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Gong, L.

Publications and source records attributed to Gong, L..

At least 37 records · Page 2Linked to original sources
bioRxiv2024

Engineered minimal type I CRISPR-Cas system for transcriptional activation and base editing in human cells

Type I CRISPR-Cas systems are widespread and have exhibited remarkable versatility and efficiency in genome editing and gene regulation in prokaryotes. However, due to the multi-subunit composition and large size, their application in eukaryotes has not been thoroughly investigated. Here, we demonstrate that the type I-F2 Cascade, the most compact among type I systems and significantly smaller than SpCas9, can be developed into programmable tools for use in human cells. For transcriptional activation, the efficiency of the tool based on the engineered I-F2 system can match or surpass that of dCas9. Besides, narrow editing windows limit the application of base editors. Although the R-loop formed by Cascade is much wider than that by Cas9 or Cas12, the potential of base editing with Cascade has not yet been explored. We successfully created a base editor with the I-F2 Cascade, which induces a considerably wide editing window ([~]30 nt) with a bimodal distribution. The wide editing window can expand the range of targetable sites and can be useful for disrupting functional sequences and genetic screening. The editing efficiency can achieve 50% in human cells. This research underscores the application potential of compact type I systems in eukaryotes and developed a new base editor with an extraordinary wide editing window.

molecular biology↗
bioRxiv2024

Embryonic origins of forebrain oligodendrocytes revisited by combinatorial genetic fate mapping

Multiple embryonic origins give rise to forebrain oligodendrocytes (OLs), yet controversies and uncertainty exist regarding their differential contributions. We established intersectional and subtractional strategies to genetically fate map OLs produced by medial ganglionic eminence/preoptic area (MGE/POA), lateral/caudal ganglionic eminences (LGE/CGE) and dorsal pallium. We found that, contrary to the canonical view, LGE/CGE-derived OLs make minimum contributions to the neocortex and corpus callosum, but dominate piriform cortex and anterior commissure. Additionally, MGE/POA-derived OLs, instead of being entirely eliminated, make small but sustained contribution to cortex with a distribution pattern distinctive from those derived from the dorsal origin. Our study provides a revised and more comprehensive view of cortical and white matter OL origins, and established valuable new tools and strategies for future OL studies.

neuroscience↗
bioRxiv2023

eRNA-IDO: a one-stop platform for identification, interactome discovery and functional annotation of enhancer RNAs

Increasing evidence proves the transcription of enhancer RNA (eRNA) and its important role in gene regulation. However, we are only at the infancy stage of understanding eRNA interactions with other biomolecules and the corresponding functionality. To accelerate eRNA mechanistic study, we present the first integrative computational platform for human eRNA identification, interactome discovery, and functional annotation, termed eRNA-IDO. eRNA-IDO comprises two modules: eRNA-ID and eRNA-Anno. Functionally, eRNA-ID identifies eRNAs from de novo assembled transcriptomes. The bright spot of eRNA-ID is indeed the inclusion of 8 kinds of enhancer makers, whose combination enables users to personalize enhancer regions flexibly and conveniently. In addition, eRNA-Anno provides cell/tissue specific functional annotation for any novel and known eRNAs through discovering eRNA interactome from the prebuilt or user-defined eRNA-coding gene networks. The pre-built networks include GTEx-based normal co-expression networks, TCGA-based cancer co-expression networks, and omics-based eRNA-centric regulatory networks. Our eRNA-IDO carries sufficient practicability and significance for understanding the biogenesis and functions of eRNAs. The eRNA-IDO server is freely available at http://bioinfo.szbl.ac.cn/eRNA_IDO/.

bioinformatics↗
bioRxiv2023

Abundant microorganisms in soil are mainly controlled by stochastic processes, while bacteria and fungi differ in rare taxa

