogenomes, representing three families and six subfamilies. Our analyses revealed highly conserved mitogenomic architecture across Hydrophiloidea, with structural variation confined to non-coding regions and AT content correlating with both habitat type and phylogenetic lineage. Phylogenetic reconstructions robustly resolved the higher-level relationships: Helophoridae and Hydrochidae formed the sister group to Hydrophilidae, within which Hydrophilinae and Sphaeridiinae were strongly supported as monophyletic clades. We detected positive selection in the energy metabolism genes cox3 and nad5 along the ancestral branch of the terrestrial subfamily Sphaeridiinae, providing the first molecular evidence linking mitochondrial adaptation to the aquatic-to-terrestrial habitat shift. However, no positive selection signals were found in high-altitude C. unipunctatus populations, suggesting that adaptation to extreme environments operates through alternative mechanisms (e.g., regulatory or structural variation) rather than protein-coding evolution. This study establishes a robust phylogenetic framework for Hydrophiloidea and reveals the diverse molecular pathways underlying their adaptive evolution, from protein-coding adaptation during aquatic–terrestrial shifts to non-coding responses in extreme high-altitude environments. Full article

The parasitic wasps of Aphelinidae (Hymenoptera) are a group of insects with significant biological control value. However, their genomic evolution and ecological adaptation mechanisms remain unclear. In this study, we focused on the genome analysis of Eretmocerus hayati and performed a comparative analysis with four other species from Aphelinidae. Our results indicated that the divergence time of Aphelinidae was approximately 119.9 million years ago. In Er. hayati, gene families related to energy metabolism and humoral immunity have significantly expanded, which may be associated with the high metabolic demands of its small body size and the immune adaptation strategies resulting from its unique parasitic methods. Additionally, genes involved in DNA replication and recombination have undergone positive selection in the ancestral branch of Aphelinidae species. Compared with 23 species within nine families in the Chalcidoidea superfamily studied here, the genome size of Er. hayati is the largest. The analysis of repetitive sequences revealed a recent burst of long terminal repeat (LTR) sequence insertions in the genome of Er. hayati. Our study indicates the evolutionary characteristics of Er. hayati in terms of gene family evolution, chromosomal collinearity, and transposon dynamics, providing a theoretical basis for understanding the environmental adaptation and biological control applications. Full article

Boule is the ancestral member of the Deleted in Azoospermia (DAZ) family and is pivotal for gametogenesis and male fertility in most animals. However, there is a dearth of information on molluscan boule. Here, we identified a counterpart (Pcbol) from the genome of Pomacea canaliculata, which has emerged as a cosmopolitan alien species and notorious pest that causes devastating damage to aquatic biodiversity, freshwater ecosystems and crop production in invaded ranges. This study aimed to investigate the biological roles of Pcbol in male reproduction and to decipher the molecular mechanisms underpinning its modulation via dsRNA-delivered RNA interference (RNAi). The bioinformatic analysis showed that the Pcbol genomic sequence is 12,934 nt in length, harboring an open reading frame of 294 nt that encodes 97 aa residues, with an RRM domain evolutionarily conserved among molluscan orthologues. Spatiotemporal expression profiling indicated the predominant abundance of Pcbol in adult males and testis tissues. dsPcbol, injected at a dose of 4 μg/per snail for 5 days, yielded optimal silencing at both transcript and translation levels of Pcbol, as revealed by qRT-PCR and Western blotting. Immunofluorescence echoed a pronounced reduction in Pcbol signal intensity following RNAi. In addition to the arrested reproductive gland phenotype, the number of sperm cells substantially dwindled upon dsPcbol treatment relative to the dsGFP control. In biochemical and fecundity assays, Pcbol depletion triggered a significant decrease in Te/SP/Arg content and suppressed the number of deposited eggs and hatchability. Furthermore, spermatogenic genes like CDC25/TSSK1/SPATA17/DDX4/Dmrt2/Sox2/Kelch10/SPO11 displayed considerable downregulation post Pcbol silencing, with molecular docking predicting a strong affinity between CDC25 and Pcbol. These molecular modules may interact with Pcbol to mediate knockdown effects on spermatogenesis dysfunction. Collectively, our findings not only confirmed that boule was indispensable for spermatogenesis and male fertility in a mollusk, but also highlighted the Pcbol-based male sterile technique (MST), which can be incorporated into precision pest management (PPM) strategies for sustainable control of P. canaliculata. Full article

