Biology subjects

Yan, Z.

Publications and source records attributed to Yan, Z..

At least 73 records · Page 4Linked to original sources

bioRxiv2023

Armillaria korhonenii, the sixteenth biological species of Armillaria from China

Armillaria korhonenii, designated as Chinese biological species Q (CBSQ) here, is described as a new species based on phylogenetic and morphological evidence as well as the results of mating tests. This species is the sixteenth biological species of Armillaria reported from China following the discovery of 15 previously known biological species. Phylogenetically, A. korhonenii is the earliest divergent lineage of the genus Armillaria as inferred from the nucleotide sequences of the Elongation Factor 1-Alpha (EF1a). Morphologically, it is characterized by its ellipsoid to elongate basidiospores, yellowish orange to honey yellow pileus with fibrillose squamules. Mating tests indicated that A. korhonenii is a tetrapolar heterogeneous species and is inter-sterile with all the tested species except partial compatibility with CBSH.

microbiology↗

bioRxiv2023

A time-resolved multi-omics atlas of transcriptional regulation in response to high-altitude hypoxia across whole-body tissues

High-altitude hypoxia acclimatization requires whole-body physiological regulation in highland immigrants, but the underlying genetic mechanism has not been clarified. Here we used sheep as an animal model for plain-to-plateau transplantation. We generated multi-omics data including time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues as well as phenotypic data from 20 bio-indicators. We characterized transcriptional changes of all genes in each tissue, and examined multi-tissue temporal dynamics and transcriptional interactions among genes. In particular, we identified critical functional genes regulating the short response to hypoxia in each tissue (e.g., PARG in the cerebellum and HMOX1 in the colon). We further identified TAD-constrained cis-regulatory elements, which suppressed the transcriptional activity of most genes under hypoxia. Phenotypic and transcriptional evidence indicated that antenatal hypoxia could improve hypoxia tolerance in offspring. Furthermore, we provided time-series expression data of candidate genes associated with human mountain sickness (e.g., BMPR2) and high-altitude adaptation (e.g., HIF1A). Our study provides valuable resources and insights for future hypoxia-related studies in mammals.

genetics↗

bioRxiv2023

Novel Epidermal Oxysterols Function as Alarm Substances in Zebrafish

Aquatic animals often use chemical cues to signal predation risk. When injured, shoaling fish skins release alarm substances that induce intense fear and a suite of anti-predator behaviors in other shoal members. However, the chemical nature of alarm substances remains largely unknown. Here we show that zebrafish alarm substance comprises 24-methyl-5-cholestane-3,7,12,24,28-pentahydroxy 28-sulfate, a novel oxysterol sulfate, and 5-cyprinol sulfate. These compounds are present in zebrafish skin extract and, at concentrations of less than one nanomolar, each induces anti-predator behaviors and increases cortisol levels. Their mixture, at its natural ratio, replicates the skin extract in eliciting the full suite of anti-predator behavior patterns. Our findings reveal a molecular-level mechanism whereby fish signal predation danger.

animal behavior and cognition↗

bioRxiv2023

Identification of Host Restriction Factors Critical for Recombinant AAV Transduction of Polarized Human Airway Epithelium

