Biology subjects

Yu, H.

Publications and source records attributed to Yu, H..

At least 199 records · Page 11Linked to original sources

bioRxiv2024

ABC-seq expands small RNAs content with randomized adapter pools operation

Cellular gene expression is widely regulated by a large number of small RNAs (smRNAs). The ability to in-depth analysis of smRNAs content is vital for comprehensive understanding their architecture and function. However, experimental approaches capable of realizing both high-content and low-byproduct sequencing analysis are lacking. Here, we develop ABC-seq (randomized Adapter pool dimer Blocking and Cleavage in smRNA sequencing). This method designs randomized adapter pools to recognize more smRNA species. Moreover, it operates two product structure-differentiated enzymatic reactions to maximally eliminate the byproducts of adapter dimers. Using ABC-seq, we detected a broader range of smRNAs including miRNAs, scRNAs, and snoRNAs in rat hypertrophic cardiomyocytes. Upon further analysis of miRNAs, we detected 66 more miRNAs compared to the control method, providing new insights into smRNA-directed gene regulation mechanisms. Furthermore, we revealed cancer drug response -associated smRNAs and uncovered their pivotal role in immune response modulation in non-small cell lung cancer. ABC-seq represents an evolutionary strategy for reshaping the smRNA landscape boundaries and paves the way for a deeper understanding of complex gene regulation networks.

genomics↗

bioRxiv2024

Accurate antibody loop structure prediction enables zero-shot design of target-specific antibodies

Protein loops, characterized by their versatile structures with varying sizes and shapes, can recognize a wide range of targets with high specificity and affinity. The variable loops of the antibody complementarity-determining region (CDR) are particularly crucial for immune responses and therapeutic applications due to their effective target recognition capabilities. Accurate structure prediction of these antibody loops is essential for the efficient in silico design of target-binding antibodies for therapeutic or industrial use. However, predicting antibody loop structures is challenging due to the lack of evolutionary information from related proteins. Thus, a successful ab initio structure prediction method, which operates without structural templates or related sequences, is crucial for the effective design of antibody loop-mediated interactions. This study demonstrates that highly accurate antibody loop structure prediction enables the effective zero-shot design of target-binding antibody loops. The performance of loop design has been shown to depend on the accuracy of ab initio loop structure prediction, as tested with two versions of our design model. The high affinity, diversity, novelty, and specificity of the antibody loops designed with these new methods were validated experimentally on four target proteins.

bioengineering↗

bioRxiv2024

MAGMa: Your Comprehensive Tool for Differential Expression Analysis in Mass-Spectrometry Proteomic Data.

Proteomics, the study of proteins and their functions, plays a vital role in understanding biological processes. In this study, we sought to address the challenges in analyzing complex proteomic datasets, where subtle changes in protein abundance are difficult to detect. Utilizing a newly developed tool, Maximal Aggregation of Good protein signal from Mass spectrometric data (MAGMa), we demonstrated its superior performance in accurately identifying true signals while effectively filtering out noise. Here we show that MAGMa strikes a balance between sensitivity and specificity on benchmarking datasets, offering a robust solution for analyzing various quantitative proteomic datasets. These findings advance the field by providing researchers with a powerful tool to uncover subtle changes in protein abundance, contributing to our understanding of complex biological systems and potentially facilitating the discovery of new therapeutic targets.

bioinformatics↗

bioRxiv2024

PlantRNA-FM: An Interpretable RNA Foundation Model for Exploration 1 Functional RNA Motifs in Plants

The complex language of plant RNA encodes a vast array of biological regulatory elements that orchestrate crucial aspects of plant growth, development, and adaptation to environmental stresses. Recent advancements in foundation models (FMs) have demonstrated their unprecedented potential to decipher complex language in biology. In this study, we introduced PlantRNA-FM, a novel high-performance and interpretable RNA FM specifically designed based on RNA features including both sequence and structure. PlantRNA-FM was pre-trained on an extensive dataset, integrating RNA sequences and RNA structure information from 1,124 distinct plant species. PlantRNA-FM exhibits superior performance in plant-specific downstream tasks, such as plant RNA annotation prediction and RNA translation efficiency (TE) prediction. Compared to the second-best FMs, PlantRNA-FM achieved an F1 score improvement of up to 52.45% in RNA genic region annotation prediction and up to 15.30% in translation efficiency prediction, respectively. Our PlantRNA-FM is empowered by our interpretable framework that facilitates the identification of biologically functional RNA sequence and structure motifs, including both RNA secondary and tertiary structure motifs across transcriptomes. Through experimental validations, we revealed novel translation-associated RNA motifs in plants. Our PlantRNA-FM also highlighted the importance of the position information of these functional RNA motifs in genic regions. Taken together, our PlantRNA-FM facilitates the exploration of functional RNA motifs across the complexity of transcriptomes, empowering plant scientists with novel capabilities for programming RNA codes in plants.

