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Increased Neanderthal ancestry in genomic regions associated with lipid catabolism in contemporary Europeans

ABSTRACT: While Neanderthals are extinct, fragments of their genome still persist in the genomes of contemporary humans. Here, we show that such Neanderthal-like sequences are not distributed randomly in contemporary human genomes. Specifically, while genome-wide frequency of Neanderthal-like sites is close to 6% in all out-of-Africa populations, genes involved in lipid catabolism contain large excess Neanderthal-like sequences in Europeans (24.3%), but not in Asians (12.4%). While lipid catabolism cannot be assayed in Neanderthals, we took advantage of genetic divergence between human populations, chimpanzees and Neanderthals to predict metabolic divergence expected from the observed excess of Neanderthal gene flow into Europeans. We confirmed predicted changes in lipid catabolism using hydrophobic metabolome measurements in the brain tissue and further linked these metabolic changes to gene expression divergence. 14 human and 6 chimpanzee samples were sequenced.

ORGANISM(S): human

SUBMITTER: Liu He

PROVIDER: E-GEOD-45263 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Increased Neanderthal ancestry in genomic regions associated with lipid catabolism in contemporary Europeans

Project description:While Neanderthals are extinct, fragments of their genome still persist in the genomes of contemporary humans. Here, we show that such Neanderthal-like sequences are not distributed randomly in contemporary human genomes. Specifically, while genome-wide frequency of Neanderthal-like sites is close to 6% in all out-of-Africa populations, genes involved in lipid catabolism contain large excess Neanderthal-like sequences in Europeans (24.3%), but not in Asians (12.4%). While lipid catabolism cannot be assayed in Neanderthals, we took advantage of genetic divergence between human populations, chimpanzees and Neanderthals to predict metabolic divergence expected from the observed excess of Neanderthal gene flow into Europeans. We confirmed predicted changes in lipid catabolism using hydrophobic metabolome measurements in the brain tissue and further linked these metabolic changes to gene expression divergence.

2014-03-31 | GSE45263 | GEO

Project description:Increased Neanderthal ancestry in genomic regions associated with lipid catabolism in contemporary Europeans

| PRJNA193073 | ENA

Increased Neanderthal ancestry in genomic regions associated with lipid catabolism in contemporary Europeans

Project description:Increased Neanderthal ancestry in genomic regions associated with lipid catabolism in contemporary Europeans

| PRJNA193342 | ENA

Excess S-Adenosylmethionine inhibits methylation via catabolism to adenine

Project description:Excess S-Adenosylmethionine inhibits methylation via catabolism to adenine

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A Stringent Systems Approach Uncovers Gene-Specific Mechanisms Regulating Inflammation [RNA-Seq]

Project description:Much has been learned about transcriptional cascades and networks from large-scale systems analyses of high-throughput data sets. However, analysis methods that optimize statistical power through simultaneous evaluation of thousands of ChIP-seq peaks or differentially expressed genes possess substantial limitations in their ability to uncover mechanistic principles of transcriptional control. By examining nascent transcript RNA-seq, ChIP-seq, and binding motif data sets from lipid A-stimulated macrophages with increased attention to the quantitative distribution of signals, we identified unexpected relationships between the in vivo binding properties of inducible transcription factors, motif strength, and transcription. Furthermore, rather than emphasizing common features of large clusters of co-regulated genes, our results highlight the extent to which unique mechanisms regulate individual genes with key biological functions. Our findings demonstrate the mechanistic value of stringent interrogation of well- defined sets of genes as a complement to broader systems analyses of transcriptional cascades and networks. Bone marrow-derived macrophages derived from C57Bl/6, Myd88-/-, Trif-/-, Irf3-/-, Ifnar-/-, and RelA-/- mice were stimulated with lipid A; C57Bl/6 macrophages were stimulated with lipid A in the presence of MAPK inhibitors or cycloheximide, or stimulated with PAM3CSK4 for 0, 15, 30, 60, and 120 minutes, or stimulated with lipid A for 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, and 60 minutes. Two biological replicates were generated for each time point for each treatment type.

2016-01-18 | E-GEOD-67355 | biostudies-arrayexpress

Deep Sequencing of the Porcine Endometrial Transcriptome on Day 14 of Pregnancy

Project description:In pigs, conceptus attachment to the uterine surface epithelium starts around day 14 of pregnancy preceded by a pronounced vascularization at the implantation zones, initiating the epitheliochorial placentation. To characterize the complex transcriptome changes in the endometrium in the course of initial conceptus attachment deep sequencing of endometrial RNA samples of pregnant animals (n=4) and corresponding cyclic controls (n=4) was performed using Illumina RNA-Seq. The obtained sequence reads were mapped to the porcine genome and relative expression values were calculated for the analysis of differential gene expression. Statistical analysis revealed 1,933 differentially expressed genes (FDR 1%), 1,229 with higher and 704 with lower mRNA concentration in the samples from pregnant animals. Expression of selected genes was validated by the use of quantitative real-time RT-PCR. The RNA-Seq data were compared to results of a microarray study of bovine endometrium on day 18 of pregnancy and additional related data sets. Bioinformatics analysis revealed for the genes with higher mRNA concentration in pregnant samples strong overrepresentation particularly for immune-related functional terms but also for apoptosis and cell adhesion. Overrepresented terms for the genes with lower mRNA concentration in pregnant samples were related to extracellular region, ion transport, cell adhesion and lipid and steroid metabolic process. In conclusion, RNA-Seq analysis revealed comprehensive transcriptome differences in porcine endometrium between day 14 of pregnancy and corresponding cyclic endometrium and highlighted new processes and pathways probably involved in regulation of non-invasive implantation in the pig. In total, 8 samples were analyzed, 4 biological replicates for pregnant animals (samples from 4 different animals) and 4 biological replicates for cyclic controls (samples from 4 different animals)

