Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Special populations”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2026

Subgroups and Special Populations in Heart Failure Clinical Trials: Insights From the HFC-ARC Expert Consensus Panel.

In the evolving landscape of heart failure (HF) management, the identification and analysis of subgroups and special populations within clinical trials are crucial for enhancing clinical decision-making, guiding further research, and understanding heterogeneity in study outcomes. This expert consensus document results from the collaborative efforts of the Heart Failure Collaboratory and the Heart Failure Collaboratory Academic Research Consortium, which brought together stakeholders from academia, industry, the U.S. Food and Drug Administration, and patient representatives. The purpose of this assembly was to propose standardized definitions and critical endpoint considerations essential for shaping the design and conduct of clinical trials for drugs and devices in the field of HF. In this context, we propose definitions and endpoints for specific subgroups and special populations in the spectrum of HF. We enhanced the precision, efficacy, and applicability of clinical research and promote more "personalized" approaches to interpretation of clinical trials. Furthermore, we explore the burgeoning field of gene therapy as a promising avenue for addressing the genetic basis of certain cardiomyopathies within these specialized patient groups. We focus especially on methodological considerations for subgroup analyses in large-scale trials, highlighting the importance of proper interpretation of subgroups and best practices for identifying heterogeneity suggestive of differential treatment effects, including when these analyses should be considered hypothesis-generating and requiring subsequent validation. We advocate for a methodical approach to clinical trial design, one that prioritizes the strategic identification of subgroups and employs appropriate statistical methodologies to ensure the reliability and clinical relevance of findings. Through this lens, we envision a pathway toward more personalized and effective treatments for HF, ultimately aiming to improve patient outcomes by leveraging the insights garnered from meticulously designed and comprehensively analyzed clinical trials.

Humans↗
PubMed2026

NSCLC in Vulnerable and Special Populations: Toward Personalized Care.

NSCLC encompasses a heterogeneous patient population whose clinical needs, biological features, and treatment outcomes differ substantially from those represented in pivotal studies. Adolescents and young adults, women, pregnant patients, individuals with actionable genomic alterations or constitutional pathogenic variants, immunocompromised patients, including those with chronic viral infections, older adults, patients with brain metastases, and survivors with second primary lung cancers remain consistently underrepresented in research programs. This limits the generalizability of current evidence and challenges the delivery of equitable precision oncology. Across these populations, distinct disease biology, differential genomic landscapes, sex- and age-related variations in pharmacology, and complex psychosocial or ethical considerations shape clinical decision-making. Advances in molecular testing and targeted therapies have improved outcomes for some subgroups; however, persistent disparities in diagnostic access, trial eligibility, and supportive care remain major barriers. In parallel, modern systemic agents including brain-penetrant targeted therapies, immunotherapy combinations, and antibody-drug conjugates have broadened therapeutic options, although their safety, effectiveness, and long-term consequences require dedicated evaluation in underrepresented populations. This review synthesizes contemporary evidence from these special NSCLC populations, highlighting shared challenges and unique considerations. We discuss implications for clinical practice, supportive care, survivorship, and research design and outline opportunities to strengthen inclusivity in precision oncology. Addressing longstanding gaps in representation, trial methodology, and structural inequities is essential to ensure that recent therapeutic advances translate into improved outcomes for the full spectrum of patients living with NSCLC.

Humans↗
PubMed2026

Recent advances in Strongyloides screening, diagnostics, therapeutics, and management.

PURPOSE OF REVIEW: Strongyloidiasis affects an estimated 30-100 million people globally and can have life-threatening consequences in immunocompromised hosts, yet it remains underdiagnosed due to limited access and performance of available diagnostics. Novel assays and anthelmintics may reshape screening, diagnosis, treatment, and prevention for at-risk populations. RECENT FINDINGS: Advances in molecular diagnostics coupled with robust stool extraction methods have supplanted traditional parasitologic methods in settings where nucleic acid amplification is feasible. Transition from standard immunoglobulin G (IgG)-based immunoassays to the new IgG- and IgG4-based rapid diagnostic tests using recombinant Strongyloides stercoralis nematode immunodominant E antigen (NIE) and/or S. stercoralis immunoreactive antigen (SsIR) has facilitated serologic screening at the point of care. The World Health Organization now conditionally recommends community-wide ivermectin mass drug administration in highly endemic settings. Regarding new treatment options, moxidectin is noninferior to ivermectin with 93-94% cure rates and a longer half-life, while emodepside shows 80-90% predicted cure rates in early trials and offers a mechanistically distinct option. Understanding of immunosuppressed populations at risk for hyperinfection has expanded, prompting updated screening recommendations. SUMMARY: Serologic and molecular tools are improving screening and diagnosis, and moxidectin and emodepside may broaden treatment options, but data in severe disease and special populations remain limited. Priorities include harmonized screening algorithms and prospective studies in high-risk groups.

