Project description:Gene order, or microsynteny, is generally thought not to be conserved across metazoan phyla. Only a handful of exceptions, typically of tandemly duplicated genes such as Hox genes, have been discovered. Here, we performed a systematic survey for microsynteny conservation in 17 genomes and identified nearly 600 pairs of unrelated genes that have remained together across over 600 million years of evolution. Using multiple genome-wide resources, including several genomic features, epigenetic marks, sequence conservation and microarray expression data, we provide extensive evidence that many of these ancient microsyntenic arrangements have been conserved in order to preserve either (i) the coordinated transcription of neighboring genes, or (ii) Genomic Regulatory Blocks (GRBs), in which transcriptional enhancers controlling key developmental genes are contained within nearby “bystander” genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos to further investigate putative GRBs in embryonic development. Finally, using chromosome conformation capture (3C) assays and stable transgenic experiments, we demonstrate that enhancers within bystander genes drive the expression of genes such as Otx and Islet, critical regulators of central nervous system development across bilaterians. These results show that ancient genomic associations are far more common in modern metazoans than previously thought – likely involving over 12% of the ancestral bilaterian genome – and that cis-regulatory constraints have played a major role in conserving the architecture of metazoan genomes. ChIP-seq H3K27me3 of 24hpf zebrafish embryos

2012-06-21 | E-GEOD-35050 | biostudies-arrayexpress

Age associated differences in microbiome in Rhesus Macaque

Project description:Aging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate aging associated gut microbiome in relation to immunologic and metabolic profile in a non-human primate (NHP) model. 12 old (age>18 years) and 4 young (age 3-6 years) Rhesus macaques were included in this study. Immune cell subsets were characterized in PBMC by flow cytometry and plasma cytokines levels were determined by bead based multiplex cytokine analysis. Stool samples were collected by ileal loop and investigated for microbiome analysis by shotgun metagenomics. Serum, gut microbial lysate and microbe-free fecal extract were subjected to metabolomic analysis by mass-spectrometry. Our results showed that the old animals exhibited higher inflammatory biomarkers in plasma and lower CD4 T cells with altered distribution of naïve and memory T cell maturation subsets. The gut microbiome in old animals had higher abundance of Archaeal and Proteobacterial species and lower Firmicutes than the young. Significant enrichment of metabolites that contribute to inflammatory and cytotoxic pathways was observed in serum and feces of old animals compared to the young. We conclude that aging NHP undergo immunosenescence and age associated alterations in the gut microbiome that has a distinct metabolic profile.

2022-02-01 | E-MTAB-10160 | biostudies-arrayexpress

Ancient Goat Genomics

Project description:Ancient Goat Genomics

| PRJEB26011 | ENA

Patient genetics is linked to chronic wound microbiome composition and healing

Project description:The clinical importance of microbiomes to the chronicity of wounds is widely appreciated, yet little is understood about patient-specific processes shaping wound microbiome composition. Here, a two-cohort microbiome-genome wide association study is presented through which patient genomic loci associated with chronic wound microbiome diversity were identified. Further investigation revealed that alternative TLN2 and ZNF521 genotypes explained significant inter-patient variation in relative abundance of two key pathogens, Pseudomonas aeruginosa and Staphylococcus epidermidis. Wound diversity was lowest in Pseudomonas aeruginosa infected wounds, and decreasing wound diversity had a significant negative linear relationship with healing rate. In addition to microbiome characteristics, age, diabetic status, and genetic ancestry all significantly influenced healing. Using structural equation modeling to identify common variance among SNPs, six loci were sufficient to explain 53% of variation in wound microbiome diversity, which was a 10% increase over traditional multiple regression. Focusing on TLN2, genotype at rs8031916 explained expression differences of alternative transcripts that differ in inclusion of important focal adhesion binding domains. Such differences are hypothesized to relate to wound microbiomes and healing through effects on bacterial exploitation of focal adhesions and/or cellular migration. Related, other associated loci were functionally enriched, often with roles in cytoskeletal dynamics. This study, being the first to identify patient genetic determinants for wound microbiomes and healing, implicates genetic variation determining cellular adhesion phenotypes as important drivers of infection type. The identification of predictive biomarkers for chronic wound microbiomes may serve as risk factors and guide treatment by informing patient-specific tendencies of infection.

2020-04-25 | GSE149314 | GEO

Ancient transposable elements transformed the uterine regulatory landscape and transcriptome during the evolution of mammalian pregnancy

Project description:A major challenge in biology is to determine how evolutionarily novel characters originate, however, mechanistic explanations for the origin of novelties are almost completely unknown. The evolution of mammalianM-BM- pregnancy is an excellent system in which to study the origin of novelties because extant mammals preserve major stages in the transition from egg-laying to live-birth. To determine the molecular bases of this transition we characterized the pregnant/gravid uterine transcriptome from tetrapods, including species in the three major mammalian lineages, and used ancestral transcriptome reconstruction to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved endometrial expression during the origins of mammalian pregnancy, including numerous genes that mediate maternal-fetal communication and immunotolerance.Furthermore we show that thousands of regulatory elements active inM-BM- decidualized human endometrial stromal cellsM-BM- are derived from ancient mammalian transposable elements which provided binding sites for transcription factors that mediate decidualization and endometrial cell-type identity.M-BM- Our results indicate that one of the defining mammalian novelties evolved via domestication of ancient mammalian transposable elements into hormone-responsive regulatory elements throughout the genome. Examination of histone modification and DNAse hypersensitivity in decidualized dESC

2015-01-30 | E-GEOD-61793 | biostudies-arrayexpress

Rapid Assay of Individual Microbiome responses to drugs part1

Project description:We developed an approach named Rapid Assay of Individual Microbiome (RapidAIM) to screen xenobiotics against individual microbiomes, and conducted a proof-of-concept (POC) study on the use of RapidAIM. We tested 43 compounds against five individual microbiomes. The individual microbiomes are cultured in 96-well plates for 24 hours and the samples are then analyzed using a metaproteomics-based analytical approach to gain functional insight into the individual microbiomes responses following drug treatments.The tested compounds significantly affected overall microbiome abundance, microbiome composition and functional pathways at multiple taxonomic levels. The microbiome responses to berberine, metformin, diclofenac, fructooligosaccharide and most antibiotics were consistent among most individual microbiomes. Interestingly, most of our tested NSAIDs, statins, and histamine-2 blockers induced individually distinct responses. Our workflow offers an effective solution to systematically study the effects of many different compounds on individual microbiomes.

2020-05-26 | PXD012724 | Pride

Dental calculus of ancient baboons

Project description:Metagenomic analysis of dental calculus of ancient baboons

| PRJEB34875 | ENA