Biology subjects

Zheng, W.

Publications and source records attributed to Zheng, W..

At least 109 records · Page 6Linked to original sources

bioRxiv2024

Structural and Functional Relevance of Charge Based Transient Interactions inside Intrinsically Disordered Proteins

Intrinsically disordered proteins (IDPs) perform a wide range of biological functions without adopting stable, well-defined, three-dimensional structures. Instead, IDPs exist as dynamic ensembles of flexible conformations, traditionally thought to be governed by weak, nonspecific interactions, which are well described by homopolymer theory. However, recent research highlights the presence of transient, specific interactions in several IDPs, suggesting that factors beyond overall size influence their conformational behavior. In this study, we investigate how the spatial arrangement of charged amino acids within IDP sequences shapes the prevalence of transient, specific interactions. Through a series of model peptides, we establish a quantitative empirical relationship between the fraction of transient interactions and a novel sequence metric, termed effective charged patch length, which characterizes the ability of charged patches to drive these interactions. By examining IDP ensembles with varying levels of transient interactions, we further explore their heteropolymeric structural behavior in phase-separated condensates, where we observe the formation of a condensate-spanning network structure. Additionally, we perform a proteome-wide scan for charge-based transient interactions within disordered regions of the human proteome, revealing that approximately 10% of these regions exhibit such charge-driven transient interactions, leading to heteropolymeric behaviors in their conformational ensembles. Finally, we examine how these charge-based transient interactions correlate with molecular functions, identifying specific biological roles in which these interactions are enriched.

biophysics↗

bioRxiv2024

Impact of carbamate and pyrethroid pesticides on bile acid profiles in an in vitro gut microbiota model

The impact on the microbial community following exposure to commonly used pesticides has recently gained increasing interest. In this study, effects of selected carbamates (carbofuran, aldicarb) and pyrethroids (cypermethrin and cyhalothrin) on gut microbiota and related bile acid metabolism were quantified using a 24 h in vitro fermentation model system with mice feces. The results obtained reveal a pesticide induced significant increase the ratio of secondary over primary bile acids, particularly resulting from the enrichment of {beta}-muricholate ({beta}MCA) accompanied by the depletion of {omega}-muricholate ({omega}MCA). Besides, the bacterial profile showed significantly increased richness of Eggerthellaceae after 24 h exposure to carbofuran and cyhalothrin, and the genera Enterorhabdus belonging to Eggerthellaceae was found to be highly correlated to the fecal bile acid profile. In conclusion, in an in vitro gut microbial model carbamates and pyrethroids caused alterations of the gut microbial community resulting in the modulation of bile acid transformation. This illustrates that the gut microbiota and its metabolism may be a novel target to consider in future pesticide safety evaluations.

microbiology↗

bioRxiv2024

GABAergic neuron dysregulation in a human neurodevelopmental model for major psychiatric disorders

"GABA dysfunction" is a major hypothesis for the biological basis of schizophrenia with indirect supporting evidence from human post-mortem brain and genetic studies. Patient-derived induced pluripotent stem cells (iPSCs) have emerged as a valuable platform for modeling psychiatric disorders, and previous modeling has revealed glutamatergic synapse deficits. Whether GABAergic synapse properties are affected in patient-derived human neurons and how this impacts neuronal network activity remain poorly understood. Here we optimized a protocol to differentiate iPSCs into highly enriched ganglionic eminence-like neural progenitors and GABAergic neurons. Using a collection of iPSCs derived from patients of psychiatric disorders carrying a Disrupted-in-Schizophrenia 1 (DISC1) mutation and their unaffected family member, together with respective isogenic lines, we identified mutation-dependent deficits in GABAergic synapse formation and function, a phenotype similar to that of mutant glutamatergic neurons. However, mutant glutamatergic and GABAergic neurons contribute differentially to neuronal network excitability and synchrony deficits. Finally, we showed that GABAergic synaptic transmission is also defective in neurons derived from several idiopathic schizophrenia patient iPSCs. Transcriptome analysis further showed some shared gene expression dysregulation, which is more prominent in DISC1 mutant neurons. Together, our study supports a functional GABAergic synaptic deficit in major psychiatric disorders.

neuroscience↗

bioRxiv2024

Effects of lambda-cyhalothrin on gut microbiota and related bile acid metabolism in mice

