Genome-wide discovery of G-quadruplexes in barley.
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ABSTRACT:
SUBMITTER: Cagirici HB
PROVIDER: S-EPMC8041835 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:G-quadruplexes are nucleic acid secondary structures formed by a stack of square planar G-quartets. G-quadruplexes were implicated in many biological functions including telomere maintenance, replication, transcription, and translation, in many species including humans and plants. For wheat, however, though it is one of the world's most important staple food, no G-quadruplex studies have been reported to date. Here, we computationally identify putative G4 structures (G4s) in wheat genome for the first time and compare its distribution across the genome against five other genomes (human, maize, Arabidopsis, rice, and sorghum). We identified close to 1 million G4 motifs with a density of 76 G4s/Mb across the whole genome and 93 G4s/Mb over genic regions. Remarkably, G4s were enriched around three regions, two located on the antisense and one on the sense strand at the following positions: 1) the transcription start site (TSS) (antisense), 2) the first coding domain sequence (CDS) (antisense), and 3) the start codon (sense). Functional enrichment analysis revealed that the gene models containing G4 motifs within these peaks were associated with specific gene ontology (GO) terms, such as developmental process, localization, and cellular component organization or biogenesis. We investigated genes encoding MADS-box transcription factors and showed examples of G4 motifs within critical regulatory regions in the VRN-1 genes in wheat. Furthermore, comparison with other plants showed that monocots share a similar distribution of G4s, but Arabidopsis shows a unique G4 distribution. Our study shows for the first time the prevalence and possible functional roles of G4s in wheat.
| S-EPMC7263691 | biostudies-literature
Project description:BackgroundG-quadruplexes are increasingly recognized as regulatory elements in human, animal, bacterial and plant genomes. The presence and function of G-quadruplexes are not well studied among herpesviruses; in particular, there are no systematic genome-wide analysis of these important secondary structures in herpesvirus genomes.ResultsWe performed genome-wide analysis of putative quadruplex sequences (PQS) in human herpesviruses. We found unusually high PQS densities among human herpesviruses. PQS are enriched in the repeat regions and regulatory regions of human herpesviruses. Interestingly, PQS densities are higher in regulatory regions of immediate early genes compared to early and late genes in most herpesviruses. In addition, the majority of genes functionally conserved across human herpesviruses contain one or more PQS within the regulatory regions. We also describe the existence of unique intramolecular PQS repeats or repetitive G-quadruplex motifs in herpesviruses. Functional studies confirm a role for G-quadruplexes in regulating the gene expression of human herpesviruses.ConclusionThe pervasiveness of PQS, their enrichment and conservation at specific genomic locations suggest that these structural entities may represent a novel class of functional elements in herpesviruses. Our findings provide the necessary framework for studies on the biological role of G-quadruplexes in herpesviruses.
| S-EPMC5117502 | biostudies-literature
Project description:G-quadruplex (G4), formed by repetitive guanosine-rich sequences, is known to play various key regulatory roles in cells. Herpesviruses containing a large double-stranded DNA genome show relatively higher density of G4-forming sequences in their genomes compared to human and mouse. However, it remains poorly understood whether all of these sequences form G4 and how they play a role in the virus life cycle. In this study, we performed genome-wide analyses of G4s present in the putative promoter or gene regulatory regions of a 235-kb human cytomegalovirus (HCMV) genome and investigated their roles in viral gene expression. We evaluated 36 putative G4-forming sequences associated with 20 genes for their ability to form G4 and for the stability of G4s in the presence or absence of G4-stabilizing ligands, by circular dichroism and melting temperature analyses. Most identified sequences formed a stable G4; 28 sequences formed parallel G4s, one formed an antiparallel G4, and four showed mixed conformations. However, when we assessed the effect of G4 on viral promoters by cloning the 20 putative viral promoter regions containing 36 G4-forming sequences into the luciferase reporter and monitoring the expression of luciferase reporter gene in the presence of G4-stabilizing chemicals, we found that only 9 genes were affected by G4 formation. These results revealed promoter context-dependent gene suppression by G4 formation. Mutational analysis of two potential regulatory G4s also demonstrated gene suppression by the sequence-specific G4 formation. Furthermore, the analysis of a mutant virus incapable of G4 formation in the UL35 promoter confirmed promoter regulation by G4 in the context of virus infection. Our analyses provide a platform for assessing G4 functions at the genomic level and demonstrate the properties of the HCMV G4s and their regulatory roles in viral gene expression.
