Biology subjects

Xue, J.

Publications and source records attributed to Xue, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Cross-species analysis identifies APOBEC3-associated spliceosomal snRNA hypermutability

Spliceosomal small nuclear RNA (snRNA) genes show unusually high germline mutation rates, with R-loop formation previously implicated in this mutability. Our cross-species rare-variant and de novo mutation analyses show that hypermutability is concentrated in RNA polymerase II-transcribed spliceosomal snRNA genes, with strong enrichment in primates but a much weaker excess in rodents and chicken, consistent with lineage differences in APOBEC3 repertoires. Human Pol II-transcribed spliceosomal snRNA genes show mutational strand asymmetry, APOBEC3-associated mutational signatures and strong APOBEC3B binding signals. R-loops are also frequent at these loci, including in mouse genes with much weaker hypermutability, indicating that R-loop formation alone is insufficient to explain the phenotype. Together, cross-species comparisons support lineage-specific APOBEC3 activity, rather than R-loop formation alone, as a major contributor to spliceosomal snRNA gene hypermutability.

genomics↗

bioRxiv2026

TRIM21 licenses pancreatic acinar fate by modulating BiP phase state through VCP-dependent retrotranslocation

The endoplasmic reticulum (ER) chaperone BiP/GRP78 sits at the center of the proteostasis network, coordinating unfolded protein response (UPR) signaling and supporting oncogenic programs of plasticity, metastasis, immune evasion, and chemoresistance. While BiP undergoes liquid-liquid phase separation in vitro, whether mammalian cells dynamically tune this physicochemical behavior to prevent functional exhaustion or pathological condensation under sustained ER stress has remained unclear. Here, we identify the E3 ubiquitin ligase TRIM21 as a phase-state regulator that suppresses BiP's liquid-to-solid phase separation, clearing, and preventing insoluble aggregates-thereby controlling BiP's localization and availability to sustain the adaptive UPR under ER stress. We found that during ER stress, BiP is prone to liquid-to-solid phase separation, a transition that renders the chaperone dysfunctional. TRIM21 is recruited to BiP, where it directly polyubiquitinates BiP at specific K547/553/554/556 sites with K6-, K27-, K33-, and K63-linked chains; VCP recognizes these marks and extracts BiP from the ER lumen via ER-associated degradation (ERAD), coupling ubiquitin tagging to retrotranslocation. This preserves chaperone availability and sustains adaptive UPR-a homeostatic mechanism broadly relevant to UPR-driven diseases. In vivo, genetic ablation of Trim21 in KrasG12D/+; Pdx1Cre/+ mice triggers aberrant BiP solidification while curtailing acinar-to-ductal transdifferentiation and tumorigenesis; notably, TRIM21 co-localizes with BiP condensates in pre-malignant human pancreatic lesions, underscoring the clinical relevance of this regulatory axis. Our findings define the TRIM21-BiP axis as a phase-control system at the interface of proteostasis and stress adaptation, offering a new framework with translational potential.

cell biology↗

bioRxiv2026

Energy quality shapes biodiversity across coastal oceans

Earth's biodiversity is distributed unevenly, typically peaking in warm, vegetated, and stable environments. This has frequently been linked to energy availability, which boosts productivity, bolsters populations, and facilitates coexistence. Here, we examine the relationship between energy and biodiversity across coastal oceans using particulate organic matter biogeochemistry and environmental DNA. We reveal that energy quantity (concentrations of carbon, nitrogen, and hydrolyzable amino acids) and salinity, two variables that co-vary with freshwater inflow, jointly predict species richness at regional and global scales. Biodiversity was lowest at sites and locations with high energy inflow and low salinity, suggesting that environmental filtering associated with the osmotic stress induced by freshwater inflow outweighs raw resource availability in governing species richness. Independent of this gradient, however, energy quality (defined via C:N ratios, {delta}C values, and amino acid profiles) was associated with higher biodiversity. Labile, protein-rich, marine-derived resources supported higher biodiversity across all taxa at the regional scale, and a larger number of planktonic consumer taxa at both regional and global scales. High energy quality sites were also enriched in key planktonic groups such as calanoid and cyclopoid copepods, suggesting that these sites act as hotspots of planktonic biodiversity across coastal seascapes. Our findings suggest that few species can directly harness the plentiful resources provided by terrestrial subsidies in coastal oceans because they arrive in low salinity waters. In turn, high-quality food attracts a diverse range of consumers, which may seed the patchy foraging hotspots that characterize open-water food webs. Altered coastal hydrodynamics and biogeochemistry may therefore affect nearshore biodiversity, food webs, and fisheries.

