Biology subjects

Liu, L.

Publications and source records attributed to Liu, L..

At least 73 records · Page 4Linked to original sources

bioRxiv2026

Generation of three induced pluripotent stem cell lines from an immune checkpoint inhibitor-induced myocarditis patient and controls

Immune checkpoint inhibitor-associated myocarditis (ICIM) is an uncommon but potentially fatal inflammatory heart disease triggered by cancer immunotherapy, with up to 40% mortality. The underlying mechanisms are still elusive, partly due to the lack of appropriate human disease models. Here, we report the generation of three induced pluripotent stem cell (iPSC) lines derived from an ICIM patient, an ICI-treated patient without myocarditis, and a healthy donor. These lines exhibit typical pluripotent stem cell morphology, express pluripotency markers, maintain normal karyotypes, and differentiate into derivatives of the three germ layers, providing a valuable platform for mechanistic studies and therapeutic discovery.

Developmental Biology↗

bioRxiv2026

Female-specific m6A remodeling in the liver correlates with post-transcriptional metabolic adaptation to high fat diet

Sex differences strongly influence susceptibility to metabolic dysfunction-associated steatotic liver disease (MASLD), yet the regulatory mechanisms underlying these differences remain incompletely understood. To examine sex-specific hepatic adaptation to a high-fat (HF) diet mouse model of MASLD, we integrated proteomics, transcriptomics, and Oxford Nanopore direct RNA sequencing for transcriptome-wide m6A profiling in male and female mouse livers. Female mice were relatively protected from HF diet-induced hepatic steatosis and exhibited distinct proteome remodeling enriched for peroxisomal pathways. In contrast, transcriptomic responses in females were dominated by inflammatory signatures and did not recapitulate the metabolic adaptations observed at the protein level, revealing extensive RNA-protein discordance and post-transcriptional remodeling. Integrated RNA-protein analyses identified female-specific amplification of peroxisomal proteins despite modest transcript-level changes. HF diet also induced sex-specific remodeling of m6A RNA methylation and altered regulation of the m6A methylation system. Notably, reduced 3' UTR m6A methylation of peroxisomal transcripts inversely correlated with increased protein abundance relative to RNA expression in female mice. Together, these findings implicate m6A-associated post-transcriptional regulation in sex-specific hepatic adaptation to HF diet exposure and the basis for discordance between many of the mRNAs and proteins in the liver.

systems biology↗

bioRxiv2026

Spatiotemporal biogenesis of thylakoid membranes in the green alga Chlamydomonas reinhardtii

Thylakoid membranes are essential for oxygenic photosynthesis, yet the mechanisms underlying their spatial and temporal biogenesis remain poorly understood. Here, using a light-induced membrane regeneration system in Chlamydomonas reinhardtii, we generate a time-resolved map of thylakoid formation and photosynthetic complex assembly at unprecedented spatial and temporal resolution by integrating super-resolution fluorescence microscopy, cryo-electron tomography, proteomics, and spectroscopy. We show that thylakoid biogenesis is globally distributed and multipolar, with new membrane formation occurring at multiple sites across the chloroplast, including regions adjacent to the inner envelope membranes in both basal and lobe regions. We identify F-ATP synthase storage membranes and map the redistribution of translating ribosomes from T-zone enrichment to a chloroplast-wide distribution at early stages of thylakoid formation, consistent with decentralized synthesis of photosynthetic complexes. We further delineate the hierarchical assembly of photosystem supercomplexes, starting with formation of reaction centers. Together, these findings refine the spatial organization of photosynthetic membrane biogenesis and establish a unified spatiotemporal framework linking thylakoid formation, translational activation, and functional maturation, providing a mechanistic basis for plastid engineering to enhance photosynthetic efficiency.

