Biology subjects

He, Q.

Publications and source records attributed to He, Q..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

evo3D: a generalised framework for structure-informed evolutionary analysis, implemented in R

At the molecular level, selection pressures often act on protein structural features, yet most evolutionary analyses remain confined to linear sequences. Early structure-informed approaches improved interpretability by mapping single-site metrics onto protein structures, and later methods introduced 3D sliding windows to capture spatially clustered signals missed by linear window approaches. These frameworks, however, are restricted to predefined statistics and narrowly defined 3D window types, limiting the scope of questions that can be addressed. We developed an R package, evo3D, as a new framework for structure-informed evolutionary analysis that supports a wide range of downstream statistics and scales from simple to complex structures. evo3D extracts structure-informed multiple sequence alignment subsets (spatial haplotypes), making the structure-informed unit of analysis directly available to users. The framework supports fixed-count and fixed-distance spatial windows, introduces residue and codon analysis modes, and extends to multimers, interfaces, and multiple structural models through a single wrapper, run_evo3d(). We demonstrate evo3Ds utility by performing an epitope-level diversity scan of Hepatitis C virus E1/E2 complex, identifying conserved spatial neighbourhoods missed by linear sliding windows, and by evaluating evo3Ds scalability on the octameric Chikungunya virus E1/E2 assembly. Importantly, evo3D formalises the core components of structure-informed analysis of molecular evolution and removes technical barriers. As a result, the framework streamlines the evaluation of evolutionary patterns directly within 3D structural contexts, and we anticipate its wide application in molecular evolution studies. The package is available at github.com/bbroyle/evo3D.

bioinformatics↗

bioRxiv2025

From genomic decay to functional advantage: Trait-based evidence for long-term host residency of a next-generation coral probiotic

A key bottleneck in microbiome engineering is ensuring the long-term host association of introduced microbes. Selecting probiotic candidates based on evolutionary genomic decay signatures of emerging host dependency offers a potential solution. The Ruegeria strain B4 of the population MC10, identified by such signatures, has shown persistent colonization in corals in a companion study. Whether this persistence translates into a measurable host benefit compared to other coral-associated Ruegeria strains, and which mechanisms underlie such benefit, remained unknown. Here we directly compare the probiotic efficacy of MC10-B4 against two sympatric Ruegeria strains isolated from the same coral colony and mucus compartment, controlling for host genotype and microenvironment. MC10-B4 inoculation significantly increased heat stress tolerance in the coral model cnidarian Aiptasia (Exaiptasia diaphana strain H2), outperforming both sympatric control strains. To understand the mechanistic basis of this probiotic efficacy, we characterized the functional profile of MC10 using an integrated multi-omics approach. The genome of MC10 is enriched in genes associated with host-interaction, including siderophore-mediated iron acquisition and exopolysaccharide biosynthesis, which were phenotypically confirmed by detectable iron scavenging and enhanced biofilm formation. Following exposure to coral tissue extract, MC10-B4 underwent a coordinated motility-to-sessility proteomic reprogramming, downregulating flagellar motor components while upregulating flagellin and biofilm regulators. This response was distinct from its sympatric relatives, which instead mounted broad upregulation of nutrient acquisition systems. MC10-B4s functional profile, particularly its sensitivity to oxidative stress, contrasts with the traits typically favored in conventional probiotic screens. Our results move beyond the descriptive identification of a coral probiotic by providing initial mechanistic insight into traits associated with long-term host association and improved thermal performance. These findings validate an evolution-guided approach that prioritizes innate colonization potential over pre-defined laboratory functionalities, informing the rational design of durable probiotics.

microbiology↗

bioRxiv2025

Insertion of an invading retrovirus regulates a novel color trait in swordtail fish

For over a century, evolutionary biologists have been motivated to understand the mechanisms through which organisms adapt to their environments. Coloration and pigmentation are remarkably variable within and between species and can serve as an important window into the mechanisms of adaptation. Here, we map the genetic basis of a newly described iridescence trait in swordtail fish to a single locus. Individuals with this trait appear to sparkle as they move through the water. We find that the trait is driven by the recent endogenization of a retrovirus that inserted near the gene alkal2a. This insertion is associated with changes in the chromatin landscape, upregulation of alkal2a, and accumulation of iridescent cells that adhere to the scales. Rather than causing diseases, our results demonstrate that invading endogenous retroviruses can also regulate novel trait variation in the host. Moreover, we find that this coloration trait may act as an important signal in interactions between fish and their predators in the natural environment.