Humans↗
PubMed2025

Tumors hijack macrophages for iron supply to promote bone metastasis and anemia.

Bone marrow is both a primary site for hematopoiesis and a fertile niche for metastasis. The mechanism of the common occurrence of anemia among patients with bone metastasis remains poorly understood. Here, we show that a specialized population of VCAM1+CD163+CCR3+ macrophages, normally essential for erythropoiesis by transporting iron to erythroblasts, are highly enriched in the bone metastatic niche in mouse models. Tumor cells hijack these macrophages for iron supply, reducing iron availability for erythroblasts, impairing erythropoiesis, and contributing to anemia. Increased iron supply enables tumor cells to produce hemoglobin in response to hypoxia, mimicking erythroblasts. We identify macrophages with similar iron-transporting features in human bone metastases and show that elevated HBB expression correlates with increased risk of bone metastasis. These findings establish iron-transporting macrophages as an essential component of the metastatic bone niche, revealing a critical interplay between immune cells, metal metabolism, and tumor cell plasticity in driving metastasis and anemia.

Animals↗
PubMed2026

Piloting a community-academic partnership to deploy acceptance and commitment therapy via telehealth for caregivers of children with Angelman syndrome.

BACKGROUND: Caregivers of children with Angelman syndrome (AS) experience substantial stressors and often experience challenges accessing mental health providers with expertise in their unique family needs. PURPOSE: Community-academic partnerships have potential for ensuring such treatments are deployed in ways that maximally benefit the patient community. METHODS: This study examined the effectiveness of using a community-centered approach to training student clinicians to deploy telehealth acceptance and commitment therapy (ACT) with a pilot sample of caregivers (n = 17) with young children diagnosed with AS. Prior to deploying the treatment, clinicians received community-led training on the unique needs of AS families. RESULTS: Upon completing the abbreviated 9-week protocol, caregivers reported decreases in depression and parenting stress and increases in parenting confidence across treatment, supporting future testing of ACT for AS in the context of randomized control trials. CONCLUSIONS: Our findings support the feasibility of leveraging community-academic partnerships to co-train graduate-level clinicians to deliver ACT to specialized populations. This is also the first study to document preliminary effectiveness of telehealth ACT in supporting caregivers of children with AS.

Humans↗
PubMed2026

Wearable wrist-watch type cuff oscillometric blood pressure monitors: consensus statement by the European Society of Hypertension Working Group on blood pressure monitoring.

Wearable wristwatch-type cuff oscillometric blood pressure (BP) monitors represent a new category of BP devices and are the first wearable monitors to use established cuff-oscillometric BP measurement technology. This consensus statement by the European Society of Hypertension Working Group on BP Monitoring reviews the published evidence on their design, accuracy, validation, clinical application, and remaining research questions. Of 281 articles identified through a systematic PubMed search, 26 were relevant. Several devices are currently available; however, only two have published validation studies performed according to established standards (Omron HeartGuide and Huawei Watch D/D2). Static validation studies generally showed acceptable accuracy, whereas data on 24-h ambulatory use, in special populations, and clinical applications remain limited. Potential advantages include self-initiated measurement at home, at work, and in other settings and conditions; more convenient and repeatable 24-h ambulatory monitoring; more convenient and accurate assessment of asleep BP; capture of stress-related and other BP-related episodes. However, proper wrist position, user adherence, ambulatory performance, and clinical applications require further investigation. More research is needed to establish the accuracy and clinical utility of these novel devices and their role in improving the diagnosis and management of hypertension.

Humans↗
PubMed2026

Host eicosanoid signals define a granuloma fibroblast population that coordinates mycobacterial containment.