Cell Biology↗

bioRxiv2026

Multitrophic interaction networks mediate biodiversity effects on ecosystem multifunctionality

Biodiversity loss threatens the multifunctionality of ecosystems on which human well-being ultimately depends. Changes in multitrophic species interactions may be key to explaining the ecological consequences of biodiversity loss, but research explicitly linking species interactions and ecosystem multifunctionality remains rare. To assess interaction-mediated biodiversity effects and underlying mechanisms, characterizing the structure of species interaction networks is invaluable. Using comprehensive species interaction and ecosystem functioning data from a large-scale tree biodiversity experiment, we find consistent effects of the structure of species interaction networks on ecosystem multifunctionality across multiple types of antagonistic and mutualistic interactions. While positive effects of network size align with expected positive effects of multitrophic species diversity, positive effects of niche overlap among interacting species and negative effects of highly connected species (i.e. high linkage density) reveal additional, interaction-mediated drivers of multifunctionality. Specifically, the effects of niche overlap suggest benefits of functionally similar species, and the effects of linkage density underscore the importance of specialized interactions in promoting ecosystem multifunctionality. These findings emphasize that to effectively safeguard ecosystem service provisioning, ecosystem management and biodiversity conservation not only need to account for biodiversity changes at multiple trophic levels, but also explicitly for how species interact among each other.

ecology↗

bioRxiv2026

Bone Morphogenetic Protein Pathway Modulates Parkinson's Disease Genetic Risk and Promotes Motor Recovery

Progress toward disease-modifying Parkinsons disease (PD) therapies is hindered by limited understanding of pathogenic drivers and lack of therapies that restore the damaged dopaminergic (DA) neurons driving motor deficits. We investigated the role of the bone morphogenetic protein (BMP) pathway in PD using common and rare genetic variants across large-scale datasets. Single-variant analyses identified nominal associations with PD risk and onset age. A BMP polygenic risk score (PRS) was significantly associated with PD risk (OR = 1.21, empirical P = 1.0 x 10-), a result replicated in proxy-case analyses (OR = 1.14, empirical P = 1.0 x 10-) and remained significant after sensitivity testing. To test the results functional relevance, we genetically and pharmacologically inhibited BMP signaling in mice, which induced motor deficits and PD-like neuropathology. In a -synuclein preformed fibril (PFF) mouse model, BMP5 and BMP7 (BMP5/7) demonstrated neuroprotective effects when administered concurrently with -synuclein PFFs. Importantly, when delivered after PFFs-induced motor symptoms onset, BMP5/7 demonstrated neurorestorative effects, ameliorating both motor impairments and neuropathology. These findings provide first evidence that BMP signaling variations contribute to polygenic PD risk, identify a physiological role for this pathway in safeguarding against PD-related pathology, and demonstrate BMPs therapeutic potential for disease modification.

neuroscience↗

bioRxiv2026

V-ATPase-Driven Lysosomal Activation Orchestrates MEK2-Induced Endothelial Reprogramming

Direct lineage reprogramming holds therapeutic promise but often depends on transcription factor overexpression, resulting in unstable phenotypes. Here, we describe a novel strategy to convert fibroblasts into endothelial-like cells by activating lysosomal activity. Constitutively active MEK2 induces an endothelial gene program via sustained MAPK/ERK signaling, leading to enhanced vacuolar ATPase (V-ATPase) activity, lysosomal acidification, extracellular matrix degradation, and angiogenic behavior. V-ATPase inhibition impairs these effects, whereas pharmacologic activation with EN6 recapitulates key features of reprogramming and promotes nuclear translocation of TFEB, a master lysosomal regulator. Consistently, TFEB overexpression-particularly a phospho-deficient mutant-boosts lysosomal function and endothelial gene expression. These findings define a MAPK-V-ATPase-TFEB axis that drives endothelial reprogramming and highlight the lysosome as a central hub for cell fate transitions, offering an organelle-centric framework for regenerative medicine. HighlightsO_LISustained MEK2 activation reprograms fibroblasts into endothelial-like cells C_LIO_LIMEK2 enhances lysosomal acidification by upregulating V-ATPase subunits C_LIO_LIV-ATPase drives acidification and ECM remodeling for endothelial reprogramming C_LIO_LIV-ATPase activation promotes TFEB nuclear entry and endothelial gene expression C_LI