The assembly mode of microbial communities helps to explain the ecological processes of soil subsurface groups, and abundant and rare microorganisms have their own unique assembly patterns. In this paper, the effect of changing vegetation types on the assembly of bacteria and fungi with different abundances in soil was investigated by iCAMP in the Tianshan Mountains. The results showed that: (i) there were differences in the distribution of rare and abundant microbial communities among different vegetation types: the main trends were forests>shrubs > grasslands, and the diversity and variability of rare microorganisms were greater than those of abundant taxa; (ii) abundant taxa were mainly affected by stochastic processes (mainly diffusion limitation), whereas among rare microbes, the main controlling process for bacteria was heterogeneous selection and for fungi was diffusion limitation; ()soil carbon, nitrogen and temperature were important determinants driving bacterial community structure. Our results deepen the understanding of the various ecological processes involved in microbial community assembly, reveal the effects of environmental factors on abundant and rare microorganisms, and provide evidence for understanding the mechanisms of soil microbial community construction among different vegetation covers in arid zones. ImportanceThe study compares the response of different vegetation types to soil microbial community processes in the arid zone and deepens the understanding of the mechanisms of soil microbial community composition at different abundances.

ecology↗
bioRxiv2023

INHBA/Activin A promotes tumor growth and induces resistance to anti-PD-L1 therapy by suppressing IFN-γ signaling

Inhibin beta A (INHBA) and its homodimer activin A have pleiotropic effects on modulation of immune responses and tumor progression, respectively, but it remains uncertain whether tumors may release activin A to regulate anti-tumor immunity. As evidenced by our RNA-Seq and in vitro results, the interferon-{gamma} (IFN-{gamma}) signaling pathway was significantly down-regulated by tumor intrinsic activin A. Tumor INHBA deficiency led to lower expression of PD-L1 induced by IFN-{gamma}, resulting in poor responsiveness to anti-PD-L1 therapy. On the other hand, decreased secretion of IFN-{gamma}-stimulated chemokines, including C-X-C motif chemokine 9 (CXCL9) and 10 (CXCL10), impaired the infiltration of effector T cells into the tumor microenvironment. Furthermore, the activin A-specific antibody garetosmab improved anti-tumor immunity and its combination with the anti-PD-L1 antibody atezolizumab showed a superior therapeutic effect to monotherapy. Our findings reveal that INHBA/activin A is involved in anti-tumor immunity by inhibiting the IFN-{gamma} signaling pathway and considered to be a potential target to overcome anti-PD-L1 resistance in clinical cancer treatment.

immunology↗
bioRxiv2023

Heparan sulfate dependent phase separation of CCL5 and its chemotactic activity

Secreted chemokines form concentration gradients in target tissues to control migratory directions and patterns of immune cells in response to inflammatory stimulation; however, how the gradients are formed is much debated. Heparan sulfate (HS) binds to chemokines and modulates their activities. In this study, we investigated the roles of HS in the gradient formation and chemoattractant activity of CCL5 that is known to bind to HS. CCL5 and heparin underwent liquid-liquid phase separation (LLPS) and formed gradient, which was confirmed using CCL5 immobilized on heparin-beads. The biological implication of HS in CCL5 gradient formation was established in CHO-K1 (wild type) and CHO-677 (lacking HS) cells by Transwell assay. The effect of HS on CCL5 chemoattractant activity was further proved by Transwell assay of human peripheral blood cells. Finally, peritoneal injection of the chemokines into mice showed reduced recruitment of inflammatory cells either by mutant CCL5 (lacking heparin binding sequence) or by addition of heparin to wild type CCL5. Our experimental data propose that co-phase separation of CCL5 with HS establishes a specific chemokine concentration gradient to trigger directional cell migration. The results warrant further investigation on other heparin binding chemokines and allows for a more elaborate insight into disease process and new treatment strategies.

cell biology↗
bioRxiv2022

Evolutionary trajectory of organelle-derived nuclear DNAs in the Triticum/Aegilops complex species

