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PubMed2025

Gene dosage architecture across complex traits.

UNLABELLED: Copy number variants (CNVs) have large effects on complex traits, but they are rare and remain challenging to study. As a result, our understanding of biological functions linking gene dosage to complex traits remains limited, and whether these functions sensitive to gene dosage are similar to those underlying the effects of rare single nucleotide variants (SNVs) and common variants remains unknown. METHODS: We developed FunBurd, a functional burden analysis, to test the association of CNVs aggregated within functional gene sets. We applied this approach in 500,000 individuals from the UK Biobank to associate 43 complex traits with CNVs disrupting 172 gene sets across tissues and cell types. We compared CNV findings with those from common variants and LoF (Loss of Function) SNVs in the same cohort using the same functional gene sets. RESULTS: All 43 traits showed FDR significant associations with CNVs. Brain tissue and neuronal cell-types showed the highest levels of pleiotropy. Most of the functional gene set associations could, in part, be explained by genetic constraint, except for brain related processes. Shared genetic contributions between pairs of traits were concordant across types of variants, but on average 2-fold higher, for rare CNVs and SNVs compared to common variants.Functional enrichment across traits found limited overlap between CNVs and common variants. Moreover, the effects of deletions and duplications were negatively correlated for most traits.In conclusion, we present new methods to separate the contributions of genetic constraint and gene function to the associations of CNVs with complex traits. Overall, the functional convergence between different types of variants -even between deletions and duplications-remains limited.

Journal Article↗

PubMed2026

Rice LSD1-like Genes: Genome-Wide Characterization and Evidence Linking OsLSD3 to Plant Height.

LSD1-like zinc-finger proteins participate in programmed cell death, redox homeostasis, and stress responses in plants, but their functional diversification and contributions to agronomic variation in rice remain poorly defined. This study aimed to characterize the rice LSD1-like gene family and evaluate the potential agronomic roles of selected members, with particular emphasis on OsLSD3. Genome-wide analyses were integrated with OsLSD3 natural variation and haplotype analyses in 4666 rice accessions, CRISPR/Cas9 mutant phenotyping in the ZH11 background, and subcellular localization assays. Seven LSD1-like genes were identified and showed substantial divergence in protein architecture, gene organization, promoter cis-element profiles, and tissue- and stress-responsive expression. OsLSD3 formed six population-structured haplotypes, and two common Japonica haplotypes differed significantly in plant height. Consistently, two independent oslsd3 mutant lines were taller than the wild type, whereas additional changes in grain-related traits were line-specific. OsLSD2 and OsLSD3 localized mainly to the nucleus, while OsLSD4 was predominantly nuclear with weak cytoplasmic localization. These results identify OsLSD3 as the strongest candidate among the examined members for further investigation of plant height- and grain-related traits, while OsLSD2 and OsLSD4 represent additional candidates for grain-trait regulation. Further validation using additional alleles and environments is required.

LSD1-like↗

PubMed2026

Genome-wide characterization of NOD-like receptor genes links NLR repertoire evolution to spleen immune responses after Aeromonas hydrophila challenge in the Chinese spiny frog (Quasipaa spinosa).

NOD-like receptors (NLRs) are cytosolic pattern-recognition receptors that detect pathogen-associated and damage-associated molecular patterns and mediate innate immune signaling in vertebrates. However, the genomic repertoire, evolutionary diversification, and infection-associated expression of NLR genes remain poorly defined in non-model amphibians. In this study, 66 NLR genes were identified from the Chinese spiny frog (Quasipaa spinosa) genome and designated as QsNLR1-QsNLR66. These genes were unevenly distributed across chromosomes and were classified into three phylogenetic groups, with most members exhibiting conserved motif architectures. Gene duplication analysis indicated that dispersed duplication was the main contributor to QsNLR expansion. Synteny analysis detected five conserved orthologous gene pairs between Q. spinosa and Pelophylax nigromaculatus, suggesting partial conservation of NLR genomic organization between the two amphibians. Ka/Ks analysis showed that several duplicated gene pairs, including NLRC3-like/QsNLR36 and NLRC3-like/QsNLR50, exhibited Ka/Ks ratios greater than one, suggesting potential sequence divergence after duplication. Spleen RNA sequencing (RNA-seq) after Aeromonas hydrophila challenge revealed enrichment of immune-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Weighted gene co-expression network analysis linked several QsNLRs to infection-associated modules, among which QsNLR57 was co-expressed with CYBB, ADAM17, SPI1, and HK2. RT-qPCR using time-matched phosphate-buffered saline (PBS) controls showed distinct temporal patterns, with stronger induction of QsNLR29, QsNLR57, and QsNLR66 and weaker or delayed responses of QsNLR50 and QsNLR56. These results characterize the NLR repertoire of Q. spinosa and identify infection-associated QsNLR candidates for future studies of antibacterial immunity in amphibians.