cell biology↗

bioRxiv2026

Accurate de novo design of peptides from programming biophysical landscape

Peptides regulate virtually every cellular process and emerge as transformative modalities in bioengineering and therapeutics. However, the de novo design of functional peptides remains challenging, as peptide-protein interactions are governed by delicate and dynamic biophysics that are difficult to model, and experimental datasets are scarce. Here we present NeoPep, a generative deep-learning framework that encodes biophysical principles to accurately design functional peptides de novo. By integrating over 5 million peptide-protein complexes spanning experimentally determined, sequence mimics, and structure ensembles, NeoPep learns the complex biophysical landscape governing peptide function and enables its programmable control. In prospective application across 10 diverse and challenging targets, NeoPep generated potent peptide binders, agonists, and antagonists with hit rates of 12.5-66.7%, even in the absence of defined binding sites or structure information. Beyond de novo co-design, NeoPep supports standalone structure or sequence redesign, readily discriminating subtle context differences. In the structure redesign mode, it generates highly selective peptides with atomic-level conformational accuracy (C RMSD < 2.0 [A] to our solved cryo-EM structure). This structural precision circumvents the need for experimental structure determination, further accelerating iterative sequence redesign to yield a 43.3-fold improvement in potency. These findings establish a general framework for translating biophysical principles into actionable peptide functions, with broad implications for basic research, bioengineering, and medicine.

molecular biology↗

bioRxiv2026

Asymmetric introgression and thermal advantage jointly drive climate-mediated lineage turnover in a mixed-ploidy reed

Species distribution forecasts commonly overlook intraspecific genetic variation, missing a potentially important mechanism of ecosystem change: climate-driven range shifts among lineages within a species native range. Here we integrate population genomic analysis of 495 individuals, multi-site common garden experiments, and species distribution modeling based on 837 occurrence records for three major genetic lineages of the foundation grass Phragmites australis in China. The octoploid FEAU lineage (haplotype P) exhibits superior heat tolerance (critical temperature Tcrit and T50) and produces significantly greater total biomass in three of four common gardens compared to the cold-adapted CN lineage (tetraploid, haplotypes O/M), which occupies a climatic niche with lower annual mean temperature (Bio1) and mean temperature of the wettest quarter (Bio8). Genomic analyses further reveal bidirectional but asymmetric introgression, with admixed individuals showing a systematic bias toward FEAU ancestry. Under the high-emission scenario (SSP5-8.5) by 2070, projected highly suitable habitat for the FEAU lineage expands by 18.6%, while the CN lineage shows a smaller relative increase. By contrast, the subtropical SW lineage (haplotypes U/I) exhibits limited and stable suitable habitat. These results demonstrate that climate change interacts with intraspecific variation among polyploidy-associated lineages, manifested through differences in thermal tolerance, biomass production, and asymmetric gene flow, to drive potential lineage replacement within a native range, a process already suggested by field observations of FEAU expansion in a plateau lake. Our findings argue for integrating evolutionary history and genetic identity into ecological forecasting to better anticipate ecosystem responses under ongoing climate warming.

ecology↗

bioRxiv2026

Conserved TIR-only proteins drive transcriptional defense and basal immunity in dicot and monocot plants

