Biology subjects

Li, D.

Publications and source records attributed to Li, D..

At least 127 records · Page 7Linked to original sources

bioRxiv2025

Short Excitatory Projections Promote Burst Activity and Modular Functional Organization in Neural Networks

Physical constraints in the brain favor short, distance-dependent connections. How-ever, short-range projections are not merely a compromise imposed by these constraints; they also serve essential functional roles. Here, we explore networks with balanced excitation and inhibition, demonstrating that short excitatory projections fundamentally increase the number of common presynaptic inputs, thereby enhancing the correlations of neural responses. Strengthened recurrent correlations can lead to bursting states, amplifying postsynaptic neuronal activity and supporting signal propagation over long distances within the network. Moreover, even without an explicitly imposed modular structure, short excitatory connections can give rise to functional clustering and support a broad spectrum of modular functions. Therefore, this structural principle provides a mechanistic basis for functional column formation and dynamic burst propagation, suggesting that the brain transforms structural wiring constraints into opportunities for complex computation and distributed processing. These findings pave the way for a deeper understanding of how the brain transforms structural limitations into opportunities for complex computation.

neuroscience↗

bioRxiv2025

Multiscale Spatial Transcriptomic Atlas of Human Basal Ganglia Cell-Type and Cellular Community Organization

We generated a multi-region, subcellular-resolution spatial transcriptomic atlas of the human basal ganglia by integrating MERFISH+ and Stereo-seq across four neurotypical donors. These datasets profiled [~]7 million cells spanning the caudate, putamen, nucleus accumbens, and globus pallidus, resolving 60 transcriptionally distinct cell types. We show region-selective, molecular and spatial diversification of medium-spiny-neuron cell types and multiple non-neuronal populations with distinct molecular identities and spatial localizations. Subcellular RNA localization captures somatic size and projection-inferred signatures that reflect direct and indirect pathway topology. Cellular community analyses reveal the enrichment of sub-clusters of astrocytes and oligodendrocytes at striosome-matrix borders, while primate-expanded interneurons are confined to matrix territories. Cross-species mapping uncovers orthologous striosome-matrix organization and conserved dorsolateral-ventromedial gene expression gradients. This atlas provides a foundational molecular and spatial framework for studying human basal ganglia architecture, offering a multi-centimeter scale resource that links cell types, spatial architecture, and subcellular transcript topography across multiple nuclei. HighlightsO_LIOur multi-centimeter scale spatial taxonomy identifies the precise locations of 60 neuronal and glial cell types of human basal ganglia. C_LIO_LIMERFISH+ and Stereo-seq platforms map consistent spatial modules that align with classical neuroanatomical nuclei. C_LIO_LID1D2 hybrid MSNs and primate-expanded interneurons show regional and domain specific organization C_LIO_LISubcellular RNA localization reports soma morphology and projection-inferred signatures. C_LI

neuroscience↗

bioRxiv2025

Representation, Alignment, and Generation: A Comprehensive Survey of Foundation Models for Non-Invasive Brain Decoding

The ability to decode human thoughts, intentions, and perceptions directly from non-invasive brain recordings holds transformative potential for healthcare, communication, and human-computer interaction. However, translating the safety and scalability of methods like Functional Magnetic Resonance Imaging (fMRI), Electroencephalography (EEG), and Magnetoencephalography (MEG) into real-world utility has traditionally been hindered by low signal-to-noise ratios, limited spatial-temporal resolution, and the difficulty to collect large-scale high-quality data from an individual user. Recently, the emergence of Foundation Models (FMs)--large-scale, pre-trained architectures--has expanded the feasible operating region of non-invasive brain decoding under controlled protocols, primarily through representation learning, neuro-semantic alignment, and strong generative priors. However, evidence for robust cross-subject and real-world deployment remains uneven, as many results are still demonstrated on limited cohorts or highly controlled settings. This survey provides a comprehensive overview of how FMs are redefining the boundaries of non-invasive brain decoding. We propose a unified methodological framework that synthesizes recent advancements into a coherent process: extracting robust, transferable representations from noisy neural signals; aligning these signals with the rich semantic spaces of pre-trained vision and language models; and leveraging powerful conditional generative priors to reconstruct high-fidelity outputs. We systematically review state-of-the-art applications across three key domains: visual reconstruction, language and speech decoding, and auditory processing. Furthermore, we critically examine the persisting challenges of computational efficiency, cross-subject generalization, and privacy governance. By mapping the current landscape and identifying key gaps, this work outlines a strategic research agenda aimed at transitioning FM-driven neurotechnology from laboratory proofs-of-concept to reliable, real-world applications.