bioinformatics↗

bioRxiv2024

Jagged-1+ Tregs Mediate Lymphatic Remodeling in Tumour-Draining Lymph Nodes

The tumour-draining lymph nodes (tdLNs) are crucial sites for early immune surveillance of tumours. During tumour development, tdLNs undergo significant stromal remodelling that impacts lymph node (LN) architecture. The reconstruction of tdLNs is dependent on the crosstalk between regulatory T cells (Tregs) and resident stromal cells. The Notch ligand Jagged1 (Jag1), highly expressed in skin Tregs, is critical for facilitating stem cell-mediated tissue regeneration. However, the role of Jag1pos Tregs in mediating the activity of tdLN-resident immune cells and stromal cells remains unexplored. Here, we used the B16-F10 tumour model to assess the role of Jag1pos Tregs during tdLN development. During tumor progression, late-stage tdLN Tregs expressed higher levels of Jag1 than early-stage tdLNs. Conditional deletion of Jag1 in Tregs markedly restrained tdLN expansion, without influencing effector T cell abundance or activation profile. Transcriptomic analysis of tdLNs revealed downregulation of lymphatic endothelial cell (LEC)-related markers in mice with Treg-specific Jag1 ablation. Disruption of lymphatic networks in the tdLN was further confirmed by flow cytometric profiling and histological analysis. In vivo permeability assessment by FITC-dextran demonstrated perturbed lymphatic drainage, likely due to suppressed LN lymphangiogenesis. Finally, we identify the presence of Jag1pos Tregs in tdLNs of human melanoma patients. Overall, our results highlight that crosstalk between Jag1pos Tregs and LECs is required for lymphatic sinus expansion, which is critical for the formation of the tdLN niche during melanoma progression.

immunology↗

bioRxiv2024

The Effects of Functional Training on Muscle Strength in Athletes: A Meta-Analysis

The study aimed to analyze the effects of functional training (FT) on athletes muscle strength compared to traditional resistance training (TRT). A systematic search was conducted in 6 databases from inception to January 2024. Baseline and outcome measures from randomized controlled trials (RCT) were assessed for the impact of FT on athlete muscle strength, across sex, age, and sports levels. Hedges g effect sizes were calculated using a random-effects model, and subgroup and single training factor analyses were performed to address potential sources of heterogeneity, along with a meta-regression analysis. The inclusion of 67 studies involving 1718 athletes revealed significant moderate to large effects of FT on maximum strength (k=11; ES=2.68; p[≤] 0.001), power (k=12; ES=0.68; p<0.001), as well as muscle endurance(k=12; ES=4.13; p<0.001).In conclusion, FT appears to offer potential benefits for enhancing muscle strength in athletes, with considerations for individual differences in sex, age, and training programs. Findings suggest that longer training sessions may be associated with improvements in maximum strength and muscle endurance, whereas shorter sessions might be more conducive to power development. Additionally, preliminary evidence hints that younger athletes may experience more pronounced training benefits, though this observation requires further investigation to establish a more definitive correlation.

physiology↗

bioRxiv2024

Application of machine learning in a rodent malaria model for rapid, accurate, and consistent parasite counts

Rodent malaria models serve as important preclinical antimalarial and vaccine testing tools. Evaluating treatment outcomes in these models often requires manually counting parasite-infected red blood cells (iRBCs), a time-consuming process, which can be inconsistent between individuals and labs. We have developed an easy-to-use machine learning (ML)-based software, Malaria Screener R, to expedite and standardize such studies by automating the counting of Plasmodium iRBCs in rodents. This software can process Giemsa-stained blood smear images captured by any camera-equipped microscope. It features an intuitive graphical user interface that facilitates image processing and visualization of the results. The software has been developed as a desktop application that processes images on standard Windows and Mac OS computers. A previous ML model created by the authors designed to count P. falciparum-infected human RBCs did not perform well counting Plasmodium-infected mouse RBCs. We leveraged that model by loading the pre-trained weights and training the algorithm with newly collected data to target P. yoelii and P. berghei mouse iRBCs. This new model reliably measured both P. yoelii and P. berghei parasitemia (R2 = 0.9916). Additional rounds of training data to incorporate variances due to length of Giemsa staining, microscopes etc, have produced a generalizable model, meeting WHO Competency Level 1 for the sub-category of parasite counting using independent microscopes. Reliable, automated analyses of blood-stage parasitemia will facilitate rapid and consistent evaluation of novel vaccines and antimalarials across labs in an easily accessible in vivo malaria model.