Recombinant (r)AAV2.5T was selected from the directed evolution of an AAV capsid library in human airway epithelium (HAE). The capsid gene of rAAV2.5T is a chimera of the N-terminal unique coding sequence of AAV2 VP1 unique (VP1u) and the VP2- and VP3-coding sequence of AAV5 with a single amino acid mutation of A581T. We conducted two rounds of genome wide CRISPR gRNA library screening for host factors limiting rAAV2.5T transduction in HeLa S3 cells. The screen identified several genes that are critical for rAAV2.5T transduction in HeLa S3 cells, including previously reported genes KIAA0319L, TM9SF2, VPS51, and VPS54, as well as a novel gene WDR63. We verified the role of KIAA0319L and WDR63 in rAAV2.5T transduction of polarized HAE by utilizing CRISPR gene knockouts. Although KIAA0319L, a proteinaceous receptor for multiple AAV serotypes, played an essential role in rAAV2.5T transduction of polarized HAE either from apical or basolateral side, our findings demonstrated that the internalization of rAAV2.5T was independent of KIAA0319L. Importantly, we confirmed WDR63 is an important player in rAAV2.5T transduction of HAE, while not being involved in vector internalization and nuclear entry. Furthermore, we identified that the basal stem cells of HAE can be significantly transduced by rAAV2.5T. SignificanceThe essential steps of a successful gene delivery by rAAV include vector internalization, intracellular trafficking, nuclear import, uncoating, double-stranded (ds)DNA conversion, and transgene expression. rAAV2.5T has a chimeric capsid of AAV2 VP1u and AAV5 VP2 and VP3 with the mutation A581T. Our investigation revealed that KIAA0319L, the multiple AAV serotype receptor, is not essential for vector internalization but remains critical for efficient vector transduction to human airway epithelia. Additionally, we identified that a novel gene WDR63, whose cellular function is not well understood, plays an important role in vector transduction of human airway epithelia but not vector internalization and nuclear entry. Our study also discovered the substantial transduction potential of rAAV2.5T in basal stem cells of human airway epithelia, underscoring its utility in gene editing of human airways. Thus, the knowledge derived from this study holds promise for the advancement of gene therapy in the treatment of pulmonary genetic diseases.

microbiology↗

bioRxiv2023

LUZP1 regulates the assembly of stress fibers by promoting maturation of contractile actomyosin bundles

Contractile actomyosin bundles play crucial roles in various physiological processes, including cell migration, morphogenesis, and muscle contraction. The intricate assembly of actomyosin bundles involves the precise alignment and fusion of myosin II filaments, yet the underlying mechanisms and factors involved in these processes remain elusive. Our study reveals that LUZP1, a leucine zipper protein, plays a central role in orchestrating the formation of thick actomyosin bundles. Loss of LUZP1 caused abnormal cell morphogenesis, migration, and the ability to exert forces on the environment. Importantly, knockout of LUZP1 results in significant defects in the concatenation and persistent association of myosin II filaments, severely impairing the assembly of myosin II stacks. The disruption of these processes in LUZP1 knockout cells provides mechanistic insights into the defective assembly of thick ventral stress fibers and the associated cellular contractility abnormalities. Overall, these results significantly contribute to our understanding of the molecular mechanism involved in actomyosin bundle formation and highlight the essential role of LUZP1 in this process.

cell biology↗

bioRxiv2023

GametesOmics: A Comprehensive Multi-Omics Database for Exploring the Gametogenesis in Humans and Mice

Gametogenesis plays an important role in the reproduction and evolution of species. The transcriptomic and epigenetic alterations in this process can influence the reproductive capacity, fertilization, and embryonic development. The rapidly increasing single-cell studies have provided valuable multi-omics resources. However, data from different layers and sequencing platforms have not been uniformed and integrated, which greatly limits their use for exploring the molecular mechanisms that underlie oogenesis and spermatogenesis. Here, we developed GametesOmics, a comprehensive database that integrated the data of gene expression, DNA methylation, and chromatin accessibility during oogenesis and spermatogenesis in humans and mice. GametesOmics provides a user-friendly website and various tools, including Search and Advanced Search for querying the expression and epigenetic modification of each gene; Analysis Tools with Differentially Expressed Gene (DEG) analysis for identifying DEGs, Correlation analysis for demonstrating the genetic and epigenetic changes, Visualization for displaying single-cell cluster and screening marker genes as well as master transcription factors (TFs), and MethylView for studying the genomic distribution of epigenetic modifications. GametesOmics also provides Genome Browser and Orthologs for tracking and comparing gene expression, DNA methylations, as well as chromatin accessibilities between humans and mice. GametesOmics offers a comprehensive resource for biologists and clinicians to decipher the cell fate transition in germ cell development, and can be accessed at http://gametesomics.cn/.

