Biology subjects

Miao, L.

Publications and source records attributed to Miao, L..

30 records · Page 2Linked to original sources

bioRxiv2023

Plant selection and ecological microhabitat drive domestications of shrub-associated microbiomes in a revegetated shrub ecosystem

Shrubs are used for revegetation of degraded dryland ecosystem worldwide and could recruit large numbers of microbes from the soil; however, the plant-associated microbiome assembly and the effect of plant introduction on the soil microbiomes are not fully understood. We detected shrub-associated microbes from five ecological microhabitats, including the leaves, litter, roots, rhizosphere, and root zone, across four xeric shrub plantations (Artemisia ordosica, Caragana korshinskii, Hedysarum mongolicum, and Salix psammophila). To detect the patterns of shrub-associated microbiome assembly, 16S and ITS2 rRNA gene sequencing was performed. PERMANOVA and differential abundance analysis demonstrated that changes in the bacterial and fungal communities were more dependent on the microhabitats rather than on the plant species, with distinct niche differentiation. Moreover, source tracking and nestedness analysis showed that shrub-associated bacteria were primarily derived from bulk soils and slightly pruned in different microhabitats; however, a similar pattern was not found for fungi. Furthermore, the surrounding zone of roots was a hotpot for microbial recruitments of revegetated shrubs. Null model analysis indicated that homogeneous selection of determinism dominated the bacterial communities, whereas dispersal limitation and undominated process of stochasticity drove the assembly of fungal communities. Our findings indicate that ecological microhabitat of revegetated shrublands was the main predictor of the bacterial and fungal compositional variances. This study will help advance our understanding of the mechanism underlying the plant-soil microbiome feedbacks during the initial plant-establishment period in a dryland ecosystem. Further, this work provides theoretical reference for establishment and sustainable management of shrublands in drylands.

microbiology↗

bioRxiv2022

Lipoprotein sorting to the cell surface via a crosstalk between the Lpt and Lol pathways during outer membrane biogenesis

Lipopolysaccharide (LPS) and lipoprotein, two essential components of the outer membrane (OM) in Gram-negative bacteria, play critical roles in bacterial physiology and pathogenicity. LPS translocation to the OM is mediated by LptDE, yet how lipoproteins sort to the cell surface remains elusive. Here we report the identification of an inventory of lipoproteins that are transported to the cell surface via LptDE. Notably, we determined crystal structures of LptDE from Pseudomonas aeruginosa and its complex with an endogenous Escherichia coli lipoprotein YifL. The paLptDE-YifL structure demonstrates that YifL translocates to the OM via LptDE, in a manner similar to LPS transport. The {beta}-barrel domain serves as a passage for the proteinaceous moiety while its acyl chains are transported outside. Our finding has been corroborated by results from native mass spectrometry, immunofluorescence, and photocrosslinking assays, revealing a unique mechanism through which lipoproteins are translocated across the OM in an ATP- and LPS-dependent manner. Moreover, our study expands the scope of current knowledge of lipoprotein sorting by disclosing a crosstalk between the Lpt and Lol pathways.

microbiology↗

bioRxiv2022

Multiple founding paternal lineages inferred from the newly-developed SNPSeqTyper 639 Y-SNP panel suggested the complex admixture and migration history of Chinese people

Non-recombining regions of the Y-chromosome are inherited male-specifically and recorded the evolutionary traces of male human populations. Recent whole Y-chromosome sequencing studies have identified previously unrecognized population divergence, expansion and admixture processes, which promotes a better understanding and application of the observed patterns of Y-chromosome genetic diversity. Here, we developed one highest-resolution Y-SNP panel for forensic pedigree search and paternal biogeographical ancestry inference, which included 639 phylogenetically informative SNPs (Y-SNPs). We genotyped these loci in 1033 Chinese male individuals from 33 ethnolinguistically diverse populations and identified 257 terminal Y-chromosomal lineages with frequency ranging from 0.010 (singleton) to 0.0687. We identified six dominant common founding lineages associated with different ethnolinguistic backgrounds, which included O2a2b1a1a1a1a1a1a1-M6539, O2a1b1a1a1a1a1a1-F17, O2a2b1a1a1a1a1b1a1b-MF15397, O2a2b2a1b1-A16609, O1b1a1a1a1b2a1a1-F2517 and O2a2b1a1a1a1a1a1-F155. The AMOVA and nucleotide diversity estimates revealed considerable differences and high genetic diversity among ethnolinguistically different populations. We constructed one representative phylogenetic tree among 33 studied populations based on the haplogroup frequency spectrum and sequence variations. Clustering patterns in principal component analysis and multidimensional scaling results showed a genetic differentiation between Tai-Kadai-speaking Li, Mongolic-speaking Mongolian and other Sinitic-speaking Han Chinese populations. Phylogenetic topology inferred from the BEAST and Network relationships reconstructed from the popART further showed the founding lineages from culturally/linguistically diverse populations, such as C2a/C2b was dominant in Mongolian people and O1a/O1b was dominant in island Li people. We also identified many lineages shared by more than two ethnolinguistically different populations with a high proportion, suggesting their extensive admixture and migration history. Our findings indicated that our developed high-resolution Y-SNP panel included major dominant Y-lineages of Chinese populations from different ethnic groups and geographical regions, which can be used as the primary and powerful tool for forensic practice. We should emphasize the necessity and importance of whole-sequencing of more ethnolinguistically different populations, which can help identify more unrecognized population-specific variations for the final promotion of Y-chromosome-based forensic applications.