microbiology↗

bioRxiv2024

Early life intestinal inflammation alters gut microbiome, impairing gut-brain communication and reproductive behavior in mice

Despite recent advances in understanding the connection between the gut microbiota and the adult brain, there remains a wide knowledge gap in how gut inflammation impacts brain development. We hypothesized that intestinal inflammation in early life would negatively affect neurodevelopment through dysregulation of microbiota communication to the brain. We therefore developed a novel pediatric chemical model of inflammatory bowel disease (IBD), an incurable condition affecting millions of people worldwide. IBD is characterized by chronic intestinal inflammation, and has comorbid symptoms of anxiety, depression and cognitive impairment. Significantly, 25% of patients with IBD are diagnosed during childhood, and the effect of chronic inflammation during this critical period of development is largely unknown. This study investigated the effects of early-life gut inflammation induced by DSS (dextran sulfate sodium) on a range of microbiota, endocrine, and behavioral outcomes, focusing on sex-specific impacts. DSS-treated mice exhibited increased intestinal inflammation, altered microbiota membership, and changes in microbiota-mediated circulating metabolites. The majority of behavioral measures were unaffected, with the exception of impaired mate-seeking behaviors in DSS-treated males. DSS-treated males also showed significantly smaller seminal vesicles, lower circulating androgens, and decreased intestinal hormone-activating enzyme activity. In the brain, microglia morphology was chronically altered with DSS treatment in a sex-specific manner. The results suggest that early-life gut inflammation causes changes in gut microbiota composition, affecting short-chain fatty acid (SCFA) producers and glucuronidase (GUS) activity, correlating with altered SCFA and androgen levels. The findings emphasize the developmental sensitivity to inflammation-induced changes in endocrine signalling and underscore long-lasting physiological and microbiome changes associated with juvenile IBD. HighlightsEarly-life gut inflammation produces sex-specific effects on i) microbiome, ii) sex hormones and iii) behaviour. Both sexes show disrupted gut bacterial members that regulate sex hormone levels. Male mice demonstrate deficits in mate seeking, which may be mediated by reduced androgen levels. Both male and female mice demonstrate shifts in hippocampal microglial morphology.

neuroscience↗

bioRxiv2024

SLC13A2-transported citrate is a metabolic signal for PKM2 acetylation and degradation to suppress tumor growth

Background and aimsMetabolic reprogramming represents as a pivotal hallmark for cancer, but TCA cycle in tumorigenesis and progression has long been neglected. Solute carrier (SLC) transporters mediate the transport of TCA cycle intermediates across membrane, but their functions in cancer pathogenesis remains unclear. Approaches & ResultsUsing integrated analysis of solute carrier (SLC) transporters for TCA cycle intermediates, we found that SLC13A2 was consistently downregulated in hepatocellular carcinoma (HCC) cells and liver tissues from human patients and heterogeneous mouse models. Adeno-associated virus (AAV)-transduced liver-specific knockout or overexpression of SLC13A2 promoted or ameliorated HCC progression in the primary mouse model, demonstrating that SLC13A2 served as a protective factor during HCC pathogenesis. SLC13A2 inhibited HCC cell proliferation by decreasing mitochondrial function via suppressed oxygen consumption and ATP production. Combined with metabolic flux analysis, we found that SLC13A2 imported citrate, which secreted acetyl-CoA as a precursor for the acetylation of pyruvate kinase muscle isozyme M2 (PKM2), which led to its protein degradation. Decreased activity of pyruvate kinase depleted pyruvate for the TCA cycle, thus inhibiting amino acid synthesis and nucleotide metabolism. Additionally, a decrease in nuclear PKM2 protein transduced to reprogrammed gene transcription for cell proliferation and metabolism which is required for tumor growth. ConclusionsThis study revealed that citrate transported by SLC13A2 acts as a signal to disrupt metabolic homeostasis for tumor growth and suggests potential drug targets for HCC therapy. graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=165 SRC="FIGDIR/small/591017v2_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@80c95eorg.highwire.dtl.DTLVardef@124750corg.highwire.dtl.DTLVardef@809ab4org.highwire.dtl.DTLVardef@12cbe74_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

