Biology subjects

Hu, C.

Publications and source records attributed to Hu, C..

At least 73 records · Page 4Linked to original sources

bioRxiv2024

Feed-forward stimulation of CAMK2 by the oncogenic pseudokinase PEAK1 generates a therapeutically "actionable" signalling axis in triple negative breast cancer

The PEAK family of pseudokinases, comprising PEAK1-3, are signalling scaffolds that play oncogenic roles in several poor prognosis human cancers, including triple negative breast cancer (TNBC). However, therapeutic targeting of pseudokinases is challenging due to their lack of catalytic activity. To address this, we screened for PEAK1 effectors by affinity purification and mass spectrometry, identifying calcium/calmodulin-dependent protein kinase 2 (CAMK2)D and CAMK2G. PEAK1 promoted CAMK2D/G activation in TNBC cells via a novel feed-forward mechanism involving PEAK1/PLC{gamma}1/Ca2+ signalling and direct binding via a consensus CAMK2 interaction motif in the PEAK1 N-terminus. In turn, CAMK2 phosphorylated PEAK1 to enhance association with PEAK2, which is critical for PEAK1 oncogenic signalling. To achieve pharmacologic targeting of PEAK1/CAMK2, we repurposed RA306, a second generation CAMK2 inhibitor under pre-clinical development for treatment of cardiovascular disease. RA306 demonstrated on-target activity against CAMK2 in TNBC cells and inhibited PEAK1-enhanced migration and invasion in vitro. Moreover, RA306 significantly attenuated TNBC xenograft growth and blocked metastasis in a manner mirrored by CRISPR-mediated PEAK1 ablation. Overall, these studies establish PEAK1 as a critical cell signalling nexus, identify a novel mechanism for regulation of Ca2+ signalling and its integration with tyrosine kinase signals, and identify CAMK2 as a therapeutically actionable target downstream of PEAK1.

cancer biology↗

bioRxiv2024

ChineseEEG: A Chinese Linguistic Corpora EEG Dataset for Semantic Alignment and Neural Decoding

An Electroencephalography (EEG) dataset utilizing rich text stimuli can advance the understanding of how the brain encodes semantic information and contribute to semantic decoding in brain-computer interface (BCI). Addressing the scarcity of EEG datasets featuring Chinese linguistic stimuli, we present the ChineseEEG dataset, a high-density EEG dataset complemented by simultaneous eye-tracking recordings. This dataset was compiled while 10 participants silently read approximately 11 hours of Chinese text from two well-known novels. This dataset provides long-duration EEG recordings, along with pre-processed EEG sensor-level data and semantic embeddings of reading materials extracted by a pre-trained natural language processing (NLP) model. As a pilot EEG dataset derived from natural Chinese linguistic stimuli, ChineseEEG can significantly support research across neuroscience, NLP, and linguistics. It establishes a benchmark dataset for Chinese semantic decoding, aids in the development of BCIs, and facilitates the exploration of alignment between large language models and human cognitive processes. It can also aid research into the brains mechanisms of language processing within the context of the Chinese natural language.

neuroscience↗

bioRxiv2024

CRISPR-repressed toxin-antitoxin provides population-level immunity against diverse anti-CRISPR elements

Prokaryotic CRISPR-Cas systems are highly vulnerable to phage-encoded anti-CRISPR (Acr) factors. How CRISPR-Cas systems protect themselves remains unclear. Here, we uncovered a broad-spectrum anti-anti-CRISPR strategy involving a phage-derived toxic protein. Transcription of this toxin is normally reppressed by the CRISPR-Cas effector, but is activated to halt cell division when the effector is inhibited by any anti-CRISPR proteins or RNAs. We showed that this abortive infection-like effect efficiently expels Acr elements from bacterial population. Furthermore, we exploited this anti-anti-CRISPR mechanism to develop a screening method for specific Acr candidates for a CRISPR-Cas system, and successfully identified two distinct Acr proteins that enhance the binding of CRISPR effector to non-target DNA. Our data highlight the broad-spectrum role of CRISPR-repressed toxins in counteracting various types of Acr factors, which illuminates that the regulatory function of CRISPR-Cas confers host cells herd immunity against Acr-encoding genetic invaders, no matter they are CRISPR-targeted or not.