neuroscience↗

bioRxiv2025

Dorsomedial hypothalamus cold-sensitive neurons drive shivering thermogenesis

Hypothermia, a decline in core body temperature below 35{degrees}C in homeotherms, elicits rapid, asynchronous involuntary shivering thermogenesis; however, the hypothalamic neurons responsible for initiating this response remain uncharacterized. Here, retrograde transsynaptic tracing combined with RNA-seq identified a distinct population of VGLUT2-positive neurons enriched with Calbindin D28k (CALB1) within the dorsomedial hypothalamic nucleus (DMHCalb1/Vglut2). Convergent evidence from chemogenetic, optogenetic, fiber photometry calcium imaging, and electromyography (EMG) experiments demonstrated that these neurons selectively mediate hypothermia-triggered shivering thermogenesis. Bidirectional perturbation of DMHCalb1/Vglut2 activity modulated shivering intensity, while CALB1-negative VGLUT2-expressing DMH neurons were responsible for non-shivering thermogenesis (NST). Genetic ablation of afferent inputs from LSI/POA/VLPAG projecting to DMHCalb1/Vglut2, as well as ex vivo pharmacological synaptic blockade, failed to eliminate shivering responses during hypothermia, indicating that their activation is independent of canonical cold-responsive circuits. Hypothermia significantly suppressed transient A-type K (IA) currents, without affecting delayed rectifier K (IK) currents, accompanied by a pronounced reduction in the IA inactivation time constant relative to normothermic 36 {degrees}C. Collectively, hypothermia elevates DMHCalb1/Vglut2 excitability through IA-dependent reshaping of action potential dynamics. Shortened action potential repolarization and afterhyperpolarization duration cooperatively boost neuronal firing, constituting an intrinsic mechanism for DMHCalb1/Vglut2 neuron-driven shivering initiation.

neuroscience↗

bioRxiv2025

Cross-Species Cortical Geometry Reveals Conserved Gradients Across Primates and Human-Specific Expansion

The primate cerebral cortex, characterized by its complex structural geometry, underlies advanced cognitive functions and represents a defining feature distinguishing primates from other mammals. However, cross-species patterns of cortical geometry and the links between human cortical geometry and transcriptional architecture remain poorly understood. We developed a geometry-based cross-species cortical alignment framework to systematically investigate the similarities and differences in structural connectivity and cortical expansion characteristics among macaques, chimpanzees, and humans, and additionally explored the transcriptional underpinnings of human cortical geometry. Our analysis revealed conserved spatial patterns of cortical geometric features across species, providing the foundation for constructing a cross-species structural common space to support the alignment framework. We found that primary sensory, somatomotor, and face-selective regions exhibited high structural connectivity similarity across species, whereas prefrontal and parietal association cortices displayed significant divergence. We also identified disproportionate cortical expansion in the default mode network, with a consistent expansion trend across different evolutionary lineages in primates. Furthermore, neuroimage-transcription analysis indicated that cortical geometric features were correlated with transcriptional profiles enriched in neurodevelopmental and connectivity-related pathways. These results highlight a conserved yet hierarchically differentiated organization of the cerebral cortex in primates, providing new insights into the biological basis of human brain evolution.

neuroscience↗

bioRxiv2025

A Porcine Model of Intervertebral Disc Injury Recapitulates Human Discogenic Pain via Notochordal Cell Loss and Pain-inducing Nucleus Pulposus Cell Emergence

Lower back pain (LBP) is one of the most common causes of disability, with up to 40% of LBP cases attributed to intervertebral disc (IVD) degeneration. While small animal models are widely used to study IVD and LBP, the small size of their IVDs limits translational and biological relevance. Large animal models more accurately emulate human disease; however, methods of measuring LBP are not well established. Pigs were also considered unfit for LBP research, due to notochordal cells (NCs) persistence through life, unlike humans. We developed a comprehensive porcine model with quantitative measure of discogenic pain via biobehavioral testing (BBT), MRI, and multi-omics tissue analysis of IVD and DRGs. MRI demonstrated the progression of IVD degeneration beginning at 4 weeks post-injury. BBTs showed the development of significant pain responses by week 4 post-injury, supported by transcriptomics of injury matched DRGs. Single cell transcriptomics, trajectory and cell-cell communication analyses suggest that, with injury, NCs are differentiating to nucleus pulposus cells (NPCs). Furthermore, NPCs showed upregulation of cellular stress, neural outgrowth, and inflammation pathway, consistent with pain-inducing distress signals found in human samples. This study establishes novel MRI and BBT-based methods for quantifying LBP in pigs and supports its translational relevance to human discogenic LBP. The identification of LBP-associated clusters mirrors our previous finding in humans. Moreover, the shift of NC to NPC phenotype further supports that the porcine model is relevant to human pathology, as the injury induced accelerated aging and loss of NCs with IVD degeneration and discogenic pain.

