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Abundant genetic variation in transcript level during early Drosophila development

ABSTRACT: Variation in gene expression may underlie many important evolutionary traits. However, it is not known at what stage in organismal development changes in gene expression are most likely to result in changes in phenotype. One widely held belief is that changes in early development are more likely to results in changes in downstream phenotypes. In order to discover how much genetic variation for transcript level is present in natural populations, we studied zygotic gene expression in nine inbred lines of Drosophila melanogaster at two time points in development. We find abundant variation for transcript level both between lines and over time: close to half of all expressed genes show a significant line effect at either time point. We examine the contribution of maternally-loaded genes to this variation, as well as the contribution of variation in upstream genes to variation in their downstream targets in two well-studied gene regulatory networks. Finally, we estimate the dimensionality of gene expression in these two networks and find that—despite large numbers of varying genes—there only appear to be two factors controlling this variation. Keywords: Genetic variation and time course

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE8892 | GEO | 2007/08/30

SECONDARY ACCESSION(S): PRJNA102277

REPOSITORIES: GEO

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Transcription profiling of Drosophila isogenic lines at two embryonic time points to identify gene expression variation underlying evolutionary traits

Project description:Variation in gene expression may underlie many important evolutionary traits. However, it is not known at what stage in organismal development changes in gene expression are most likely to result in changes in phenotype. One widely held belief is that changes in early development are more likely to results in changes in downstream phenotypes. In order to discover how much genetic variation for transcript level is present in natural populations, we studied zygotic gene expression in nine inbred lines of Drosophila melanogaster at two time points in development. We find abundant variation for transcript level both between lines and over time: close to half of all expressed genes show a significant line effect at either time point. We examine the contribution of maternally-loaded genes to this variation, as well as the contribution of variation in upstream genes to variation in their downstream targets in two well-studied gene regulatory networks. Finally, we estimate the dimensionality of gene expression in these two networks and find that despite large numbers of varying genesthere only appear to be two factors controlling this variation. Experiment Overall Design: Two chips for each of nine isogenic lines sampled at two time points (=36 arrays).

2008-03-13 | E-GEOD-8892 | biostudies-arrayexpress

Expression data of 20 Arabidopsis thaliana accessions at dusk, dawn and after an extension of the night

Project description:Large-scale identification of transcripts with large cross-genotype differences in abundance provides a genome-wide approach to identify natural variation in gene function. Transcript profiling was performed in 20 Arabidopsis accessions at dusk, dawn and after a 6h extension of the night. Individual genes with a high variance in transcript abundances across accessions were identified by inspection at each individual time point and by ANOVA across all three time points. Up to 40% of genes show significant changes in transcript abundance between accessions, with over-enrichment for biotic resistance, including pathogenesis resistance proteins and glucosinolate metabolism, cell wall modification, minor carbohydrate metabolism, amino acid degradation, brassinosteroid metabolism, redox and abiotic stress and underrepresentation of photosynthesis, DNA synthesis, RNA processing, regulation of transcription, protein synthesis and protein targeting. Some functional classes were enriched at all three time points. Genes related to carbon starvation-responses were enriched specifically at dawn, when their transcript abundance varied independently of carbohydrate levels, pointing to genetic variation in the sensitivity with which low carbon is sensed. Cross-accession correlation networks were generated at each time point to identify sets of genes whose transcripts show coordinated change in abundance between accessions. A cluster that was highly enriched for cold-response genes was found at dusk and after an extension of the night. Another cluster found at all three time points was highly enriched for glucosinolate biosynthesis, and correlated with glucosinolate content. We conclude that genes involved in stress and defense related processes show especially large and coordinated natural variation in transcript abundance.

2023-12-31 | GSE71188 | GEO

Impact of Regulatory Variation from RNA to Protein

Project description:Genetic variants that impact gene regulation are important contributors to human phenotypic variation. For this reason, considerable efforts have been made to identify genetic associations with differences in mRNA levels of nearby genes, namely, cis expression quantitative trait loci (eQTLs). The phenotypic consequences of eQTLs are presumably due, in most cases, to their ultimate effects on protein expression levels. Yet, only few studies have quantified the impact of genetic variation on proteins levels directly. It remains unclear how faithfully eQTLs are reflected at the protein level, and whether there is a significant layer of cis regulatory variation acting primarily on translation or steady state protein levels. To address these questions, we measured ribosome occupancy by high-throughput sequencing, and relative protein levels by high-resolution quantitative mass spectrometry, in a panel of lymphoblastoid cell lines (LCLs) in which we had previously measured transcript expression using RNA sequencing. We then mapped genetic variants that are associated with changes in transcript expression (eQTLs), ribosome occupancy (rQTLs), or protein abundance (pQTLs). Most of the QTLs we detected are associated with transcript expression levels, with consequent effects on ribosome and protein levels. However, we found that eQTLs tend to have significantly reduced effect sizes on protein levels, suggesting that their potential impact on downstream phenotypes is often attenuated or buffered. Additionally, we confirmed the presence of a class of cis QTLs that specifically affect protein abundance with little or no effect on mRNA levels; most of these QTLs have little effect on ribosome occupancy, and hence may arise from differences in post-translational regulation.