bioinformatics↗

bioRxiv2023

Two-way feedback between chromatin compaction and histone modification state explains S. cerevisiae heterochromatin bistability

Compact chromatin is closely linked with gene silencing in part by sterically masking access to promoters, inhibiting transcription factor binding and preventing polymerase from efficiently transcribing a gene. Here, we propose a broader view: chromatin compaction can be both a cause and a consequence of the histone modification state, and this tight bidirectional interaction can underpin bistable transcriptional states. To test this theory, we developed a mathematical model for the dynamics of the HMR locus in S. cerevisiae, that incorporates activating histone modifications, silencing proteins and a dynamic, acetylation-dependent, three-dimensional locus size. Chromatin compaction enhances silencer protein binding, which in turn feeds back to remove activating histone modifications, leading to further compaction. The bistable output of the model was in good agreement with prior quantitative data, including switching rates from expressed to silent states, and vice versa, and protein binding levels within the locus. We then tested the model by predicting changes in switching rates as the genetic length of the locus was increased, which were then experimentally verified. This bidirectional feedback between chromatin compaction and the histone modification state may be an important regulatory mechanism at many loci. SignificanceChromatin is the complex formed by proteins, including histones, and DNA to form chromosomes. Specific chromatin structures and states are thought to be key factors regulating transcription. A common view proposes that histone modifications activate or inhibit transcription either via specific activation or inhibition of RNA polymerase binding/elongation at a locus, or by expanding/compacting the locus, thereby modulating its accessibility to many macromolecules. In this work, we elucidated a broader hypothesis that chromatin compaction may both inhibit transcription, and feedback via silencing proteins to remove histone modifications that further control chromatin compaction and correlate with gene activity. We developed a model incorporating these ideas and showed that it explains quantitative experimental data for a silent locus in budding yeast.

systems biology↗

bioRxiv2023

RFC1 AAGGG pentanucleotide repeats form parallel G-quadruplex: structural implications for aberrant molecular cascades in CANVAS

A pentanucleotide repeat expansion (PRE) of (AAGGG)n in the replication factor C subunit 1 (RFC1) gene is recently identified as the genetic cause of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), and also linked to several other neurodegenerative disorders including the Parkinsons disease. However, the molecular mechanism by which RFC1 PRE drives pathology remains poorly understood. Here, for the first time we discovered and determined the high-resolution structures of parallel G-quadruplex formed by AAGGG repeats within the pathogenic RFC1 PRE, revealing an intriguing conformational plasticity at the 3-termi that allows stacking of multiple G4s. We further identify a molecular mechanism by which the DNA G4 in RFC1 PRE impedes polymerase processivity leading to replication stalling and transcription inhibition in vitro in a repeat-length-dependent manner, and the transcription inhibition could partially contribute to a reduced gene expression in cells. Our results demonstrate that the DNA G-quadruplex of RFC1 PRE participate in aberrant molecular cascades, and provide an unprecedented high-resolution structural target to discover helicases and ligands that resolve the pathogenic G4 for therapeutic intervention.

biochemistry↗

bioRxiv2023

Butyrate Protects against SARS-CoV-2-induced Tissue Damage in Golden Hamsters.

Butyrate, produced by gut microbe during dietary fiber fermentation, plays anti-inflammatory and antioxidant effects in chronic inflammation diseases, yet it remains to be explored whether butyrate has protective effects against viral infections. Here, we demonstrated that butyrate alleviated tissue injury in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected golden hamsters with supplementation of butyrate before and during the infection. Butyrate-treated hamsters showed augmentation of type I interferon (IFN) response and activation of endothelial cells without exaggerated inflammation. In addition, butyrate regulated redox homeostasis by enhancing the activity of superoxide dismutase (SOD) to inhibit excessive apoptotic cell death. Therefore, butyrate exhibited an effective prevention against SARS-CoV-2 by upregulating antiviral immune responses and promoting cell survival. IMPORTANCESince SARS-CoV-2 has caused severe disease characterized by acute respiratory distress syndrome (ARDS) in humans, it is essential to develop therapeutics based on relieving such severe clinical symptoms. Current therapy strategies mainly focus on individuals who have COVID-19, however, there is still a strong need for prevention and treatment of SARS-CoV-2 infection. This study showed that butyrate, a bacterial metabolite, improved the response of SARS-CoV-2-infected hamsters by reducing immunopathology caused by impaired antiviral defenses and inhibiting excessive apoptosis through reduction in oxidative stress.