developmental biology↗

bioRxiv2025

NanoporeDB: A Structural Resource Of Multimeric Protein Nanopores In Single-Molecule Sensing

Protein nanopores are essential molecular gateways in biology and have inspired transformative technologies in biosensing and single-molecule sequencing. While this technology has transformed genomics and biosensing, the discovery of novel nanopore scaffolds remains limited due to the scarcity of experimentally resolved pore structures. Here, we present NanoporeDB, an open-access structural resource comprising over 6,600 high-confidence multimeric models across four representative pore types. Candidate proteins were systematically mined from large-scale datasets, including the AlphaFold Protein Structure Database, UniRef90, and MGnify90, and assembled using AlphaFold-Multimer and AlphaFold3. We performed membrane embedding, pore axis annotation, and constriction profiling to enable functional interpretation. NanoporeDB features an interactive web interface with 3D visualization and quantitative metrics such as insertion depth, tilt angle, and pore geometry. This resource provides a structural foundation for advancing nanopore-based molecular sensing, precision diagnostics, and synthetic biology.

bioinformatics↗

bioRxiv2025

Stage-specific regulation of the Plasmodium falciparum proteasome activity reveals adaptive rewiring in artemisinin resistance

The ubiquitin-proteasome system (UPS) is essential for Plasmodium falciparum to maintain protein homeostasis, adapt to proteotoxic stress, and regulate parasite growth and stage transitions. The proteolytic 20S proteasome core is the central component of the UPS, where unfolded protein substrates are degraded into oligopeptides. Mechanisms regulating malaria parasite proteasome activity are poorly understood and have not been thoroughly studied. This knowledge gap is especially critical in the context of artemisinin (ART) resistance, where parasite survival depends on an enhanced stress response, including a greater reliance on the UPS. Here, we profiled proteasome activity and abundance across the parasite intraerythrocytic developmental cycle (IDC) in both ART-sensitive (ART-S) Dd2 and ART-resistant (ART-R) Dd2K13R539T parasites. We uncovered striking stage-specific regulation: proteasome activity was abundant in the ring stage, decreased in trophozoites, and then peaked in schizonts. Furthermore, ART-R Dd2K13R539T parasites exhibited higher ring-stage proteasome activity than ART-S Dd2, despite reduced proteasome abundance, suggesting a unique adaptive rewiring of proteasome function. To study proteasome regulation in the parasite, we manipulated proteasome abundance in Dd2 and Dd2K13R539T by creating a conditional knockdown of PfUMP1, a conserved proteasome maturation factor. PfUMP1 depletion disrupted 20S assembly, decreased proteasome activity, and led to parasite death. These experiments uncovered two key features of proteasome regulation in P. falciparum: (1) the absence of canonical transcriptional regulation of proteasome genes in response to downregulation of proteasome activity, and (2) ART-R parasites exhibit a ring-stage specific increased sensitivity to proteasome downregulation. Together, our findings reveal a previously unrecognized layer of proteasome regulation in malaria parasites and how, as part of their survival adaptations to decreased hemoglobin uptake associated with ART resistance, these parasites alter proteasome function to survive. This work reinforces the therapeutic potential of the proteasome as a stage- and resistance-specific antimalarial target.

microbiology↗

bioRxiv2025

Neural ensembles for music production recruit more language instruments as rhythmic complexity increases