Background: Velvet worms (Onychophora) occupy a pivotal phylogenetic position for deciphering the evolution of Panarthropoda, yet their exact placement within this clade remains debated. Furthermore, early studies in some onychophoran species revealed extensive gene rearrangements and the truncation or even loss of canonical transfer RNAs (tRNAs), features uncommon in other panarthropods. However, due to sparse representation, the pervasiveness and evolutionary significance of these genomic peculiarities across the phylum remain poorly understood. Methods: We sequenced and assembled three novel mitogenomes representing both extant onychophoran families (Epiperipatus barbadensis [Peripatidae]; Euperipatoides rowelli and Phallocephale tallagandensis [Peripatopsidae]) and conducted comparative analyses with five published species. Results: Onychophoran mitogenomes displayed high A+T content (mean 77.32%) but revealed a family-level divergence in GC skew. All genomes contained the standard 13 protein-coding genes (PCGs) and two ribosomal RNAs, yet tRNA counts varied significantly (ranging from 13 to 22), reflecting lineage-specific tRNA loss. Ancestral state reconstruction uncovered deep architectural divergence: Peripatopsidae retains the ancestral onychophoran gene arrangement, whereas Peripatidae exhibits a stable but derived gene order. Despite this architectural plasticity, synonymous codon usage patterns remained strictly conserved across the phylum, with all but one PCG evolving under strong purifying selection. Maximum likelihood phylogenetic reconstruction based on PCGs strongly supported Onychophora as the sister group to Arthropoda within Panarthropoda. Conclusions: Our findings provide robust molecular evidence supporting the Antennopoda hypothesis over the Tactopoda hypothesis for Panarthropoda phylogeny. Furthermore, we demonstrate extensive mitogenomic remodeling between the two extant onychophoran families, including divergent GC-skew patterns, tRNA contents, and gene arrangements. Full article

Background/Objectives: Pygmy rabbits (Brachylagus idahoensis) are closely associated with sagebrush steppe habitat across the western United States, and loss and fragmentation of this habitat has contributed to the near extirpation of the Columbia Basin population in Washington state (CB). The CB pygmy rabbit was listed under the Endangered Species Act in 2003, and recovery efforts have included captive breeding, reintroduction, and genetic rescue with the translocation of rabbits from populations across the species range. Methods: We used restriction site-associated DNA sequencing (RADseq) on samples from across the species range, including CB pygmy rabbits captured prior to genetic rescue and admixture. We determined population genetic structure across the pygmy rabbit range, tested for genomic signatures of adaptive divergence among populations, assessed the genetic distinctiveness of the ancestral CB population, and identified loci useful for monitoring ancestry in the current admixed CB population. Results: Our dataset included 9794 single-nucleotide polymorphisms (SNPs) across 123 individuals. We identified four distinct genetic groups, including the central portion of the species range and three peripheral populations: CB, northern Utah/Wyoming, and southern Utah. The ancestral CB population showed the highest degree of genetic distinctiveness using multiple clustering, ordination, and genetic differentiation analyses. We identified evidence for putatively adaptive variation among populations, but no significant gene ontology associated with local adaptation. Conclusions: Our results highlight the long-term isolation of the ancestral CB population as well as historical isolation of other peripheral populations. Our results also provide SNP loci for monitoring the consequences of genetic rescue efforts in the current admixed CB population. Full article

Formerly considered nonfunctional “junk DNA,” pseudogenes have been re-evaluated in light of technological advances in bioinformatics and high-throughput sequencing. The limited research to date on pseudogenes in hexaploid common wheat (Triticum aestivum L.) is largely confined to individual gene families, thus hindering our understanding of the long-term evolutionary dynamics among the A, B, and D subgenomes. Using the IWGSC RefSeq v2.1 genome assembly, we performed genome-wide identification, classification, and analysis of pseudogenes in wheat, including their distribution, evolutionary history, and parental gene functions. Marked asymmetries in pseudogene abundance, distribution, evolutionary dynamics, and constraints were detected among the subgenomes. The B subgenome harbored significantly more pseudogenes and showed distinct evolutionary patterns compared with the A and D subgenomes. Pseudogenes were strongly associated with transposable elements and peaks in their formation were incongruent with ancient genomic upheavals of wheat ancestral lineages. The parent genes were predominantly enriched in non-core functions and showed tissue-specific expression. The findings provide direct evidence for long-term asymmetric, post-polyploidization evolution in wheat, enhance our understanding of polyploid genome evolution, and offer a methodological framework for research on other genetically complex polyploid crops. Full article