microbiology↗

bioRxiv2023

Glucocorticoids rapidly modulate CaV1.2-mediated calcium signals through Kv2.1 channel clusters in hippocampal neurons

The precise regulation of Ca2+ signals plays a crucial role in the physiological functions of neurons. Here, we investigated the rapid effect of glucocorticoids on Ca2+ signals in hippocampal neurons. In cultured hippocampal neurons, glucocorticoids inhibited the spontaneous somatic Ca2+ spikes generated by Kv2.1-organized Ca2+ microdomains. Furthermore, glucocorticoids rapidly reduced the cell surface expressions of Kv2.1 and CaV1.2 channels in hippocampal neurons. In HEK293 cells transfected with Kv2.1 alone, glucocorticoids significantly reduced the surface expression of Kv2.1 with little effect on K+ currents. Glucocorticoids inhibited CaV1.2 currents but had no effect on the cell surface expression of CaV1.2 in HEK293 cells transfected with CaV1.2 alone. Notably, in the presence of wild-type Kv2.1, glucocorticoids caused a decrease in the surface expression of CaV1.2 channels in HEK293 cells. However, this effect was not observed in the presence of non-clustering Kv2.1S586A mutant channels. Live cell imaging showed that glucocorticoids rapidly decreased Kv2.1 clusters on the plasma membrane. Correspondingly, western blot results indicated a significant increase in the cytoplasmic level of Kv2.1, suggesting the endocytosis of Kv2.1 clusters. Glucocorticoids rapidly decreased the intracellular cAMP concentration and the phosphorylation level of PKA in hippocampal neurons. The PKA inhibitor H89 mimicked the effect of glucocorticoids on Kv2.1, while the PKA agonist forskolin abrogated the effect. In conclusion, glucocorticoids rapidly regulate CaV1.2-mediated Ca2+ signals in hippocampal neurons by promoting the endocytosis of Kv2.1 channel clusters through reducing PKA activity. Significance StatementThe rapid non-genomic effect of glucocorticoids on the central nervous system is not fully understood. CaV1.2-mediated Ca2+ signaling microdomains control somatic Ca2+ signals and regulate excitation-transcription coupling in hippocampal neurons. Here, we demonstrate that glucocorticoids rapidly inhibit CaV1.2-mediated somatic Ca2+ spikes in hippocampal neurons. Glucocorticoids reduce the surface expression of Kv2.1 clusters but do not affect the surface expression of non-clustering Kv2.1. Moreover, glucocorticoids induce the endocytosis of CaV1.2 channels through wild-type Kv2.1. However, glucocorticoids cannot induce the endocytosis of CaV1.2 channels through Kv2.1S586A mutant channels, which cannot form clusters. This study sheds light on the intricate interplay between glucocorticoids, Kv2.1 channels, and CaV1.2 channels, unraveling a dual mechanism that influences both overall Ca2+ signaling and the intricate organization of neural microdomains.

neuroscience↗

bioRxiv2023

Climate change impacts dryland multifunctionality: A cascade of precipitation variability to species replacement in multitrophic microbiota

In the Anthropocene, the pervasive impacts of climate change on arid ecosystems are increasingly evident, resulting in significant alterations in both biodiversity and functionality. Although soil microbes are anticipated to be sensitive to changes in precipitation regimes, the mechanisms through which multifaceted precipitation changes impair the delivery of multiple functions by multitrophic microbiota in soils remain largely unexplored. In the drylands of Northwestern China, we examined the direct effects of historical precipitation regimes on the soil multifunctionality of biocrusts, a model system, and their indirect impacts mediated by microbial communities. Among abiotic predictors, precipitation variability, rather than mean annual precipitation, emerged as the primary driver of multifunctionality, leading to a convergence of less functionally beneficial species. By utilizing a biodiversity-ecosystem function relationship framework, our results underscore the crucial roles of - and {beta}-diversity of heterotrophic bacteria, fungi, and phototrophic cyanobacteria in maintaining soil functionality. However, the underlying mechanisms are distinct. We found that the local richness of heterotrophs and phylogenetic dissimilarity of photoautotrophs exert positive influences on multifunctionality, while species replacement, a component of {beta}-diversity, primarily enhances the variance in soil multifunctionality. Importantly, the findings illuminate the cascading effect of precipitation variability on dryland ecosystems, amplified by microbial diversity, potentially triggering a silent collapse of vulnerable arid habitats. Our study highlights the importance of considering indirect climate impacts via soil microbiota, contributing to a deeper understanding of the real-world consequences of climate change on drylands, and offering valuable insights for the management of biodiversity theory-inspired ecosystem restoration.