genetics↗

bioRxiv2022

Pangenome-based dynamic trajectories of intracellular gene transfers in Poaceae unveil a high rate of unceasing integration and selective retention in Triticeae

Intracellular gene transfers (IGTs) between the nucleus and organelles, including plastids and mitochondria, constantly reshapes the nuclear genome during evolution. Despite the substantial contribution of IGTs to genome variation, the dynamic trajectories of IGTs at the pangenomic level remain elusive. Here, we propose a novel approach, IGTminer, to map the evolutionary trajectories of IGTs by collinearity and gene reannotation across multiple genome assemblies. IGTminer was applied to create a nuclear organelle gene (NOG) map across 67 genomes covering 15 Poaceae species, including important crops, revealing the polymorphisms and trajectory dynamics of NOGs. The NOGs produced were verified by experimental evidence and resequencing datasets. We found that most of the NOGs were recently transferred and lineage specific, and that Triticeae species tended to have more NOGs than other Poaceae species. Wheat had a higher retention rate of NOGs than maize and rice, and the retained NOGs were likely involved in the photosynthesis and translation pathways. Large numbers of NOG clusters were aggregated in hexaploid wheat during two rounds of polyploidization and contributed to the genetic diversities among modern wheat varieties. Finally, we proposed a radiocarbon-like model illustrating the transfer and elimination dynamics of NOGs, highlighting the unceasing integration and selective retention of NOGs over evolutionary time. In addition, we implemented an interactive webserver for NOG exploration in Poaceae. In summary, this study provides new resources and clues for the roles of IGTs in shaping inter- and intraspecies genome variation and driving plant genome evolution.

evolutionary biology↗

bioRxiv2022

linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells

Thousands of long intergenic non-coding RNAs (lincRNAs) are transcribed throughout the vertebrate genome. A subset of lincRNAs enriched in developing brains has recently been found to contain cryptic open reading frames and are speculated to encode micropeptides. However, systematic identification and functional assessment of these transcripts have been hindered by technical challenges caused by their small size. Here we show that two putative lincRNAs (linc-mipep and linc-wrb) encode micropeptides with homology to the vertebrate-specific chromatin architectural protein, Hmgn1, and demonstrate that they are required for development of vertebrate-specific brain cell types. Specifically, we show that NMDA receptor-mediated pathways are dysregulated in zebrafish lacking these micropeptides and that their loss preferentially alters the gene regulatory networks that establish cerebellar cells and oligodendrocytes - evolutionarily newer cell types that develop postnatally in humans. These findings highlight the power of screening for unexplored micropeptide functions by revealing a key missing link in the evolution of vertebrate brain cell development and illustrating a genetic basis for how some neural cell types are more susceptible to chromatin disruptions, with implications for neurodevelopmental disorders and disease.

developmental biology↗

bioRxiv2021

Comprehensive epigenomic profiling of human alveolar epithelial differentiation identifies key epigenetic states and transcription factor co-regulatory networks for maintenance of distal lung identity