The SARS-CoV-2 Omicron variant and its descendants accumulated unprecedented numbers of spike substitutions yet remained transmissible, implying compensatory mechanisms that preserve entry while eroding humoral immunity. We analyzed 32 variants for sequence-level mutation, physicochemical profiling, and epitope disruption; 25 had growth-advantage estimates, and 18 underwent molecular dynamics/MM-PBSA simulations. We applied a systems-virology framework to the SARS-CoV-2 receptor-binding domain (RBD), integrating immunodominance-weighted epitope conservation (567 B-cell and 97 T-cell epitopes) across variants (Wuhan-Hu-1 to KP.3) with molecular dynamics, molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) binding energetics, and deep mutational scanning (DMS) benchmarking. B-cell epitope conservation declined from a median of 72.7% in pre-Omicron variants to 28.8% in BA.1 and 10.6% in KP.3, and was strongly inversely associated with a breakthrough-infection proxy (Spearman ρ = −0.8246, p < 0.001), whereas RBD T-cell epitopes remained comparatively conserved (91.5% to 87.2%). Despite the loss of the ancestral K417–ACE2 D30 salt bridge, Omicron reconfigured the interface via alternative electrostatic contacts (Q493R–E35 and Q498R–D38), producing compensatory interactions captured by MM-PBSA, but with only modest agreement with DMS affinity changes (r = 0.682, p = 0.007), consistent with enthalpy–entropy compensation. Finally, mutation tolerance shifted toward stronger epistatic buffering in Omicron (two-fold higher epistasis than pre-Omicron; p = 0.0093), enabling extensive antigenic change without structural collapse. Together, these results support a multi-objective evolutionary strategy—epitope erosion, interface rewiring, and epistatic compensation—that can be operationalized to prioritize emerging lineages for surveillance and to inform vaccine designs that emphasize conserved T-cell targets. Full article

Mpox is a zoonosis caused by the monkeypox virus. Here, we report Mali’s index Mpox case, which was clinically identified at the Mali–Guinea border by the national telemedicine center and confirmed by PCR. The library prepared with NextGenPCR™ MPXV Sequencing Library Prep and sequenced on Minion MK1C revealed a genome length of 197,122 bp with an average depth of 1284.4×. The strain belonged to Clade IIb G1 lineage and exhibited 85 mutations relative to NC_063383.1. To decipher genomic epidemiology, genomes ≥ 195 kb were retrieved from NCBI and aligned with MAFFT. Time-resolved phylogenetic reconstruction and ancestral trait inference were performed with TreeTime v0.11.4. A median joining network was built with Popart v1.7. Phylogeographic analysis revealed clustering with Clade IIb (G.1 lineage) linked to the May 2025 outbreak in Sierra Leone. Full article

The emergence of Sundaland during the Pleistocene glaciation has played a crucial role, as the Indo-Pacific Barrier (IPB), in shaping the genetic structure of marine taxa and coastal flora, specifically mangroves. This study investigated the genetic diversity, population structure, demographic history and phylogeography of Avicennia marina and two other Indo-West Pacific (IWP) Avicennia species, Avicennia alba and Avicennia officinalis, across the Andaman Sea (Indian Ocean) and the Gulf of Thailand (Pacific Ocean). Using Restriction-site-Associated DNA sequencing (RADseq), we generated thousands of genome-wide SNPs for 362 Avicennia individuals and revealed a pronounced East–West genetic divergence, separating the Andaman and Gulf of Thailand populations. Phylogeographic and demographic analyses suggest that colonization events by distinct ancestral lineages (Indian and West Pacific Ocean lineages), the Indo-Pacific Barrier (Sundaland), and Pleistocene sea-level fluctuations shaped the population structure and contributed to low genetic diversity (H_o = 0.073–0.083) and high inbreeding coefficients (F_IS = 0.169–0.501). This study highlights the importance of Thailand, as part of the Indo-Pacific interface, in harboring genetic resources from both Indian and West Pacific Ocean lineages, as exemplified in A. marina. Consequently, Andaman and Thai Gulf populations should be managed as distinct evolutionarily significant units (ESUs). Full article

HIV-1 diversified for decades within the Democratic Republic of the Congo (DRC) before spreading globally in the early 1980s. Thus, the DRC is home to some of the most ancestral and diverse HIV-1 strains. Recent serosurveys conducted from 2017 to 2019 in Kinshasa, DRC, indicated high prevalence of HIV-1, yet sequence data is lacking from this period. Given the history of circulating rare HIV-1 subtypes in the DRC, a viral whole-genome sequencing study was conducted to determine current diversity in the greater Kinshasa area. Next-generation sequencing (NGS) through metagenomic and target enrichment methods was conducted on 197 specimens collected from 2017 to 2019. A large array of HIV subtypes (A, B, C, D, F1, G, H, J, and K), circulating recombinant forms (CRF01_AE, CRF02_AG, CRF05_DF, CRF11_cpx, CRF13_cpx, CRF25_cpx, CRF 45_cpx, and CRF92_C2U), unique recombinant forms, and unclassifiable sequences were observed, with many branching in basal positions within, or outside of, many subtypes on phylogenetic trees. Incorporating these new sequences into Bayesian inference of phylogeny pushes back the dates of the most recent common ancestors of HIV-1 group M and the rare subtypes G, H, and J by between 3 and 7 years each. The DRC continues to harbor diverse and rare HIV-1 subtypes that could challenge diagnostic tests, treatments, and vaccines. In addition to shifting subtype emergence dates, the sequences from our study are evidence that rare strains continue to circulate and should be regularly monitored. Full article