ecology↗

bioRxiv2023

Saturation genome editing-based functional evaluation and clinical classification of BRCA2 single nucleotide variants

Germline BRCA2 loss-of function (LOF) variants identified by clinical genetic testing predispose to breast, ovarian, prostate and pancreatic cancer. However, variants of uncertain significance (VUS) (n>4000) limit the clinical use of testing results. Thus, there is an urgent need for functional characterization and clinical classification of all BRCA2 variants. Here we report on comprehensive saturation genome editing-based functional characterization of 97% of all possible single nucleotide variants (SNVs) in the BRCA2 DNA Binding Domain hotspot for pathogenic missense variants that is encoded by exons 15 to 26. The assay was based on deep sequence analysis of surviving endogenously targeted haploid cells. A total of 7013 SNVs were characterized as functionally abnormal (n=955), intermediate/uncertain, or functionally normal (n=5224) based on 95% agreement with ClinVar known pathogenic and benign standards. Results were validated relative to batches of nonsense and synonymous variants and variants evaluated using a homology directed repair (HDR) functional assay. Breast cancer case-control association studies showed that pooled SNVs encoding functionally abnormal missense variants were associated with increased risk of breast cancer (odds ratio (OR) 3.89, 95%CI: 2.77-5.51). In addition, 86% of tumors associated with abnormal missense SNVs displayed loss of heterozygosity (LOH), whereas 26% of tumors with normal variants had LOH. The functional data were added to other sources of information in a ClinGen/ACMG/AMP-like model and 700 functionally abnormal SNVs, including 220 missense SNVs, were classified as pathogenic or likely pathogenic, while 4862 functionally normal SNVs, including 3084 missense SNVs, were classified as benign or likely benign. These classified variants can now be used for risk assessment and clinical care of variant carriers and the remaining functional scores can be used directly for clinical classification and interpretation of many additional variants. SummaryGermline BRCA2 loss-of function (LOF) variants identified by clinical genetic testing predispose to several types of cancer. However, variants of uncertain significance (VUS) limit the clinical use of testing results. Thus, there is an urgent need for functional characterization and clinical classification of all BRCA2 variants to facilitate current and future clinical management of individuals with these variants. Here we show the results from a saturation genome editing (SGE) and functional analysis of all possible single nucleotide variants (SNVs) from exons 15 to 26 that encode the BRCA2 DNA Binding Domain hotspot for pathogenic missense variants. The assay was based on deep sequence analysis of surviving endogenously targeted human haploid HAP1 cells. The assay was calibrated relative to ClinVar known pathogenic and benign missense standards and 95% prevalence thresholds for functionally abnormal and normal variants were identified. Thresholds were validated based on nonsense and synonymous variants. SNVs encoding functionally abnormal missense variants were associated with increased risks of breast and ovarian cancer. The functional assay results were integrated into a ClinGen/ACMG/AMP-like model for clinical classification of the majority of BRCA2 SNVs as pathogenic/likely pathogenic or benign/likely benign. The classified variants can be used for improved clinical management of variant carriers.

genomics↗

bioRxiv2023

Single-cell RNA sequencing unveils the hidden powers of zebrafish kidney for generating both hematopoiesis and adaptive antiviral immunity