Genetic variation at the leukotriene A4 hydrolase (LTA4H) locus is associated with tuberculosis (TB) severity and outcome. Here, we define a unique population of peripheral fibroblasts at the mycobacterial granuloma, the central immune structure in TB, whose recruitment and functions are coordinated by lta4h-dependent signals. Using single-cell profiling of zebrafish mycobacterial infections, we identify a layer of lta4h-dependent recruited fibroblasts at the granuloma's edge with mesenchymal and stem-like expression signatures, including aldh1a3 expression. Ablation of these cells compromises bacterial containment at the structure's periphery. Similarly, genetic disruption of apolipoprotein D, produced specifically in granuloma-associated fibroblasts, results in an altered eicosanoid balance, decreased inflammation, and increased dissemination of infection. In humans, this granuloma-associated fibroblast population is distinct from myofibroblasts, interacts with LTA4H-expressing macrophages, and is prominent across diverse TB granuloma types. These results link a host genetic susceptibility locus to the recruitment and function of a specialized fibroblast population that limits bacterial dissemination.

Animals↗
PubMed2014

Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility.

A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4(+) T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis.

Adolescent↗
PubMed2026

Development of a PCR-based technique for genotyping UGT1A1 gene and distribution of rs3064744 alleles in the Russian population.

BACKGROUND: Accurate determination of tandem thymine-adenine (TA) repeat numbers in the UGT1A1 promoter region (rs3064744) is essential for diagnosing Gilbert's syndrome and personalizing therapy with toxic agents like irinotecan and atazanavir. However, traditional polymerase chain reaction (PCR) assays face severe limitations due to the AT-rich sequence and overlapping melting temperatures (Tm) of the highly homologous 7TA and 8TA alleles. In this context, melting curve analysis (MCA) employing fluorophore-quencher systems has emerged as a promising alternative. The purpose of this study was to develop a novel genotyping approach combining optimized aPCR-MCA analysis with an automated classifier to overcome the limitations posed by the differentiation of highly homologous alleles and to demonstrate its practical application, providing the distribution of rs3064744 genotypes across four regional cohorts of the Russian population. METHODS: A specialized Dual Head 1D-convolutional neural network (1D-CNN) ensemble with Test-Time Augmentation (TTA) was developed. The model was trained and internally validated on 1,620 engineered plasmid samples, and independently evaluated on an external clinical test set of 440 unique patient genomic DNA specimens. Real-time PCR was performed on CFX96 and DTprime platforms. Additionally, population-wide screening was conducted on 997 archival clinical samples from Moscow, Sakha (Yakutia), Dagestan, and Rostov regions. RESULTS: While 5TA and 6TA alleles were easily separated, absolute Tm distributions of 7TA and 8TA alleles overlapped significantly, and non-uniform Tm shifts of 0.8 °C-1.4 °C occurred across platforms. Conventional absolute Tm thresholding was therefore inadequate. By assessing relative morphological curve divergence against co-amplified 7TA/7TA and 7TA/8TA reference anchors, the 1D-CNN ensemble neutralized instrument noise. It achieved 100% accuracy on internal validation and 100% concordance (440/440) with clinical reference pyrosequencing. Population screening revealed that Dagestan, Yakutia, and Rostov cohorts closely align with the European population. Rare 5TA and 8TA alleles were detected at low frequencies in Yakutia and Moscow. CONCLUSION: Combining LNA-modified aPCR-MCA with a comparative 1D-CNN model successfully circumvents thermodynamic limitations and eliminates human operator bias. This integrated system offers an accessible, high-throughput, and clinically valid solution for routine UGT1A1 pharmacogenetic testing.

1D-CNN↗
PubMed2026

Digest: Chromosomal architecture of behavioral isolation in marine isopods.

How do reproductive barriers persist when diverging species come back into contact? Ribardière et al. (2026) investigated this question in 2 marine isopods, Jaera albifrons and Jaera praehirsuta, whose males court females using divergent specialized setae. By combining population genomics and controlled crosses, the authors show that genomic regions resisting interspecific gene flow are concentrated on sex chromosomes and rearranged chromosomes-regions of low recombination that harbor the genetic bases of divergent male courtship traits.

Animals↗
PubMed2025

Distinct transcriptional and epigenomic programs define Hofbauer cells in term placenta.