Toll/interleukin-1/resistance (TIR) domain NADase enzymes signal in plant immunity by producing ribosylated nucleotide second messengers which activate EDS1 dimer-helper NLR pathways to restrict pathogen growth. Members of a small, distinctive group of TIR-only proteins are conserved between dicots and monocots, yet their functions remain poorly understood. Here, we show that conserved TIR-only proteins in Arabidopsis and barley share a fundamental enzymatic role in promoting basal defense against virulent filamentous pathogens, independently of NLR mediated effector-triggered immunity. Metabolite analysis of transiently expressed Arabidopsis and barley TIR-only proteins revealed their capacity to produce ribosylated cyclic nucleotides in vivo. By comparing phenotypes of tir-only and eds1 pad4 CRISPR mutants in the two species, as well as adr1 mutants in barley, we established that the TIR-only proteins promote PAMP-triggered transcriptional defenses associated with pathogen restriction. Barley possesses just one essential TIR-only enzyme and mutations of the two conserved TIR-only members in Arabidopsis were not compensated for by numerous other TIR-domain genes in the basal immune response. These findings suggest that conserved TIR-only proteins make a crucial contribution to TIR basal defense signaling networks of Arabidopsis and barley. We propose that a shared function in transcriptional defense regulation could explain the evolutionary retention of this discrete TIR-only group across monocot and dicot lineages.

plant biology↗

bioRxiv2026

Germline regulation of tumor evolutionary dynamics shapes multiple myeloma progression

Germline variation shapes cancer risk, yet its influence on the evolutionary dynamics of established tumors remains poorly understood. In multiple myeloma, subclonal diversification drives disease progression and treatment failure, but the heritable factors that modulate this process are unknown. Here, we show that germline variation is associated with tumor evolutionary features, implicating inherited regulation in subclonal expansion. Integrating germline variation with tumor evolutionary parameters identifies variants associated with evolutionary features, with signals enriched in regulatory regions, consistent with a transcriptional basis. We further identify TBKBP1 as a key locus linking germline variation to tumor evolution and clinical outcome. Germline variation at this locus is associated with TBKBP1 expression and subclonal expansion, and TBKBP1 expression correlates with adverse prognosis, consistent across independent cohorts. Functional analyses demonstrate that TBKBP1 promotes proliferation and activates MYC, mTORC1 and non-canonical NF-{kappa}B signaling pathway. Together, these findings establish germline regulatory variation as a determinant of tumor evolutionary dynamics and identify TBKBP1 as a mediator linking inherited variation to subclonal expansion and disease progression in multiple myeloma.

bioinformatics↗

bioRxiv2026

Long-read RNA-seq resolves isoform-level and context-specific regulatory architecture of complex traits in cattle

Traditional short-read RNA-seq lacks the resolution to fully capture full-length isoforms and complex alternative splicing, leaving a "missing regulation" gap in existing molecular atlases. Here, we present a population-scale, multi-omics dissection of bovine complex traits using matched deep whole-genome sequencing (30x), long-read (ONT) and short-read RNA-seq, as well as metabolome data from 432 dairy cows across four distinct lactation stages. We expanded the bovine transcript atlas with 13,177 novel isoforms and fine-mapped 1,088,900 regulatory effects across 11 diverse molecular phenotypes. Notably, long-read mapping uncovered 606 genes with isoform expression quantitative trait loci (12.8%, eQTL) and 1,116 genes with detailed splicing QTL (sQTL) (31.8%) that were missed by conventional short-read mapping. We further showed that lactation-specific regulation was profoundly mediated by the metabolic microenvironment (46.8%) and cellular composition (4.3%). Across genome-wide associations (GWAS) of 90 bovine complex traits, isoform-level and context-specific regulatory effects captured GWAS loci missed by short-read eQTL and sQTL analyses, increasing colocalized loci from 35.2% to 60.3%. These regulatory variants also exhibited evolutionary constraints with human immune and metabolic loci. Our study establishes an invaluable resource (https://cattleblr.farmgtex.org) demonstrating that long-read transcriptomics is essential for resolving the complexity of regulatory mechanisms underlying mammalian physiology.