Animals↗

PubMed2026

Molecular evolution and immune expression analysis of ELF transcription factors in Lethenteron reissneri.

As important members of the ETS superfamily, the E74-like factor (ELF) transcription factor family regulates gene transcription through a conserved ETS domain and plays critical roles in immune regulation. However, the evolutionary characteristics and functions of this family in lampreys (Lethenteron reissneri) remain unclear. In this study, the ELF gene family of lampreys (Lr-ELF1, Lr-ELF2, Lr-ELF3, and Lr-ELF5) was systematically identified, and their molecular evolutionary features and immune response functions were investigated. Phylogenetic analysis revealed evolutionary characteristics reflecting the transition from jawless to jawed vertebrates. Domain architecture, gene structure, and three-dimensional structural analyses indicated that these genes appear to be conserved among vertebrates, with their three-dimensional structures showing high similarity to the core secondary structural elements of human homologous proteins. Synteny analysis demonstrated significant differences in the genomic neighborhoods of ELF genes between lampreys and jawed vertebrates. Quantitative real-time PCR (qRT-PCR) was performed with three biological and three technical replicates; relative expression levels were calculated using the ΔCt method, and statistical analysis was carried out with GraphPad Prism 9. Quantitative real-time PCR (qRT-PCR) results suggested that the ELF gene family may be involved in immune defense. This study not only enriches our understanding of the evolution of ELF genes but also provides new insights into the roles of lamprey ELFs in immune defense.

Animals↗

PubMed2026

Genome-Wide Characterization of the ZIP Transporter Family in Sea Island Cotton (Gossypium barbadense L.) and Expression Profiling Under Heavy Metal and Pathogen Stresses.

G. barbadense represents an indispensable germplasm resource for high-quality textile fiber and disease resistance; nevertheless, systematic information regarding its ZRT/IRT-like protein (ZIP) gene family remains limited. Here, a total of 46 GbZIP genes were identified across the G. barbadense genome. Comprehensive bioinformatic investigations revealed uneven chromosomal distribution and confirmed that segmental/whole-genome duplications, supplemented by localized tandem duplications, drove family expansion. Members clustered within the same phylogenetic clades shared conserved motif organization and gene architecture, while promoter regions harbored abundant cis-acting elements associated with phytohormone and stress signaling. Transcriptome profiling indicated distinct expression patterns across vegetative/reproductive tissues, fiber and ovule developmental stages, and diverse abiotic stress conditions (cold, hot, drought, and salt). Quantitative Real-Time PCR (qRT-PCR) further validated that several GbZIP candidates exhibited temporal expression variations upon exposure to cadmium toxicity, V. dahliae infection, and combined Cd-V. dahliae stress. Specifically, GbZIP13, GbZIP18, GbZIP27, and GbZIP36 displayed prominent broad-spectrum responses to all three stress conditions, whereas GbZIP16, GbZIP29, and GbZIP30 showed stress-specific regulatory divergence. Overall, this study aims to systematically analyze the evolutionary characteristics and expression patterns of the GbZIP family, and to specifically evaluate the response differences under Cd stress, V. dahliae stress, and combined stress, in order to identify potential key candidate genes.

Gossypium barbadense↗

PubMed2026

Promoter identity shapes splicing outcomes and fidelity.