Organelle-derived nuclear DNAs, nuclear plastid DNAs (NUPTs) and nuclear mitochondrial DNAs (NUMTs), have been identified in plants. Most, if not all, genes residing in NUPTs/NUMTs (NUPGs/NUMGs) are known to be inactivated and pseudogenized. However, the role of epigenetic control in silencing NUPGs/NUMGs and the dynamic evolution of NUPTs/NUMTs with respect to organismal phylogeny remain barely explored. Based on the available nuclear and organellar genomic resources of the Triticum/Aegilops complex species, we investigated the evolutionary fates of NUPTs/NUMTs in terms of their epigenetic silencing and their dynamic occurrence rates in the nuclear diploid genomes and allopolyploid subgenomes. NUPTs and NUMTs possessed similar genomic atlas, including preferential integration to the transposable element-rich intergenic regions and generating sequence variations in the nuclear genome. The global transcriptional silencing of NUPGs/NUMGs with disrupted and intact open reading frames can be mainly attributed to their repressive chromatin states, namely high levels of DNA methylation and low levels of active histone modifications. Phylogenomic analyses suggested that the species-specific and gradual accumulation of NUPTs/NUMTs accompanied the speciation processes. Moreover, based on further pan-genomic analyses, we found significant subgenomic asymmetry in the NUPT/NUMT occurrence, which accumulated during allopolyploid wheat evolution. Our findings provide novel insights into the dynamic evolutionary fates of organelle-derived nuclear DNA in plants.

genomics↗
bioRxiv2022

Metaplasticity: Dark exposure boosts excitability and visual plasticity in adult human cortex

AO_SCPLOWBSTRACTC_SCPLOWAn interlude of dark exposure for about one week is known to shift the excitatory/inhibitory (E/I) balance of the mammalian visual cortex, promoting cortical plasticity across species and accelerating visual recovery in animals that have experienced cortical lesions during development. However, the translational impact of our understanding of dark exposure from animal studies on humans remains elusive. Here, we use magnetic resonance spectroscopy as a probe for E/I balance in the primary visual cortex (V1) to determine the effect of 60-min dark exposure, and measure binocular combination as a behavioral assay to assess visual plasticity in 18 normally sighted human adults (13 females). To induce neuroplastic changes in the observers, 60-min monocular deprivation was performed, which is known to shift sensory eye balance in favor of the previously deprived eye. We report that prior dark exposure strengthens cortical excitability in V1 and boosts visually plasticity in normal adults. Our findings are surprising, given the fact that the interlude is very brief. We present direct evidence that an environmental manipulation that reduces intracortical inhibition can act as a metaplastic facilitator for visual plasticity in adult humans.

neuroscience↗
bioRxiv2022

Viruses Diversity and Interactions with Hosts in Deep-Sea Hydrothermal Vents

BackgroundDeep-sea harbor enormous viruses, yet their diversity and interactions with hosts in hydrothermal ecosystem are largely unknown. Here, we analyzed the viral composition, distribution, host preference and metabolic potential in different inhabits of global hydrothermal vents. ResultsFrom 34 samples of eight vent sites, a total of 4,662 viral populations were recovered from the metagenome assemblies, encompassing diverse phylogenetic groups and defining many novel lineages. Apart for the abundant unclassified viruses, tailed phages are most predominant across the global hydrothermal vents, while single-stranded DNA viruses including Microviridae and small eukaryotic viruses also constitute a significant part of the viromes. These viral populations were grouped into 1,138 genus-level clusters by protein-sharing network analysis. More than half were exclusively of hydrothermal origin, reflecting the remarkable novelty of hydrothermal viruses. Among the typical niches, vent plumes own the largest number of viral clusters compared to diffuse flows and sediments. Moreover, merely 11% of the viral populations can be linked to specific hosts, which are the key microbial taxa of hydrothermal habitats, such as Gammaproteobacteria and Campylobacteraeota. Intriguingly, vent viromes shared some metabolic features in common that they encode auxiliary genes extensively involved in metabolisms of carbohydrate, amino acid, cofactors and vitamins. Specifically in plume viruses, various auxiliary genes related with the methane, nitrogen and sulfur metabolisms were observed, indicating their contribution to hosts energy conservation. Moreover, the prevalence of sulfur relay pathway genes notified the significant role of vent virus in stabilizing tRNA structure, which promotes hosts adaptation to the steep environmental gradients. ConclusionsThe deep-sea hydrothermal systems reserve an untapped viral diversity with novelty. They may affect both vent prokaryotic and eukaryotic communities, and modulate host metabolisms related to vent adaptability. More explorations are needed to depict global vent virus diversity and their role in the unique ecosystem.