ecology↗

bioRxiv2026

A Tumor-Pituitary-Stromal Axis Promotes Colorectal Cancer Progression

Peripheral tumors can reprogram systemic physiology, yet how they engage central endocrine organs to remodel the local tumor microenvironment is unknown. We found that colorectal cancer (CRC) elevates circulating BMP2, which activates pituitary signaling and enhances endocrine output. Increased pituitary-derived growth hormone acted on growth hormone receptor-expressing cancer-associated fibroblasts (CAFs), inducing a p21-dependent senescence-like state and tumor-promoting secretory program. Disruption of pituitary BMP signaling or fibroblast GHR reduced tumor growth, whereas fibroblast-specific depletion of p21 abrogated GHR-dependent tumor promotion. In patients with CRC, elevated pituitary metabolic activity correlated with stromal p21 expression and tumor burden. Our study reveals a tumor-pituitary-stromal signaling axis through which a peripheral malignancy recruits a central endocrine organ to remotely shape its own microenvironment and promote disease progression.

cancer biology↗

bioRxiv2026

DPF3a couples H3K36me2-dependent chromatin remodeling to genome architecture during myogenesis

Chromatin remodelers are generally thought to regulate gene expression through nucleosome mobilization and modulation of local chromatin accessibility. Whether these complexes can instead control transcription through higher-order chromatin organization remains poorly understood. Here we identify the BAF subunit DPF3a as an essential regulator of skeletal muscle regeneration and myogenic differentiation. DPF3a functions through association with the H3K36me2/3 reader HRP2 and preferentially localizes to a distinctive chromatin state characterized by focal depressions within broad H3K36me2 domains. Biochemical reconstitution demonstrates that H3K36 methylation directly enhances remodeling activity of the DPF3a-containing cBAF complex. Unexpectedly, despite profound transcriptional defects, loss of DPF3a produces minimal changes in local chromatin accessibility. Instead, DPF3a is required for long-range chromatin looping associated with activation of myogenic genes. Together, our findings uncover a non-canonical mechanism whereby a chromatin remodeler regulates transcription primarily through three-dimensional genome organization rather than local accessibility control, and establish histone modification-guided chromatin remodeling as a key principle in gene regulation.

molecular biology↗

bioRxiv2026

DYNAMIC CONFORMATIONS IN THE ACTIVATION OF PINK1 KINASE

Under mitochondrial stress, the mitochondrial kinase PINK1 is activated to phosphorylate ubiquitin, which in turn recruits the E3 ligase Parkin, thereby initiating clearance of damaged mitochondria. Dysregulation of the PINK1-Parkin signaling pathway is associated with early-onset autosomal recessive Parkinson's disease. However, the mechanisms governing PINK1 conformational dynamics and activation in response to mitochondrial stress remain poorly understood. Here, we report that Tribolium castaneum PINK1 (TcPINK1) forms specific symmetric dimers via interactions between the kinase N-lobe and the regulatory C-terminal domain. These dimers undergo dynamic conformational transitions across distinct states, including an autoinhibited state, an inactive intermediate state, a primed-activation state and an active state. Moreover, TcPINK1 undergoes lateral trans-phosphorylation through dimer-dimer interactions. Notably, symmetric dimer formation is essential for Parkin recruitment during mitophagy. These findings provide a framework for understanding the conformational plasticity and allosteric regulation of PINK1 in mitophagy.

biophysics↗

bioRxiv2026

MOLECULAR BASIS FOR PINK1 MATURATION

Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), a key regulator of mitophagy, has been linked to the pathogenesis of Parkinson's disease (PD). PINK1 recruits Parkin, an E3 ubiquitin ligase, triggering mitophagy in response to mitochondrial damage. During mitophagy, the quantity, stability, and activity of PINK1 must be strictly regulated; however, the mechanisms governing these parameters under cellular stress are still unclear. Herein, we determined the structural basis for PINK1 maturation mediated by heat shock protein 90/cell division cycle 37/FK506-binding protein 51 (HSP90/CDC37/FKBP51) chaperone complex. We identified PINK1-associated proteins using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and determined the structures of the complexes using Cryo-Electron Microscopy (Cryo-EM). Results showed that FKBP51 potentially interacts with a conserved leucine-proline-phenylalanine (LPF) motif on the activation loop of PINK1 and negatively regulates PINK1 functions in mitophagy. A PINK1 mutation located at the FKBP51 recognition site is linked to mitophagy deficiency, which can be partially rescued by specific inhibition of FKBP51. These findings reveal a general mechanism for PINK1 recognition by the HSP90/CDC37/FKBP51 chaperone complex and suggest a potential approach for upregulating PINK1 activity, which is impaired in PD.