evolutionary biology↗

bioRxiv2025

Activation of IRF7/ISG15 axis in microglia inhibits NLRP3 Expression and Improves the Prognosis of Ischemia/Reperfusion in Mice

Ischemic stroke is a leading cause of disability and mortality, with neuroinflammation playing a key role in post-stroke injury. The molecular mechanisms remain incompletely defined. This study explored the functions of IRF7 and its downstream target ISG15 in stroke-associated neuroinflammation and prognosis of ischemic stroke. Bioinformatic analysis of transcriptomic datasets from microglia and ischemic brain tissues identified both molecules as hub genes. Their expression was validated in a mouse transient middle cerebral artery occlusion (tMCAO) model and in microglial cultures exposed to oxygen-glucose deprivation/reoxygenation (OGD/R). The effects of these molecules were assessed using siRNA knockdown, conditioned media assays with SY5Y neuronal cells, in vivo overexpression of ISG15, histological and functional assessments. Both IRF7 and ISG15 were significantly upregulated after stroke. IRF7 knockdown reduced ISG15 expression, whereas ISG15 knockdown did not affect IRF7, suggesting a unidirectional regulatory relationship. Conditioned media from microglia treated with siIRF7 or siISG15 increased SY5Y cell mortality, with a stronger effect in the siISG15 group, highlighting neuroprotective role of ISG15. ISG15 knockdown also enhanced microglial migration. Conversely, microglial ISG15 overexpression in vivo promoted a shift toward reduced neuroinflammation, improved neuronal survival, and enhanced functional recovery. Mechanistically, ISG15 stabilized NLRP3 protein but more strongly decreased its mRNA stability through accelerated degradation. These findings demonstrate that the activation of IRF7/ISG15 axis in microglia inhibits NLRP3 Expression and improve the prognosis of ischemia/reperfusion in mice, with ISG15 exerting stronger neuroprotective effects. Targeting microglial ISG15 may offer a promising therapeutic strategy for ischemic stroke. MAIN POINTSO_LIISG15 shows a stronger neuroprotective effect than IRF7 in ischemic stroke. C_LIO_LIISG15 stabilizes NLRP3 protein but more strongly decreases its mRNA stability. C_LIO_LIMicroglial ISG15 overexpression in vivo improves the prognosis of ischemic stroke in mice. C_LI

neuroscience↗

bioRxiv2025

LRP8 is a Receptor for Yellow Fever Virus

Yellow fever virus (YFV), an arbovirus causing substantial human morbidity and mortality, was the first human virus discovered over a century ago. The live-attenuated 17D vaccine is among the most successful vaccines in medicine. Despite the importance of YFV, its receptor has remained unknown. Here, we performed a barcoded, genome-wide human ORF library screen and identified LRP8 (also named APOER2) as a receptor for YFV. We show that LRP8 expression specifically boosts YFV infection in cell lines by promoting entry. AAV-mediated expression of human LRP8 in mouse liver aggravates infection and pathology. LRP8 knockdown abolishes YFV infection in brain cells, primary human hepatocytes, and notably in mosquitoes. Biochemically, LRP8 directly interacts with YFV particles via the viral envelope protein. This function of LRP8 is conserved across species, particularly in mosquitoes and primates. A soluble LRP8 decoy protein can block YFV infection in vitro and in mice, providing a potential therapeutic or prophylactic strategy. Our findings provide groundwork for understanding YFV entry, tropism, and pathogenesis, and may enable development of novel therapeutics to treat YFV infection.

microbiology↗

bioRxiv2025

Lipid Metabolism Remodeling in Human Cardiomyocyte Differentiation and Maturation