BackgroundSince the gut microbiota plays a crucial role in host metabolism and homeostasis, its alterations induced by xenobiotics, such as pesticides, could pose a risk to host health. Our previous in vitro fermentation study showed that pyrethroid pesticides could affect the mouse bacterial community and related bile acid profiles. Hence in the present study, the effects of the selected pyrethroid lambda-cyhalothrin on the intestinal microbial community and its related bile acid metabolism were evaluated in male and female mice. ResultsThe total amount of bile acids in plasma and fecal samples from lambda-cyhalothrin treated mice markedly increased compared to controls, which could be mainly ascribed to the significantly raised proportions of taurine conjugated bile acids in plasma, and the increase in fecal secondary bile acids. In gut microbial profiles, a significantly increased richness of Prevotellacea and a depletion of Lachnospiraceae were found at the family level upon the treatment with lambda-cyhalothrin. ConclusionTreatment of mice with lambda-cyhalothrin affected the gut microbiota with accompanying changes in bile acid homeostasis. The effects on fecal bile acid profiles were in line with those previously observed in our in vitro study and corroborate that pyrethroid pesticides could affect gut microbiota and related bile acid profiles.

microbiology↗

bioRxiv2024

Gut Commensal Bacteria-Derived Methionine is Required for Host Reproduction by Modulating RNA m6A Methylation of the Insulin Receptor

Gut commensal bacteria promote host reproduction by modulating metabolism and nutrition, yet the molecular mechanisms by which microbes modulate reproduction remain unclear. Here, we show that gut commensal bacteria promote host reproduction by providing amino-acid methionine, which controls the RNA m6A modification level of insulin receptor (InR) in the ovary of the invasive insect Bactrocera dorsalis. RNA m6A levels and S-adenosyl-methionine (SAM) titers in the ovaries were sharply reduced in antibiotic treated B. dorsalis compared with untreated insects, resulting in arrested ovarian development and decreased fecundity. The intestinal commensal bacteria Enterobacter hormaechei or the E. hormaechei-derived metabolite methionine restored the decreased RNA m6A level and the reproductive defects. Notably, knockdown of METTL3 and METTL14, two genes encoding the RNA m6A methyltransferases, led to a decrease in the mRNA level of InR and underdevelopment of ovaries in B. dorsalis, and blocked the promoting effect of methionine on ovarian development and fecundity. Collectively, our study identifies an unrecognized role of RNA m6A methylation modification that underlies microbial control of host reproduction. Our findings further expand the functional landscape of m6A modification to include nutrient-dependent control of ovarian development and highlight the essential role of epigenetic regulation in microbe-host interactions.

microbiology↗

bioRxiv2024

Endocytic dynamin deficiency impairs the host colonization of phytopathogenic fungi

During host-pathogen interactions, fungal pathogens exploit the endolysosomal trafficking network to fine-tune their responses to host and environmental stimuli, thereby facilitating disease progression. However, the molecular mechanisms underlying the fungal-specific functions of the endolysosomal network require further investigation. Here, we systematically characterized the endolysosomal network in Fusarium graminearum using the dynamin-like GTPase FgVps1 as an entry point. Functional analysis revealed that FgVps1 is essential for the release of retromer- and sorting nexin-associated vesicles from endosomes, thereby facilitating the trafficking of v-SNARE protein FgSnc1 and promoting fungal development and pathogenicity. Building on this, we further discovered that the retromer core subunit FgVps35 interacts with sorting nexin FgSnx4 and identified the corresponding interaction interface, which involves residues FgVps35N383 and FgSnx4E373. In addition, the ESCRT-II component FgVps36 bridges ESCRT-I and -III and interacts with both FgVps35 and FgSnx4, thereby preventing their mislocalization to the vacuole and maintaining endolysosomal trafficking. Notably, we demonstrated that inhibition of FgVps1 function, either by blocking its GTPase activity or by disrupting actin polymerization, effectively impaired endosomal trafficking and attenuates fungal pathogenicity. Altogether, our results uncover key mechanisms underlying the function of fungal endolysosomal network and providing a promising broad-spectrum strategy for controlling phytopathogenic fungi.

microbiology↗

bioRxiv2024

Recycling of trans-Golgi SNAREs is essential for apoplastic effector secretion and effective pathogenicity of Magnaporthe oryzae