biophysics↗

bioRxiv2026

Single-cell analysis of chromatin accessibility and gene expression in Drosophila melanogaster embryos following hypoxia treatment

Limited oxygen supply or hypoxia can impair fetal development and lead to developmental disorders, but the molecular mechanism underlying this phenomenon remains poorly understood. It is also well known that hypoxia results in transcriptomic alterations and epigenetic reprogramming. Drosophila melanogaster (fruit fly) has been used for decades as a powerful model to dissect the molecular mechanisms regulating development. To better understand the role of early hypoxic stress on development, we performed single-cell joint analysis of chromatin accessibility and transcriptome to characterize the influence of hypoxia on Drosophila embryonic development. We identified hypoxia-induced alterations in both gene expression and chromatin accessibility across 22 cell groups, especially in the genes regulating organogenesis and development of neuronal, tracheal, and muscular systems, including a reduction of germ cells, suggesting a long-lasting influence of hypoxic stress at an early embryonic stage on development and reproduction. In summary, this study demonstrates that early embryonic hypoxia induces cell type- and dose-dependent changes in chromatin accessibility and gene expression, leading to distinct developmental phenotypic responses, such as reduced number of germ cells under both 3% and 5% O2. We further conclude that the tramtrack (ttk) gene is critical in germ cell development and reproduction in Drosophila melanogaster.

developmental biology↗

bioRxiv2026

Slc25a34-Mediated Mitochondrial-to-Cytoplasmic AMP Transport Activates Brown Adipose Tissue Thermogenesis

Metabolites are emerging as signaling molecules that mediate cellular function, extending beyond their well-established roles in metabolic pathways. Members of the solute carrier (SLC) family mediate metabolite transport across cellular compartments, raising the possibility that these proteins may sense environmental stimuli and regulate cellular biological processes by triggering signaling cascades linked to metabolite transport. This study investigated the response of the SLC25A family, a unique set of inner mitochondrial membrane-localized transporters, to cold as an environmental stimulus in mediating metabolic reprogramming; and whether this reprogramming, driven by the metabolites transported by SLC25A proteins, subsequently promotes the activation of thermogenesis in brown adipocytes. After screening members of the SLC25A family for their responsiveness to cold stimuli and brown adipose tissue (BAT) activation, we found that Slc25a34 was robustly induced under these conditions. We further demonstrated that Slc25a34 mediates the transport of adenosine monophosphate (AMP), derived from de novo glucose synthesis, from mitochondria to the cytosol. This transport potentiates AMP-activated protein kinase (AMPK) signaling and glycolytic flux in brown adipocytes, both of which facilitate BAT thermogenesis during cold exposure. Intriguingly, cold exposure directly promoted the activation of peroxisome proliferator-activated receptor gamma (PPAR{gamma}), which transcriptionally upregulated Slc25a34 expression. More importantly, genetic ablation of Slc25a34 impaired BAT thermogenesis. Thus, our study reveals a novel cold-induced metabolite-sensing pathway, where Slc25a34-mediated AMP transport between mitochondria and the cytosol serves as a critical signal for activating BAT thermogenesis. These findings provide compelling evidence that metabolite transport across cellular compartments acts as a key driver of cellular physiology, thereby offering novel insights into metabolite-based therapeutic strategies for metabolic diseases. HighlightsO_LISlc25a34 is cold-responsive and transcriptionally regulated by PPAR{gamma}. C_LIO_LISlc25a34 functions specifically to mediate the mitochondrial-to-cytosolic transport of AMP in brown adipocytes. C_LIO_LIMitochondrially sequestered de novo synthesized AMP acts as a signaling reservoir, and its Slc25a34-mediated efflux to the cytosol activates AMPK and glycolysis, supporting BAT thermogenesis. C_LI

cell biology↗

bioRxiv2026

Structural basis of substrate recognition and allosteric inhibition in human B0AT2

