Genome-wide Scale Research Articles

ArtSymbioCyc, a metabolic network database collection dedicated to arthropod symbioses: a case study, the tripartite cooperation in Sipha maydis.

Most arthropods live in close association with bacteria. The genomes of associated partners have co-evolved, creating situations of interdependence that are complex to decipher despite the availability of their complete sequences. We developed ArtSymbioCyc, a metabolism-oriented database collection gathering genomic resources for arthropods and their associated bacteria. ArtSymbioCyc uses the powerful tools of the BioCyc community to produce high-quality annotations and to analyze and compare metabolic networks on a genome-wide scale. We used ArtSymbioCyc to study the case of the tripartite symbiosis of the cereal aphid Sipha maydis focusing on amino acid and vitamin metabolisms, as these compounds are known to be important in this strictly phloemophagous insect. We showed that the metabolic pathways of the insect host and its two obligate bacterial associates are interdependent and specialized in the exploitation of Poaceae phloem, particularly for the biosynthesis of sulfur-containing amino acids and most vitamins. This demonstrates that ArtSymbioCyc does not only reveal the individual metabolic capacities of each partner and their respective contributions to the holobiont they constitute but also allows to predict the essential inputs that must come from host nutrition.IMPORTANCEThe evolution has driven the emergence of complex arthropod-microbe symbiotic systems, whose metabolic integration is difficult to unravel. With its user-friendly interface, ArtSymbioCyc (https://artsymbiocyc.cycadsys.org) eases and speeds up the analysis of metabolic networks by enabling precise inference of compound exchanges between associated partners and helps unveil the adaptive potential of arthropods in contexts such as conservation or agricultural control.

Dissecting genomes of multiple yak populations: unveiling ancestry and high-altitude adaptation through whole-genome resequencing analysis

The present study was undertaken to elucidate the population structure and differentiation of Indian yak from Chinese and wild cohorts on genome-wide scale by identifying the selection sweeps and genomic basis of their adaptation across different comparisons while analyzing whole genome sequencing (WGS) data using latest bioinformatics tools. The study included 105 individuals from three distinct yak populations i.e., Indian yak (n = 29); Chinese yak (n = 61) and wild yak (n = 15), hypothesized to be related along the evolutionary timescale. Efficient variant calling and quality control in GATK and PLINK programs resulted in around 1 million (1,002,970) high-quality (LD-independent) SNPs with an average genotyping rate of 96.55%. The PCA, ADMIXTURE and TREEMIX analysis revealed stratification of the yak groups into three distinct clusters. The empirical distribution pattern of minor allele frequency (MAF) of SNPs on genome-wide scale was also elucidated for three yak cohorts revealing unique distribution across five different bins. The selection signature analysis revealed candidate genes that are important for the adaptation of Indian yak against harsh environmental conditions in their habitats. Under iHS analysis, several genes were identified to be under selection pressure in Indian yak including ABCA12, EXOC1, JUNB, KLF1, PRDX2, NANOS3, RFX1, RFX2, and CACNG7. On the other hand, across population analysis revealed the genes like NR2F2, OSBPL10, CIDEC, WFIKKN2, ADCY, THSD7A, ADGRB3, TRPC1, VASH2, and ABHD5 to be part of selective sweeps under these comparisons. A total of 53 genes were found common between intra- and inter-population selection signature analysis of Indian yak. Notably, the genes harbouring the SNPs under selection pressure were significant for adaptation traits including lipidogenesis, energy metabolism, thermogenesis, hair follicle formation, oxidation–reduction reactions, hypoxia and reproduction. These genes may be evaluated as candidate genes for livestock adaptation to harsh environmental conditions and to further the research and application in the present era of climate change.