Hofbauer cells (HBCs) are fetal macrophages located in the placenta that contribute to antimicrobial defense, angiogenesis, tissue remodeling, and metabolic processes within the chorionic villi. Although their roles in placental biology are increasingly recognized, the mechanisms that regulate HBC identity and function are not yet fully defined. This study aimed to define the core transcriptomic and epigenomic features of HBCs in term placentas and to examine their capacity for transcriptional responsiveness and phenotypic variation. Using chromatin accessibility profiling and bulk RNA-seq, we found that HBCs exhibit a unique gene expression and chromatin accessibility profile compared with other fetal and adult macrophages. We identified a coordinated transcriptional network involving nuclear receptors (NRs) NR4A1-3, the glucocorticoid receptor, and RFX family members (RFX1, RFX2, RFX5) that appears to shape HBC identity, particularly through pathways linked to lipid metabolism and angiogenesis. Although exploratory in nature, in vitro stimulation studies showed that HBCs exhibited increased transcriptional activity in response to combined IL-4 and rosiglitazone treatment, including induction of the lipid transporter CD36. Mass cytometry analysis revealed surface markers indicative of both immature and mature macrophage states. These results together indicate that HBCs are a distinct and diverse population of macrophages with a specialized, adaptable regulatory program in the human placenta.

Female↗
PubMed2026

SNP-derived CpG variation and DNA methylation linking genetic susceptibility to metabolic disease.

DNA methylation at CpG dinucleotides represents a key epigenetic mechanism linking genetic variation to gene regulation in complex human diseases. Single-nucleotide polymorphisms (SNPs) that create or disrupt CpG sites can alter local DNA methylation and transcriptional activity, thereby influencing disease susceptibility. These CpG-modifying variants provide a functional interface between inherited genetic variation and epigenetic regulation in complex metabolic disorders. This review summarizes current evidence on SNP-derived CpG variation and its role in allele-specific DNA methylation and gene regulation in metabolically relevant tissues. By integrating findings from genome-wide association studies, epigenome-wide association studies, and multi-omics research, this review provides a mechanistic framework explaining how CpG-modifying polymorphisms influence adipogenesis, pancreatic β-cell function, inflammation, and glucose metabolism. Special emphasis is placed on South Asian populations, who exhibit early β-cell dysfunction and increased visceral adiposity. Many CpG-modifying variants act as methylation quantitative trait loci (meQTLs), influencing allele-specific methylation and gene expression. Understanding SNP-CpG-methylation interactions may improve functional interpretation of disease-associated genetic variants, enhance biomarker discovery, and support precision medicine strategies for metabolic disease.

Humans↗
PubMed2026

Evolution of virulence of a plant RNA virus in developmental stage-structured host populations.

Natural host populations are age-structured, and developmental stages differ in susceptibility and within-host pathogen dynamics, potentially imposing distinct selective pressures on viruses. However, the evolutionary consequences of host age structure remain poorly understood. We experimentally evolved turnip mosaic potyvirus for 5 passages in Arabidopsis thaliana populations spanning 7 demographic regimes, from juvenile- to mature-dominated cohorts. We quantified disease progression, symptom severity, and viral load, cross-inoculated evolved lineages across host stages to construct infection matrices, and performed whole-population sequencing at passages 1 and 5. Disease traits changed markedly with passage, demography, and their interaction. Disease progression evolved faster in older populations, whereas symptom severity was independent of median age, indicating demographic reweighting of virulence components. Viral load increased across passages and positively correlated with severity, linking within-host fitness to symptoms. Cross-inoculation assays revealed a modular infection network: juvenile-evolved lineages specialized on juvenile hosts, whereas lineages from intermediate and older populations were more generalist. Genomically, we detected both parallel and demography-specific adaptations, including recurrent changes in the viral protein VPg (involved in translation, replication, and host interactions) as well as synonymous variants showing consistent or opposing selection across host population stage structures. Overall, host age structure emerges as a major ecological driver of virulence evolution, shaping tradeoffs between disease progression and severity and determining specialization versus generalism. These results integrate phenotypic and genomic responses and suggest that manipulating crop age structure could steer virus evolution toward less damaging outcomes.

Virulence↗
PubMed2025

Clinical impact of obsessive-compulsive disorder comorbidity in bipolar disorder: a systematic review and meta-analysis.