CD74+ fibroblasts proliferate upon mechanical stretching to promote angiogenesis in keloid

The healing of human skin wounds is susceptible to perturbation caused by excessive mechanical stretching, resulting in enlarged scars, hypertrophic scars, or even keloids in predisposed individuals. Keloids are fibro-proliferative scar tissues that extend beyond the initial wound boundary, consisting of the actively progressing leading edge and the quiescent center. The stretch-associated outgrowth and enhanced angiogenesis are two features of the leading edge of keloids. However, which cell population is responsible for transducing the mechanical stimulation to the pathological alterations of keloid tissues remains unclear. Herein, through joint analysis of single-cell RNA sequencing of keloid specimens and RNA sequencing of stretched keloid fibroblasts, we identified CD74+ fibroblasts, a previously unappreciated subset of fibroblasts, as a key player in stretch-induced keloid progression. Examination of macrophage markers suggested a possible myeloid origin of the CD74+ fibroblasts. Immunostaining of keloid cryosections depicted a predominant distribution of CD74+ fibroblasts in the leading edge, interacting with vasculature. CD74+ fibroblasts possessed pro-angiogenic and migratory capacities, as revealed by in vitro transwell and tube formation assays on purified CD74+ fibroblasts. Additionally, these cells underwent proliferation upon stretching, through PIEZO1-mediated calcium influx and the downstream ERK and AKT signaling. Collectively, our findings propose a model wherein CD74+ fibroblasts serve as pivotal drivers of stretch-induced keloid progression, fueled by their proliferative, pro-angiogenic, and migratory capacities. Targeting the attributes of CD74+ fibroblasts hold promise as a therapeutic strategy for keloid management. Significance statementKeloids are fibro-proliferative scars resulting from aberrant skin wound healing processes, consisting of the actively progressing leading edge and the quiescent center. Mechanical stretching and neo-vascularization have both been implicated in keloid progression, yet little is known about whether they are interconnected. Herein, we demonstrated that CD74+ fibroblasts, a previously undiscovered fibroblast subset, possessed heightened pro-angiogenic and migratory capacities, and underwent proliferation upon mechanical stretching, thereby facilitating the progression of the leading edge of keloids. Examination of macrophage markers suggested a possible myeloid origin of CD74+ fibroblasts. Our findings uncover the connection between stretch-induced keloid progression and neo-vascularization through CD74+ fibroblasts and provide valuable insights into potential therapeutic interventions.

cell biology↗

bioRxiv2024

Diversity and ecological potentials of viral assemblages from the seamount sediments of the Northwest Pacific Ocean

Viruses are the most abundant life forms in the sea, influencing the community structure and metabolism of host cells as well as biogeochemical cycles. However, the diversity and ecological roles of viruses within seamount ecosystems, natural microbiota havens characterized by high biodiversity, remain unknown. Here, the first seamount viral genome (SMVG) dataset, based on a metagenomic analysis of twelve seamount sediment samples collected from the seamount regions of the Northwest Pacific Ocean, is established. A total of 78,069 viral operational taxonomic units (vOTUs) were found, spanning 18 viral classes and 63 viral families. The detection of sixteen viral auxiliary metabolic genes (vAMGs) suggests that viruses may participate in both the complex metabolic dynamics associated with sediment microbial communities and also biogeochemical cycles, including carbon, sulfur, metal, heme, and cobalamin cycling. vAMGs involved in the metabolism of heme, cobalamin and metals, in particular, are more often detected in seamount sediments than in trenches, cool seeps, and hydrothermal vents. This investigation of the viral communities in these seamount sediments provides new insights into the high diversity and ecological potential of the viruses and establishes a foundation for the future study of benthic viruses from deep-sea seamounts.

ecology↗

bioRxiv2024

Engineering PEG10 assembled endogenous virus-like particles with genetically encoded neoantigen peptides for cancer vaccination