Copy number variation contributes to parallel local adaptation in an invasive plant

Adaptation is a critical determinant of the diversification, persistence, and geographic range limits of species. Yet the genetic basis of adaptation is often unknown and potentially underpinned by a wide range of mutational types-from single nucleotide changes to large-scale alterations of chromosome structure. Copy number variation (CNV) is thought to be an important source of adaptive genetic variation, as indicated by decades of candidate gene studies that point to CNVs underlying rapid adaptation to strong selective pressures. Nevertheless, population-genomic studies of CNVs face unique logistical challenges not encountered by other forms of genetic variation. Consequently, few studies have systematically investigated the contributions of CNVs to adaptation at a genome-wide scale. We present a genome-wide analysis of CNV contributing to the adaptation of an invasive weed, Ambrosia artemisiifolia. CNVs show clear signatures of parallel local adaptation between North American (native) and European (invaded) ranges, implying widespread reuse of CNVs during adaptation to shared heterogeneous patterns of selection. We used a local principal component analysis (PCA) to genotype CNV regions in whole-genome sequences of samples collected over the last two centuries. We identified 16 large CNV regions of up to 11.85 megabases in length, eight of which show signals of rapid evolutionary change, with pronounced frequency shifts between historic and modern populations. Our results provide compelling genome-wide evidence that CNV underlies rapid adaptation over contemporary timescales of natural populations.

Epigenome-wide association study of pregnancy exposure to green space and placental DNA methylation.

Epigenome-wide association study of pregnancy exposure to green space and placental DNA methylation.

Hi-C sequencing data from cortex of laboratory rats.

The three-dimensional conformation and packaging of chromosomes modulates the spatial organization of the nucleus, orchestrating DNA replication and repair, maintaining genome stability and integrity, and regulating gene expression. Hi-C methods provide high-resolution data on chromatin-to-chromatin interactions both within and among chromosomes at a genome-wide scale. Hi-C resolves topologically-associated domains (TADs) and chromatin loops that are linked to cell-specific transcriptional control. We present a comprehensive Hi-C dataset generated from the frontal cortex of laboratory rats, encompassing a diverse group of inbred strains (SHR/OlaIpcv, BN-Lx/Cub, BXH6/Cub, HXB2/Ipcv, HXB10/Ipcv, HXB23/Ipcv, HXB31/Ipcv, LE/Stm, F344/Stm) and an F1 hybrid (SHR/Olalpcv x BN/NHsdMcwi). This dataset serves as a valuable resource for studying the mechanisms by which three-dimensional chromatin architecture governs gene expression in the brain. Strain-specific variations in genome organization can illuminate the influence of chromatin structure on gene expression, neuronal functionality, and the predisposition to neurological and behavioral disorders.

Investigating the shared genetic structure between rheumatoid arthritis and stroke

BackgroundRheumatoid arthritis (RA) increases the risk of stroke. However, the relationship between RA and stroke remains unclear. This study aimed to explore the shared genetics architecture (i.e., common genetic basis between different traits, diseases, or phenotypes) of RA and stroke, aiming to improve the intervention and management of patients with RA and stroke.MethodsPooled statistics from publicly available genome-wide association studies for RA (8,255 cases and 409,001 controls) and stroke (43,132 cases and 43,132 controls) were used. A genome-wide positive association was conducted to (examine the comprehensive effects of genetic variants on a particular trait, disease, or phenotype at the genome-wide scale). Local genetic correlation studies used linkage disequilibrium score regression and super genetic covariance analyzer. Single nucleotide polymorphisms (SNPs) at risk were identified using genome-wide association study multiple trait analysis and PLINK software (Psnp <5e-08), followed by functional localization and annotation using Functional Mapping and Annotation of Genome-Wide Association Studies to identify specific genes and genetic variants that may contribute to the disease. Finally, a transcriptome-wide association study explored the relationship between genes and their association with RA risk.ResultsA genome-wide significant positive correlation was evident between RA and stroke (genetic correlation = 0.3756). Among the localized genomic regions, the correlation between RA and stroke in the region of chr2:201572564–202,829,668 was the most significant (p = 0.0015). We identified 179 significant SNPs and five common risk genes for RA and stroke (IRF5, RNASET2, ZNF438, UBE2LS, and SYNGR1). These genes are involved in the immune-inflammatory pathway.ConclusionsThe findings suggest a shared genetic structure between RA and stroke. These findings may provide new insights into RA and stroke pathogenesis, and contribute to the development of new diagnostic markers and therapeutic targeted drugs to improve the clinical outcomes of patients with RA and stroke.