microbiology↗
bioRxiv2022

Suppression of tumor/host intrinsic CMTM6 drives anti-tumor cytotoxicity in a PD-L1 independent manner

CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) has been identified as a regulator of membranal programmed death ligand 1 (PD-L1) stability and a factor associated with malignancy progression, but the effects and mechanisms of CMTM6 on tumor growth, as well as its potential for therapy, are still largely unknown. Here, we show that tumor CMTM6 increased with progression in both clinical patients and mice. Ablation of CMTM6 resulted in significant retardation of human and murine tumor growth dependent on T-lymphocyte immunity. Tumor CMTM6 suppression broke resistance to immune checkpoint inhibitors and remodeled the tumor immune microenvironment, as specific antitumor cytotoxicity was enhanced and contributed primarily to tumor inhibition. Further, without the PD-1/PD-L1 axis, CMTM6 suppression still significantly dampened tumor growth dependent on cytotoxic cells. Notably, we identified that CMTM6 was widely expressed on immune cells. T-cell CMTM6 increased with sustained immune activation and intratumoral immune exhaustion and affected the T-cell-intrinsic PD-L1 levels. Host CMTM6 knockout significantly restrained tumor growth dependent on CD8+ T-cells, and similarly, not entirely dependent on PD-L1. Thus, we developed and evaluated the antitumor efficacy of CMTM6-targeting adeno-associated virus (AAV), which effectively mobilized antitumor immunity and could be combined with various antitumor drugs. Our findings reveal that both tumor and host CMTM6 are deeply involved in tumor immunity with or without the PD-1/PD-L1 axis and that gene therapy targeting CMTM6 is a promising strategy for cancer immunotherapy. One Sentence SummaryEven in the absence of the PD-1/PD-L1 axis, tumor or host CMTM6 deficiency can mediate cytotoxicity-dependent anti-tumor immune responses, allowing CMTM6 to be a novel target for scAAV-mediated oncoimmunology gene therapy and combination treatment.

immunology↗
bioRxiv2022

Sympathetic blockage attenuates fasting-induced hepatic steatosis

Background and AimAlthough it is clear that the central nervous system coordinates whole-body metabolism, the neural mechanism for hepatic steatosis remains unclear. This study is aimed to explore the neural mechanism of fasting-induced hepatic steatosis. MethodsMice were pretreated with 6-hydroxydopamine to block sympathetic nerve activity before fasting, and explored the potential effects of chemical sympathectomy on fasting-induced hepatic steatosis and transcriptional changes. ResultsProlonged fasting led to obvious hepatic steatosis, low core temperature, and similar effects to cold-induced white adipose lipolysis. The alterations in hepatic mRNA expression revealed that the hepatic lipid accumulation did not result from the increase of hepatic lipogenesis or the decrease of fatty acid oxidation but from the enhanced fatty acid uptake as indicated by the upregulation of CD36. Blockage of the sympathetic nervous system via chemical sympathectomy attenuated fasting-induced hepatic steatosis and suppressed CD36 upregulation in the liver, but did not obviously alter the expression of genes associated with lipogenesis or fatty acid oxidation. ConclusionsThese findings indicate that the sympathetic nervous system orchestrates the mechanism for fasting-induced hepatic steatosis via modulating CD36 expression and adipose fat trafficking into the liver, which provides clues to reveal new targets for fatty liver diseases. HIGHLIGHTSO_LIProlonged fasting causes obvious hepatic steatosis C_LIO_LISympathectomy attenuates fasting-induced hepatic steatosis C_LIO_LISympathectomy attenuates steatosis via suppressing CD36 upregulation C_LI IN BRIEFProlonged fasting contributes to sympathetic hyperactivity, but its role in the pathogenesis of hepatic steatosis remains unclear. Here, we found prolonged fasting led to obvious hepatic steatosis, low core temperature, and subsequent sympathetic stimulation that promoted white adipose lipolysis, hepatic upregulation of CD36, and adipose fat trafficking into the liver.