Language and music, two core forms of human communication, both rely on rhythmic control. To date, the neural ensembles supporting their real-time production are not fully characterized. Using rapid phase-encoded fMRI, we mapped the spatiotemporal brain dynamics of overt language and music production under varying rhythm control demands. We observed overlapping hemodynamic traveling waves across domains, with auditory-motor regions activated earlier, followed by visual, posterior parietal, and Sylvian parietal-temporal (Spt) regions, supporting sensorimotor transformation and online monitoring of production. Increasing rhythmic complexity elicited slower and stronger activations in both domains: compared with baseline, regular rhythm control elicited delayed and amplified responses, while irregular rhythm control produced the slowest and strongest responses. During music production, rhythm-related activity expanded into frontal and temporal language regions, suggesting that higher rhythmic demands engage language resources. These findings reveal dynamic neural ensembles that can flexibly reconfigure shared resources to support temporal precision in sequence production.

neuroscience↗

bioRxiv2025

Multimodal AI Decodes Extreme Environment Functional Dark Matter Beyond Homology

Functional annotation of proteins from extreme environments represents a major bottleneck for bioresource discovery, as a vast reservoir of functional dark matter defies existing homology-based methods. We demonstrate that environmental pressures impart conserved physicochemical energy signatures that co-determine protein function with sequence and structure. Here we developed ACCESS, a multimodal graph neural network employing hierarchical contrastive learning with a tailored label-sample co-embedding to fuse energy, sequence, and structural information and overcome homology scarcity. ACCESS surpasses state-of-the-art methods including BLASTp and CLEAN in annotating low-identity enzymes. Applied to extreme environmental metagenomics, we constructed a function map of extremophile enzymes to expand the biocatalyst library, pinpointed functionally critical residues to guide rational design, and enabled large-scale, function-based macro-evolutionary analyses. This paradigm transcends the limitations of homology, illuminating protein dark matter and accelerating the exploration of the biospheres functional diversity for applications in biotechnology and therapeutic development.

bioinformatics↗

bioRxiv2025

PRC2 Restricts Malignant Peripheral Nerve Sheath Tumorigenesis in a Genetically Engineered Mouse Model of MPNST

Polycomb Repressive Complex 2 (PRC2), which normally regulates transcriptional silencing, chromatin compaction, and stem cell biology, has both oncogenic and tumor suppressor roles in cancer development depending on tumor type. Malignant peripheral nerve sheath tumor (MPNST), characterized by NF1, CDKN2A and PRC2 loss, is an aggressive subtype of sarcoma with poor prognosis and no effective therapy. In high-grade human MPNSTs, inactivating mutations in PRC2 core components SUZ12 or EED are prevalent and contributes to oncogenic transformation and progression of MPNST. How PRC2 inactivation contributes to MPNST pathogenesis, however, remains incompletely understood. Here we show that genetic inactivation of Eed in addition to Nf1 and Cdkn2a in the Schwann-progenitor lineage leads to widespread tumorigenesis within the sciatic nerve compartment of mice. In contrast, loss of Nf1 and Cdkn2a is insufficient to drive tumorigenesis in the sciatic nerve but leads to MPNST development in other anatomic locations with a longer latency. Single-nucleus multiome sequencing of the sciatic nerves revealed that PRC2-loss reprograms Nf1/Cdkn2a-deficient Schwann-lineage cells toward a dedifferentiated, neural crest stem cell-like state that resembles the transcriptomic signatures of human PRC2-loss MPNST. Together, these findings suggest a context-dependent tumor suppressive role for PRC2 within the sciatic nerve and establish a novel mouse model that recapitulates human PRC2-loss MPNST. SIGNIFICANCEWe present a novel genetically engineered mouse model that faithfully recapitulates human PRC2-loss MPNST, enabling mechanistic and preclinical studies of malignant transformation in the context of PRC2 loss.

cancer biology↗

bioRxiv2025

A Study on the Pharmacokinetic/Pharmacodynamic Profiles of the Novel PPAR Pan Agonist Chiglitazar Sodium in Rats with Hypoalbuminemia

ObjectiveTo compare the changes in the pharmacokinetic/pharmacodynamic (PK/PD) profiles of Chiglitazar Sodium between healthy rats and those with hypoalbuminemia, and to evaluate the medication safety of Chiglitazar in rats with hypoalbuminemia. MethodsLiquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method was employed to determine the plasma concentration ofChiglitazar Sodium in both healthy rats and rats with hypoalbuminemia after administration. Pharmacokinetics were calculated based on the measured data. Blood glucose levels were monitored and recorded in both groups to observe pharmacodynamic changes. ResultsPharmacokinetic analysis revealed that, compared to the healthy group, only the Tmax in the hypoalbuminemia group was significantly earlier by 34.3% (P<0.001), while other pharmacokinetic parameters showed no significant differences. Pharmacodynamic studies indicated that blood glucose levels remained stable in both healthy rats and rats with hypoalbuminemia during the 0.25-10 hour monitoring period. ConclusionExcept for Tmax, there were no significant differences in PK/PD parameters between rats with hypoalbuminemia and healthy rats. Blood glucose levels remained stable in both groups after oral administration of Chiglitazar Sodium. The animal experimental results suggest that, under normal conditions, hypoalbuminemia does not affect the pharmacokinetic and pharmacodynamic profiles of Chiglitazar Sodium.