Genome-wide analysis of the FKBP gene family and the potential role of GhFKBP 13 in chloroplast biogenesis in upland cotton

BackgroundIn plants, FK506-binding proteins (FKBPs) have been shown to participate in various biological processes such as photosynthetic system reaction, stress response, and growth and development. However, the roles of FKBPs in cotton are less well known.ResultsIn this study, we investigated FKBP family genes on a genome-wide scale in four Gossypium species. A total of 147 FKBP genes were identified from these four Gossypium species and placed into three classes based on phylogenetic analysis. Collinearity analysis indicated that whole-genome duplication events and segmental duplication events were the main sources of gene amplification during the evolution of FKBP genes. Conserved motif, expression profiles and cis-acting elements prediction of the GhFKBPs analysis revealed that GhFKBPs were differentially expressed in different tissues and under abiotic stress. qRT-PCR analysis showed that some GhFKBPs were predominantly expressed in leaves. The analysis of cis-acting elements prediction revealed that MYB, MYC and ERE related binding sites in the promoters of GhFKBP genes were the most abundant. Furthermore, the composition and distribution of these cis-acting elements exhibited differences between homologous GhFKBP gene pairs. Silencing of GhFKBP13 in cotton resulted in disruption of chloroplast structure and starch metabolism disorders.ConclusionsTaken together, 147 FKBP family genes in four Gossypium species are comprehensively characterized, and GhFKBP13 play a critical role in chloroplast biogenesis in upland cotton.

Epidermal growth factor dampens pro-inflammatory gene expression induced by interferon-gamma in global transcriptome analysis of keratinocytes

BackgroundEpidermal growth factor receptor inhibitors (EGFRIs) are used to treat certain cancers but frequently cause cutaneous inflammation that can hinder treatment. This is due in part to the effects of EGFRIs on pro-inflammatory signaling by interferon-γ (IFN-γ). However, the impact of EGFR ligands (i.e. EGF) on interferon signaling is unclear. The purpose of this study was to investigate the impact of EGF on IFN-γ transcriptional responses on a genome-wide scale in keratinocytes.MethodsRNA-seq was performed in human keratinocyte (HaCaT) cells treated with IFN-γ, EGF, both, or neither (control). Differentially expressed genes in each treatment group, relative to control, were identified using DESeq2 with a false discovery rate (FDR) threshold of 0.01. Associated biologic processes and gene pathways were examined in gene-set enrichment analyses. Correlations between gene expression were investigated in vivo using RNA-seq data from biopsies of psoriatic and matched normal skin, which were collected from 116 individuals with psoriasis enrolled in the AMAGINE randomized clinical trials.ResultsOf the 2,792 differentially expressed genes following IFN-γ treatment, 2,083 (75%) were no longer differentially expressed when EGF was added. IFN-γ-induced genes with significantly lower expression in the presence of EGF included CXCL10, IL-6, IL-1 A, HLA-DMA, and GBP5 (activator of the NLRP3 inflammasome); the top enriched biologic processes and pathways were related to MHC-class II antigen presentation (GO:0019886) and cytokine signaling (KEGG:04060). Consistent with our in vitro findings, the expression of CXCL10 and GBP5, as well as the combined expression z-scores of genes in the enriched MHC-class II and cytokine signaling pathways, were significantly lower in skin biopsies with higher EGF expression compared to those with lower EGF expression among individuals with psoriasis.ConclusionsOur findings suggest that the pro-inflammatory IFN-γ-induced transcriptome may be globally attenuated by EGF in keratinocytes, supporting an immunomodulatory role of EGF in the skin. These studies provide insights for the non-canonical immunomodulatory role of EGF signaling and why blocking EGFR signaling (e.g., with EGFRIs) can cause cutaneous inflammation.

Comprehensive analysis of class III peroxidase genes revealed PePRX2 enhanced lignin biosynthesis and drought tolerance in Phyllostachys edulis.