During cardiac development, metabolic remodeling is characterized by a transition from glycolysis-dependent energy production to reliance on fatty acid oxidation. Lipids function as essential energy substrates and structural components throughout cardiac formation and maturation. However, the dynamic changes in endogenous lipid species during human cardiac development remain incompletely elucidated. In this study, we delineated distinct lipidomic profiles of human embryonic stem cells (ESCs), mesoderm (MES), cardiac progenitors (CPCs), immature cardiomyocytes (CMs), and mature CMs derived from ESCs using high-performance liquid chromatography (HPLC). Notably, ceramide concentrations peaked at the CPC stage, suggesting a pivotal role in mediating the MES-to-CPCs transition. Concurrently, lipid metabolites including GM3, phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and lysophosphatidic acid (LPA) were significantly upregulated in mature CMs. Integrative transcriptomic and chromatin accessibility analyses further refined the landscape of lipid remodeling during CM differentiation. Functional assays demonstrated that LPA enhances the stability of the beating rhythm in CPCs, while both PC and LPA facilitate CM maturation. Collectively, our findings establish a comprehensive and dynamic lipidomic atlas of human cardiogenesis, providing a novel framework to advance the understanding of lipid-mediated regulatory mechanisms in human heart development.

developmental biology↗

bioRxiv2025

Human Organoids Reveal PTEN-driven Mesendoderm Specification via Retinoic Acid Signaling Suppression

During early embryogenesis, epiblast cells ingress through the primitive streak (PS) and commit to a mesendoderm (MES) fate, giving rise to both mesodermal and endodermal lineages. Despite advancements in human organoid technology for modeling pre-implantation blastocyst stage, robust systems that accurately recapitulate MES specification and PS formation during the post-implantation stage remain limited. Here, we show that human induced pluripotent stem cells can be used to generate three-dimensional MES organoids that faithfully mimic in vivo human MES specification, particularly from the anterior PS. We demonstrate that MES organoid formation is dependent on PTEN expression and that loss of PTEN severely impairs the formation of mesoderm and definitive endoderm derivatives arising from MES organoids. To elucidate the molecular mechanisms underlying these defects, we conducted an integrative multi-omics analysis, including transcriptome, chromatin accessibility profiling, metabolism, and phosphoproteomics, on wild-type and PTEN-/-MES cells. These analyses revealed that PTEN suppresses retinoic acid (RA) signaling during MES lineage commitment. Furthermore, we identified the RA-degrading enzyme CYP26A1 as a downstream effector of PTEN. Notably, while excessive RA induced by PTEN ablation is detrimental to MES cell generation, physiological levels of RA are necessary. Collectively, our human MES organoids offer a valuable model for dissecting early human development, and our findings identify PTEN as a key regulator of MES fate commitment through inhibition of RA signaling.

developmental biology↗

bioRxiv2025

Across-breed analyses of genome-wide association studies for stature and mammary gland morphology in cattle reveal pleiotropic effects of the Friesian POLLED haplotype

BackgroundGenome-wide association studies (GWAS) in cattle populations have traditionally relied on progeny-derived phenotypes such as estimated breeding values (EBVs) as input phenotypes to identify additive quantitative trait loci (QTL) for complex traits. Increasing availability of cow genotype data now enables GWAS using own performance records to detect both additive and non-additive QTL. ResultsSequence-variant genotypes were imputed for 57,863 cows from the Holstein, Brown Swiss, Original Braunvieh, and Simmental cattle populations that had own performance records for stature and three mammary gland morphology traits (fore udder position, central ligament, front teat position). Genomic heritability ranged from 0.25 to 0.33 for fore udder position, 0.27 to 0.43 for udder central ligament, 0.49 to 0.59 for front teat position and 0.61 to 0.73 for stature. Additive genetic effects explained most of the SNP-based heritability for all traits and breeds. Within-breed genome-wide association studies identified 118 additive and 29 non-additive QTL for the four traits. Non-additive associations were only detected for stature. Although the majority of lead variants were in non-coding regions, we prioritized four missense variants in HMGA2 (rs385670251), ZBTB20 (rs470925681), ARSI (rs447362502) and CRAMP1 (rs445465383) as plausible causal variants for four stature QTL. Meta-analysis of the additive GWAS identified 63 mammary gland morphology and 43 stature QTL. A Holstein-specific mammary gland morphology QTL (Chr1:2748715, p=7.59e-35) colocalized with the POLLED locus on chromosome 1. Fine-mapping of this region revealed undesired effects of the Friesian POLLED haplotype on mammary gland morphology traits. ConclusionDirect phenotypes for a large cohort of genotyped cows provide high statistical power for additive and non-additive association testing. Sequence-based association studies revealed QTL and candidate causal variants for stature and mammary gland morphology traits. Pleiotropic effects of the Friesian POLLED haplotype highlight the need for careful monitoring of potential unintended consequences when selecting for polledness in cattle.