Gene expression is a complex process subject to regulation at multiple functionally interconnected levels. One prominent example is the crosstalk between transcription and splicing regulation. Past work has shown that transcription can influence splicing in multiple ways, but a systematic investigation of this complex interplay is lacking. Here we employ massively parallel reporter assays of large combinatorial promoter-splice site libraries to dissect how promoter identity and transcription dynamics affect alternative splicing in human cells. We find that promoter identity, rather than expression level, exerts strong and highly context-specific effects on cassette exon inclusion, exceeding the effect of pharmacological inhibitors of transcription initiation or elongation. Groups of exons display coordinated promoter-dependent splicing behavior, and we identified predictive sequence and structural features underlying this sensitivity. Promoter and gene architecture also shape isoform diversity by modulating cryptic splice site usage. These findings present promoters as central regulators of splicing outcomes and fidelity.

Humans↗

PubMed2025

Gene regulatory network structure informs the distribution of perturbation effects.

Gene regulatory networks (GRNs) govern many core developmental and biological processes underlying human complex traits. Even with broad-scale efforts to characterize the effects of molecular perturbations and interpret gene coexpression, it remains challenging to infer the architecture of gene regulation in a precise and efficient manner. Key properties of GRNs, like hierarchical structure, modular organization, and sparsity, provide both challenges and opportunities for this objective. Here, we seek to better understand properties of GRNs using a new approach to simulate their structure and model their function. We produce realistic network structures with a novel generating algorithm based on insights from small-world network theory, and we model gene expression regulation using stochastic differential equations formulated to accommodate modeling molecular perturbations. With these tools, we systematically describe the effects of gene knockouts within and across GRNs, finding a subset of networks that recapitulate features of a recent genome-scale perturbation study. With deeper analysis of these exemplar networks, we consider future avenues to map the architecture of gene expression regulation using data from cells in perturbed and unperturbed states, finding that while perturbation data are critical to discover specific regulatory interactions, data from unperturbed cells may be sufficient to reveal regulatory programs.

Gene Regulatory Networks↗

PubMed2025

Comparative genomics of carbapenem-resistant Acinetobacter baumannii isolated from pediatric patients in a tertiary care hospital.

Acinetobacter baumannii is a short gram-negative bacillus, notable for its intrinsic multidrug resistance and genomic plasticity, which facilitates the acquisition of additional resistance genes via mobile genetic elements. Due to its increasing carbapenem resistance, the World Health Organization has classified it as a critical priority pathogen. This study performed a comparative genomic analysis of 20 carbapenem-resistant A. baumannii clinical strains isolated from the Hospital Infantil de México Federico Gómez (CRAB-HIMFG), alongside 11 genomes from other Mexican strains. The pangenome was determined to be open, and core genome single-nucleotide polymorphism-based analysis grouped the CRAB-HIMFG strains within CC758/IC5 and CC92/IC2. A novel sequence type (ST) in the MLST-Pasteur scheme was identified, related to STPas156, and in the MLST-Oxford scheme, associated with STOxf758 and STOxf1054. Virulence and resistance genes comprised 0.61% to 2.23% of the pangenome. Oxacillinase genes and efflux pumps primarily mediated carbapenem resistance, while virulence genes included those encoding biofilm and type IV pili. Capsule typing revealed a correlation with established international clones, IC2 and IC5. Plasmids exhibited high diversity, harboring maintenance modules and toxin-antitoxin systems, with the dissemination of resistance genes linked to insertion sequences. Biofilm formation and twitching motility were not always expressed, as they depend on additional environmental factors. Our study shows that comparative genomics is an essential tool to analyze clinically and epidemiologically significant genomes, providing critical insights into gene distribution, genomic architecture, and horizontal gene transfer mechanisms in microbial populations.IMPORTANCEIn recent years, a reported increase in the mortality rate associated with infections caused by A. baumannii, along with a rise in carbapenem resistance, poses a serious clinical challenge. The WHO considered this microorganism critical for research into alternative therapies and epidemiological surveillance. Despite advances in bioinformatics, genomic studies have yet to fully elucidate the structural rearrangements and secretion systems of A. baumannii. This knowledge gap hinders our understanding of its remarkable genomic plasticity and its ability to acquire and spread resistance and virulence genes through horizontal gene transfer.

Acinetobacter baumannii↗

PubMed2026

Transcriptome mining and comparative genomics reveal 36 putative novel marafivirus species and conserved evolution of the marafibox regulatory element.