microbiology↗

bioRxiv2023

Assessing RNAi feasibility and susceptibility to environmental RNAi in Trichogramma dendrolimi (Hymenoptera: Trichogrammatidae)

Trichogramma, a genus of egg parasitoid wasps, are widely used as biological control agents and serve as model organisms in parasitoid research. Despite their significance, the understanding of RNA interference (RNAi) in Trichogramma remains very limited. In this study, we investigated RNAi-associated genes by bioinformatic approaches and experimentally assessed the feasibility of RNAi and the susceptibility of environmental RNAi in Trichogramma. We found that Trichogramma genomes contain a complete set of genes in the RNAi pathway and exhibit extensive gene expansion of dsRNase, which may influence RNAi efficiency by degrading dsRNA. We demonstrated successful RNAi through pupal microinjection in T. dendrolimi Matsumura, providing a technical approach for future gene functional studies. In addition, we observed no evidence of susceptibility to environmental RNAi in either T. dendrolimi adults or larvae, which might be attributed to the extensive expansion of dsRNase. This low environmental RNAi sensitivity in Trichogramma could suggest a reduced risk of RNAi-based pest management strategies affecting nontarget Trichogramma populations. Overall, this study presents a technical approach for conducting gene functional studies in Trichogramma and provides a foundation for evaluating the nontarget effects of RNAi-based pest control strategies on Trichogramma.

molecular biology↗

bioRxiv2023

Use of Artificial Intelligence for Automated Detection and Surveillance of Red Imported Fire Ants Nests

The red imported fire ant, Solenopsis invicta Buren is a destructive invasive species that has spread around the world. Early detection of S. invicta nests is critical for effective monitoring and control in invaded regions. This study presents a novel surveillance system for S. invicta nests combining artificial intelligence and robotic dogs. The system was designed with intelligent recognition algorithms to accurately identify S. invicta nests. With a precision rate of 95%, the system yielded efficient detection of S. invicta nests with increased sensitivity and low missing and false discovery rates, which can aid or even replace humans in locating and delivering pesticides to fire ant nests in open fields to effective control of this invasive pest.

ecology↗

bioRxiv2023

A parasitoid serpin gene that disrupts host immunity shows adaptive evolution of alternative splicing

Alternative splicing (AS) is a major source of protein diversity in eukaryotes, but less is known about its evolution compared to gene duplication (GD). How AS and GD interact is also largely understudied. By constructing the evolutionary trajectory of a serpin gene PpSerpin-1 (Pteromalus puparum serpin 1) in parasitoids and other insects, we found that both AS and GD jointly contribute to serpin protein diversity. These two processes are negatively correlated and show divergent features in both protein and regulatory sequences. Furthermore, parasitoid wasps exhibit higher numbers of serpin protein/domains than nonparasitoids, resulting from more GD but less AS in parasitoids. Nevertheless, PpSerpin-1 shows an exon expansion of AS compared to other parasitoids. We find that several isoforms of PpSerpin-1 are involved in the wasp immune response, have been recruited to both wasp venom and larval saliva, and suppress host immunity. In summary, we report the differential features of AS and GD in the evolution of insect serpins and their associations with the parasitic life strategy, and we provide an example of how a parasitoid serpin gene adapts to parasitism through AS.