genetics↗

bioRxiv2025

Translation Inhibition by Rocaglamide A Enhances Susceptibility of Yeasts to Caspofungin

Fks1 catalyzes the synthesis of {beta}-1,3-glucans, a major structural component of the fungal cell wall, and is the primary target of the antifungal drug caspofungin. Mutations in Fks1 confer caspofungin resistance by disrupting its interaction with the drug, thereby reducing inhibition of Fks1 enzymatic activity. Previous studies demonstrated that translation of the FKS1 mRNA was highly dependent on the translation initiation helicases eIF4A and Ded1 (1). Therefore, we investigated whether treatment of Saccharomyces cerevisiae cells with the eIF4A inhibitor Rocaglamide A (RocA) or mutation of Ded1 affects translation of FKS1 and susceptibility to caspofungin. Using WT and temperature-sensitive ded1-ts strains, we demonstrated that RocA enhanced caspofungin-mediated growth inhibition and translation repression. Sensitivity to both drugs was further enhanced in ded1-ts strains, suggesting specifically targeting Ded1 in fungi could be an effective mechanism to prevent caspofungin resistance. We extended the analysis to Candida glabrata, a related fungal pathogen, and found similar results. Importantly, combining RocA with caspofungin was fungicidal in both species, suggesting the combination could decrease development of caspofungin resistance in pathogenic yeasts. Together these findings highlight the potential of targeting translation initiation helicases for effective combination antifungal treatments.

molecular biology↗

bioRxiv2025

Genetic analysis of iris pigmentation in Swiss pig breeds identifies a missense KITLG variant as a potential causal factor for pale and heterochromatic irises

BackgroundIris pigmentation is a heritable trait with a complex genetic architecture. While the genetic basis of iris pigmentation has been extensively studied in humans, little is known about iris pigmentation in pigs. Iris pigmentation in pigs varies from different shades of brown or pale irises to heterochromia manifesting either as different colors between both irises (heterochromia iridum) or multiple colors within a single iris (heterochromia iridis). This study investigates the genetics of iris pigmentation variability in the Swiss Landrace and Swiss Large White pig breeds. ResultsIris pigmentation was phenotyped in 837 Swiss Landrace and 328 Swiss Large White pigs of which the majority also had array-derived genotypes. A high prevalence of heterochromia iridum (18.6%) was observed in the Swiss Landrace breed. Heritability estimates for iris pigmentation were high in both breeds (h{superscript 2} = 56.0-57.2%). Iris pigmentation was not genetically correlated with production traits. Genome-wide association analysis identified several loci associated with iris pigmentation, including regions near functional candidate genes such as TYR, ALX4 and DCT. The strongest association was detected near the KITLG gene, which was identified as a candidate gene for iris pigmentation in a previous study on Italian Large White pigs. Fine-mapping identified a highly significantly associated (P=3.8x10-11) missense variant in KITLG (5_94084790_G>A, rs342599807, p.R124K) as a potential causal variant for pale and heterochromatic iris pigmentation in Swiss pigs. ConclusionsOur findings provide new insights into the genetic architecture of iris pigmentation in pigs and indicate that KITLG plays a key role. The identification of a putative causal missense variant offers a foundation for further functional studies aiming to better understand pigmentation traits in pigs.

genomics↗

bioRxiv2025

Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons

The end-stage pathology of Parkinsons disease (PD) involves the loss of dopamine-producing neurons in the substantia nigra pars compacta (SNc). However, synaptic deregulation of these neurons begins much earlier. Understanding the mechanisms behind synaptic deficits is crucial for early therapeutic intervention, yet these remain largely unknown. In the SNc, different dopamine neuron subtypes show varying susceptibility patterns to PD, complicating our understanding. This study uses intersectional genetic mouse models to uncover synaptic perturbations in vulnerable dopamine neurons, focusing on the LRRK2 kinase, a protein closely linked to PD. Through a combination of immunofluorescence and advanced proximity labeling methods, we found higher LRRK2 expression in the most vulnerable dopamine neuron subclusters. High-resolution imaging revealed that pathogenic LRRK2 disrupts release sites in vulnerable dopamine axons, leading to decreased in vivo spontaneous and evoked striatal dopamine release in mice with LRRK2 mutations. Proteomic and biochemical analyses indicate that mutant LRRK2 increases the phosphorylation of RAB3 proteins, reducing their interactions with RIM1and RIM2 effector proteins and impacting their synaptic functions. Overall, this research highlights the cell-autonomous dysfunctions caused by mutant LRRK2 in neurons, which are primarily affected by the disease. It also provides a framework for future therapeutic strategies for early nigrostriatal synaptic deficits in PD.