pathology↗
bioRxiv2022

JQ-1 ameliorates schistosomiasis liver granuloma in mice by suppressing male and female reproductive systems and egg development of Schistosoma japonicum

Schistosomiasis is a serious and widespread parasitic disease caused by infection with Schistosoma japonicum. Because the parasites eggs are primarily responsible for schistosomiasis dissemination and pathogenesis, inhibiting egg production is a potential approach to control the spread and severity of the disease. The bromodomain and extra-terminal (BET) proteins represent promising targets for the development of epigenetic drugs against Schistosoma. JQ-1 is a selective inhibitor of the BET protein family. In the present study, JQ-1 was applied S. japonicum in vitro. By using laser confocal scanning microscopy and EdU incorporation assays, we showed that application of JQ-1 to worms in vitro affected egg laying and the development of both the male and female reproductive systems. JQ-1 also inhibited the expression of the reproductive-related genes SjPlk1 and SjNanos1 in S. japonicum. Mice infected with S. japonicum were treated with JQ-1 during egg granuloma formation. JQ-1 treatment significantly reduced the size of the liver granulomas and levels of serum alanine aminotransferase and aspartate aminotransferase in mice and suppressed both egg laying and the development of male and female S. japonicum reproductive systems in vivo. Moreover, the mRNA expression levels of some proinflammatory cytokines were decreased in the parasites. Our findings suggest that JQ-1 treatment attenuates S. japonicum egg- induced hepatic granuloma due at least in part to suppressing the development of the reproductive system and egg production of S. japonicum. These findings further suggest that JQ-1 or other BET inhibitors warrant additional study as a new approach for the treatment or prevention of schistosomiasis. Author summaryAmong neglected tropical diseases, schistosomiasis is a serious disease caused by infection with the parasite Schistosomiasis japonicum. Treatment of schistosomiasis is currently almost exclusively with praziquantel, which kills mainly adult parasites, with minimal effectiveness against immature schistosomes and eggs. However, the parasites eggs are primarily responsible for schistosomiasis dissemination and pathology. In addition, overuse of praziquantel in epidemic areas has led to drug resistance and a reduced cure rate. Thus, new parasite targets for the development of novel therapeutics are crucial. Here, we evaluated the potential of JQ-1, a bromodomain and extra-terminal protein inhibitor, to suppress the production of S. japonicum eggs. Application of JQ-1 to S. japonicum in vitro decreased the number of mature germ cells, the rates of oviposition, and the number of eggs produced in each male-female pairing. JQ-1 treatment of mice infected with S. japonicum ameliorated hepatic granuloma and decreased serum liver enzymes, suggesting improved liver function. These results indicate that JQ-1 inhibits reproductive development and egg production in S. japonicum, providing supporting evidence that JQ-1 warrants additional study for use as a novel approach in the prevention or treatment of schistosomiasis.