BACKGROUND: Marafiviruses are plant-infecting RNA viruses associated with several economically important crops, but their genomic diversity remains incompletely characterized. OBJECTIVE: This study aimed to identify previously unrecognized marafivirus genomes and investigate their genomic features and evolutionary relationships. METHODS: Publicly available plant transcriptome datasets were systematically mined to detect marafivirus-like sequences. Recovered genomes were analyzed using comparative sequence analysis, phylogenetic reconstruction, and genome organization characterization. RESULTS: A total of 62 marafivirus-like genomes were recovered from 33 independent sources representing diverse plant hosts. Polyprotein-based comparative and phylogenetic analyses grouped these genomes into 36 lineages likely representing novel species. All newly identified viruses clustered within the Marafivirus clade. Genome organization analysis revealed conserved polyprotein architecture and widespread presence of the marafibox promoter element. Conservation of additional open reading frames among closely related isolates aided identification of potentially functional genes. CONCLUSION: These findings substantially expand the known diversity of marafiviruses and demonstrate the effectiveness of transcriptome mining for discovering previously unrecognized plant viruses.

Phylogeny↗

PubMed2025

Cis-regulatory elements: systematic identification and horticultural applications.

Cis-regulatory elements (CREs) are the genetic DNA fragments bound by transcription factors (TFs). CREs function as molecular switches that precisely modulate the dosage and spatiotemporal patterns of gene expression. The systematic identification of CREs not only facilitates the annotation of the functional non-coding genome but also provides essential insights into the architecture of gene regulatory networks and sheds light on an accurate selection of the target sites for genetic engineering of crops. In this review, we summarize the current high-throughput methodologies used for identifying CREs, illustrate the associations between CREs and agronomic traits in horticultural crops, and discuss how CREs can be exploited to facilitate crop breeding.

Breeding↗

PubMed2026

Genomic signatures of host-range divergence in the generalist Beauveria bassiana and the specialist Beauveria brongniartii.

Entomopathogenic fungi of the genus Beauveria are widely used biological control agents that infect diverse insect hosts and can also associate with plants as rhizosphere colonizers and endophytes. Within this genus, Beauveria bassiana is a cosmopolitan generalist, whereas Beauveria brongniartii exhibits a narrower host range, primarily targeting soil-dwelling coleopteran larvae with limited evidence of plant colonization. To explore genomic differentiation associated with this ecological divergence, the commercially exploited B. brongniartii strain BIPESCO2 and B. bassiana ATHUM 4946 were sequenced using Oxford Nanopore technology, followed by comparative genomic analyses across multiple strains. Orthology identified species-specific gene families, although overall genome architecture and core gene content were highly conserved. The CAZyme repertoires were nearly identical, indicating retention of a versatile enzymatic toolkit supporting plant association, saprotrophy, and insect pathogenicity. In contrast, biosynthetic gene clusters displayed substantial variation, including structural remodeling of Beauveria-specific virulence-associated clusters and expansion of type I polyketide synthase clusters in B. brongniartii. Effector prediction revealed a conserved core of largely uncharacterized proteins alongside species-specific orthogroups enriched in adhesion-, immunity-, and cuticle-interaction domains. Together, these findings indicate that host-range divergence in Beauveria is associated with compartmentalized genomic differentiation, particularly in secondary metabolism and a limited subset of lineage-specific virulence factors, rather than in the conserved core infection machinery.

Beauveria↗

PubMed2026

Mirror worlds: The shared regulatory architecture of cell fate in development and cancer.

Lineage plasticity has emerged as a central mechanism through which cancer cells adapt to therapeutic pressure, evade immune surveillance, and acquire aggressive phenotypes. Although recognized across tumor types, the regulatory principles governing how cancer cells reprogram cellular identity remain incompletely understood. In this review, we propose that lineage plasticity in cancer reflects the redeployment of regulatory frameworks established during normal development. Rather than representing a stochastic byproduct of genomic instability, cancer plasticity frequently unfolds within gene regulatory architectures that also govern cell fate specification, lineage commitment, and controlled state transitions during embryogenesis and tissue homeostasis. Developmental transcription factors, including members of the SOX family, FOXA1, ASCL1, NKX2-1, and epithelial-mesenchymal transition regulators, function as lineage gatekeepers during development but are repurposed in cancer to destabilize lineage commitment and enable phenotypic switching. Similarly, epigenetic regulators that guide developmental trajectories, including chromatin remodeling complexes, Polycomb group proteins, and DNA methylation machinery, are frequently dysregulated or redistributed in tumors, altering the repression of lineage-stabilizing and alternative lineage programs and thereby weakening epigenetic barriers to lineage transitions. Together, these observations support a model in which development and cancer operate as mirror regulatory systems: one establishing and stabilizing cellular identity, the other exploiting the same regulatory architecture to permit adaptive reprogramming under selective pressure. We further discuss how emerging single-cell and spatial multi-omics technologies, integrated with artificial intelligence-based modeling, enable mapping of cell state landscapes and transitional trajectories, transforming lineage plasticity from a descriptive phenomenon into a measurable and predictable property of tumor evolution.