Disruption of alveolar epithelial cell (AEC) differentiation is implicated in peripheral lung diseases strongly impacting morbidity and mortality worldwide, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and lung adenocarcinoma. Elucidating underlying disease pathogenesis requires a mechanistic molecular understanding of AEC differentiation. However, to date no study has comprehensively characterized the dynamic epigenomic alterations that facilitate this critical process in humans. We comprehensively profiled the epigenomic states of human AECs during type 2 to type 1-like cell differentiation, including the methylome and chromatin functional domains, and integrated this with transcriptome-wide RNA expression. Enhancer regions were drastically altered during AEC differentiation. Transcription factor binding analysis within enhancer regions revealed diverse interactive networks with enrichment for dozens of transcription factors, including NKX2-1 and FOXA family members, as well as transcription factors with previously uncharacterized roles in lung differentiation, such as members of the MEF2, TEAD, and AP1 families. Additionally, associations between transcription factors changed during differentiation, implicating a complex network of heterotrimeric complex switching may be involved in facilitating differentiation. Integration of AEC enhancer states with the catalog of enhancer elements in the Roadmap Epigenomics Mapping Consortium and Encyclopedia of DNA Elements (ENCODE) revealed that human mammary epithelial cells (HMEC) have a similar epigenomic structure to alveolar epithelium, with NKX2-1 serving as a distinguishing feature of distal lung differentiation. Taken together, our results suggest that enhancer regions with dynamic transcription factor interactions are hotspots of epigenomic alteration that help to facilitate AEC differentiation. Author SummaryHuman health and disease states are heavily influenced by the critical cellular processes that regulate and protect our genomes. One of these safeguards is the epigenome; the coordinated set of signals overlaid on top of our DNA that controls what can happen to a given stretch DNA. Hence, epigenomic signatures play a critical role in the development and maintenance of cellular fate and function. To determine the relationship between epigenomic alterations and cellular fates of distal lung cells in humans during the process that regenerates the human lung epithelial layer after injury, we performed comprehensive genome-wide profiling of many epigenetic modifications that have roles in regulating the function of the underlying DNA. We found that changes to enhancer regions, which act to turn on associated gene expression, were the major alterations to the epigenome during distal lung differentiation, and that within those regions dynamic changes in transcription factor associations were occurring to facilitate this process. We then characterize what was similar and distinct to the enhancers of distal lung from among other epithelial tissues and describe a novel role for specific transcription factors in this process that previously had no known role in normal lung repair.

genomics↗

bioRxiv2021

Natural selections on both amino acid sequences and expression levels are determinants of ohnolog retention

The mechanism of ohnolog retention is a subject of concern in evolutionary biology. Natural selections on coding sequences and gene dosages have been proposed to be determinants of ohnolog retention. However, the relationship between the two models is not widely accepted, and the role of regulatory sequences on ohnolog retention has long been neglected. In this study, based on a model of complex traits genetic architecture, we compared the natural selections strength on corresponding sequences between ohnologs and non-ohnologs by comparing complex traits heritability enrichments. We showed that complex traits regulatory sequences heritability enrichments (p = 1.1 x 10-5 in 5 kb flanking regions) and expression-mediated heritability enrichments (p = 2.1 x 10-5) of ohnologs were significantly higher than non-ohnologs. Then, we deduced that regulatory sequences of ohnologs were under substantial natural selection, which was also a determent of ohnolog retention. Meanwhile, we showed that in coding sequences, the complex traits heritability enrichments of ohnologs were significantly higher than of non-ohnologs (p = 9.9 x 10-5), supporting the ohnolog retention model of natural selection on coding sequences. We also showed that complex traits causal gene expression effect sizes of ohnologs were significantly larger than of non-ohnologs (p = 8.8 x 10-6), supporting the ohnolog retention model of natural selection on gene dosages. In conclusion, we provide the first unified framework to show that both amino acid sequences and expression levels of ohnologs are under substantial selection, which may end the long-standing debate on ohnolog retention models.

evolutionary biology↗

bioRxiv2020

Genome sequencing sheds light on the contribution of structural variants to Brassica oleracea diversification

Brassica oleracea includes several morphologically diverse, economically important vegetable crops. Here we present high-quality chromosome-scale genome assemblies for two B. oleracea morphotypes, cauliflower and cabbage. Direct comparison of these two assemblies identifies ~120 K high-confidence structural variants (SVs). Population analysis of 271 B. oleracea accessions using these SVs clearly separates different morphotypes, suggesting the association of SVs with B. oleracea intraspecific divergence. Genes affected by SVs selected between cauliflower and cabbage are enriched with functions related to response to stress and stimulus and meristem and flower development. Furthermore, genes affected by selected SVs and involved in the switch from vegetative to generative growth that defines curd initiation, inflorescence meristem proliferation for curd formation, maintenance and enlargement, are identified, providing insights into the regulatory network of curd development. This study reveals the important roles of SVs in diversification of different morphotypes of B. oleracea, and the newly assembled genomes and the SVs provide rich resources for future research and breeding.

plant biology↗

bioRxiv2020

Synergistic activity of Nanog, Pou5f3, and Sox19b establishes chromatin accessibility and developmental competence in a context-dependent manner

Genome-wide chromatin reprogramming is a fundamental requirement for establishing developmental competence in the newly-formed zygote. In zebrafish, Nanog, Pou5f3 and Sox19b play partially redundant roles in zygotic genome activation, however their interplay in establishing chromatin competency, the context in which they do so and their mechanism of action remain poorly defined. Here, we generated a triple maternal-zygotic nanog-/-;pou5f3-/-;sox19b-/- mutant and assessed the causal relationship between transcription factor (TF) occupancy, chromatin accessibility and genome activation. Analyses of this triple mutant and combinatorial rescues revealed highly synergistic and context-dependent activity of Nanog, Pou5f3, and Sox19b (NPS) in establishing chromatin competency at >50% of active enhancers. Motif analysis revealed a network of TFs that depend on NPS for establishing chromatin accessibility, including the endodermal determinant Eomesa, whose binding we show is regulated by NPS pioneer-like activity. Finally, we demonstrated that NPS play an essential role in establishing H3K27ac and H3K18ac at enhancers and promoters, and that their function in transcriptional activation can be bypassed by targeted recruitment of histone acetyltransferases to individual genes. Altogether, our findings reveal a large network of TFs that function to establish developmental competency, many of which depend on the synergistic and highly context-dependent role of NPS in establishing chromatin accessibility and regulating histone acetylation in order to activate the genome.

