Biology subjects

Lei, L.

Publications and source records attributed to Lei, L..

8 recordsLinked to original sources

bioRxiv2018

Discovery of barley gene candidates for low temperature and drought tolerance via environmental association

Barley (Hordeum vulgare ssp. vulgare) is cultivated from the equator to the Arctic Circle. The wild progenitor species, Hordeum vulgare ssp. spontaneum, occupies a relatively narrow latitudinal range (~30 - 40{degrees} N) primarily at low elevation (< 1,500 m). Adaptation to the range of cultivation has occurred over ~8,000 years. The genetic basis of this adaptation is amenable to study through environmental association. Using genotyping from 7,864 SNPs in 803 barley landraces, we performed mixed model association analysis relative to bioclimatic variables and analysis of allele frequency differentiation across multiple partitions of the data. Using resequencing data from a subset of these landraces, we tested for linkage disequilibrium (LD) between SNPs queried in genotyping and SNPs in neighboring loci. Six loci previously reported to contribute to adaptive differences in flowering time and abiotic stress in barley and six loci previously identified in other plant species were identified in our analyses. In many cases, patterns of LD are consistent with the causative variant occurring in the immediate vicinity of the queried SNP. The identification of barley orthologs to well characterized genes may provide new understanding of the nature of adaptive variation and could permit a more targeted use of potentially adaptive variants in barley breeding and germplasm improvement.

genomics↗

bioRxiv2018

Altered Bacteria-Fungi Inter-Kingdom Network in Gut of Ankylosing Spondylitis Patients

Intestinal bacterial dysbiosis has been increasingly linked to Ankylosing Spondylitis (AS), which is a prototypic and best studied subtype of Spondyloarthritis (SpA). Fungi and bacteria coexist in human gut and interact with each other, although they have been shown to contribute actively to health or diseases, no studies have investigated whether fungal microbiota in AS patients is perturbed. In this study, fecal samples of 22 AS patients, with clinical and radiographic assessments, and 16 healthy controls (HCs) were collected to systematically characterize the gut microbiota and mycobiota in AS patients by 16S rDNA and ITS2-based DNA sequencing. The relationships between therapeutic regimens, disease activity, radiographic damage of AS and gut micro/mycobiome were investigated. Our results showed a distinct mycobiota pattern in AS in addition to microbiota dysbiosis. The gut mycobiome of AS patients was characterized by higher taxonomic levels of Ascomycota, especially the class of Dothideomycetes, and decreased abundance of Basidiomycota, which was mainly contributed by the decease of Agaricales. Compared to HCs, changing of the ITS2/16S biodiversity ratio, and bacteria-fungi interkingdom network were observed in AS patients. Alteration of gut mycobiota was associated with different therapeutic regimens, disease activity, as well as different degrees of radiographic damage. Moreover, we unraveled a disease-specific interkingdom network alteration in AS. Finally, we also identified some trends suggesting that different therapeutic regimens may induce changing of both bacterial and fungal microbiota in AS.\n\nIMPORTANCEHuman gut is colonized by diverse fungi (mycobiome), and they have long been suspected in the pathogenesis of Spondyloarthritis (SpA). Our study unraveled a disease-specific interkingdom network alteration in AS, suggesting that fungi, or the interkingdom interactions between bacteria and fungi, may play an essential role in AS development. However, limited by sample size and indeep mechanism studies, further large scale investigations on the characterization of gut mycobiome in AS patients are needed to form a foundation for research into the relationship between mycobiota dysbiosis and AS development.

microbiology↗

bioRxiv2017

A systems approach to refine disease taxonomy by integrating phenotypic and molecular networks

The International Classification of Diseases (ICD) relies on clinical features and lags behind the current understanding of the molecular specificity of disease pathobiology, necessitating approaches that incorporate growing biomedical data for classifying diseases to meet the needs of precision medicine. Our analysis revealed that the heterogeneous molecular diversity of disease chapters and the blurred boundary between disease categories in ICD should be further investigated. Here, we propose a new classification of diseases (NCD) by developing an algorithm that predicts the additional categories of a disease by integrating multiple networks consisting of disease phenotypes and their molecular profiles. With statistical validations from phenotype-genotype associations and interactome networks, we demonstrate that NCD improves disease specificity owing to its overlapping categories and polyhierarchical structure. Furthermore, NCD captures the molecular diversity of diseases and defines clearer boundaries in terms of both phenotypic similarity and molecular associations, establishing a rational strategy to reform disease taxonomy.