Vesicle transport is an essential process that mediates the growth, development and virulence of pathogenic fungi. However, the intricate mechanisms underlying how vesicle transport regulates the secretion of effector proteins remain to be fully elucidated. Here, we unveiled a novel pathway in which retromer and trans-Golgi (TGN) SNARE proteins co-regulate the proper secretion of apoplastic effectors in the rice blast fungus Magnaporthe oryzae. A TGN-associated SNARE complex consisting of MoSnc1, MoTlg1, MoTlg2, and MoVti1 was found to be essential for growth, development and pathogenicity in the fungus. Moreover, the TGN-associated SNARE complex is indispensable for accurate secretion of apoplastic effectors. Furthermore, we have elucidated that the dynamin-like protein MoVps1, an upstream regulator of the retromer complex, regulates the fission of MoVps35-coated vesicle and the proper localization of the TGN-associated SNARE complex. Additionally, we employed prochlorperazine, which identified as a potent dynamin inhibitor, elicits a developmental response in M. oryzae akin to MoVPS1 disruption, highlighting the pivotal regulatory role of dynamin and its potential as a therapeutic target for rice blast disease management. In conclusion, the study uncovered a specific mechanism by which MoVps1 and the retromer complex regulate the positioning of TGN-associated SNARE proteins to effectively promote effector secretion. It provides a deeper understanding of the molecular mechanisms of effector secretion in fungi and underscores the importance of vesicle transport in fungal pathogenesis. ImportanceVesicle transport is essential for pathogenic fungi as it controls the secretion of effectors that modulate interactions with the host and infection processes. The detailed mechanisms of effector secretion via vesicular pathways in these fungi are not yet fully understood. In this study, we have discovered a new regulatory pathway involving the retromer complex and trans-Golgi SNARE proteins that is critical for the proper secretion of apoplast effectors in M. oryzae. We have identified an important TGN-associated SNARE complex, consisting of MoSnc1, MoTlg1, MoTlg2 and MoVti1, which is required for the development and pathogenicity of M. oryzae. Our results emphasize the importance of this SNARE complex for the precise secretion of effectors into the apoplast, a key step in pathogenesis. Additionally, we demonstrated that the dynamin-like protein MoVps1, a protein acting upstream of the retromer complex, is vital for the correct localization of the TGN-associated SNARE complex. Furthermore, our research underscores the critical regulatory role of dynamin in M. oryzae pathogenesis, with prochlorperazine serving as an inhibitor that mimics the phenotypic effects of MoVps1 disruption, thereby highlighting its potential as a biopesticide candidate for rice blast disease management. Our study has uncovered a specific regulatory mechanism in which MoVps1 and the retromer complex control the positioning and function of TGN-associated SNARE proteins, thereby facilitating effector secretion. This work not only advances our understanding of the molecular basis of effector secretion in fungi, but also has implications for the development of novel strategies to control fungal diseases.

microbiology↗

bioRxiv2024

A simple in vitro fermentation model to detect alterations in gut microbiota-dependent bile acid profiles

A previous in vivo study showed that lincosamide antibiotics (lincomycin and clindamycin) could induce changes in the gut bacterial community, leading to significant changes in fecal bile acid profiles. Herein, our aim is to develop an animal alternative in vitro model for studying gut microbiota-dependent bile acid profiles induced by xenobiotics. The effects of lincosamides were evaluated using this model, and results obtained were verified by comparing with those of the previous in vivo study. Fecal sample processing and bile acid incubation conditions were developed and optimized using feces collected from Wistar rats, and prepared samples were incubated for 24 h with or without lincosamides. Upon treatment of the fecal gut microbiota with lincosamides primary and secondary bile acids showed obviously increased and decreased levels respectively. Moreover, the changes in bile acid profile could be linked to a reduced richness of family Erysipelotrichaceae, Bacteroidacea and Lactobacillaceae or Prevotellaceae. The consistent consequences of in vivo and in vitro provides a proof of principle for further application on elucidating effects of other xenobiotics on the gut bacterial community and related bile acid metabolism, thereby contributing to the 3Rs (replacement, reduction and refinement) in animal testing.