Class III peroxidase (PRX) is the key enzyme in lignin biosynthesis and critical for maintaining the redox balance in plants to respond to stress. In moso bamboo (Phyllostachys edulis), a globally significant non-timber forestry species, the potential roles of PRX genes remain largely unknown. In this research, a total of 179 PePRXs was identified on a genome-wide scale in moso bamboo. Phylogenic relationship, conserved motifs, gene structure, collinearity and cis-acting elements were investigated. Analysis of gene expression indicated that PePRXs exhibited tissue-specific expression and different response patterns to hormones and abiotic stresses. Based on the transcriptome data, 10 PePRXs with positive correlations between expression levels and lignification degree were screened out. Among them, PePRX2 was selected as a candidate gene according to the co-expression network. Y1H and Dual-Luc assays demonstrated that PeMYB61 could bind to the promoter of PePRX2 and enhance its transcription. The result of in situ hybridization showed that PePRX2 was specifically expressed in the vascular bundle sheath cells of bamboo shoot. As a secreted protein, PePRX2 was located on the cell wall. Overexpression of PePRX2 led to a significant increase in lignin content in transgenic poplar, indicating that PePRX2 could promote lignin polymerization. In comparison with the WT, the PePRX2-OE poplar lines exhibited increased peroxidase activity and decreased levels of MDA, O2- and H2O2 under drought stress, indicating enhanced drought resistance. This thorough analysis of the PRX family in moso bamboo provided new insight into the roles of PePRXs in lignin biosynthesis and drought adaptation.

Alternative polyadenylation in cancer: Molecular mechanisms and clinical application.

Alternative polyadenylation in cancer: Molecular mechanisms and clinical application.

Single-molecule toxicogenomics: Optical genome mapping of DNA-damage in nanochannel arrays.

Single-molecule toxicogenomics: Optical genome mapping of DNA-damage in nanochannel arrays.

Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretion.

Smads and their transcription factor partners mediate the transcriptional responses of target cells to secreted ligands of the transforming growth factor-β (TGF-β) family, including those of the conserved bone morphogenetic protein (BMP) family, yet only a small number of direct target genes have been well characterized. In C. elegans, the BMP2/4 ortholog DBL-1 regulates multiple biological functions, including body size, via a canonical receptor-Smad signaling cascade. Here, we identify functional binding sites for SMA-3/Smad and its transcriptional partner SMA-9/Schnurri based on ChIP-seq peaks (identified by modEncode) and expression differences of nearby genes identified from RNA-seq analysis of corresponding mutants. We found that SMA-3 and SMA-9 have both overlapping and unique target genes. At a genome-wide scale, SMA-3/Smad acts as a transcriptional activator, whereas SMA-9/Schnurri direct targets include both activated and repressed genes. Mutations in sma-9 partially suppress the small body size phenotype of sma-3, suggesting some level of antagonism between these factors and challenging the prevailing model for Schnurri function. Functional analysis of target genes revealed a novel role in body size for genes involved in one-carbon metabolism and in the endoplasmic reticulum (ER) secretory pathway, including the disulfide reductase dpy-11. Our findings indicate that Smads and SMA-9/Schnurri have previously unappreciated complex genetic and genomic regulatory interactions that in turn regulate the secretion of extracellular components like collagen into the cuticle to mediate body size regulation.

A modulatory role of CG methylation on gene expression in soybean implicates its potential utility in breeding.

Cytosine methylation (mCG) is an important heritable epigenetic modification, yet its functions remain to be fully defined in important crops. This study investigates mCG in soybean following the loss-of-function mutation of two GmMET1 genes. We generated knockout mutants of GmMET1s by CRISPR-Cas9 and conducted comprehensive methylome and transcriptome analyses. Our findings unravel the functional redundancy of the two GmMET1s, with GmMET1b being more critically involved in maintaining mCG levels, and complete knockout of both copies is lethal. We establish that genome-wide mCG levels scale with aggregated expression of GmMET1s. We identify a set of mCG-regulated genes whose expression levels were quantitatively modulated by upstream, body, or downstream mCG. Moreover, we find genes that were negatively regulated by upstream or body mCG are enriched in specific biological processes such as that of jasmonic acid metabolism. Notably, >80% of the differentially methylated genes (DMGs) in the mutants also exist as DMGs in natural soybean populations. Phenotypically, mutants that are heterozygous for GmMET1a and homozygous for GmMET1b knockouts (GmMET1a+/-GmMET1b-/-) exhibited early flowering, which was inherited by their selfed progeny (GmMET1a+/+GmMET1b-/-) with otherwise normal growth and development. Moreover, mutation of either GmMET1s, with slight reduction of mCG levels and similar phenotypes compared to the wild type under normal conditions, showed enhanced tolerance to cold and drought stresses. Together, our results underscore highly orchestrated regulatory effects of mCG on gene expression in soybean, which dictates growth, development and stress responses, implicating its utility in the improvement of soybean for better adaptability and higher yield.

Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretion.

Smads and their transcription factor partners mediate the transcriptional responses of target cells to secreted ligands of the Transforming Growth Factor-β (TGF-β) family, including those of the conserved bone morphogenetic protein (BMP) family, yet only a small number of direct target genes have been well characterized. In C. elegans, the BMP2/4 ortholog DBL-1 regulates multiple biological functions, including body size, via a canonical receptor-Smad signaling cascade. Here, we identify functional binding sites for SMA-3/Smad and its transcriptional partner SMA-9/Schnurri based on ChIP-seq peaks (identified by modEncode) and expression differences of nearby genes identified from RNA-seq analysis of corresponding mutants. We found that SMA-3 and SMA-9 have both overlapping and unique target genes. At a genome-wide scale, SMA-3/Smad acts as a transcriptional activator, whereas SMA-9/Schnurri direct targets include both activated and repressed genes. Mutations in sma-9 partially suppress the small body size phenotype of sma-3, suggesting some level of antagonism between these factors and challenging the prevailing model for Schnurri function. Functional analysis of target genes revealed a novel role in body size for genes involved in one-carbon metabolism and in the endoplasmic reticulum (ER) secretory pathway, including the disulfide reductase dpy-11. Our findings indicate that Smads and SMA-9/Schnurri have previously unappreciated complex genetic and genomic regulatory interactions that in turn regulate the secretion of extracellular components like collagen into the cuticle to mediate body size regulation.

Uncovering the whole genome silencers of human cells via Ss-STARR-seq

Silencers, the yin to enhancers’ yang, play a pivotal role in fine-tuning gene expression throughout the genome. However, despite their recognized importance, comprehensive identification of these regulatory elements in the genome is still in its early stages. We developed a method called Ss-STARR-seq to directly determine the activity of silencers in the whole genome. In this study, we applied Ss-STARR-seq to human cell lines K562, LNCaP, and 293 T, and identified 134,171, 137,753, and 125,307 silencers on a genome-wide scale, respectively, these silencers function in various cells in a cell-specific manner. Silencers exhibited a substantial enrichment of transcriptional-inhibitory motifs, including REST, and demonstrated overlap with the binding sites of repressor transcription factors within the endogenous environment. Interestingly, H3K27me3 did not reflect silencer activity but facilitated the silencer’s inhibitory role on gene expression. Additionally, the silencer did not have any significant histone markers at the genome-wide level. Our findings unveil that aspect-silencers not only transition into enhancers throughout diverse cell lines but also achieve functional conversion with insulators. Regarding to biological effects, knockout experiments underscored the functional redundancy and specificity of silencers in regulating gene expression and cell proliferation. In summary, this study pioneers the elucidation of the genome-wide silencer landscape in human cells, delineates their global regulatory features, and identifies specific silencers influencing cancer cell proliferation.

The expansion and loss of specific olfactory genes in relatives of parasitic lice, the stored-product psocids (Psocodea: Liposcelididae)