2013-03-07 | E-GEOD-43667 | biostudies-arrayexpress

Primate transcript and protein expression levels evolve under compensatory selection pressures

Project description:Variation in gene regulation is thought to have played an important role in the evolution of primates, and many studies have documented differences in mRNA expression levels across primate species. However, it is not yet known to what extent measurements of divergence in mRNA levels reflect divergence in protein expression levels, which are more directly tied to phenotypic differences. To address this question, we used high-resolution, quantitative mass spectrometry to collect thousands of protein expression measurements from human, chimpanzee, and rhesus macaque lymphoblastoid cell lines (LCLs). We also used RNA sequencing to collect transcript expression data from the same samples. Considering the two datasets jointly we found that there is much more inter-species divergence at the mRNA level than at the protein level. Remarkably, we found dozens of genes with significant expression differences between species at the mRNA level yet little or no difference in protein expression. Overall, our data suggest a much stronger evolutionary constraint on protein expression levels than on mRNA levels. We conclude that inter-species mRNA expression differences may often have limited functional consequences due to either buffering or compensatory changes in post-transcriptional or posttranslational regulation of proteins. Gene expression patterns were compared between human, chimpanzee, and rhesus macaque lymphoblastoid cell lines (5 individuals from each species) using RNA-Seq. These gene expression patterns were also compared to protein expression patterns based on mass-spec data, which are available separately (see publication for details).

2013-10-17 | E-GEOD-49682 | biostudies-arrayexpress

The SNF2 and RING domain proteins FRG1 and 2 are required for RNA-directed DNA methylation in Arabidopsis [mRNA-Seq]

Project description:DNA methylation in Arabidopsis thaliana is maintained by at least four different enzymes: MET1, CMT3, DRM2, and CMT2. However, DNA methylation is established exclusively by the enzyme DRM2, which acts in the RNA-directed DNA methylation (RdDM) pathway. Some RdDM components belong to gene families and have partially redundant functions, such as DICER-LIKE 2, 3 and 4, and IDN2- LIKE 1 and 2. Traditional mutagenesis screens usually fail to detect genes if they are redundant, since the loss of one gene can be compensated by a related gene. In an effort to circumvent this issue, we utilized co-expression data to identify closely related genes that are co-regulated with genes in the RdDM pathway. Here we report the discovery of two redundant proteins, SNF2-RING-HELICASE-LIKE1 and 2 (FRG1 and 2) that are putative chromatin-related paralogous proteins. Analysis of genome–wide bisulfite sequencing shows that simultaneous mutations of FRG1 and 2 cause broad defects in methylation at RdDM targeted loci. We also show that FRG1 stably associates with Su(var)3-9-related SUVR2, a known RdDM component, in vivo. Combined, our results identify FRG1 and FRG2 as novel components of the RdDM machinery. mRNA profiles of 14 days old seedlings of Columbia 0 wild type and frg1-1 frg2-1 double mutants, 3 biological replicates each.

2014-11-25 | E-GEOD-62799 | biostudies-arrayexpress

Ab initio identification of transcription start sites (TSSs) in the Rhesus macaque genome by histone modification and RNA-Seq

Project description:We addressed the lack of experimentally supported transcript annotations in the Rhesus macaque genome by ab initio identification of the transcription start sites (TSSs). We took advantage of histone H3 lysine 4 trimethylation (H3K4me3)'s ability to mark TSSs and the recently developed ChIP-Seq and RNA-Seq technology to survey the transcript structures in the macaque brain. We then integrated the two types of our newly generated data with genomic sequence features and extended a TSS prediction algorithm to ab initio predict and verify 16,833 of previously electronically annotated transcription start sites at 500 bp resolution and predicted ~10,000 new TSSs. We took advantage of histone H3 lysine 4 trimethylation (H3K4me3)M-bM-^@M-^Ys ability to mark transcription start sites (TSSs) and the recently developed ChIP-Seq and RNA-Seq technology to survey the transcript structures. By integrating the ChIP-seq, RNA-seq and small RNA-seq data (previously uploaded to GEO as GSM450615 by our collaborator) with genomic sequence features and extending and improving a state-of-the-art TSS prediction algorithm, we ab initio predicted and verified previously electronically annotated TSSs at a high resolution, and predicted some novel TSSs.

2010-10-18 | E-GEOD-24538 | biostudies-arrayexpress

Organelle interactions compartmentalize hepatic fatty acid trafficking and metabolism

Project description:Organelle interactions play a significant role in compartmentalizing metabolism and signaling. Lipid droplets (LDs) interact with numerous organelles including mitochondria, which is largely assumed to facilitate lipid transfer and catabolism. However, quantitative proteomics of hepatic peridroplet (PDM) and cytosolic mitochondria (CM) revealed that CM are enriched in proteins comprising various oxidative metabolism pathways whereas PDM are enriched in proteins involved in lipid anabolism. Isotope tracing and super-resolution imaging confirmed that fatty acids (FAs) are selectively trafficked to and oxidized in CM during fasting. In contrast, PDM facilitate FA esterification and LD expansion in nutrient-replete media. Additionally, mitochondrial-associated membranes (MAMs) around PDM and CM differed in their proteomes and ability to support distinct lipid metabolic pathways. We conclude that CM and CM-MAM support lipid catabolic pathways whereas PDM and PDM-MAM allow hepatocytes to efficiently store excess lipids in LDs to prevent lipotoxicity in contrast to existing dogma.

2023-03-28 | MSV000091575 | MassIVE

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