The vertebrate kidneys play two evolutionary conserved roles in waste excretion and osmoregulation. Besides, the kidney of fish is considered as a functional ortholog of mammalian bone marrow that serves as a hematopoietic hub for generating blood cell lineages and immunological responses. However, knowledge about the properties of kidney hematopoietic cells, and the functionality of kidney in fish immune systems remain to be elucidated. To this end, our present study generated a comprehensive atlas with 59 hematopoietic stem/progenitor cell (HSPC) and immune-cell types from zebrafish kidney via single-cell transcriptome profiling analysis. These populations included almost all known cells associated with innate and adaptive immunity, and displayed differential responses to viral infection, indicating their diverse functional roles in antiviral immunity. Remarkably, HSPCs were found to have extensive reactivities to viral infection, and the trained immunity can be effectively induced in certain HSPCs. In addition, the antigen-stimulated adaptive immunity can be fully generated in kidney, suggesting kidney acting as a secondary lymphoid organ. These results indicated that fish kidney is a dual-functional entity with functionalities of both primary and secondary lymphoid organs. Our findings illustrated the unique features of fish immune system, and highlighted the multifaced biology of kidney in ancient vertebrates.

immunology↗

bioRxiv2023

Evolution of gene expression across brain regions in behaviorally divergent deer mice

The evolution of innate behaviors is ultimately due to genetic variation likely acting in the nervous system. Gene regulation may be particularly important because it can evolve in a modular brain-region specific fashion through the concerted action of cis- and trans-regulatory changes. Here, to investigate transcriptional variation and its regulatory basis across the brain, we perform RNA sequencing (RNA-Seq) on ten brain subregions in two sister species of deer mice (Peromyscus maniculatus and P. polionotus) - which differ in a range of innate behaviors, including their social system - and their F1 hybrids. We find that most of the variation in gene expression distinguishes subregions, followed by species. Interspecific differential expression (DE) is pervasive (52-59% of expressed genes), whereas the number of DE genes between sexes is modest overall ([~]3%). Interestingly, the identity of DE genes varies considerably across brain regions. Much of this modularity is due to cis-regulatory divergence, and while 43% of genes were consistently assigned to the same gene regulatory class across subregions (e.g., conserved, cis-, or trans-regulatory divergence), a similar number were assigned to two or more different gene regulatory classes. Together, these results highlight the modularity of gene expression differences and divergence in the brain, which may be key to explain how the evolution of brain gene expression can contribute to the astonishing diversity of animal behaviors.

evolutionary biology↗

bioRxiv2023

Metabolites with benzene ring from sugarcane leaf play important role in plant-Spodoptera frugiperda interaction

Secondary metabolism plays important role in plant growth and development, however, the relationship between secondary metabolism and adaptive plant-insect communication is largely unknown. The present study used sugarcane line highly susceptible to Spodoptera frugiperda and sister line with medium resistance to analyze the role of plant non-volatile organic compounds (NOCs) and volatile organic compounds (VOCs) in sugarcane-S. frugiperda interaction. A total of 46 plant NOCs and 15 plant VOCs significantly different between resistant and susceptible lines and were continuously up-regulated and down-regulated at different time points before/after S. frugiperda treatment were screened. Phenolic acids containing benzene ring accounted for the largest proportion of differential NOCs. Levels of 66.7% of these phenolic acids were higher in susceptible line. Feeding supplemented with NOCs showed that phenoxyacetic acid (phenolic acid) and 4-methoxybenzaldehyde (aromatic phenolic acid) both increased the male-to-female ratio of S. frugiperda. Aromatics containing benzene ring, accounted for the largest of differential VOCs in susceptible line. Two aromatics, p-cymene and benzene and 1-ethenyl-4-methoxy-, with higher level in susceptible line, were attractive to S. frugiperda. Terpenoids, aldehyde, and esters accounted for most of higher-in-resistant VOCs, with most tested to be repellent to S. frugiperda. Furthermore, transcriptome analysis of S. frugiperda feeding on susceptible and resistant lines combined with feeding assays revealed that tryptophan, as a precursor of aromatic compounds that also contains benzene ring, could promote the growth and development of S. frugiperda in nutritional deficiency condition. These findings together suggested that benzene-ring containing compounds play a critical role in plant-Spodoptera frugiperda interaction.