BackgroundBooklice, belonging to the genus Liposcelis (Psocodea: Liposcelididae), commonly known as psocids, infest a wide range of stored products and are implicated in the transmission of harmful microorganisms such as fungi and bacteria. The olfactory system is critical for insect feeding and reproduction. Elucidating the molecular mechanisms of the olfactory system in booklice is crucial for developing effective control strategies. In this study, we aim to bridge this knowledge gap by leveraging the transcriptome and genome data from five Liposcelis species.ResultUsing HMMER method and manual annotation, we have identified common gene families associated with olfactory processes, including odorant binding proteins (OBPs), chemosensory proteins (CSPs), odorant receptors (ORs), ionotropic receptors (IRs), and sensory neuron membrane proteins (SNMPs). Specifically, we identified 94, 118, 26, 47, and 34 olfactory-related genes in L. bostrychophila, L. tricolor, L. entomophila, L. decolor, and L. yangi, respectively. Comparison of quantities revealed that the number of ORs and IRs in the genome is significantly higher than those identified in the transcriptome. This discrepancy may be due to the specific expression of these genes in certain tissues or their lack of expression during the experimental stage. Simultaneously, analysis of gene expression profiles across different developmental stages revealed varying periods of peak expression for olfactory-related genes. These results suggest that the identification of olfactory-related genes in booklice on a genome-wide scale is more feasible and reliable than using a transcriptome-based approach. Additionally, compared to parasitic lice, booklice possess significantly more olfactory-related genes. This increase may be due to the inability of parasitic lice to survive without a host, whereas booklice have a wide range of feeding habits and live in complex and variable environments. Furthermore, we observed that the IR gene family in L. tricolor has undergone a certain degree of amplification, which may facilitate its adaptation to diverse environmental conditions.ConclusionsWe identified olfactory-related genes of five Liposcelis species for the first time, providing valuable insights for future functional investigations into olfactory genes associated with pheromone and odorant recognition. These discoveries present promising targets for effectively managing psocid pests.

Population Genomics of Japanese Macaques (Macaca fuscata): Insights Into Deep Population Divergence and Multiple Merging Histories.

The influence of long-term climatic changes such as glacial cycles on the history of living organisms has been a subject of research for decades, but the detailed population dynamics during the environmental fluctuations and their effects on genetic diversity and genetic load are not well understood on a genome-wide scale. The Japanese macaque (Macaca fuscata) is a unique primate adapted to the cold environments of the Japanese archipelago. Despite the past intensive research for the Japanese macaque population genetics, the genetic background of Japanese macaques at the whole-genome level has been limited to a few individuals, and the comprehensive demographic history and genetic differentiation of Japanese macaques have been underexplored. We conducted whole-genome sequencing of 64 Japanese macaque individuals from 5 different regions, revealing significant genetic differentiation and functional variant diversity across populations. In particular, Japanese macaques have low genetic diversity and harbor many shared and population-specific gene loss, which might contribute to population-specific phenotypes. Our estimation of population demography using phased haplotypes suggested that, after the strong population bottleneck shared among all populations around 400 to 500 kya, the divergence among populations initiated around 150 to 200 kya, but there has been the time with strong gene flow between some populations after the split, indicating multiple population split and merge events probably due to habitat fragmentation and fusion during glacial cycles. These findings not only present a complex population history of Japanese macaques but also enhance their value as research models, particularly in neuroscience and behavioral studies. This comprehensive genomic analysis sheds light on the adaptation and evolution of Japanese macaques, contributing valuable insights to both evolutionary biology and biomedical research.

Profiling translation in the nervous system

Abstract Regulation at the level of translation is critical for functions in the nervous system, such as the formation of cell-type specific proteomes or plastic changes in neural circuits. While current knowledge of the translatome is relatively limited compared to transcriptome, a growing array of tools to analyze translation is becoming available. In this review, we introduce techniques for profiling translation on a genome-wide scale with a special emphasis on cell-type specific analyses in the nervous system. This includes polysome-profiling-seq, Translating Ribosome Affinity Purification (TRAP)-seq and ribosome profiling (Ribo-seq). We review recent advances to achieve spatial resolution of translatome analysis, such as genetic labeling of the targeted cells and cell sorting, and discuss the biological implications of translational regulation in the brain and potential future extensions.

Genomic reconstruction reveals impact of population management strategies on modern Galápagos dogs.

Genomic reconstruction reveals impact of population management strategies on modern Galápagos dogs.

ALFIN-like proteins link histone H3K4me3 to H2A ubiquitination and coordinate diverse chromatin modifications in Arabidopsis.

ALFIN-like proteins link histone H3K4me3 to H2A ubiquitination and coordinate diverse chromatin modifications in Arabidopsis.