developmental biology↗

bioRxiv2020

A Substantia Innominata-midbrain Circuit Controls a General Aggressive State

While aggressive behaviors are universal and essential for survival, uncontrollable and abnormal aggressive behaviors in animals or humans may have severe adverse consequences or social costs. Neural circuits regulating specific forms of aggression under defined conditions have been described, but how brain circuits govern a general aggressive response remains unknown. Here, we found that posterior substantia innominata (pSI) neurons responded to several aggression-provoking cues with the graded activity of differential dynamics, predicting the aggressive state and the topography of aggression in mice. Activation of pSI neurons projecting to the periaqueductal gray (PAG) increased aggressive arousal and robustly initiated/promoted all the types of aggressive behavior examined in an activity level-dependent manner. Inactivation of the pSI circuit largely blocked diverse aggressive behaviors but not mating. By encoding a general aggressive response, the pSI-PAG circuit universally drives multiple aggressive behaviors and may provide a potential target for alleviating human pathological aggression. In BriefZhu et al. find that the posterior substantia innominata neurons universally drive aggressive behaviors by representing aggressive state and topography of aggression in mice. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/047670v2_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@19d72org.highwire.dtl.DTLVardef@7cc4corg.highwire.dtl.DTLVardef@1f5c3dborg.highwire.dtl.DTLVardef@d9743_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIpSI neuronal dynamics reflect aggressive state and the topography of aggression C_LIO_LIThe pSI-PAG circuit promotes arousal and elicits thirteen aggressive behaviors C_LIO_LIThe pSI controls various aggressive behaviors in an activity level-dependent manner C_LIO_LIInactivation of the pSI circuit blocks diverse aggressive behaviors but not mating C_LI

neuroscience↗

bioRxiv2018

Identification of TTN as a novel candidate gene for atrioventricular block in a Chinese pedigree by whole-exome sequencing

PurposeCardiovascular diseases are the most common cause of death globally. In which atrioventricular block (AVB) is a common disorder with genetic causes, but the responsible genes have not been fully identified yet. To determine the underlying causative genes involved in cardiac AVB, here we report a three-generation Chinese family with severe autosomal dominant cardiac AVB that has been ruled out as being caused by known genes mutations.\n\nMethodsWhole-exome sequencing was performed in five affected family members across three generations, and co-segregation analysis was validated on other members of this family.\n\nResultsWhole-exome sequencing and subsequent co-segregation validation identified a novel germline heterozygous point missense mutation, c.49287C>A (p.N16429K), in the titin (TTN, NM_001267550.2) gene in all 5 affected family members, but not in the unaffected family members. The point mutation is predicted to be functionally deleterious by in-silico software tools. Our finding was further supported by the conservative analysis across species.\n\nConclusionBased on this study, TTN was identified as a potential novel candidate gene for autosomal dominant AVB; this study expands the mutational spectrum of TTN gene and is the first to implicate TTN mutations as AVB disease causing in a Chinese pedigree.

genetics↗

bioRxiv2018

Brd4 and P300 regulate zygotic genome activation through histone acetylation

The awakening of the zygote genome, signaling the transition from maternal transcriptional control to zygotic control, is a watershed in embryonic development, but the factors and mechanisms controlling this transition are still poorly understood. By combining CRISPR-Cas9-mediated live imaging of the first transcribed genes (miR-430), chromatin and transcription analysis during zebrafish embryogenesis, we observed that genome activation is gradual and stochastic, and the active state is inherited in daughter cells. We discovered that genome activation is regulated through both translation of maternal mRNAs and the effects of these factors on the chromatin. We show that chemical inhibition of H3K27Ac writer (P300) and reader (Brd4) block genome activation, while induction of a histone acetylation prematurely activates transcription, and restore genome activation in embryos where translation of maternal mRNAs is impaired, demonstrating that they are limiting factors for the activation of the genome. In contrast to current models, we do not observe triggering of genome activation by a reduction of the nuclear-cytoplasmic (N/C) ratio or slower cell division. We conclude that genome activation is controlled by a time-dependent mechanism involving the translation of maternal mRNAs and the regulation of histone acetylation through P300 and Brd4. This mechanism is critical to initiating zygotic development and developmental reprogramming.

developmental biology↗