BACKGROUND: Bipolar disorder (BD) is commonly comorbid with other psychiatric conditions, such as obsessive-compulsive disorder (OCD). Despite increasing interest in this comorbidity, quantitative data on its clinical characteristics remain limited. This systematic review and meta-analysis aimed to evaluate the clinical impact of OCD comorbidity in BD by comparing individuals with BD and OCD (BD-OCD) to those with BD without OCD. METHODS: We systematically searched the PubMed/MEDLINE, Scopus, PsycINFO, and Web of Science databases up to April 15, 2024. Meta-analyses were conducted to compare BD-OCD and BD without OCD groups across multiple clinical domains. RESULTS: From 11,959 initial records screened, 26 studies were included in the qualitative synthesis, with 22 eligible for meta-analysis. Individuals with BD-OCD showed higher odds of experiencing chronic mood episodes (OR = 9.42; 95%CI = 2.23, 39.9), rapid cycling (OR = 1.92; 95%CI = 1.04, 3.53), comorbid eating disorders (OR = 3.37; 95%CI = 1.99, 5.7), panic disorder (OR = 3.3; 95%CI = 2.11, 5.2), substance use disorders (OR = 1.39; 95%CI = 1.02, 1.89), and lifetime suicide attempts (OR = 1.85; 95%CI = 1.21, 2.84). Additionally, they presented earlier onset of BD (SMD = -0.27; 95%CI = -0.52, -0.01) and reduced functioning (SMD = -0.42; 95%CI = -0.59, -0.24). Most data were derived from adult populations, limiting the evidence available for children and adolescents. CONCLUSIONS: BD-OCD presents a more severe and complex clinical profile, requiring specialized assessment and integrated treatment approaches. Identifying these features may support earlier recognition and inform personalized interventions for this population.

Humans↗
PubMed2026

Interspecies Exchange of Mobile Genetic Elements During a Plant Disease Outbreak.

Outbreak sequencing provides insight into the origin and evolutionary processes acting on emerging pathogens. Sequencing a historic multihost outbreak of Ralstonia spp. in Martinique shows the outbreak was caused by two lineages that diverged at separate times from mainland populations. One lineage (Ralstonia pseudosolanacearum I-18) was originally introduced from Asia to South America, where it became well established prior to its dissemination to Martinique, where it retains a signature of specialization on solanaceous hosts. The novel lineage first identified during the outbreak (Ralstonia solanacearum IIB-4NPB) arose from a mainland population endemic to the Americas prior to its arrival in Martinique, where host-range expansion was observed. In contrast to minor changes in secreted effector protein repertoires, the emergent R. solanacearum IIB-4NPB acquired a novel integrative and conjugative element (ICERsoRUN1145). After identifying all Ralstonia spp. ICEs and mapping their spatial and phylogenetic distribution among Ralstonia spp. sampled during the outbreak, we found closely related ICEs circulating in mainland populations of R. pseudosolanacearum, indicating likely exchange between introduced and endemic Ralstonia spp. The family of ICEs in Ralstonia (ICERs) has a conserved bipartite structure and display a striking pattern of functional specialization in each cargo gene insertion hotspot: the first hotspot is a target for metabolic gene acquisition, and the second is a target for defense element acquisition. This work provides unparalleled phylogenetic and spatial resolution of an unusual outbreak and highlights the role of horizontal transfer in shaping the ecological success of an emerging pathogen.

Plant Diseases↗
PubMed2025

Transposable elements create distinct genomic niches for effector evolution among Magnaporthe oryzae lineages.

BACKGROUND: Plant-pathogen interactions are characterized by evolutionary arms races. At the molecular level, fungal effectors can target important plant functions, while plants evolve to improve effector recognition. Rapid evolution in genes encoding effectors can be facilitated by transposable elements (TEs). In Magnaporthe oryzae, the causal agent of blast disease in several cereals and grasses, TEs play important roles in chromosomal evolution as well as the gain or loss of effector genes in host specialized lineages. However, a global understanding of TE dynamics driving effector evolution at population scale and across lineages is lacking. RESULTS: Here, we focus on 16 AVR effector loci assessed across a global sampling of 11 reference genomes and 447 newly generated draft genome assemblies from publicly available short-read sequencing data across all major M. oryzae lineages and outgroups. We classified each effector based on evidence for duplication, deletion and translocation processes among lineages. Next, we determined AVR gain and loss dynamics across lineages allowing for a broad categorization of effector dynamics. Each AVR was integrated in a distinct genomic niche determined by the TE activity profile contributing to the diversification at the locus. We quantified TE contributions to effector niches and found that TE identity helped diversify AVR loci. We used the large genomic dataset to recapitulate the evolution of the rice blast AVR1-CO39 locus. CONCLUSIONS: Taken together, our work demonstrates how TE dynamics are an integral component of M. oryzae effector evolution, likely facilitating escape from host recognition. In-depth tracking of effector loci is a valuable tool to predict the durability of host resistance.