Humans↗

PubMed2025

Proteins driving liquid-liquid phase separation and histone modifications cooperatively associate with chromatin looping and transcriptional regulation.

BACKGROUND: Although liquid-liquid phase separation (LLPS) proteins are known to participate in genome organization and transcriptional regulation through the formation of biomolecular condensates, their functional interplay with other regulatory proteins and histone modifications in chromatin loop formation remains poorly characterized. By combining Hi-C chromatin interaction data with ChIP-seq profiles of 12, 27, and 24 LLPS proteins in GM12878, K562, and HepG2 cell lines, respectively, we identified chromatin loops associated with LLPS proteins and systematically analysed patterns of cooperative protein binding and histone modification enrichment within these loop-associated peaks. RESULTS: We identified 162, 313, and 431 chromatin loops associated with LLPS proteins in GM12878, K562, and HepG2 cell lines, respectively. These loops were relatively small in size and predominantly anchored at enhancer regions. Examination of cooperative binding of proteins within loop-associated peaks revealed that transcriptional repressor IKZF1, HDAC1, and SAP130 most frequently co-localized with LLPS proteins in GM12878, K562, and HepG2 cells, respectively. Further analysis of histone modification enrichment patterns revealed that active histone modifications, such as H3K4me2, H3K4me3, H3K9ac, and H3K27ac, co-localized at loop-associated peaks, with H3K4me1 exhibiting additional specific co-localization with these four histone modifications at enhancer-localized loop-associated peaks. Notably, bivalent chromatin domains where H3K27me3 co-localized with active histone modifications were identified at promoter-localized loop-associated peaks in HepG2 cells, and elevated H3K27me3 occupancy at these peaks was associated with transcriptional repression of target genes. Moreover, quantitative RNA-seq analysis revealed that the expression of target genes associated with enhancer-promoter loops was correlated with both the binding of LLPS proteins and the enrichment patterns of histone modifications within their ChIP-seq peaks at loop anchors. CONCLUSIONS: Our study suggests that LLPS proteins may cooperate with transcriptional repressors to facilitate chromatin looping. Furthermore, local enrichment of histone modifications at loop-associated peaks provides additional regulatory control over chromatin architecture and gene transcription.

Humans↗

PubMed2026

Feeding the epigenome: EZH2 as a metabolic integrator of cell fate in development and cancer.

Epigenetic regulation is intimately linked to cellular metabolism, enabling environmental and nutritional cues to shape gene expression programs through dynamic modifications of chromatin structure. This metabolism-epigenetics interface is mediated, in part, by the dependence of chromatin-modifying enzymes on key metabolites, including S-adenosylmethionine (SAM), acetyl-CoA, UDP-GlcNAc, and α-ketoglutarate, which serve as substrates or cofactors for DNA and histone modifications. Among these regulators, EZH2, the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), has emerged as a key mediator linking metabolic state to epigenetic regulation by translating metabolic inputs into changes in chromatin architecture and gene expression. EZH2 governs developmental cell fate through H3K27me3-mediated gene repression and is frequently dysregulated in cancer, where it promotes dedifferentiation, tumor progression, and metabolic reprogramming. Importantly, EZH2 activity is itself modulated by cellular metabolic status through posttranslational modifications, including phosphorylation, acetylation, methylation, ubiquitination, and O-GlcNAcylation, which influence its stability, catalytic activity, and chromatin-binding capacity. These modifications are responsive to nutrient availability and signaling pathways involving glucose, SAM, NAD+, and other metabolic intermediates. Consequently, disruption of this finely tuned regulatory network can contribute to developmental abnormalities, metabolic dysfunction, and oncogenesis. In this review, we examine the molecular mechanisms governing EZH2 regulation and discuss how metabolic control of EZH2 shapes chromatin dynamics, cell fate decisions, and disease pathogenesis. Elucidating how metabolic signals modulate EZH2 activity will advance our understanding of development and disease while uncovering potential therapeutic opportunities to target metabolism-driven epigenetic dysregulation.