genetics↗

bioRxiv2026

Convergent Evolution in Tumor Genomes Targets Functional Domains

Tumor evolution is shaped by selective pressures that repeatedly favor similar functional outcomes across genetically distinct cancers. While convergent evolution in cancer has been studied at the gene level, this work investigates selection on smaller functional units, namely protein domains. Using >9,500 primary tumor exomes from The Cancer Genome Atlas, we quantified selection strengths acting on missense and truncating mutations aggregated by protein domain. This analysis identified 818 domains under significant positive selection across tumor types. Notably, approximately half of these domains belonged to genes that would be difficult to implicate using conventional gene-centric approaches due to low mutational recurrence or mutations outside functionally critical regions. We classified positively selected domains by evolutionary antiquity. The most ancient domains trace back to pre-eukaryotes and are involved in core cellular processes (e.g., DNA mismatch repair and metabolism) and tend to accumulate the highest numbers of mutations. The majority of positively selected domains originated in early eukaryotes and are enriched for regulatory control and cellular organization, whereas metazoan-specific domains are primarily associated with signaling and cell-cell communication. These results suggest that cancer preferentially exploits deeply conserved biology, with regulatory complexity driving tumor adaptation, while recent evolutionary innovations are relatively fragile and dispensable. Collectively, these findings establish a domain-centered framework for understanding disease mechanisms and developing therapeutic strategies. By focusing on shared functional domains, this framework enables the identification of functionally convergent therapeutic targets and provides a new perspective for interpreting drug resistance, tumor recurrence, and relapse.

bioinformatics↗

bioRxiv2026

A phage-encoded small RNA that mimics chimeric guide to inhibit CRISPR-Cas9

CRISPR-Cas9 relies on a dual crRNA-tracrRNA guide, yet whether RNA-based anti-CRISPRs exist for this system has remained unknown. Here we identify a phage-encoded small non-coding RNA, rAcrIIA1, that adopts an unexpected chimeric crRNA-tracrRNA architecture, faithfully recapitulating the entire single-guide RNA (sgRNA) of Cas9. Cryo-EM structures of the Cas9-rAcrIIA1 binary complex and the Cas9-rAcrIIA1-DNA ternary complex reveal that rAcrIIA1 engages Cas9 nearly identically to the native sgRNA, competitively blocking crRNA and tracrRNA loading and thereby abolishing DNA interference. Strikingly, beyond its natural inhibitory function, rAcrIIA1 is fully reprogrammable: with variable guide sequences, it directs Cas9 for sequence-specific DNA cleavage with efficiency comparable to the canonical sgRNA, and it activates trans-cleavage more potently. Thus, rAcrIIA1 provides the first experimentally validated, mechanistically resolved RNA-based inhibitor of CRISPR-Cas9, reveals a distinct anti-CRISPR mechanism through complete sgRNA mimicry, and serves as a versatile bifunctional scaffold for genome editing and diagnostics.

biochemistry↗

bioRxiv2026

Assessing and Optimizing Low-Frequency Somatic Mutation Detection: A Multi-Platform High-Throughput Sequencing Perspective

The availability of multiple commercial short-read sequencing platforms necessitates systematic cross-platform performance comparisons, particularly for challenging applications such as low-frequency somatic mutation detection. Here, a large-scale targeted sequencing dataset from five Genome in a Bottle (GIAB) human genomic DNA reference standards, HG001 to HG005, alongside Twist Biosciences cfDNA reference standards featuring 1% variant allele frequency (VAF), was generated by six platforms (NovaSeq 6000, NovaSeq X, FASTASeq 300, GenoLab M, SURFSeq 5000, and MGISEQ-T7). To build a realistic benchmark while keeping authentic sequencing backgrounds, we developed PosMix, a simulating tool that generates position-specific VAFs. To overcome the limitations of conventional variant callers (high recall with poor precision for VarScan2, higher precision with lower recall for Strelka2/Mutect2), we developed SomaticXGB, a machine learning-based caller. In this study, SURFSeq 5000 consistently exhibited the lowest error rates and achieved superior accuracy for VAFs as low as 0.5%, outperforming all other sequencing platforms. On the other hand, SomaticXGB attained F1 scores of approximately 0.92 on simulated datasets with VAFs ranging from 0.5% to 1.5% and 0.89 on Twist 1% standards, substantially outperforming conventional methods. This work delivers a valuable rich multi-platform data resource, offering a standardized pipeline for performance benchmarking and a machine learning-based strategy for optimized somatic mutation detection.