bioinformatics↗

bioRxiv2017

Native or promiscuous? Analyzing putative dimethylsulfoniopropionate lyases using a substrate proofing approach

Enzyme promiscuity is widely spread. Foremost, within superfamilies, the native function of one enzyme is typically observed as promiscuous activity in related enzymes. The native function usually exhibits high catalytic efficiency while promiscuous activities are weak, but this is not always the case. Thus, for certain enzymes it remains questionable whether their currently known activity is native or promiscuous. Dimethylsulfon-iopropionate (DMSP) is an abundant marine metabolite cleaved via {beta}-elimination to release dimethylsulfide (DMS). Eight different gene families have been identified as putative DMSP lyases, 5 of them belonging to the same superfamily (cupin-DLL; see the accompanying paper). Some of these enzymes exhibit very low activity, but this can be due to suboptimal folding or reaction conditions. We developed a substrate profiling approach with the aim of distinguishing native DMSP lyases from enzymes that promiscuously act as DMSP lyases. In a native DMSP lyase, relatively small changes in the structure of DMSP should induce significant activity drops. We thus profiled substrate selectivity by systematically modifying DMSP while retaining reactivity. Three enzymes that exhibit the highest activity with DMSP also exhibited high sensitivity to perturbation of DMSPs structure (Alma, DddY, and DddL). The two enzymes with the weakest DMSP lyase activity also showed the highest crossreactivity (DddQ, DddP). Combined with other indications, it appears that the DMSP lyase activity of DddQ and DddP is promiscuous although their native function remains unknown. Systematic substrate profiling could help identify and assign potential DMSP lyases, and possibly applied to other enzymes.\n\nAbbreviationsDMSP, dimethylsulfoniopropionate; DMS, dimethylsulfide; cupin-DLL, cupin DMSP lyase and lyase-like.\n\nFundingFinancial support by the Estate of Mark Scher, and the Sasson & Marjorie Peress Philanthropic Fund, are gratefully acknowledged. D.S.T. is the Nella and Leon Benoziyo Professor of Biochemistry.

biochemistry↗

bioRxiv2017

DddY is a bacterial dimethylsulfoniopropionate lyase representing a new cupin enzyme superfamily with unknown primary function

Dimethylsulfide (DMS) is released at rates of >107 tons annually and plays a key role in the oceanic sulfur cycle and ecology. Marine bacteria, algae, and possibly other organisms, release DMS via cleavage of dimethylsulfoniopropionate (DMSP). Different genes encoding proteins with DMSP lyase activity are known belonging to different superfamilies and exhibiting highly variable levels of DMSP lyase activity. DddY shows the highest activity among all reported bacterial lyases yet is poorly characterized. Here, we describe the characterization of recombinant DddY is from different marine bacteria. We found that DddY activity demands a transition metal ion cofactor. DddY also shares two sequence motifs with other bacterial lyases assigned as cupin-like enzymes, DddQ, DddL, DddK, and DddW. These cupin motif residues are essential for DddY activity, as for the other cupin DMSP lyases, and all these enzymes are characterized by a common metal-chelator inhibitor (TPEN). Analysis of all sequences carrying these cupin motifs defined a superfamily: Cupin-DLL (DMSP lyases and lyase-like). The DMSP lyase families are sporadically distributed suggesting that DMSP lyases evolved within this superfamily independently along multiple lineages. However, the specific activity levels, genomic context analysis, and systematic profiling of substrate selectivity as described in the accompanying paper, indicate that for only some of these families, most distinctly DddY and DddL, DMSP lyase is the primary, native activity. In other families, foremost DddQ, DMSP lyase seems to be merely a promiscuous activity. The native function of DddQ, and of nearly all members of this newly identified Cupin-DLL superfamily, remains unknown.\n\nAbbreviations\n\nFundingFinancial support by the Estate of Mark Scher, and the Sasson & Marjorie Peress Philanthropic Fund, are gratefully acknowledged. D.S.T. is the Nella and Leon Benoziyo Professor of Biochemistry.