Humans↗

PubMed2026

Single-nucleotide transcription start sites profiling via Nascent Strand-Specific RNA sequencing uncovers IFN-γ-induced promoter dynamics.

Transcriptional regulation is a highly dynamic process in which nascent RNAs provide the most immediate readout of transcriptional activity. Precise mapping of transcription start sites (TSSs) is therefore critical for understanding promoter architecture and gene regulation, yet remains technically challenging. Here, we introduce Nascent Strand-Specific RNA sequencing (NSS-seq), a robust and streamlined method for genome-wide profiling of the capped 5' ends of nascent RNAs. By directly capturing transcription initiation events, NSS-seq overcomes the temporal delay inherent to conventional RNA-seq and enables time-resolved interrogation of transcriptional dynamics. Applied to interferon-γ (IFN-γ)-stimulation, NSS-seq uncovers previously unrecognized IFN-γ-responsive genes and transient transcription factor activation patterns underlying interferon-mediated tumor-suppressive functions. Together, NSS-seq provides a cost-effective and technically accessible platform for dissecting promoter-level regulatory dynamics during cellular responses.

Promoter Regions, Genetic↗

PubMed2026

Genome mining reveals an architecturally expanded pyoluteorin-associated biosynthetic gene cluster and a divergent flavin-dependent halogenase-like sequence in deep-sea Pseudomonas Aeruginosa from the Gulf of Guinea.

BACKGROUND: Marine deep-sea environments harbour microorganisms with extraordinary biosynthetic potential, yet their secondary metabolite repertoires remain largely uncharacterised. RESULTS: This study reports the isolation, phenotypic characterisation, and whole-genome analysis of Pseudomonas aeruginosa strain E1, recovered from deep Atlantic seawater (Gulf of Guinea, ~2500 m depth), which exhibits antifungal activity against multidrug-resistant Candida parapsilosis. Three presumptive P. aeruginosa isolates (E1, E17, and E44) showed > 99% 16S rRNA gene sequence identity to P. aeruginosa reference sequences, while whole-genome dDDH analysis of strain E1 yielded 95.2% (95% CI: 93.6-96.4%; formula d4) relative to the P. aeruginosa type strain DSM 50071ᵀ (= ATCC 10145ᵀ), supporting its species-level assignment. Antifungal screening and PCR-based detection of flavin-dependent halogenase genes identified strain E1 as the primary candidate for genomic investigation. Illumina whole-genome sequencing produced a 6.33 Mb draft genome assembly (113 contigs, 5862 protein-coding genes, 66.4% GC content). Genome mining with antiSMASH 8.0 identified 27 biosynthetic gene clusters (BGCs) spanning nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), phenazine, terpene, and metallophore pathways. Region 7.1 of strain E1 harbours a predicted 50.8 kb pyoluteorin-associated BGC, comprising 34 genes, substantially larger than its terrestrial counterpart (~ 22 kb, ~ 17 genes), and featuring nine transport genes and three regulatory elements. Phylogenetic analysis resolved three halogenase genes: ctg7_146 showed 98.7% amino acid identity to PltA, and ctg7_149 showed 99.2% amino acid identity to PltM, supporting their annotation as PltA-like and PltM-like components of the predicted pyoluteorin biosynthetic pathway. Among the characterised reference enzymes included in this analysis, ctg7_143 showed the highest amino acid identity to PltM from P. fluorescens Pf-5. However, the identity remained low at approximately 30.4%, supporting its placement as a divergent FDH-like sequence rather than a close PltM orthologue. CONCLUSION: This study provides the first comprehensive genomic characterisation of a pyoluteorin-BGC-harbouring marine P. aeruginosa strain, demonstrating conservation of the core biosynthetic machinery alongside an expanded transport architecture and a divergent FDH-like sequence that may represent a candidate for future biochemical investigation. These findings expand current knowledge of FDH-like sequence diversity in deep-sea bacteria and support further investigation of Gulf of Guinea microorganisms as a potential source of biosynthetic and enzymatic diversity.