evolutionary biology↗

bioRxiv2023

The genomic landscape of swine influenza A viruses in Southeast Asia

Swine are a primary source for the emergence of pandemic influenza A viruses. The intensification of swine production, along with global trade, has amplified the transmission and zoonotic risk of swine influenza virus (swIAV). Effective surveillance is essential to uncover emerging virus strains, however gaps remain in our understanding of the swIAV genomic landscape in Southeast Asia. By collecting more than 4,000 nasal swabs and 4,000 sera from pigs in Cambodia, we unmasked the co-circulation of multiple lineages of genetically diverse swIAV of pandemic concern. Genomic analyses revealed a novel European avian-like H1N2 swine reassortant variant with North American triple reassortant internal genes, that emerged approximately seven years before its first detection in pigs in 2021. Using phylogeographic reconstruction, we identified south central China as the dominant source of swine viruses disseminated to other regions in China and Southeast Asia. We also identified nine distinct swIAV lineages in Cambodia, which diverged from their closest ancestors between two to 15 years ago, indicating significant undetected diversity in the region, including reverse zoonoses of human H1N1/2009 pandemic and H3N2 viruses. A similar period of cryptic circulation of swIAVs occurred in the decades before the H1N1/2009 pandemic. The hidden diversity of swIAV observed here further emphasizes the complex underlying evolutionary processes present in this region, reinforcing the importance of genomic surveillance at the human-swine interface for early warning of disease emergence to avoid future pandemics.

microbiology↗

bioRxiv2022

The pan-genome and local adaptation of Arabidopsis thaliana

Arabidopsis thaliana has been used as a model species for research in a diverse collection of plant species. However, previous studies based on single reference genomes and short-read sequencing data are restricted to detecting variable genes and large structural variation (SV) underlying local adaptation. Here we de novo assemble high-quality chromosomal genomes of 38 A. thaliana ecotypes (with 6 relict ones) using PacBio-HiFi long-read sequencing. From these newly assembled genomes, we annotate several thousand new genes through pan-genomic analysis in comparison to the previous reference genome. The identified variable genes are mainly enriched in and associated with ecological adaptation and this species substantially expands its gene repertoire for local adaptation. We construct a graph-based pan-genome and identify 62,525 SVs which overlap with 14,243 genes. These genes are enriched in multiple ecological adaptation functions, including secondary metabolic processes, enzyme regulation, and biotic/abiotic stimulus. For example, a 566 bp insertion in the promoter of the light-adaptation KNAT3 gene was specific to the high-altitude relict Tibet-0 ecotype. This SV reduces the expression level of KNAT3 and promotes A. thaliana adaptation to habitats high in light radiation. In addition, compared with the SNPs, the SVs identified in this study captured the missing heritability and we detected novel SV associations with environmental variables in their native range, highlighting the value of SVs in environmental adaptation. The genome resources presented here will help pinpoint genetic changes that include both SVs and the ecotype-specific genes for local adaptation of A. thaliana and increase our understanding of the molecular mechanisms in this model species to respond to varied habitats.

genomics↗

bioRxiv2022

Long-read genome assemblies reveals a cis-regulatory landscape associated with phenotypic divergence in two sister Siniperca fishes

BackgroundDissecting the genetic basis of variation in the regulation of gene expression is essential for understanding phenotypic evolution. Structural variants intersecting the cis-regulatory elements are found to cause gene expression variation in several developmental genes, resulting in morphological divergence between species. Due to the difficulty of identifying structural variants accurately across the genome, a comprehensive study of impacts of structural variants in cis-regulatory divergence of closely related species, especially fish species, is still scarce. Recently identified broad H3K4me3 domains are essential for the regulation of genes involved in several biological processes. However, the role of broad H3K4me3 domains in phenotypic divergence remain poorly understood. Siniperca chuatsi and S. scherzeri are two closely related fish species diverge in several phenotypic traits, making them an ideal model to study cis-regulatory evolution in closely related species. ResultsWe generated chromosome-level genomes of S. chuatsi and S. scherzeri. The evolutionary histories of S. chuatsi and S. scherzeri were studied by inferring the dynamic changes in the ancestral population sizes. The genetic basis of adaptation in S. chuatsi and S. scherzeri was dissected by performing gene family expansion and contraction analysis and identifying positively selected genes (PSGs). To investigate the role of SVs in cis-regulatory divergence of closely related fish species, we identified high-quality SVs between S. chuatsi and S. scherzeri, as well as H3K27ac and H3K4me3 domains. Integrated analysis revealed that cis-regulatory divergence caused by SVs played an essential role in the differentiation of metabolism, skin pigmentation, and immunity between S. chuatsi and S. scherzeri. Additionally, divergent broad H3K4me3 domains were found to mostly associate with cancer-related genes in S. chuatsi and S. scherzeri and contribute to their phenotypic divergence. ConclusionsOur analysis reveals SVs play an essential role in cis-regulatory variation between the two sister fish species, which in turn contributes to their phenotypic divergence. The divergence of broad H3K4me3 domains contributes to phenotypic divergence between closely related species. Additionally, the association of broad H3K4me3 domains and cancer-related genes has an ancient origin.