The SLC6 family is a major target for neuropsychiatric therapeutics. Human B0AT2 (SLC6A15) regulates amino acid homeostasis and glutamatergic transmission and is linked to major depressive disorder, yet its transport and inhibition mechanisms remain unclear. Here we report cryo-EM structures of B0AT2 in apo state and in complex with substrates (proline, leucine, methionine) and inhibitors (loratadine, tiagabine), capturing outward-open, early substrate-bound intermediate, outward-occluded, and inward-open conformations along the transport cycle. These structures reveal an early substrate-sensing mechanism at the substrate-binding pocket (S1), where a substrate-dependent rotameric switch of Phe308 remodels pocket geometry to tune substrate accommodation and selectivity. Loratadine stabilizes an outward-occluded state via allosteric inhibition at the extracellular S2 pocket, whereas tiagabine stabilizes the inward-open state through cooperative multi-site inhibition involving S1 and two previously unrecognized intracellular cavities (S3 and S4). Together with functional assays, these data define the molecular basis of B0AT2 substrate selectivity and state-dependent inhibition. Notably, the two intracellular cavities are conserved across SLC6 transporters, reflecting a shared intracellular vestibular architecture and enabling rational design of conformation-selective modulators for neuropsychiatric disorders.

biophysics↗

bioRxiv2026

Hypermutability of ultraconserved histone genes and its contribution to human disease

Histone genes are among the most evolutionarily conserved sequences in eukaryotes, reflecting their essential role in nucleosome architecture. Intriguingly, our analysis reveals unexpectedly high germline mutation rates in replication-dependent histone genes across vertebrates. We provide multiple lines of evidence suggesting that this hypermutability is largely driven by off-target mutagenic effects of AID/APOBEC enzymes, representing an unintended fitness cost associated with vertebrate immune system innovation. To characterize the impact of these mutations, we develop HistMTR, a paralog-aware missense constraint framework that outperforms existing tools in predicting the pathogenicity of histone mutations. Applying this framework to large-scale human genomic data, we demonstrate that both coding and regulatory histone mutations contribute to a spectrum of diseases, including developmental disorders and reproductive failure. Analyses of allele transmission ratios and the distribution of fitness effects indicate intense ongoing negative selection against deleterious histone mutations in humans. Together, these findings uncover a hidden vulnerability of ultraconserved histone genes and establish HistMTR as an important framework for characterizing the underappreciated role of histone mutations in human disease.

evolutionary biology↗

bioRxiv2026

Identification of scavenger receptor BI as a scavenger of free heme that is essential for protection against hemolysis

Severe hemolysis is a life-threatening condition with limited therapeutic options. Although haptoglobin and hemopexin sequester hemoglobin and heme, these protective systems are rapidly saturated during acute hemolysis, leading to the accumulation of cytotoxic free heme. In this study, we identify scavenger receptor BI (SR-BI) as a critical mediator of free heme clearance. SR-BI binds heme and facilitates its hepatic uptake under pathological conditions. Mice lacking hepatic SR-BI exhibit impaired heme clearance and increased susceptibility to heme- and hemolysis-induced lethality. Pharmacological upregulation of hepatic SR-BI via imatinib or adenoviral delivery confers protection against heme toxicity. Using a humanized model of sickle cell disease (SCD), we further demonstrate that sickle hepatopathy significantly reduces hepatic SR-BI expression compared to non-SCD littermates, potentially increasing vulnerability to heme-induced injury. Notably, adenoviral-mediated SR-BI upregulation rescues SCD mice from heme toxicity. These findings reveal a previously unrecognized mechanism of heme detoxification via hepatic SR-BI and identify a promising therapeutic target for hemolytic disorders. One-Sentence SummaryIdentification of scavenger receptor BI as a targetable scavenger of heme in hemolysis

physiology↗

bioRxiv2026

Bovine H5N1 influenza viruses have adapted to more efficiently use receptors abundant in cattle