bioinformatics↗

bioRxiv2026

Objective curriculum-guided design of multi-property proteins

Designing functional proteins that simultaneously possess multiple bio-chemical properties remains a significant challenge, as key protein properties, such as solubility, stability, binding affinity, and chemical resistance, are often interdependent or even conflicting. Current approaches typically attempt to jointly optimize multiple functional objectives in one shot, followed by extensive screening to identify rare feasible designs. Here, we introduce OCDesign, an objective curriculum-guided framework for multi-property protein design. OCDesign is based on the objective curriculum principle, i.e., the order in which objectives are introduced can shape the accessibility of functional solutions. In each design round of OCDesign, candidate sequences are generated in silico, assessed across multiple properties, selected based on Pareto-optimal trade-offs, and experimentally validated, with each experimental stage testing the role of the newly introduced objective within the curriculum. Using antibody-binding protein A as a model system, we show that one-shot optimization fails to yield functional designs, whereas a staged curriculum--progressing from solubility and structural consistency to binding affinity, and then to alkaline resistance--enables the design of proteins possessing multiple desired properties through substantially fewer wet-lab experiments. These results establish OCDesign as a practical computational-experimental strategy for organizing and integrating multiple objectives in protein design, and suggest that objective ordering is a key determinant of accessibility in high-dimensional design spaces.

bioengineering↗

bioRxiv2026

Decoding Immune Reconstitution Failure in People Living with HIV through Single-cell Genomics

Immune non-responders (INRs), a subset of people living with HIV (PLWH), fail to achieve full immune reconstitution and remain at increased risk of morbidity, mortality, and non-AIDS-related illnesses. As the mechanisms underlying this impaired immune recovery remain poorly understood, we performed single-cell multi-omics profiling on peripheral blood mononuclear cells from 43 INRs, 47 immune responders and 53 healthy donors. Our dataset comprises 2,744,009 transcriptomes and 1,226,658 chromatin-accessibility profiles across 58 identified immune cell types. INRs exhibited markedly elevated inflammatory signaling, increased apoptotic activity, and dysregulation of immune-activating ligand-receptor interactions. Additionally, we identified 2,996 interaction cis-eGenes and 5,938 cis-caPeaks, and validated key cell type-specific cis-xQTL effects associated with immune reconstitution failure. Furthermore, we identified 3,551 sc-eQTLs and 872 cell-state interaction eQTLs (ieQTLs) in CD4+ T cells. A genotype-specific upregulation of OAS3 in INRs, likely regulated by STAT1, was identified based on these results. We developed scPRISM (single cell Predictive Reconstitution Immune Status Model), a multi-modal framework that integrates scRNA-seq and scATAC-seq data to perform the dual tasks of differentiating disease states and predicting gene expression from chromatin accessibility, thereby deciphering the cell type-specific cis-regulatory basis of the disease. Our study delineates the transcriptional and epigenomic landscape of immune dysregulation in INRs and provides new genetic insights into HIV-associated immune reconstitution failure. These findings offer a foundation for developing biomarkers and precision therapies to restore immune function in PLWH.

genetics↗

bioRxiv2026

Immunometabolic Remodeling of Perivascular Adipose Tissue in Murine Lupus: Implications for Lupus Vasculopathy