2014-12-19 | PXD001406 | Pride

Natural Genetic Variation Influences Protein Abundances in C. elegans Developmental Signalling Pathways

Project description:Complex traits, including common disease-related traits, are affected by many different genes that function in multiple pathways and networks. The apoptosis, MAPK, Notch and Wnt signalling pathways play important roles in development and disease progression. At the moment we have a poor understanding of how allelic variation affects gene expression in these pathways at the level of translation. Here we report the effect of natural genetic variation on transcript and protein abundance involved in developmental signalling pathways in Caenorhabditis elegans. We used selected reaction monitoring to analyse proteins from the abovementioned four pathways in a set of recombinant inbred lines (RILs) generated from the wild-type strains Bristol N2 and Hawaii CB4856 to enable quantitative trait loci (QTL) mapping. Variation in gene expression was greater in the RILs than in the parental lines, at the proteome as well as at the transcriptome levels. We detected a trans-QTL on the left arm of chromosome II that affected protein abundance of the phosphatidylserine receptor protein PSR-1, and two separate QTLs that influenced embryonic and ionizing radiation-induced apoptosis on chromosome IV. Our results demonstrate that natural variation in C. elegans is sufficient to cause significant changes in signalling pathways both at the gene expression (transcript and protein abundance) and phenotypic levels.

2016-02-16 | GSE77905 | GEO

MicroRNA-124 and -137 cooperativity controls caspase-3 activity through BCL2L13 in hippocampal neural stem cells.

Project description:Adult neurogenesis continuously contributes new neurons to hippocampal circuits and the programmed death of a subset of immature cells provides a primary mechanism controlling this contribution. Epileptic seizures induce strong structural changes in the hippocampus, including the induction of adult neurogenesis, changes in gene expression and mitochondrial dysfunction, which may all contribute to epileptogenesis. However, a possible interplay between this factors remains largely unexplored. Here, we investigated gene expression changes in the hippocampal dentate gyrus shortly after prolonged seizures induced by kainic acid, focusing on mitochondrial functions. Using comparative proteomics, we identified networks of proteins differentially expressed shortly after seizure induction, including members of the BCL2 family and other mitochondrial proteins. Within these networks, we report for the first time that the atypical BCL2 protein BCL2L13 controls caspase-3 activity and cytochrome C release in neural stem/progenitor cells. This work has been published in Sci Rep. 2015 Jul 24;5:12448. doi: 10.1038/srep12448.

2016-03-14 | PXD003744 | Pride

Identification of Common Genetic Variants that Account for Transcript Isoform Variation between Human Populations

Project description:In addition to the differences between populations in transcriptional and translational regulation of genes, alternative pre-mRNA splicing (AS) is also likely to play an important role in regulating gene expression and generating variation in mRNA and protein isoforms. Recently, the genetic contribution to transcript isoform variation has been reported in individuals of recent European descent. We report here results of an investigation of the differences in AS patterns between human populations. AS patterns in 176 HapMap lymphoblastoid cell lines derived from individuals of European and African ancestry were evaluated using the Affymetrix GeneChip Human Exon 1.0 ST Array. A variety of biological processes such as immune response and mRNA metabolic process were found to be enriched among the differentially spliced genes. The differentially spliced genes also include some involved in human diseases that have different prevalence or susceptibility between populations. The genetic contribution to the population differences in transcript isoform variation was then evaluated by a genome-wide association using the HapMap genotypic data on single nucleotide polymorphisms (SNPs). The results suggest that local and distant genetic variants account for a substantial fraction of the observed transcript isoform variation between human populations.

2009-03-23 | GSE9703 | GEO

Identification of Common Genetic Variants that Account for Transcript Isoform Variation between Human Populations

2010-08-19 | E-GEOD-9703 | biostudies-arrayexpress

Natural Genetic Variation Influences Protein Abundances in C. elegans Developmental Signalling Pathways

2016-02-16 | E-GEOD-77905 | biostudies-arrayexpress

Genetic Architecture of Protein Expression and its Regulation in the Mouse Brain

Project description:Natural variation in protein expression is common in all organisms and contribute to phenotypic differences among individuals. While variation in gene expression at the transcript level has been extensively investigated, the genetic mechanisms underlying variation in protein expression have lagged considerably behind. Here we investigate genetic architecture of protein expression by profiling a deep mouse brain proteome of two inbred strains, C57BL/6J (B6) and DBA/2J (D2), and their reciprocal F1 hybrids using two-dimensional liquid chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) technology. By comparing protein expression levels in the four mouse strains, we observed 329 statistically significant differentially expressed proteins between the two parental strains and identified four common inheritance patterns, including dominant, additive, over- and under-dominant expression. We further applied the proteogenomic approach to detect variant peptides and define protein allele-specific expression (pASE).

2021-11-01 | PXD025830 | Pride

Disentangling pro-mitotic signaling during cell cycle progression using time-resolved single-cell imaging

Project description:Cells rely on input from extracellular growth factors to control their proliferation during development and adult homeostasis. Such mitogenic inputs are transmitted through multiple signaling pathways that synergize to precisely regulate cell cycle entry and progression. While the architecture of these signaling networks has been characterized in molecular detail, their relative contribution especially at later cell cycle stages remain largely unexplored. By combining quantitative time-resolved measurements of fluorescent reporters in untransformed human cells with targeted pharmacological inhibitors and statistical analysis, we quantified EGF-induced signal processing in individual cells over time and decomposed the dynamic contribution of downstream pathways. We define signaling features that encode information about extracellular ligand concentrations and critical time windows for inducing cell cycle transitions. We show that both ERK and PI3K activity is necessary for initial cell cycle entry, while only PI3K affect the duration of S-phase at later stages of mitogenic signaling.

2020-03-21 | GSE147259 | GEO

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