biochemistry↗

bioRxiv2017

Plant organ evolution revealed by phylotranscriptomics in Arabidopsis

The evolution of species phenotypes occurs through changes both in protein sequence and gene expression levels. Though much of plant morphological evolution can be explained by changes in gene expression, examining its evolution has challenges. To gain a new perspective on organ evolution in plants, we applied a phylotranscriptomics approach. We combined a phylostratigraphic approach with gene expression based on the strand-specific RNA-seq data from seedling, floral bud, and root of 19 Arabidopsis thaliana accessions to examine the age and sequence divergence of transcriptomes from these organs and how they adapted over time. Our results indicate that, among the sense and antisense transcriptomes of these organs, the sense transcriptomes of seedlings are the evolutionarily oldest across all accessions and are the most conserved in amino acid sequence for most accessions. In contrast, among the sense transcriptomes from these same organs, those from floral bud are evolutionarily youngest and least conserved in sequence for most accessions. Different organs have adaptive peaks at different stages in their evolutionary history, however, from the Magnoliophyta stage to the Brassicale stage, all three organs show a common adaptive signal. Our research is significant because it offers novel evolutionary insight on plant organs revealed by phylotranscriptomics.

evolutionary biology↗

bioRxiv2017

Temporal fitness fluctuations in experimental Arabidopsis thaliana populations

Understanding the genetics of lifetime fitness is crucial to understand a species ecological preferences and ultimately predict its ability to cope with novel environmental conditions. Yet, there is a dearth of information regarding the impact of the ecological variance experienced by natural populations on expressed phenotypic and fitness differences. Here, we follow the natural dynamics of experimental A. thaliana populations over 5 successive plantings whose timing was determined by the natural progression of the plants life cycle and disentangle the environmental and genetic factors that drive plant ecological performance at a given locality. We show that, at the intermediate latitude where the experiment was conducted, a given genotype can experience different life cycles across successive seasons. Lifetime fitness across these seasons varied strongly, with a fall planting yielding 36-fold higher fitness compared to a spring planting. In addition, the actual life-stage at which plant overwinter oscillated across years, depending on the timing of the end of the summer season. We observed a rare but severe fitness differential after inadequate early flowering in one of the five planting. Substrate variation played a comparatively minor role, but also contributed to modulate the magnitude of fitness differentials between genotypes. Finally, reciprocal introgressions on chromosome 4 demonstrated that the fitness effect of a specific chromosomal region is strongly contingent on micro-geographic and seasonal fluctuations. Our study contributes to emphasize the extent to which the fitness impact of phenotypic traits and the genes that encode them in the genome can fluctuate. Experiments aiming at dissecting the molecular basis of local adaptation must apprehend the complexity introduced by temporal fluctuations because they massively affect the expression of phenotype and fitness differences.

evolutionary biology↗

bioRxiv2017

Comparative genomics approaches accurately predict deleterious variants in plants

Recent advances in genome resequencing have led to increased interest in prediction of the functional consequences of genetic variants. Variants at phylogenetically conserved sites are of particular interest, because they are more likely than variants at phylogenetically variable sites to have deleterious effects on fitness and contribute to phenotypic variation. Numerous comparative genomic approaches have been developed to predict deleterious variants, but the approaches are nearly always assessed based on their ability to identify known disease-causing mutations in humans. Determining the accuracy of deleterious variant predictions in nonhuman species is important to understanding evolution, domestication, and potentially to improving crop quality and yield. To examine our ability to predict deleterious variants in plants we generated a curated database of 2,910 Arabidopsis thaliana mutants with known phenotypes. We evaluated seven approaches and found that while all performed well, their relative ranking differed from prior benchmarks in humans. We conclude that deleterious mutations can be reliably predicted in A. thaliana and likely other plant species, but that the relative performance of various approaches does not necessarily translate from one species to another.

bioinformatics↗