Tumor neoantigen peptide vaccines hold potential for boosting cancer immunotherapy, yet efficiently co-delivering peptides and adjuvants to antigen-presenting cells in vivo remains challenging. Virus-like particle (VLP), which is a kind of multiprotein structure organized as virus, can deliver therapeutic substances into cells and stimulate immune response. However, the weak targeted delivery of VLP in vivo and its susceptibility to neutralization by antibodies hinder their clinical applications. Here, we firstly designed a novel protein carrier using the mammalian-derived capsid protein PEG10, which can self-assemble into endogenous VLP (eVLP) with high protein loading and transfection efficiency. Then, an engineered tumor vaccine, named ePAC, was developed by packaging genetically encoded neoantigen into eVLP with further modification of CpG-ODN on its surface to serve as an adjuvant and targeting unit to dendritic cells (DCs). Significantly, ePAC can efficiently target and transport neoantigens to DCs, and promote DCs maturation to induce neoantigen-specific T cells. Moreover, in mouse orthotopic liver cancer and humanized mouse tumor models, ePAC combined with anti-TIM-3 exhibited remarkable antitumor efficacy. Overall, these results support that ePAC could be safely utilized as cancer vaccines for antitumor therapy, showing significant potential for clinical translation.

cancer biology↗

bioRxiv2024

AMHY and sex determination in egg-laying mammals

The sex chromosomes of egg-laying mammals (monotremes), which lack the sex determining gene SRY1, evolved independently to those of all therian mammals2,3. Here we characterise the candidate monotreme sex determining gene, the Y-localised anti-Mullerian hormone gene (AMHY)4,3 and trace its expression during the period of sexual differentiation. Monotreme AMHX and AMHY gametologues have significant sequence divergence at the promoter, gene and protein level, likely following an original allele inversion in the common monotreme ancestor but retain conserved features of TGF-{beta} molecules. Expression of sexual differentiation genes in the echidna fetal gonad were significantly different from that of therian mammals. AMHY expression was seen exclusively in the male gonad during sexual differentiation, whereas AMHX was expressed in both sexes. Experimental ectopic expression of platypus AMHX or AMHY in the chicken embryo did not masculinise the female urogenital system, a possible result of mammalian specific changes to AMH proteins preventing function in the chicken. Our results provide fundamental insight into the first steps of monotreme sex chromosome evolution and sex determination with developmental expression data strongly supporting AMHY as the primary male sex determination gene.

evolutionary biology↗

bioRxiv2024

DeProt: A protein language model with quantizied structure and disentangled attention

Protein language models (PLMs) have shown remarkable capabilities in various protein function prediction tasks. However, while protein function is intricately tied to structure, most existing PLMs do not incorporate protein structure information. To address this issue, we introduce ProSST, a Transformer-based protein language model that seamlessly integrates both protein sequences and structures. ProSST incorporates a structure quantization module and a Transformer architecture with disentangled attention. The structure quantization module translates a 3D protein structure into a sequence of discrete tokens by first serializing the protein structure into residue-level local structures and then embeds them into dense vector space. These vectors are then quantized into discrete structure tokens by a pre-trained clustering model. These tokens serve as an effective protein structure representation. Furthermore, ProSST explicitly learns the relationship between protein residue token sequences and structure token sequences through the sequence-structure disentangled attention. We pre-train ProSST on millions of protein structures using a masked language model objective, enabling it to learn comprehensive contextual representations of proteins. To evaluate the proposed ProSST, we conduct extensive experiments on the zero-shot mutation effect prediction and several supervised downstream tasks, where ProSST achieves the state-of-the-art performance among all baselines. Our code and pretrained models are publicly available 2.

bioinformatics↗

bioRxiv2024

Androgen receptor-negative prostate cancer is vulnerable to SWI/SNF-targeting degrader molecules

Proteolysis targeting chimera (PROTAC) therapies degrading SWI/SNF ATPases offer a novel approach to interfere with androgen receptor (AR) signaling in AR-dependent castration-resistant prostate cancer (CRPC-AR). To explore the utility of SWI/SNF therapy beyond AR-sensitive CRPC, we investigated SWI/SNF-targeting agents in AR-negative CRPC. SWI/SNF targeting PROTAC treatment of cell lines and organoid models reduced the viability of not only CRPC-AR but also WNT-signaling dependent AR- negative CRPC (CRPC-WNT). The CRPC-WNT subgroup represents 11% of around 400,000 cases of CRPC worldwide who die yearly of CRPC. We discovered that SWI/SNF ATPase SMARCA4 depletion interfered with the master transcriptional regulator TCF7L2 (TCF4) in CRPC-WNT. Functionally, TCF7L2 maintains proliferation via the MAPK signaling axis in this subtype of CRPC. These data suggest a mechanistic rationale for interventions that perturb the DNA binding of the pro-proliferative TCF7L2 transcription factor (TF) and/or direct MAPK signaling inhibition in the CRPC-WNT subclass of advanced prostate cancer. Statement of significanceAndrogen receptor (AR)-negative prostate cancer (PCa) remains a clinical challenge due to the lack of targeted therapeutic options. Here, we identified a lineage-defining molecular axis in a subtype of AR- negative PCa, accounting for around 10% of castration-resistant PCa (CRPC) that can be interfered with by SWI/SNF-targeting agents.