ecology↗

bioRxiv2023

Elimination of subtelomeric repeat sequences exerts little effect on telomere functions in Saccharomyces cerevisiae

Telomeres, which are chromosomal end structures, play a crucial role in maintaining genome stability and integrity in eukaryotes. In the bakers yeast Saccharomyces cerevisiae, the X-and Y-elements are subtelomeric repetitive sequences found in all thirty-two and seventeen telomeres, respectively. While the Y-elements serve as a backup for telomere functions in cells lacking telomerase, the function of the X-elements remains unclear. This study utilized the S. cerevisiae strain SY12, which has three chromosomes and six telomeres, to investigate the role of X-elements (as well as Y-elements) in telomere maintenance. Deletion of Y-elements (SY12Y{Delta}), X-elements (SY12XY{Delta}+Y), or both X- and Y-elements (SY12XY{Delta}) did not impact the length of the terminal TG1-3 tracks or telomere silencing. However, inactivation of telomerase in SY12Y{Delta}, SY12XY{Delta}+Y, and SY12XY{Delta} cells resulted in cellular senescence and the generation of survivors. These survivors either maintained their telomeres through homologous recombination-dependent TG1-3 track elongation or underwent microhomology-mediated intra-chromosomal end-to-end joining. Our findings indicate the non-essential role of subtelomeric X-and Y-elements in telomere regulation in both telomerase-proficient and telomerase-null cells and suggest that these elements may represent remnants of S. cerevisiae genome evolution. Furthermore, strains with fewer or no subtelomeric elements exhibit more concise telomere structures and offer potential models for future studies in telomere biology.

genetics↗

bioRxiv2023

Exploiting Activation and Inactivation Mechanisms in Type I-C CRISPR-Cas3 for Genome Editing Applications

Type I CRISPR-Cas systems utilize the RNA-guided Cascade complex to identify matching DNA targets, and the nuclease-helicase Cas3 to degrade them. Among seven subtypes, Type I-C is compact in size and highly active in creating large-sized genome deletions in human cells. Here we use four cryo-electron microscopy snapshots to define its RNA-guided DNA binding and cleavage mechanisms in high resolution. The non-target DNA strand (NTS) is accommodated by I-C Cascade in a continuous binding groove along the juxtaposed Cas11 subunits. Binding of Cas3 further traps a flexible bulge in NTS, enabling efficient NTS nicking. We identified two anti-CRISPR proteins AcrIC8 and AcrIC9, that strongly inhibit N. lactamica I-C function. Structural analysis showed that AcrIC8 inhibits PAM recognition through direct competition, whereas AcrIC9 achieves so through allosteric inhibition. Both Acrs potently inhibit I-C-mediated genome editing and transcriptional modulation in human cells, providing the first off-switches for controllable Type I CRISPR genome engineering.

biochemistry↗

bioRxiv2023

Engineering transposon-associated TnpB-1 ωRNA system for efficient gene editing and disease treatment in mouse

Transposon-associated ribonucleoprotein TnpB is known to be the ancestry endonuclease of diverse Cas12 effector proteins from type-V CRISPR system. Given its small size (409 aa), it is of interest to examine whether engineered TnpB could be used for efficient mammalian genome editing. Here, we showed that the gene editing activity of native TnpB in mouse embryos was already higher than previously identified small-sized Cas12f1. Further stepwise engineering of noncoding RNA ({omega}RNA or reRNA) component of TnpB significantly elevated the nuclease activity of TnpB. Notably, an optimized TnpB-{omega}RNA system could be efficiently delivered in vivo with single adeno-associated virus (AAV) and prevented the disease phenotype in a tyrosinaemia mouse model. Thus, the engineered miniature TnpB system represents a new addition to the current genome editing toolbox, with the unique feature of the smallest effector size that facilitate efficient AAV delivery for editing of cells and tissues.

molecular biology↗

bioRxiv2023

Immuno-Engineered Mitochondria for Efficient Therapy of Acute Organ Injuries via Modulation of Inflammation and Cell Repair