Multigene Family↗

PubMed2026

The antimicrobial gut resistome of the Wayampi reveals a shared background of antibiotic and metal resistance genes with industrialized populations, underscoring the "robust-yet-fragile" architecture of human gut microbiomes.

BACKGROUND: Metagenomics enables detailed profiling of genes encoding antimicrobial resistance. However, most studies focus exclusively on antibiotic resistance genes (ARGs), excluding those associated with non-antibiotic antimicrobials (metals, biocides), and often rely on methods with low-sensitivity and low-specificity. Furthermore, they rarely examine populations exposed to minimal anthropogenic pollution. We analyzed fecal resistomes of 95 Wayampi individuals, an Indigenous community in remote French Guiana, using a targeted metagenomic capture platform covering 8667 genes, including ARGs, metal resistance genes (MRGs) and biocide resistance genes (BRGs) (PMID: 29335005). Resistome profiles were compared with those of Europeans to assess population-level differences. RESULTS: ARG richness was similar between groups (259 in Wayampi vs. 264 in Europeans, 159 shared), but MRGs + BRGs gene richness was significantly higher in Wayampi (11,930 vs. 7419). Most genes appeared in a minority of individuals (mean 5% for ARGs, 2% for MRGs + BRGs), but several ARGs for tetracyclines [tet(32), tet(40), tet(O), tet(Q), tet(W), tet(X), tetAB(P)], aminoglycosides (ant6'-I, aph3-III), macrolides (ermB, ermF, mefA), and sulfonamides (sul2) were present in all individuals. Tetracycline resistance genes predominated overall, while beta-lactam resistance genes were more common in Wayampi, and genes conferring resistance to aminoglycosides, amphenicols, and folate inhibitors were more frequent in Europeans. Among MRGs, copper and arsenic resistance genes prevailed in both groups, followed by those for zinc, iron, cobalt, and nickel. Up to 76% of Wayampiis carried acquired MRGs for copper (pcoABCDRS and tcrB), silver (silACFPRS), arsenic (ars), and mercury (mer) detoxification. Shannon diversity indices were similar for ARGs, MRGs, and BRGs, but composition and evenness differed significantly. UMAP and ADONIS analyses distinguished cohorts based on ARG profiles (p < 0.001), but not on MRGs or BRGs. Correlation analysis revealed conserved gene-sharing networks and introgression of acquired ARGs and MRGs within both gut microbiomes. CONCLUSIONS: The diverse and balanced Wayampi resistome reflects a less perturbed microbiome compared to industrialized populations, and reveals a background of "core" and "shell" acquired ARGs and MRGs, consistent with the "robust-yet-fragile" architecture of scale-free networks. The patchy yet resilient gene distribution suggests varying levels of conserved gene sharing highways among populations, likely shaped by long-term microbial-human evolution, and supports a broader view on acquired antimicrobial resistance. Video Abstract.

Humans↗

PubMed2026

Hox/Meis-dependent gene-regulatory transition underlies cardiopharyngeal neural crest diversification.

Neural crest cells (NCCs) are multipotent migratory cells essential for cardiac development, yet the lineage trajectories and gene regulatory networks underlying their differentiation in the cardiopharyngeal region remain unclear. Here, we integrate single-cell RNA-seq, spatial transcriptomics, and multiomic analyses to construct a comprehensive map of NCC lineages in developing mouse cardiopharyngeal tissues. We identify a transition from Hox-positive pharyngeal NCCs to Hox-negative intracardiac populations associated with the outflow tract cushion, accompanied by a shift in Meis transcription factor binding and gene-regulatory network architecture. By contrast, NCCs forming the aorticopulmonary septum and great vessel smooth muscle retain distinct Hox-codes. A Meis2-Sox9-Scx gene-regulatory network defines a skeletogenic progenitor-like intermediate state that gives rise to coronary artery smooth muscle and semilunar valves. Our findings suggest that the loss of Hox-dependent regional identity enables pharyngeal NCCs to acquire new fates upon entering the cardiac cushion, providing insight into the developmental origins of coronary and valvular calcification.

Journal Article↗