BackgroundPatients with systemic lupus erythematosus (SLE) face markedly increased cardiovascular disease (CVD) risk driven by mechanisms beyond traditional risk factors. Thoracic aortic perivascular adipose tissue (tPVAT) is dysfunctional in lupus and exacerbates endothelial dysfunction, yet the molecular basis of this dysfunction remains poorly defined. MethodsIntegrated multi-omics profiling, including bulk RNA-seq, untargeted proteomics, lipidomics, and high-dimensional spectral flow cytometry, was performed on tPVAT from 15-week-old MRL/lpr mice (active lupus, n = 4-6) and MRL control mice (n = 5-6). Adipogenic differentiation capacity of tPVAT adipose stromal and progenitor cells (ASPCs) from MRL/lpr was assessed by Oil Red O staining at 5 (pre-dieasea) and 15 weeks (active disease), with subcutaneous ASPCs used as depot controls. ResultsTranscriptomic profiling of tPVAT from MRL/lpr mice identified 2,742 upregulated and 1,494 downregulated genes (adjusted p < 0.001, |log2FC| > 1), with strong activation of interferon, IL6-JAK-STAT3, and TNFA signaling pathways together with suppression of fatty acid metabolism, oxidative phosphorylation, and adipogenic pathways. Proteomic and lipidomic analyses were concordant, revealing broad downregulation of mitochondrial bioenergetic machinery, depletion of cardiolipin and acylcarnitines, and enrichment of ceramide phosphoinositols and lysophosphatidylcholines. Cardiolipin strongly correlated with the mitochondrial/metabolic protein module (r = 0.95) and inversely with the immune/inflammatory protein module (r = -0.92). Spectral flow cytometry confirmed marked CD45+ leukocyte infiltration dominated by T cells, together with a significantly reduced Treg/CD4+ ratio indicating loss of local immunoregulatory balance. ASPCs derived from PVAT of 15-week-old MRL/lpr mice exhibited impaired white and beige adipogenic differentiation, while APCs from PVAT of 5-week-old MRL/lpr mice, and from subcutaneous adipose tissues of 15-week-old MRL/lpr mice, had normal white and beige differentiation, consistent with an acquired, depot-specific, disease-stage-dependent progenitor defect in PVAT of MRL/lpr mice. ConclusionsLupus tPVAT undergoes a concordant cross-platform molecular reprogramming of mitochondrial bioenergetic genes coupled with establishment of an interferon-dominant immune niche and acquired loss of ASPC adipogenic capacity. These findings provide a molecular framework for lupus PVAT dysfunction and identify restoration of mitochondrial function, suppression of interferon-driven inflammation, and renewal of progenitor differentiation as potential therapeutic strategies for lupus vasculopathy.

molecular biology↗

bioRxiv2026

Genetic canalization of nutrient resorption: evidence from a widespread grass under effective salt stress

Nutrient resorption is a key plant strategy for nutrient conservation, yet whether it responds plastically to non-nutrient stressors such as salinity remains unresolved. Using a common garden experiment with 110 genotypes of the cosmopolitan grass Phragmites australis, we first established that the imposed salinity treatment induced strong multi-level stress responses: above-ground biomass declined by >60%, sodium accumulated 3- to 5-fold across all leaf stages, and 484 metabolites showed significant differential accumulation, including canonical markers of osmotic and oxidative stress. Against this backdrop of confirmed stress, we found that nutrient resorption efficiency (NuRE) remained largely unaffected by salinity. Instead, NuRE was strongly correlated with phylogeographic lineage, ecotype, and latitude of origin, demonstrating evolutionary canalization rather than short-term acclimation. Element-specific regulatory patterns were also evident: while phosphorus resorption followed concentration-dependent control regardless of stress, nitrogen control was disrupted under salinity, and potassium resorption showed no such dependence. Our findings reveal that intraspecific variation in nutrient resorption is predominantly shaped by historical adaptation and geographic context, not by plasticity to salinity. This genetic canalization of a key functional trait implies that predictions of nutrient cycling under global change must account for the phylogeographic composition of plant populations.

ecology↗