microbiology↗
bioRxiv2022

Scale Bar of Aging Trajectories for Screening Personal Rejuvenation Treatments

Although aging is an increasingly severe healthy, economic, and social global problem, it is far from well-modeling aging due to the aging processs complexity. To promote the aging modeling, here we did the quantitative measurement based on aging blood transcriptome. Specifically, the aging blood transcriptome landscape was constructed through ensemble modeling in a cohort of 505 people, and 1138 age-related genes were identified. To assess the aging rate in the linear dimension of aging, we constructed a simplified linear aging clock, which distinguished fast-aging and slow-aging populations and showed the differences in the composition of immune cells. Meanwhile, the non-linear dimension of aging revealed the transcriptome fluctuations with a crest around the age of 40 and showed that this crest came earlier and was more vigorous in the fast-aging population. Moreover, the aging clock was applied to evaluate the rejuvenation effect of molecules in vitro, such as Nicotinamide Mononucleotide (NMN) and Metformin. In sum, this study developed a de novo aging clock to evaluate agedependent precise medicine by revealing its fluctuation nature based on comprehensively mining the aging blood transcriptome, promoting the development of personal aging monitoring and anti-aging therapies.

bioengineering↗
bioRxiv2021

Effects of homoeologous exchange on gene expression and alternative splicing in a newly formed allotetraploid wheat

Homoeologous exchange (HE) is a major mechanism generating post-polyploidization genetic variation with important evolutionary consequences. However, the direct impacts of HE without entangling with additional evolutionary forces on gene expression remains to be fully understood. Here, we analyzed high-throughput RNA-seq data of young leaves from individuals of a synthetic allotetraploid wheat (AADD), which contain variable numbers of HEs. We aimed to investigate if and to which extent HE directly impacts gene expression and alternative splicing (AS). We found that HE impacts expression of genes located within HE regions primarily via cis-acting dosage effect, which led to significant changes in the total expression of homoeolog pairs, especially for homoeologs whose original expression was biased. In parallel, HE influences expression of a large amount of genes residing in non-HE regions by trans-regulation leading to convergent expression of homoeolog pairs. Intriguingly, when taking into account of the original relative homoeolog expression states, homoeolog pairs under trans-effect are more prone to showing convergent response to HE whereas those under cis-effect trended to show subgenome-specific expression. Moreover, HE induced quantitative, largely individual-specific, changes of alternative splicing (AS) events. Like homoeologs expression, homoeo-AS events which related to trans effect were more responsive to HE. HE therefore exerts multifaceted immediate effects on gene expression and, to a less extent, also transcript diversity in nascent allopolyploidy.

plant biology↗
bioRxiv2021

Spatiotemporal dynamics of molecular expression pattern and intercellular interactions in glial scar responding to spinal cord injury

Adult regeneration in spinal cord is poor in mammalian but remarkable in the neonatal mammals and some vertebrates, including fish and salamanders. Increasing evidences basis of this interspecies and ontogeny highlighted the pivotal roles of neuron extrinsic factors-the glial scar, which exert confusing inhibiting or promoting regeneration function, but the spatiotemporal ordering of cellular and molecular events that drive repair processes in scar formation remains poorly understood. Here, we firstly constructed tissue-wide gene expression measurements of mouse spinal cords over the course of scar formation using the spatial transcriptomics (ST) technology in Spinal cord injury (SCI) repair. We analyzed the transcriptomes of nearly 15449 spots from 32 samples and distinguished normal and damage response regions. Compared to histological changes, spatial mapping of differentiation transitions in spinal cord injury site delineated the possible trajectory between subpopulations of fibroblast, glia and immune cell more comprehensively and defined the extent of scar boundary and core more accurately. Locally, we identified gene expression gradients from leading edge to the core of scar areas that allow for re-understanding of the scar microenvironment and found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophage, CD36 and Postn in fibroblast, Plxnb2 and Nxpe3 in microglia, Clu in astrocyte and CD74 in oligodendrocyte. Last, we profiled the bidirectional ligand-receptor interactions at the neighbor cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found GPR37L1_PSAP and GPR37_PSAP were top 2 enriched gene-pairs between microglia and fibroblast or microglia and astrocyte. Together, the establishment of these profiles firstly uncovered scar spatial heterogeneity and lineage trajectory, provide an unbiased view of scar and served as a valuable resource for CNS injury treatment. HighlightsO_LISpatial illustration of gene expression pattern after T10 right lateral hemisection. C_LIO_LISpatial atlas of scar formation by 21 cell types around damaged area. C_LIO_LIThe origin, trajectory reconstruction and functional diversity of cell types in different stages of scar formation. C_LIO_LINovel insights for glial scar boundary and potential benefits for recovery intervention after SCI. C_LI