genomics↗

bioRxiv2022

Single-cell analysis of prenatal and postnatal human cortical development

We analyze more than 700,000 single-nucleus RNA-seq profiles from 106 donors during prenatal and postnatal developmental stages and identify lineage-specific programs that underlie the development of specific subtypes of excitatory cortical neurons, interneurons, glial cell types and brain vasculature. By leveraging single-nucleus chromatin accessibility data, we delineate enhancer-gene regulatory networks and transcription factors that control commitment of specific cortical lineages. By intersecting our results with genetic risk factors for human brain diseases, we identify the cortical cell types and lineages most vulnerable to genetic insults of different brain disorders, especially autism. We find that lineage-specific gene expression programs upregulated in female cells are especially enriched for the genetic risk factors of autism. Our study captures the molecular progression of cortical lineages across human development. One Sentence SummarySingle-cell transcriptomic atlas of human cortical development identifies lineage and sex-specific programs and their implication in brain disorders.

neuroscience↗

bioRxiv2022

Comparing Inference under the MSC versus the MSC-with-Recombination

Accurate inference of population parameters plays a pivotal role in unravelling the evolutionary histories. While recombination has been universally accepted as a fundamental process in the evolution of sexually reproducing organisms, it remains challenging to model it exactly. Thus, existing coalescent-based approaches make different assumptions or approximations to facilitate phylogenetic inference, which can potentially bring about biases in estimates of evolutionary parameters when recombination is present. In this article, we evaluate the performance of population parameters estimation using three classes of methods: StarBEAST2, SNAPP, and diCal2. We performed whole-genome simulations in which recombination rates, mutation rates, and levels of ILS were varied. We show that StarBEAST2 using short or medium-sized loci is robust to realistic rates of recombination, which is in agreement with previous studies. SNAPP, as expected, is generally unaffected by recombination events. Most surprisingly, diCal2, a method that is designed to explicitly account for recombination, performs considerably worse than other methods under comparison.

evolutionary biology↗

bioRxiv2022

"Correcting'' gene trees to be more like species trees increases topological error when incomplete lineage sorting is high

The evolutionary histories of individual loci in a genome can be estimated independently, but this approach is error-prone due to the limited amount of sequence data available for each gene, which has led to the development of a diverse array of gene tree error correction methods which reduce distance to the species tree. We investigate the performance of two representatives of these methods: TRACTION and TreeFix, in the case where incomplete lineage sorting is high. We found that gene tree error correction only increases the level of error in gene tree topologies by "correcting" them to be closer to the species tree, even when the true gene and species trees are discordant. We confirm that full Bayesian inference of the gene trees under the multispecies coalescent model is more accurate than independent inference. Gene tree correction must be considered a multi-locus task where the gene tree distribution is taken into account, rather than treating gene trees independently. Significance statementGene tree information is essential for studying elucidating gene, genome, species, and phenotypic evolution, and a wide array of phylogenetic methods have been developed for gene tree estimation. Given that gene tree estimates are often inaccurate, several methods for "correcting" gene tree estimates have been devised. Here we show that correction methods that neglect the distribution of gene trees that is induced by the species phylogeny could produce poor results, calling for the development of species phylogeny-aware gene tree correction.

evolutionary biology↗