pharmacology and toxicology↗

bioRxiv2025

Insights into the regulation of VPS13 family bridge-like lipid transfer proteins from the structure of VPS13C.

Bridge-like lipid transfer proteins (BLTPs) play central roles in redistributing lipids from their primary site of synthesis in the endoplasmic reticulum to other organelles. They comprise bridge-domains spanning between organelles at contact sites that allow lipids to transit the cytosol between adjacent membranes. The assembly of BLTPs into complexes with adaptor proteins enables their lipid transfer ability. To address the mechanisms underlying assembly and regulation of BLTP complexes, we used cryo-EM to resolve the structure of one such BLTP, the Parkinsons protein VPS13C, at near-atomic resolution. The structure identifies a lipid-transfer-nonpermissive conformation, where the built-in C-terminal VAB adaptor module blocks the end of the lipid transfer bridge, interfering with lipid delivery. We also identify calmodulin, central to calcium signaling, as a VPS13 partner, suggesting calcium regulation of VPS13 function. Altogether, this structure of intact VPS13C serves as starting point to understand its regulation and, more broadly, that of other BLTPs.

cell biology↗

bioRxiv2025

VariantFormer: A hierarchical transformer integrating DNA sequences with genetic variations and regulatory landscapes for personalized gene expression prediction

1Accurately predicting gene expression from DNA sequence remains a central challenge in human genetics. Current sequence-based models overlook natural genetic variation across individuals, while population-based models are restricted to variants observed within specific cohorts. Here, we present VariantFormer, a 1.2-billion-parameter transformer that predicts gene-level RNA abundance directly from personalized diploid genomes. Trained on 21,004 genome-transcriptome pairs from 2,330 donors, VariantFormer achieves state-of-the-art performance across both sequence- and population-based prediction tasks, while generalizing better to out-of-distribution contexts--including somatic mutation settings in cancer cell lines--and main-taining robustness across ancestries. Beyond expression prediction, VariantFormer improves eQTL effect size estimation compared to prior methods, with notable gains for lower-frequency and ancestry-specific variants. In applications to Alzheimers disease, VariantFormer gene embeddings prioritize likely causal genes and relevant tissue contexts, and in silico mutagenesis of known APOE alleles faithfully recovers known risk modifying effects. Together, these results establish VariantFormer as a scalable, diploid-aware framework for variant interpretation and personalized gene expression modeling across tissues and populations.

genomics↗

bioRxiv2025

Comprehensive benchmarking of somatic single-nucleotide variant and indel detection at ultra-low allele fractions using short- and long-read data

Mosaic mutations in normal tissues occur at low variant allele fractions (VAFs), complicating detection. To benchmark strategies, the SMaHT Network created a cell-line mixture (1:49) and produced ultra-deep whole-genome sequencing using short and long reads (five centers, 180-500x each). We assembled a reference of 44,008 mosaic SNVs and 2,059 Indels, cross-validation between platforms to expose limits of short-read analysis. We also partitioned the genome by mappability to examine the impact of genomic context, added a negative reference set, and accounted for culture-derived mutations. When seven institutions applied eleven algorithms to mixture data, call sets were largely discordant across tools and replicates, partly reflecting stochastic presence of low-VAF mutations in biological replicants. For >2% VAF SNVs, sensitivity and precision approached [~]80% at [≥]300x, with little gain from additional sequencing. This work provides a comprehensive framework for reliable detection of low-VAF mutations in non-cancer tissues and a valuable resource for the community.

bioinformatics↗

bioRxiv2025

Dynamic electrocortical states and paradoxical complexity during desflurane anesthesia