neuroscience↗
bioRxiv2021

Botrytis cinerea BcPTP1 is a late infection phase, cysteine rich protein cytotoxic effector

Botrytis cinerea is a broad-host-range necrotrophic phytopathogen responsible for serious crops diseases. To facilitate infection, B. cinerea secretes a large number of effectors that induce plant cell death. In screening secretome data of B. cinerea during infection stage, we identified a phytotoxic protein (BcPTP1) that can also induce immune resistance in plants. BcPTP1 is a small (90 aa), cysteine rich protein without any known domains. Transiently expression of BcPTP1 in leaves caused chlorosis that intensifies with time and eventually lead to cell death. Point mutations in eight of the 10 cysteine residues of BcPTP1 abolished the toxic effect, however residual toxic activity remained after heating the peptide, suggesting contribution of unknown epitopes to protein phytotoxic effect. The transcript level of the bcptp1 gene was low during the first 36 h after inoculation and increased sharply upon transition to the late infection stage, suggesting a role of BcPTP1 in lesion spreading. While statistically insignificant, deletion of the bcptp1 gene led to slightly smaller lesions on bean leaves. Further analyses indicated that BcPTP1 is internalized into plant cells after secreting into the apoplast and its phytotoxic effect is negatively regulated by the receptor-like kinases BAK1 and SOBIR1. Collectively, our findings show that BcPTP1 is a virulence factor that toxifies the host cells and facilitates lesion spreading during the late infection stage.

pathology↗
bioRxiv2021

Genome sequences of the five Sitopsis species of Aegilops and the origin of polyploid wheat B-subgenome

Bread wheat (Triticum aestivum L., BBAADD) is a major staple food crop worldwide. The diploid progenitors of the A- and D-subgenomes have been unequivocally identified, that of B however remains ambiguous and controversial but is suspected to be related to species of Aegilops, section Sitopsis. Here, we report the assembly of chromosome-level genome sequences of all five Sitopsis species, namely Ae. bicornis, Ae. longissima, Ae. searsii, Ae. sharonensis, and Ae. speltoides, as well as partial assembly of Ae. mutica genome for phylogenetic analysis. Our results support that the donor of bread wheat B-subgenome is a distinct, probably extinct, diploid species that diverged from an ancestral progenitor of the B-lineage similar to Ae. mutica and Ae. speltoides. The five Sitopsis species have variable genome sizes (4.11-5.89 Gb) with high proportions of repetitive sequences (85.99-89.81%); nonetheless, they retain high collinearity with other wheat genomes. Differences in genome size are primarily due to independent post-speciation amplification of transposons rather than to inter-specific genetic introgression. We also identified a set of Sitopsis genes pertinent to important agronomic traits that can be harnessed for wheat breeding. These resources provide a new roadmap for evolutionary and genetic studies of the wheat group. SignificanceThe origin of the B-subgenome of hexaploid bread wheat remains unknown. Here we report the assembly of chromosome-level genome sequences of all five Sitopsis species of the genus Aegilops, which are previously considered as possible direct progenitors or contributors to the B-subgenome. Our comparative genomic analyses reveal that the B-subgenome originated from an unknown, most likely extinct species phylogenetically distinct from Ae. speltoides, its extant closest relative. We also provide evidence that Ae. speltoides is neither the direct progenitor of the G-subgenome of tetraploid wheat Triticum timopheevii. The high-quality Sitopsis genomes provide novel avenues to identify new important genes for wheat breeding.

evolutionary biology↗