Sustained mammal-to-mammal transmission of high pathogenicity H5N1 avian influenza viruses is reshaping the host range of these pathogens. One of the longest-running mammalian transmission chains involves the B3.13 genotype circulating in U.S. dairy cattle which was detected in early 2024. Genomic analyses revealed selection and rapid fixation of haemagglutinin mutations D104G and V147M. We demonstate, via glycomic profiling, that bovine tissues, including the mammary gland, are enriched in N- and O-linked glycans capped with N-glycolylneuraminic acid (NeuGc), a sialic acid absent in humans and birds, which instead express only N-acetylneuraminic acid (NeuAc). Early cattle H5 viruses poorly recognized NeuGc, but D104G and V147M enabled efficient engagement of both NeuAc- and NeuGc-containing receptors. These mutations enhanced replication in bovine mammary tissue without major attenuation of replication in human lung and primary nasal epithelial cells. NeuGc-driven receptor adaptation therefore promotes viral fitness in cattle while potentially limiting immediate zoonotic risk. Deep mutational scanning further identified alternative haemagglutinin substitutions that confer NeuGc usage and represent surveillance markers for emerging cattle H5 lineages.

microbiology↗

bioRxiv2026

Farnesoid X receptor-dependent microbiome-bile acid signaling mediates obstructive sleep apnea-induced atherosclerosis

Intermittent hypoxia and hypercapnia (IHC), a hallmark of obstructive sleep apnea (OSA), accelerates atherosclerosis, yet the underlying mechanisms remain unclear. The gut microbiota and metabolites, specifically bile acids, change with IHC and thus the bile acid receptor farnesoid X receptor (FXR) might mediate IHC-induced atherosclerosis. In this study, ApoE-/- and ApoE-/- FXR-/- mice were exposed to IHC or room air and fed with a high-fat, high-cholesterol diet for 10 weeks. Markers of atherosclerosis, fecal microbiome, and metabolome were then examined via Sudan IV staining, absolute abundance shotgun metagenomics, and untargeted liquid chromatography tandem mass spectrometry (LC-MS/MS). IHC markedly increased aortic atherosclerosis in ApoE-/-mice, an increase that was abolished by FXR deficiency. In addition, IHC reshaped gut microbial composition, promoting enrichment of bile acid-modifying taxa and increasing levels of microbial hydroxysteroid dehydrogenase (hsdh). The bile acid pool was also remodeled and associated with aortic atherosclerosis via FXR-dependent metabolic signals in ApoE-/- mice. Knockout of FXR disrupted microbiome shift under IHC and uncoupled microbial bile acid metabolism from vascular lesion development, thereby protecting against aortic atherosclerosis. These findings show that FXR has a central role in linking IHC, microbial bile acid metabolism, and cardiovascular pathology.

microbiology↗

bioRxiv2026

Wnt/β-catenin signaling restrains developmental beiging and imprints long-term energy expenditure

Beige adipocytes that emerge during the peri-weaning period support sympathetic nervous system (SNS)-independent thermogenesis, yet the mechanisms governing this spontaneous beiging remain unclear. Here, by integrating transcriptomic profiling with adipocyte-targeted Ctnnb1 deletion in mice, we identify the canonical Wnt signaling as an endogenous brake on developmental beige thermogenesis. Peri-weaning inguinal fat from adipocyte Ctnnb1 knockout mice exhibits enhanced beige adipocyte biogenesis, with increased thermogenesis-related gene expression and mitochondrial oxidative capacity, which programs durable activation of adaptive thermogenesis and augmented whole-body energy expenditure into adulthood. Mechanistically, suppression of Wnt/{beta}-catenin signaling induces a non-canonical Wnt5a-Ca2-AMPK axis that promotes triglyceride lipolysis and subsequent PPAR-driven fatty acid oxidation, thereby fueling mitochondrial respiration. Genetic or pharmacological disruption of this axis blunts thermogenic responses induced by {beta}-catenin inhibition in both murine and human subcutaneous adipocytes, indicating that Wnt5a-Ca2-AMPK axis is required for the cell-autonomous activation of beige fat. These results reveal Wnt/{beta}-catenin signaling as a developmental constraint on beige adipocyte formation and suggest an SNS-independent route to sustainably raise energy expenditure and improve metabolic health.