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Project description:Although commonplace in human disease genetics, genome-wide association (GWA) studies have only relatively recently been applied to plants. Using 32 phenotypes in the inbreeding crop barley, we report GWA mapping of 15 morphological traits across ∼500 cultivars genotyped with 1,536 SNPs. In contrast to the majority of human GWA studies, we observe high levels of linkage disequilibrium within and between chromosomes. Despite this, GWA analysis readily detected common alleles of high penetrance. To investigate the potential of combining GWA mapping with comparative analysis to resolve traits to candidate polymorphism level in unsequenced genomes, we fine-mapped a selected phenotype (anthocyanin pigmentation) within a 140-kb interval containing three genes. Of these, resequencing the putative anthocyanin pathway gene HvbHLH1 identified a deletion resulting in a premature stop codon upstream of the basic helix-loop-helix domain, which was diagnostic for lack of anthocyanin in our association and biparental mapping populations. The methodology described here is transferable to species with limited genomic resources, providing a paradigm for reducing the threshold of map-based cloning in unsequenced crops.
| S-EPMC3003063 | biostudies-literature
Project description:BackgroundGenome-wide association studies (GWAS) based on linkage disequilibrium (LD) provide a promising tool for the detection and fine mapping of quantitative trait loci (QTL) underlying complex agronomic traits. In this study we explored the genetic basis of variation for the traits heading date, plant height, thousand grain weight, starch content and crude protein content in a diverse collection of 224 spring barleys of worldwide origin. The whole panel was genotyped with a customized oligonucleotide pool assay containing 1536 SNPs using Illumina's GoldenGate technology resulting in 957 successful SNPs covering all chromosomes. The morphological trait "row type" (two-rowed spike vs. six-rowed spike) was used to confirm the high level of selectivity and sensitivity of the approach. This study describes the detection of QTL for the above mentioned agronomic traits by GWAS.ResultsPopulation structure in the panel was investigated by various methods and six subgroups that are mainly based on their spike morphology and region of origin. We explored the patterns of linkage disequilibrium (LD) among the whole panel for all seven barley chromosomes. Average LD was observed to decay below a critical level (r2-value 0.2) within a map distance of 5-10 cM. Phenotypic variation within the panel was reasonably large for all the traits. The heritabilities calculated for each trait over multi-environment experiments ranged between 0.90-0.95. Different statistical models were tested to control spurious LD caused by population structure and to calculate the P-value of marker-trait associations. Using a mixed linear model with kinship for controlling spurious LD effects, we found a total of 171 significant marker trait associations, which delineate into 107 QTL regions. Across all traits these can be grouped into 57 novel QTL and 50 QTL that are congruent with previously mapped QTL positions.ConclusionsOur results demonstrate that the described diverse barley panel can be efficiently used for GWAS of various quantitative traits, provided that population structure is appropriately taken into account. The observed significant marker trait associations provide a refined insight into the genetic architecture of important agronomic traits in barley. However, individual QTL account only for a small portion of phenotypic variation, which may be due to insufficient marker coverage and/or the elimination of rare alleles prior to analysis. The fact that the combined SNP effects fall short of explaining the complete phenotypic variance may support the hypothesis that the expression of a quantitative trait is caused by a large number of very small effects that escape detection. Notwithstanding these limitations, the integration of GWAS with biparental linkage mapping and an ever increasing body of genomic sequence information will facilitate the systematic isolation of agronomically important genes and subsequent analysis of their allelic diversity.
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Project description:Secretion systems play a crucial role in microbe-microbe or host-microbe interactions. Among these systems, the extracellular contractile injection system (eCIS) is a unique bacterial and archaeal extracellular secretion system that injects protein toxins into target organisms. However, the specific proteins that eCISs inject into target cells and their functions remain largely unknown. Here, we developed a machine learning classifier to identify eCIS-associated toxins (EATs). The classifier combines genetic and biochemical features to identify EATs. We also developed a score for the eCIS N-terminal signal peptide to predict EAT loading. Using the classifier we classified 2,194 genes from 950 genomes as putative EATs. We validated four new EATs, EAT14-17, showing toxicity in bacterial and eukaryotic cells, and identified residues of their respective active sites that are critical for toxicity. Finally, we show that EAT14 inhibits mitogenic signaling in human cells. Our study provides insights into the diversity and functions of EATs and demonstrates machine learning capability of identifying novel toxins. The toxins can be employed in various applications dependently or independently of eCIS.
| S-SCDT-10_1038-S44320-024-00053-6 | biostudies-other
Project description:One of the central aims of cancer research is to identify and characterize cancer-causing alterations in cancer genomes. In recent years, unprecedented advances in genome-wide sequencing, functional genomics technologies for RNA interference screens and methods for evaluating three-dimensional chromatin organization in vivo have resulted in important discoveries regarding human cancer. The cancer-causing genes identified from these new genome-wide technologies have also provided opportunities for effective and personalized cancer therapy. In this review, we describe some of the most recent technologies for cancer gene discovery. We also provide specific examples in which these technologies have proven remarkably successful in uncovering important cancer-causing alterations.
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