BackgroundHow general anesthesia alters the dynamics of electrocortical activity is crucial to understand the neural mechanisms of unconsciousness. Local cortical activity undergoes spontaneous transitions at constant anesthetic concentration. The spatial organization and temporal dynamics of state transitions in large-scale electrocortical activity is incompletely understood. MethodsEpidural electrocorticogram was recorded from the right hemisphere in 8 rats (14 experiments) using chronically implanted 32-channel flexible electrode arrays during desflurane anesthesia at 6%, 4%, 2%, 0% inhaled concentrations, each maintained for 1 hour. Cortical states were identified by principal component analysis of power spectrograms followed by density-based clustering simultaneously across all anesthetic conditions. State-specific spatiotemporal complexity was quantified by the normalized Lempel-Ziv algorithm to capture signal variability beyond spectral effects. Temporal dynamics were assessed by state occurrence, dwell times, and transition probabilities. ResultsSeven cortical states were identified. Six states generally tracked anesthetic depth with an increase in delta power and decrease in complexity, but their occurrence was not tied to any anesthetic level (p<0.001). The 7th state was a paradoxical, activated state that mostly occurred during deep anesthesia and was marked by reduced delta (p<0.001) and elevated complexity (p<0.001). Cortical activity was more likely to remain in a given state than to switch (mean dwell time of 136.55 s, persistence likelihood of 99.36%). When transitions occurred, they followed structured, non-random dynamics, primarily within light- or deep-anesthesia states (FDR-corrected p<0.05), with a mild tendency to exit deep states and enter light states (p=0.0039), consistent with anesthetic emergence. ConclusionsElectrocortical activity is not a unitary function of anesthetic concentration but involves spontaneous dynamics and paradoxically activated states with increased global complexity during deep anesthesia. The results suggest ongoing spontaneous reorganization of cortical activity during prolonged anesthetic challenge and provide new insight into anesthesia-induced brain dynamics that may inform future strategies for monitoring and manipulating the state of consciousness and facilitating recovery from general anesthesia.

neuroscience↗

bioRxiv2025

Proteome Landscapes Decode Organelle Vulnerabilities in cortical and dopaminergic-like induced neurons Across Lysosomal Storage Disorders

Lysosomes maintain cellular homeostasis by degrading proteins delivered via endocytosis and autophagy, and by recycling building blocks for organelle biogenesis. Lysosomal Storage Disorders (LSDs) comprise a group of diseases affecting diverse lysosomal functions. To facilitate molecular phenotyping across diverse LSD gene classes, we are developing a library of human embryonic stem cells engineered to lack individual LSD genes as a resource for the field. Here, we report our initial stem cell toolkit lacking one of 23 LSD genes, including the majority of genes associated with sphingolipidoses and neuronal ceroid lipofuscinoses, and its use in the generation of a proteomic resource for induced cortical-like and midbrain dopaminergic-like neurons In-depth abundance and correlation profiling across organelles and sub-organelle components revealed potential vulnerabilities that reflect distinct patterns of proteome alterations across both genotypes and neuronal cell types. We characterize alterations in the mitochondrial proteome associated with GBA1 and ASAH1 deficiency and identify synaptic and mitochondrial defects in ASAH1-/- induced neurons that correlate with defects in neuronal firing rates. Moreover, we developed an informatic pipeline for proteome-wide identification of individual protein interactions and protein complexes that may be disrupted as a result of LSD gene deficiency. Finally, we visualized structural alterations of ASAH1-deficient endolysosomes in situ using cryo-electron tomography, revealing swollen organelles that were largely devoid of dense internal membranes characteristic of wild-type cells, but containing numerous intralumenal vesicle compartments. This toolkit and associated proteomic landscapes provide a resource for defining molecular signatures associated with LSD gene dysfunction and organelle vulnerability.

cell biology↗

bioRxiv2025

A gap-free telomere-to-telomere pig reference genome provides insight in centromere evolution and breed-specific selection

The domestic pig is a key agricultural species and biomedical model, yet its reference genome has remained incomplete. Using PacBio HiFi, Oxford Nanopore reads, and Hi-C sequencing, we assembled the first telomere-to-telomere (T2T), gap-free pig genome (T2T-Sscrofa). Importantly, this assembly derives from the same individual pig that provided the original reference genome, thereby completing the long-standing foundation of pig genomics. This assembly resolves 274.8 Mb of previously unassembled sequence, including centromeres, segmental duplications, and ribosomal DNA arrays, and identifies 255 new protein-coding genes. Comparative analyses reveal a Robertsonian translocation in the western European wild boar and extensive structural variation across global pig populations. T2T-Sscrofa provides a comprehensive genomic foundation for agricultural, evolutionary, and biomedical research.

zoology↗