Ascomycota↗
PubMed2026

Characteristics and assembly mechanisms of tobacco-associated bacteria in typical tobacco-planting regions across China.

INTRODUCTION: Plant-associated microbiota critically modulates host growth and environmental adaptation, yet assembly mechanisms, niche differentiation, and ecological strategies of bacterial communities inhabiting tobacco microhabitats remain poorly elucidated across geographical gradients. METHODS: Here, we systematically characterized bacterial microbiome assembly across five tobacco-associated niches (bulk soil, rhizosphere soil, root, stem, and leaf) from seven typical tobacco-planting regions using 16S rRNA amplicon sequencing, genome annotation, and niche breadth analysis. The independent and interactive effects of geographical location and host compartment on community structure, and further compared genomic traits, functional profiles, and life-history strategies between specialist and generalist bacterial populations were quantified. RESULTS: The results revealed a deterministic soil-plant continuum stratification of bacterial communities and diversity, with progressively simplified communities and decreasing alpha diversity from bulk soil to above-ground tissues, accompanied by progressive dominance of Proteobacteria. Geographical factors predominantly structured soil microbial communities via divergent edaphic properties, while host filtering acted as a universal dominant driver shaping endophytic microbiome assembly. Niche differentiation analysis demonstrated that niche-specialized bacterial ASVs overwhelmingly dominated all microhabitats and geographical sites, whereas generalist taxa only constituted auxiliary populations. Although specialist and generalist microbes exhibited highly conserved core genomic architectures and overall functional repertoires, they displayed distinct niche-specific functional divergence in metabolic pathways, stress resistance, and secondary metabolism across host compartments. Life-history strategy analysis further revealed that Y-strategist represented the core adaptive bacterial population, especially enriched in above-ground tobacco tissues. DISCUSSION: Our study establishes a hierarchical dual-filtering assembly model for tobacco microbiota, clarifies the ecological differentiation and functional adaptation of specialist and generalist bacteria, and provides fundamental insights into the assembly rules and adaptive mechanisms of crop-associated microbiomes for future microbial resource utilization and agricultural microbiome regulation.

biogeography↗
PubMed2025

Comparative genomic analysis of Acer tsinglingense and A. davidii provides insights into nervonic acid biosynthesis, population evolution and genome vulnerability of endangered A. tsinglingense.

Global biodiversity is facing threats from climate change, habitat fragmentation, and anthropogenic activities-pressures that particularly endanger endemic and narrowly distributed species. In this study, the high-quality chromosome-level genomes of two ecologically divergent maples were assembled: the endangered and range-restricted Acer tsinglingense (791.40 Mb) and its widespread congener Acer davidii (1291.99 Mb). Phylogenomic analysis indicates that the two species diverged ~16.3 million years ago, with A. tsinglingense showing notable gene family expansions in secondary metabolite pathways. Notably, the 3-ketoacyl-CoA synthase gene family, which is involved in nervonic acid biosynthesis, underwent significant expansion and tandem duplication in A. tsinglingense, exhibiting high expression in buds. Population genomic analysis revealed that, compared with the widely distributed A. davidii, A. tsinglingense possesses lower genetic diversity, higher harmful mutation load, and signatures of a severe population bottleneck during the Late Pleistocene. Genome-environment association analysis further identified climate-adaptive genomic variations linked to five key environmental factors and projected potential genomic offsets under future climate scenarios. The southern lineage of A. tsinglingense exhibited greater climate sensitivity and genomic vulnerability under strong selective pressures, underscoring its importance as a conservation priority. Our research reveals that metabolic specializations in A. tsinglingense (such as the synthesis of nervonic acid) may confer competitive advantages in specific habitats. However, factors including its restricted distribution, historical population bottlenecks, and accumulated genetic load severely constrain its evolutionary potential to cope with rapid climate change. These findings emphasize the importance of elucidating the genomic basis and mechanisms of endangerment in metabolically specialized and threatened plant species to inform effective conservation strategies.

Genome, Plant↗