cancer biology↗

bioRxiv2024

Development of a generalisable tryptophan-optimised quenchbody biosensor based on a synthetic nanobody library

Quenchbodies, antibodies labelled with fluorophores that increase in intensity upon antigen binding, offer great promise for biosensor development. Nanobody-based quenchbodies are particularly attractive due to their small size, ease of expression, high stability, rapid evolvability, and amenability to protein engineering. However, existing designs for protein detection show limited dynamic range, with fluorescence increases of only 1.1-1.7 fold. Here we identify the tryptophan residues in the nanobody complementarity-determining regions (CDRs) that are critical to quenchbody performance. Using a combination of rational design and molecular dynamics simulations, we developed an optimised nanobody scaffold with tryptophans introduced at key positions. We used this scaffold in an in vitro directed-evolution screen against human inflammatory cytokine interleukin-6 (IL-6). This yielded quenchbodies with 1.5-2.4-fold fluorescence increases, enabling IL-6 detection down to 2 nM. Our scaffold provides a valuable platform for developing biosensors for diverse protein targets, with applications in research, diagnostics, and environmental monitoring.

bioengineering↗

bioRxiv2024

Flight performance, activity and behaviour of breeding pied flycatchers in the wild, revealed with accelerometers and machine learning

Flight behaviours have been extensively studied from different angles such as their kinematics, aerodynamics and more general their migration pattern. Nevertheless, much is still unknown about the daily flight activity of birds, in terms of their performance, behaviour and the potential differences between males and females. The recent development of miniaturized accelerometers allows us a glimpse into the daily life of a songbird. Here, we tagged 26 pied flycatchers (Ficedula hypoleuca) with accelerometers and analysed using machine learning approaches their flight performance, activity and behaviour during their chick rearing period. We found that during two hours of foraging chick-rearing pied flycatchers were flying 13.7% of the time. Almost all flights (>99%) were short flights lasting less than 10s. Flight activity changed throughout the day and was highest in the morning and lowest in the early afternoon. Male pied flycatcher had lower wing loading than females, and peak flight accelerations were inversely correlated with wing loading. Despite this, we found no significant differences in flight activity and performance between sexes. This suggests that males possess a higher potential flight performance, which they not fully utilized during foraging flights. Our results thus suggest that male and female pied flycatcher invest equally in parental care, but that this comes at a reduced cost by the male, due to their higher flight performance potential.

animal behavior and cognition↗

bioRxiv2024

The origin and evolution of cultivated rice and genomic signatures of heterosis for yield traits in super-hybrid rice

Unraveling evolutionary history and genomic basis of heterosis is fundamental for advancing rice productivity. We developed a genome-scale phylogeny of Oryzeae by coalescing 39,984 gene trees. Our analysis supports parallel, independent origins and nearly synchronous evolutionary trajectories leading to the subsequent domestication of indica and japonica, evidenced by molecular dating and synonymous substitution rates for syntenic and domestication-associated genes. Our survey of 1,383 gene duplications in ancestor of O. sativa uncovers their roles in vital biological processes, highlighting the significance in environmental adaptability. Additionally, we confirm the lack of hybridization event among subspecies ancestors through gene tree topology and D-statistical analyses. We generated 71.67 GB whole-genome sequencing data for five super-hybrid rice varieties and their progenitors, revealing differential positive selection and genetic exchanges between subspecies, essential for heterosis formation. Crucially, our study underscores the role of non-additive gene expression in heterosis, particularly in genes associated with DNA repair and recombination, which may confer resistance traits. Furthermore, eQTL and de novo mutation analyses identify key developmental and stress response genes, offering targets for enhancing heterosis in rice. Overall, our research reveals crucial insights into the genetics of rice domestication and heterosis, offering a genomic resource to improve rices agricultural productivity.

evolutionary biology↗