Acute organ injuries represent a major public health concern, and despite recent advances in organ support therapy, managing patients with organ failure stemming from such injuries remains a formidable challenge. The pathogenesis of acute organ injuries is driven by a cascade of inflammatory reactions and mitochondrial dysfunction-mediated cell damage, two interrelated events that fuel a vicious cycle of disease progression. In this study, we engineered neutrophil membrane-fused mitochondria (nMITO) that inherit the injury-targeting and broad-spectrum anti-inflammatory activities from neutrophil membrane proteins while retaining the cell-repairing activity of mitochondria. We demonstrated that nMITO can effectively block the inflammatory cascade and replenish mitochondrial function to simultaneously modulate these two key mechanisms in diverse acute organ injuries. Furthermore, by virtue of the {beta}-integrin inherited from neutrophils, nMITO exhibit selective homing to injured endothelial cells and can be efficiently delivered to damaged tissue cells via tunneling nanotubes, amplifying their regulatory effects on local inflammation and cell injury. In mouse models of acute myocardial injury, acute liver injury, and acute pancreatitis, nMITO effectively ameliorated immune dysfunction and repaired damaged tissues. Our findings suggest that nMITO represents a promising therapeutic strategy for managing acute organ injuries.

bioengineering↗

bioRxiv2023

Spp1 secreted by macrophages impairs osteogenic ability of Ctsk+Fmod+ periosteal cells in jaw bone

Periosteum, which covers the surface of most bones, mediates bone regeneration through endochondral ossification during fracture repair and intramembranous ossification under steady state. Periosteal cells (PCs) of jaw bones are different from those of long bones in phenotypic characteristics and functions. So far, the role of periosteum in jaw bones during bone grafting remain unclarified. Here we propose a subperiosteal bone grafting model based on the clinical procedures. By integrating single-cell RNA sequencing (scRNA-seq) and spatial transcriptomic (ST), we found a functional Ctsk+Fmod+ subset of PCs in jaw bones. The Ctsk+Fmod+ PCs had the potential of multi-directional differentiation. Furthermore, Spp1 secreted by macrophages could impair the osteogenic capacity of Ctsk+Fmod+ PCs, which could be partly rescued by blocking Spp1. The identification of this Ctsk+Fmod+ subclusters, which shows osteoprogenitor characteristics and close interaction with macrophages, reveals the heterogeneity of periosteal cells in jaw bones, and may provide target of intervention to improve osteogenesis during bone augmentation surgery.

cell biology↗

bioRxiv2023

Spider: a flexible and unified framework for simulating spatial transcriptomics data

Spatial transcriptomics technology provides a valuable view for studying cellular heterogeneity due to its ability to simultaneously acquire gene expression profile and cell location information. However, benchmarking these rapidly accumulating spatial transcriptomics analysis tools is challenging owing to the limited diversity and accuracy of "gold standard" data sets annotated by pathologists. To address this issue, we proposed Spider, a flexible and unified simulator for spatial transcriptomics data guided by cell type proportion and transition matrix of adjacent cell types. Taking advantage of a heuristic batched simulated annealing algorithm (BSA) in assigning simulated cell type labels, Spider can generate spatial transcriptomics data for one million cells in just five minutes. Furthermore, Spider can generate various types of spatial transcriptomics data, including immune hot/cold tumor samples by specifying different immune cell proportions and transition matrices and layered tissue samples via an interactive interface. In addition, Spider is also a unified framework for ST data simulation in which we have implemented diverse simulators proposed by other researchers as special cases. We have systematically evaluated the performance of Spider and competing tools, and demonstrated Spiders remarkable power to capture the spatial pattern of the reference dataset. Spider is available at https://github.com/YANG-ERA/Artist.

bioinformatics↗

bioRxiv2023

Distinct interactions stabilize EGFR dimers and higher-order oligomers in cell membranes