physiology↗

bioRxiv2026

Illuminating the renal response to pH stress with single-nucleus RNA sequencing

Maintenance of whole-body pH is essential for human health. The kidneys play a crucial role in defending pH homeostasis by excreting excess acid in the urine and returning alkali buffers to the blood. Consequently, renal insufficiency causes serious and harmful effects on pH balance. While a serious and common complication of chronic kidney disease (CKD), pH imbalances themselves appear to be catalysts of kidney injury. Renal adaptations to pH imbalances contribute to compensated acid-base disorders and are vital to correcting whole-body pH. However, overstimulation of these adaptive processes can cause renal inflammation and lead to long-term kidney injury. Surprisingly, the acute and chronic effects of pH challenges on the whole kidney are poorly defined. The upregulation of ammoniagenesis in the proximal tubule due to acidosis, and the coordinated secretion of protons from the collecting ducts is a well-documented phenomenon. However, there is a significant gap in knowledge regarding how the other segments of the nephron respond to acidosis or alkalosis. Therefore, to determine the cell-specific impact of overt metabolic acidosis and alkalosis on the kidney, we performed single-nucleus RNA sequencing on male and female WT mice following 48-hours of acid-base challenge (280mM NH4Cl (acid), 280mM NaHCO3 (alkali), 280mM NaCl (isosmotic control)). The results of our studies reveal the sex-specific single-cell transcriptional response by the kidney to pH imbalances, including a proximal straight tubule cell cluster that arises de novo following both acidosis and alkalosis. We label these proximal tubule cells PT S3a and demonstrate that their transcriptional profile is distinct from other injured PT cells that arise from ischemic injury. These studies lay the foundation for future research into the long-term renal adaptations to pH challenges that may lead to renal insufficiency and the development of CKD.

physiology↗

bioRxiv2026

Molecular mechanisms of mitochondrial Ca2+ exchanger NCLX

Mitochondrial Ca2+ homeostasis is maintained through coordinated influx and efflux processes, with NCLX long recognized as the primary Ca2+ extruder operating via Na+/Ca2+ exchange. Here, we report cryo-EM structures of rat NCLX in cytosolic-facing occluded and open states. The central transmembrane (TM) domain of NCLX comprises ten helices arranged in two inverted, structurally similar halves, with two -repeats forming a central ion-binding pocket. Peripheral TMs 1 and 6 are loosely associated with the core and likely mediate alternative access to this site. These structural features closely resemble those of NCXs, indicating a conserved ion exchange mechanism. While NCLX retains the canonical Ca2+-binding site, it lacks several key Na+-binding residues found in NCXs, suggesting broader ion selectivity. Consistently, cell-based Ca2+ uptake assays show that NCLX mediates Ca2+ exchange using Na+, K+, Li+, and potentially protons as counterions. Based on the structural symmetry of NCLX and its bidirectional exchange capability, we propose a matrix-facing model and an alternating-access mechanism in which TMs 1 and 6 undergo sliding motions to enable ion exchange between cytosolic and matrix sides, analogous to NCX. These findings provide a structural and mechanistic framework for understanding NCLX-mediated Ca2+ transport in mitochondria.

biophysics↗

bioRxiv2026

Evolutionary genomics of local adaptation, climate vulnerability, and linarin metabolism in Opisthopappus longilobus

Global climate change and human activities are posing substantial threats to biodiversity. The genus Opisthopappus (O. taihangensis and O. longilobus), endemic to Chinas Taihang Mountains, possesses great ecological, ornamental and medicinal value. However, it is confronted with the pressures of habitat fragmentation and climate change. Here, we present the first haplotype-resolved, chromosome-scale genome assembly of O. longilobus ([~]2.95 Gb) and re-sequence 115 individuals across its range. Comparative analyses show Opisthopappus is sister to Artemisia-Chrysanthemum, with Opisthopappus and Chrysanthemum diverging at 5.15-5.18 million years ago. A profound genetic divergence is evident between O. taihangensis and O. longilobus, resulting in two distinct lineages within each species, driven by geography and climate. Our analyses indicate restricted gene flow, low diversity, and recurrent demographic bottlenecks collectively contribute to their endangerment. By integrating population genomics and environmental variables, we identified 4,437 core adaptive genes linked to water deprivation, and metabolism. Genomic offset predicts higher maladaptation risk in populations under drastic climate change. Furthermore, diverged promoters of two O-methyltransferase genes, OMT250 and OMT310, likely underlie the differential acacetin/linarin accumulation between C. morifolium and O. longilobus. These findings advance understanding of Opisthopappus evolution and climate vulnerability, offering a model for genomics-guided biodiversity conservation.

plant biology↗