neuroscience↗

bioRxiv2025

An Eco-Evolutionary Framework to Predict Long-term Strain Diversity and Turnover in Infectious Diseases

Pathogen strain diversity varies widely across diseases, yet the processes that govern its emergence, maintenance, and turnover remain unclear. We present MultiSEED, a fast numerical framework that captures strain dynamics across ecological and evolutionary timescales. Unlike previous models, MultiSEED distinguishes between transient and established strains, allowing classification of diseases into regimes of extinction, replacement, or coexistence. When applied to influenza A, HIV-1, pneumococcus, and malaria, the model reproduces observed strain diversity and turnover while revealing the key drivers of these differences. We show that susceptible host replenishment is central to long-term strain persistence, host population size and R0 shape overall diversity, and innovation rates strongly influence dynamic regimes, with their combined interactions ultimately determining pathogen strain diversity and turnover. This unifying framework can be readily applied across systems, enabling the rapid prediction of pathogen responses to environmental and demographic changes and guiding strategies for disease control.

evolutionary biology↗

bioRxiv2025

Development of high-affinity, single-domain protein binders for neutralizing household allergens

Feline, canine, and human dust mite allergens drive significant IgE-mediated allergies in the household environment. Here, we describe the discovery and characterization of novel protein binders, termed AVA, which efficiently bind and disrupt major allergens from cats (Fel d 1), dogs (Can f 1, Can f 2), and dust mites (Der p 1, Der p 2). Leveraging camelid single-domain variable-heavy chain (VHH) antibodies, we identified and optimized VHH sequences with robust affinity towards the individual allergens. AVA disrupted critical allergen substructures (Fel d 1) and catalytic functions (Der p 1) in molecular dynamics simulations and in in vitro assays, respectively. Paired with robust thermostability and non-toxic in vitro viability profiles, AVA represents a promising approach for downstream household allergen mitigation.

bioengineering↗

bioRxiv2025

Measure Sodium Transport in Cells with NMR

Sodium ions (Na+) are fundamental to numerous physiological functions, such as maintaining electrolyte balance, enabling nerve impulse transmission, and facilitating muscle contraction. Dysregulation of Na+ transport across cell membranes is implicated in a range of health issues, including metabolic syndromes, neurological conditions, and cardiovascular diseases. However, current methods for assessing cellular Na+ activity often face limitations; they can be invasive or fail to capture dynamic changes. In this study, we introduce a non-invasive 23Na nuclear magnetic resonance (NMR) methodology designed to directly quantify the transport rate of sodium ions in living cells. Our technique integrates relaxation exchange spectroscopy (REXSY) with a multi-site exchange model, enabling the investigation of Na+ transport dynamics on a timescale of sub-seconds. A key advantage is its ability to differentiate between intracellular and extracellular Na+ pools based on the endogenous NMR relaxation difference, thereby avoiding the need for potentially disruptive exogenous reagents. Experiments conducted on human cell lines successfully demonstrated the techniques capacity to distinguish between various physiological states, such as when ion channels are pharmacologically blocked or activated. The resulting measurements of Na+ transport rates and intracellular Na+ fractions show a clear correlation with cellular metabolic activity, offering valuable quantitative markers for monitoring transmembrane ion dynamics in vitro.

cell biology↗

bioRxiv2025

Spatial and spectral mapping of traffic-related air pollution (TRAP) nanoparticles in relation to plaques and inflammatory markers in an Alzheimer disease model