biochemistry↗

bioRxiv2024

Transient Non-local Interactions Dominate the Dynamics of Measles Virus NTAIL

The RNA genome of measles virus is encapsidated by the nucleoprotein within a helical nucleocapsid that serves as template for both transcription and replication. The intrinsically disordered domain of the nucleoprotein (NTAIL), partly protruding outward from the nucleocapsid, is essential for binding the polymerase complex responsible for viral transcription and replication. As for many IDPs, binding of NTAIL occurs through a short molecular recognition element (MoRE) that folds upon binding, with the majority of NTAIL remaining disordered. Though NTAIL regions far from the MoRE influence the binding affinity, interactions between them and the MoRE have not been investigated in depth. Using an integrated approach, relying on photo-induced electron transfer (PET) experiments between tryptophan and cysteine pairs placed at different positions in the protein under varying salt and pH conditions, combined with simulations and analytical models, we identified transient interactions between two disordered regions distant in sequence, which dominate NTAIL dynamics, and regulate the conformational preferences of both the MoRE and the entire NTAIL domain. Co-evolutionary analysis corroborates our findings and suggests an important functional role for the same intramolecular interactions. We propose mechanisms by which these non-local interactions may regulate binding to the measles phosphoprotein, polymerase recruitment, and ultimately viral transcription and replication. Our findings may be extended to other IDPs, where non-local intra-protein interactions affect the conformational preferences of intermolecular binding sites.

biophysics↗

bioRxiv2024

The penetration ring is a novel infection structure formed by the penetration peg for invading plant cell membrane in rice blast fungus

Many fungal pathogens develop specialized infection structures such as appressoria to penetrate plant cells. However, it is not clear whether special structures are formed after cell wall penetration before invading host plasma membrane in hemibiotrophic pathogens. Here, we showed that a penetration ring consisting of Ppe1 secreted proteins is formed after appressorium-mediated cell wall penetration and remained at the base of penetration site after invading plant plasma membrane by the rice blast fungus Magnaporthe oryzae. The same persistent Ppe1 ring is formed after the penetration of neighboring cells by transpressoria. PPE1 is specifically expressed during plant infection and the {Delta}ppe1 mutant is defective in penetration and invasive growth. Blockage of penetration peg formation impedes the development of the Ppe1 ring. Close examinations showed that the penetration ring is formed at the collar of penetration pegs between the plant cell wall and plasma membrane and it is persistent as a fixed ring even after invasive hyphae invaded neighboring cells. Furthermore, Ppe1 is a member of an expanded family of secreted proteins that are unique to fungal pathogens using extreme appressorium turgor for plant penetration. Other members of the Ppe1 family also localize to the penetration ring for anchoring on plasma membrane during plant infection. Taken together, a penetration ring consisting of a family of secreted proteins is formed between plant cell wall and plasma membrane, which may function as a novel physical structure at the interface between the tip of penetration pegs and plant plasma membrane before the differentiation of invasive hyphae. Significance StatementLike many other plant pathogens, the rice blast fungus forms melanized appressoria (specialized infection structures) to penetrate plant cells. In this study, we showed that a penetration ring is formed by penetration pegs after appressorium-mediated penetration of plant cell wall. This ring of secreted proteins is persistent at the point of penetration pegs invading plant plasma membrane to form invasive hyphae. Therefore, after the penetration of plant cell wall, the rice blast fungus forms a penetration ring that consists of a family of secreted proteins unique to pathogens using extreme appressorium turgor for penetration and may function as a physical structure for anchoring onto plant plasma membrane and developing invasive hyphae in penetrated cells.

pathology↗

bioRxiv2024

Visualizing the translation landscape in human cells at high resolution

Obtaining comprehensive structural descriptions of macromolecules within their natural cellular context holds immense potential for understanding fundamental biology and improving health. Here, we present the landscape of protein synthesis inside human cells in unprecedented detail obtained using an approach which combines automated cryo-focused ion beam (FIB) milling and in situ single-particle cryo-electron microscopy (cryo-EM). With this in situ cryo-EM approach we resolved a 2.19 [A] consensus structure of the human 80S ribosome and unveiled its 21 distinct functional states, nearly all higher than 3 [A] resolution. In contrast to in vitro studies, we identified protein factors, including SERBP1, EDF1 and NAC/3, not enriched on purified ribosomes. Most strikingly, we observed that SERBP1 binds to the ribosome in almost all translating and non-translating states to bridge the 60S and 40S ribosomal subunits. These newly observed binding sites suggest that SERBP1 may serve an important regulatory role in translation. We also uncovered a detailed interface between adjacent translating ribosomes which can form the helical polysome structure. Finally, we resolved high-resolution structures from cells treated with homoharringtonine and cycloheximide, and identified numerous polyamines bound to the ribosome, including a spermidine that interacts with cycloheximide bound at the E site of the ribosome, underscoring the importance of high-resolution in situ studies in the complex native environment. Collectively, our work represents a significant advancement in detailed structural studies within cellular contexts.