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) with important roles in many cellular processes as well as cancer and other diseases. EGF binding promotes EGFR dimerization and autophosphorylation through interactions that are well understood structurally. However, it is not clear how these dimers relate to higher-order EGFR oligomers detected at the cell surface. We used single-particle tracking (SPT) and Forster resonance energy transfer (FRET) imaging to examine how each domain within EGFR contributes to receptor dimerization and the rate of its diffusion in the cell membrane. We show that the EGFR extracellular region is sufficient to drive receptor dimerization, but that the EGF-induced EGFR slow-down seen by SPT requires formation of higher order oligomers, mediated in part by the intracellular tyrosine kinase domain - but only when in its active conformation. Our data thus provide important insight into higher-order EGFR interactions required for EGF signaling.

biophysics↗

bioRxiv2023

Chromosome-level genome assembly provides insights into adaptive evolution of chromosome and important traits in the gecko Gekko japonicus

Gekko japonicus possess excellent flexible climbing and detoxification ability under insectivorous habits, and its chromosomes and the genetic evolutionary mechanisms behind these traits are still unclarified. Here, we assembled a chromosome-level genome of G. japonicus with a total size of 2.53 Gb contained in 19 pairs of chromosomes. The evolutionary breakpoint regions (EBRs) are significantly enriched for some repetitive elements compared to the rest of genome and the genes located in the EBRs are enriched in defense response pathway. G. japonicus specific gene families, expanded gene families and positively selected genes are mainly enriched in some pathways related to the immune, sensory and nervous systems. These results from comprehensive comparative genomics and evolutionary genomics analyses indicated that bitter taste receptor type 2 (T2Rs) expanded in different lineages by tandem gene duplication. The expansion and independent duplication events of T2Rs and positively selected branches were predominantly present in insectivorous species, suggests that T2Rs are associate with clearance of bitter toxins in gekkotans. Detoxification genes in detox and biosynthetic cytochrome P450 of G. japonicas have frequent duplication and loss events, suggests that they undergo more birth and death processes compared to biosynthesis type genes. Pro, Cys, Gly and Ser are the most abundant amino acids in 66 epidermis formation corneous beta proteins (CBPs) of G. japonicas, the abundance of Gly and Cys in CBPs implying significant effects on the flexibility and setae adhesiveness of gekkotans. Some thermosensitive thermoregulatory transient receptor potential channels under relaxed purifying selection or positive selection in G. japonicus, implying that one of the important factors improve the ability to adapt to climate change.

genomics↗

bioRxiv2023

Two haplotype-resolved genomes of highly heterozygous AAB allotriploid bananas provide insights into subgenome asymmetric evolution and banana wilt control

Bananas (Musa spp.) are one of the most important tropical fruits and staple food, which are of great significance to human societies. Plantain and Silk are two important banana subgroups, which are both triploid hybrids (AAB) between the wild diploid Musa acuminata and M. balbisiana. In this study, we reported the first haplotype-resolved genome assembly of Plantain and Silk bananas with genome size of approximately 1.4 Gb. We discovered widespread asymmetric evolution in the subgenomes of Plantain and Silk, which could be linked to frequent homologous exchanges (HEs) events. This is the first study to uncover the genetic makeup of triploid banana and verify that subgenome B harbors a rich source of resistance genes. Of the 88,078 and 94,988 annotated genes in Plantain and Silk, only 58.5% and 59.4% were present in all three subgenomes, with >50% genes containing differently expressed alleles in different haplotypes. We also found that Plantain is more resistant to banana Fusarium wilt, exhibiting a much faster defense response after pathogenic fungi infection. Many differentially expressed genes in abscisic acid, ethylene, jasmonic acid and salicylic acid pathways were identified in Plantain. Our analysis revealed that MpMYB36 promotes the biosynthesis of secondary cell wall and deposition of lignin by directly binding to the promoter of MpPAL and MpHCT, which allows Plantain to inhibit the penetration of early infection. Moreover, the insertion of the key carotenoid synthesis gene (CRTISO) may be the potential genetic basis for the richness of carotenoids in Plantain. Our study provides an unprecedented genomic basis for basic research and the development of elite germplasm in cultivated bananas.

plant biology↗