Chronic exposure to traffic-related air pollution (TRAP) is linked to increased risk of neurodegenerative diseases, including Alzheimer disease (AD). Ultrafine particulate matter (UFPM) is a suspected driver of TRAP neurotoxicity, but its spatial interactions with AD pathology remain poorly defined. We investigated the distribution, composition, and pathological context of TRAP-derived UFPM in the hippocampus of TgF344-AD rats chronically exposed to TRAP or filtered air (FA) for 14 months. Using a multimodal imaging workflow that combines enhanced darkfield hyperspectral imaging (EDF-HSI) with confocal immunofluorescence for microglia (CD68/Iba1) and amyloid beta (A{beta}) plaques (Thioflavin S), we mapped the localization and spectral properties of UFPM in situ. UFPM accumulation was elevated in TRAP-exposed females, suggesting sex-specific vulnerability in blood-brain barrier (BBB) permeability or particle retention. Particles near plaques showed red-shifted spectral signatures, consistent with biochemical transformation. Dimension reduction revealed clustering of particle spectra by TRAP exposure and plaque proximity. However, UFPM was rarely found within plaques or microglia, implying indirect neuroimmune modulation. These findings highlight a novel spatial and spectral imaging approach for characterizing environmental nanoparticle interactions in the brain and suggest that chronic TRAP exposure may influence AD-related inflammation and pathology in a sex-and region-dependent manner. SynopsisThis study shows that chronic traffic-related air pollution alters ultrafine particulate matter deposition and neuroinflammation in a rodent Alzheimer model, revealing region- and sex-specific vulnerability in the brains response to environmental exposure.

pharmacology and toxicology↗

bioRxiv2025

Evolutionary trade-offs between functional and immune selection shape multigene families in pathogens

Major surface antigens in many pathogens are encoded by rapidly diversifying multigene families, generating fitness variation through antigenic and functional differences. These variations align with the niche and absolute fitness axes of Modern Coexistence Theory (MCT). Yet, how such gene families evolve along these axes under competition for hosts and across transmission gradients remains poorly understood, as prior MCT studies have not explicitly accounted for evolutionary dynamics in high dimensions. We use a stochastic computational model of Plasmodium falciparum transmission to examine how transmission intensity and selection shape var multigene family evolution and composition within parasite genomes. Results show that selection alone cannot maintain the observed stable ratio of two gene groups within parasite genomes, indicating that group-based classifications do not clearly reflect transmission strategy or virulence. When a trade-off exists between diversification rates and absolute fitness, strong immune selection under high transmission favors fast-recombining genes while attenuating functional selection on R0-associated traits. In general, stronger immune selection increases the invasion probability of novel antigens and the niche differentiation among parasite genomes, while reducing the variance in gene-level transmissibility and expression duration, and therefore R0. This outcome, combining enhanced niche differentiation and reduced absolute fitness variation, departs from MCT predictions.

evolutionary biology↗

bioRxiv2025

Agropyron cristatum genome provides a new insight for wheat improvement with wild relatives

Exploring novel genetic variation for target traits is crucial for advancing wheat breeding and genetic improvement. Since 1990, we have been transferring genes from Agropyron cristatum, a promising wild relative genetic resource featuring robust spike morphology and stress tolerance, into common wheat by distant hybridization. To efficiently harness A. cristatum genes, we de novo assembled a 25.62-Gb high-quality genome of an autotetraploid accession Z559 with 28 chromosomes, and uncovered its specific genome features and an extensive repertoire of genes associated with yield and resistance to abiotic and biotic stresses. We systematically characterized A. cristatum genome introgressions by resequencing 431 wheat-A. cristatum derivatives and cloned the gene AcGNS1, which functions in the regulation of grain number per spike in wheat. Subsequently, we developed an optimized genome-selection model for wheat-A. cristatum breeding derivatives, enabling the rapid selection of new potential varieties. These findings demonstrate a genomic breeding strategy for leveraging novel genetic resources of wild relatives and advancing wheat improvement.

genomics↗

bioRxiv2025

Evolutionary Genomics Guides Scalable Coral Probiotics for Climate Resilience

A universal bottleneck limiting probiotic efficacy in medicine, aquaculture, agriculture, and wildlife conservation is uncertain long-term colonization, necessitating repeated administration. We present an evolution-guided framework for probiotic identification based on genomic hallmarks of emerging host dependency, including widespread pseudogenization and insertion sequence proliferation driving genomic restructuring. Applied to coral reefs, we screened over 1,200 coral-associated bacterial isolates and identified Ruegeria MC10 as exhibiting these signatures. Its presence was associated with increased thermal tolerance of a model cnidarian. Following nursery application, MC10 persisted in reef corals for an 8-month monitoring period through a natural bleaching event, improving color retention and retaining algal photosynthesis performance. This work establishes a predictive, scalable pipeline for selecting persistent probiotics, directly addressing a central constraint on microbiome-based interventions across host systems.

microbiology↗