molecular biology↗

bioRxiv2024

Epigenetic delineation of the earliest cardiac lineage segregation by single-cell multi-omics

The mammalian heart is formed from multiple mesoderm-derived cell lineages. However, it remains largely unknown when and how the specification of mesoderm towards cardiac lineages is determined. Here, we systematically depict the transcriptional trajectories toward cardiomyocyte in early mouse embryo, and characterize the epigenetic landscapes underlying the early mesodermal lineage specification by single-cell multi-omics analyses. The analyses also reveal distinct core regulatory networks (CRN) in controlling specification of mesodermal lineages. We further demonstrate the essential role HAND1 and FOXF1 in driving the earliest cardiac progenitors specification. These key transcription factors occupy at distinct enhancers, but function synergistically and hierarchically to regulate the expression of cardiac-specific genes. In addition, HAND1 is required for exiting from the nascent mesoderm program, while FOXF1 is essential for driving cardiac differentiation during juxta-cardiac field (JCF) specification. Our findings establish transcriptional and epigenetic determinants specifying the early cardiac lineage, providing insights for the investigation of congenital heart defects.

molecular biology↗

bioRxiv2024

Channel width modulates the permeability of DNA origami based nuclear pore mimics

Nucleoporins (nups) in the central channel of nuclear pore complexes (NPCs) form a selective barrier that suppresses the diffusion of most macromolecules while enabling rapid transport of nuclear transport receptors (NTRs) with bound cargos. The complex molecular interactions between nups and NTRs have been thought to underlie the gatekeeping function of the NPC. Recent studies have shown considerable variation in NPC diameter but how altering NPC diameter might impact the selective barrier properties remains unclear. Here, we build DNA nanopores with programmable diameters and nup arrangement to mimic NPCs of different diameters. We use hepatitis B virus (HBV) capsids as a model for large-size cargos. We find that Nup62 proteins form a dynamic cross-channel meshwork impermeable to HBV capsids when grafted on the interior of 60-nm wide nanopores but not in 79-nm pores, where Nup62 cluster locally. Furthermore, importin-{beta}1 substantially changes the dynamics of Nup62 assemblies and facilitates the passage of HBV capsids through NPC mimics containing Nup62 and Nup153. Our study shows the transport channel width is critical to the permeability of nup barriers and underscores the role of NTRs in dynamically remodeling nup assemblies and mediating the nuclear entry of viruses.

biophysics↗

bioRxiv2024

Fast, Accurate, and Versatile Data Analysis Platform for the Quantification of Molecular Spatiotemporal Signals

Optical recording of intricate molecular dynamics is becoming an indispensable technique for biological studies, accelerated by the development of new or improved biosensors and microscopy technology. This creates major computational challenges to extract and quantify biologically meaningful spatiotemporal patterns embedded within complex and rich data sources, many of which cannot be captured with existing methods. Here, we introduce Activity Quantification and Analysis (AQuA2), a fast, accurate, and versatile data analysis platform built upon advanced machine learning techniques. It decomposes complex live imaging-based datasets into elementary signaling events, allowing accurate and unbiased quantification of molecular activities and identification of consensus functional units. We demonstrate applications across a wide range of biosensors, cell types, organs, animal models, and imaging modalities. As exemplar findings, we show how AQuA2 identified drug-dependent interactions between neurons and astroglia, and distinct sensorimotor signal propagation patterns in the mouse spinal cord.

neuroscience↗

bioRxiv2024

How Mycobacterium tuberculosis builds a home: Single-cell analysis reveals M. tuberculosis ESX-1-mediated accumulation of anti-inflammatory macrophages in infected mouse lungs.

Mycobacterium tuberculosis (MTB) infects and replicates in lung mononuclear phagocytes (MNPs) with astounding ability to evade elimination. ESX-1, a type VII secretion system, acts as a virulence determinant that contributes to MTBs ability to survive within MNPs, but its effect on MNP recruitment and/or differentiation remains unknown. Here, using single-cell RNA sequencing, we studied the role of ESX-1 in MNP heterogeneity and response in mice and murine bone marrow-derived macrophages (BMDM). We found that ESX-1 is required for MTB to recruit diverse MNP subsets with high MTB burden. Further, MTB induces an anti-inflammatory signature in MNPs and BMDM in an ESX-1 dependent manner. Similarly, spatial transcriptomics revealed an upregulation of anti-inflammatory signals in MTB lesions, where monocyte-derived macrophages concentrate near MTB-infected cells. Together, our findings suggest that MTB ESX-1 mediates the recruitment and differentiation of anti-inflammatory MNPs, which MTB can infect and manipulate for survival.

microbiology↗

bioRxiv2024

High-resolution In-situ Structures of Mammalian Mitochondrial Respiratory Supercomplexes in Reaction within Native Mitochondria

Mitochondria play a pivotal role in ATP energy production through oxidative phosphorylation, which occurs within the inner membrane via a series of respiratory complexes. Despite extensive in-vitro structural studies, revealing the atomic details of their molecular mechanisms in physiological states remains a major challenge, primarily because of the loss of the native environment during purification. Here, we directly image porcine mitochondria using an in-situ cryo-electron microscopy approach. This enables us to determine the structures of various high-order assemblies of respiratory supercomplexes in their native states, achieving up to 1.8-[A] local resolution. We identify four major supercomplex organizations: I1III2IV1, I1III2IV2, I2III2IV2, and I2III4IV2, which can potentially expand into higher-order arrays on the inner membranes. The formation of these diverse supercomplexes is largely contributed by protein-lipids-protein interactions, which in turn dramatically impact the local geometry of the surrounding membranes. Our in-situ structures also capture numerous reactive intermediates within these respiratory supercomplexes, shedding light on the dynamic processes of the ubiquinone/ubiquinol exchange mechanism in complex I and the Q-cycle in complex III. By comparing supercomplex structures from mitochondria treated under distinct conditions, we elucidate how conformational changes and ligand binding states interplay between complexes I and III in response to environmental redox alterations. Our approach, by preserving the native membrane environment, enables structural studies of mitochondrial respiratory supercomplexes in reaction at high resolution across multiple scales, spanning from atomic-level details to the broader subcellular context.

molecular biology↗

bioRxiv2024

Phase Separation and Aggregation of α-Synuclein Diverge at Different Salt Conditions

The coacervation and structural rearrangement of the protein alpha-synuclein (Syn) into cytotoxic oligomers and amyloid fibrils are considered pathological hallmarks of Parkinsons disease. While aggregation is recognized as the key element of amyloid diseases, liquid-liquid phase separation (LLPS) and its interplay with aggregation have gained increasing interest. Previous work showed that factors promoting or inhibiting amyloid formation have similar effects on phase separation. Here, we provide a detailed scanning of a wide range of parameters including protein, salt and crowding concentrations at multiple pH values, revealing different salt dependencies of aggregation and phase separation. The influence of salt on aggregation under crowded conditions follows a non-monotonic pattern, showing increased effects at medium salt concentrations. This behavior can be elucidated through a combination of electrostatic screening and salting-out effects on the intramolecular interactions between the N-terminal and C-terminal regions of Syn. By contrast, we find a monotonic salt dependence of phase separation due to the intermolecular interaction. Furthermore, we observe the time evolution of the two distinct assembly states, with macroscopic fibrillar-like bundles initially forming at medium salt concentration but subsequently converting into droplets after prolonged incubation. The droplet state is therefore capable of inhibiting aggregation or even dissolving the aggregates through a variety of heterotypic interactions, thus preventing Syn from its dynamically arrested state.

biophysics↗

bioRxiv2024

Super Pangenome of Grapevines Empowers Improvement of the Oldest Domesticated Fruit

Grapevine (Vitis) is the oldest domesticated fruit crop with great cultural and economic importance. Here, we assemble and annotate haplotype-resolved genomes of 72 Vitis accessions including 25 wild and 47 cultivated grapevines, and a haplotype-resolved complete genome of V. vinifera. Coalescent phylogenomics of 142 haplotype genomes disentangles the mysterious hybridization history of grapevines, revealing enormous genetic diversity among species. Pangenome analysis together with phenotyping data reveals that European cultivars, more susceptible to the most destructive disease downy mildew (DM), had a smaller repertoire of disease resistance genes of NLR family. Through extensive structural variation (SV) characterization, phenotyping, transcriptome profiling of 113 Vitis accessions, and SV-eQTL analysis, we have identified over 79 SVs and their relevant genes significantly associated with DM resistance, exemplified by a lysine histidine transporter, VvLHT8. This haplotype-resolved complete genome and pangenome of Vitis genus will accelerate grapevine breeding and enrich our understanding of the evolution and biology of grapevines.

plant biology↗