Pleiotropic effects of trans-regulatory mutations on gene expression and fitness
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ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE175398 | GEO | 2021/05/25
REPOSITORIES: GEO
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Project description:Pleiotropic effects of trans-regulatory mutations on gene expression and fitness
| PRJNA732302 | ENA
Project description:Gene expression differences between species are driven by both cis and trans effects. Whereas cis effects on gene expression are due to nearby genetic variants, trans effects are due to distal genetic variants that affect diffusible elements such as transcription factors. However, as previous studies have mostly assessed the impacts of cis and trans effects at the gene level, how cis and trans effects differentially impact regulatory elements such as enhancers and promoters remains poorly understood. Here, we used massively parallel reporter assays to directly measure cis and trans effects between human and mouse embryonic stem cells at thousands of individual regulatory elements, including enhancers as well as promoters of both protein-coding and long non-coding RNA genes. Our approach revealed that cis effects are widespread across regulatory elements, and the strongest cis effects are associated with the disruption of motifs recognized by strong transcriptional activators. Conversely, we found that trans effects are rare but stronger in enhancers than promoters, and can be attributed to a subset of transcription factors that are differentially expressed between human and mouse. While previous gene-based studies have found extensive co-occurrence of cis and trans effects in opposite directions that stabilize gene expression between species—or compensatory cis-trans effects—we find that cis-trans compensation is uncommon within individual regulatory elements. Moreover, regulatory elements that do show compensatory cis-trans effects are often less redundant than regulatory elements lacking compensatory cis-trans effects. Thus, our results are consistent with a model wherein compensatory cis-trans effects occur more often through crosstalk between multiple redundant regulatory elements than within a single individual regulatory element. Together, these results indicate that studying the evolution of individual regulatory elements is pivotal to understand the tempo and mode of gene expression evolution.
2019-11-19 | GSE140574 | GEO
Project description:Gene-expression divergence between species shapes morphological evolution, but the molecular basis is largely unknown. Here we show cis- and trans-regulatory elements and chromatin modifications on gene-expression diversity in genetically tractable Arabidopsis allotetraploids. In Arabidopsis thaliana and Arabidopsis arenosa, both cis and trans with predominant cis-regulatory effects mediate gene-expression divergence. The majority of genes with both cis- and trans-effects are subjected to compensating interactions and stabilizing selection. Interestingly, chromatin modifications correlate with cis - and trans -regulation. In F1 allotetraploids, Arabidopsis arenosa trans factors predominately affect allelic expression divergence. Arabidopsis arenosa trans factors tend to upregulate Arabidopsis thaliana alleles, whereas Arabidopsis thaliana trans factors up- or down-regulate Arabidopsis arenosa alleles. In resynthesized and natural allotetraploids, trans effects drive expression of both homoeologous loci into the same direction. We provide evidence for natural selection and chromatin regulation in shaping gene-expression diversity during plant evolution and speciation. Examination of gene expression in 5 tetraploid Arabidopsis using mRNA-seq
2012-05-31 | E-GEOD-29687 | biostudies-arrayexpress
Project description:Gene-expression divergence between species shapes morphological evolution, but the molecular basis is largely unknown. Here we show cis- and trans-regulatory elements and chromatin modifications on gene-expression diversity in genetically tractable Arabidopsis allotetraploids. In Arabidopsis thaliana and Arabidopsis arenosa, both cis and trans with predominant cis-regulatory effects mediate gene-expression divergence. The majority of genes with both cis- and trans-effects are subjected to compensating interactions and stabilizing selection. Interestingly, chromatin modifications correlate with cis - and trans -regulation. In F1 allotetraploids, Arabidopsis arenosa trans factors predominately affect allelic expression divergence. Arabidopsis arenosa trans factors tend to upregulate Arabidopsis thaliana alleles, whereas Arabidopsis thaliana trans factors up- or down-regulate Arabidopsis arenosa alleles. In resynthesized and natural allotetraploids, trans effects drive expression of both homoeologous loci into the same direction. We provide evidence for natural selection and chromatin regulation in shaping gene-expression diversity during plant evolution and speciation.
2012-05-31 | GSE29687 | GEO
Project description:Gene expression evolution can be caused by changes in cis- or trans-regulatory elements or both. As cis and trans regulation operate through different molecular mechanisms, cis and trans mutations may show different inheritance patterns and may be subjected to different selective constraints. To investigate these issues, we obtained and analyzed gene expression data from two Saccharomyces cerevisiae strains and their hybrid, using high-throughput sequencing. Our data indicate that compared to other types of genes, those with antagonistic cis-trans interactions are more likely to exhibit over- or under-dominant inheritance of expression level. Moreover, in accordance with previous studies, genes with trans variants tend to have a dominant inheritance pattern while cis variants are enriched for additive inheritance. In addition, cis regulatory differences contribute more to expression differences between species than within species, whereas trans regulatory differences show a stronger association between divergence and polymorphism. Our data indicate that in the trans component of gene expression differences genes subjected to weaker selective constraints tend to have an excess of polymorphism over divergence compared to those subjected to stronger selective constraints. In contrast, in the cis component, this difference between genes under stronger and weaker selective constraint is mostly absent. To explain these observations, we propose that purifying selection more strongly shapes trans polymorphism than cis polymorphism. Study the gene expression patterns in two strains of yeast (BY and RM)
2013-11-10 | E-GEOD-46838 | biostudies-arrayexpress
Project description:Divergence of gene function is a hallmark of evolution, but assessing functional divergence over deep time is not trivial. The few alleles available for cross-species studies often fail to expose the entire functional spectrum of genes, potentially obscuring deeply conserved pleiotropic roles. Here, we explore the functional divergence of WUSCHEL HOMEOBOX9 (WOX9), suggested to have species-specific roles in embryo and inflorescence development. Using a cis-regulatory editing drive system, we generated a comprehensive allelic series in tomato, which revealed hidden pleiotropic roles for WOX9. Analysis of accessible chromatin and conserved cis-regulatory sequences identified the regions responsible for this pleiotropic activity, the functions of which were conserved in groundcherry, a tomato relative. Mimicking these alleles in arabidopsis, distantly related to tomato and groundcherry, revealed new inflorescence phenotypes, exposing a deeply conserved pleiotropy. We suggest that targeted cis-regulatory mutations can uncover conserved gene functions and reduce undesirable effects in crop improvement.
2021-01-14 | GSE164297 | GEO
Project description:Gene regulation can evolve either by cis-acting local changes to regulatory element DNA sequences or by global changes to the trans-acting regulatory environment; however, the modes favored during recent human evolution are unknown. To date, studies investigating gene regulatory divergence between closely-related species have produced limited estimates on the relative contributions of cis and trans effects on DNA regulatory element activities at a global-scale. By leveraging a comparative ATAC-STARR-seq framework, we identified 10,779 regulatory regions with divergent activity in cis and 10,608 regulatory regions with divergent activity in trans between human and rhesus macaque lymphoblastoid cell lines (LCLs). This revealed substantially more trans effects than predicted and indicates trans-regulatory mechanisms play a larger role in human evolution than previously expected. We also discover that most species-specific regulatory elements (67%) diverge in both cis and trans, suggesting these two mechanisms jointly drive divergent regulatory activity in a single sequence.
2023-12-22 | GSE216917 | GEO
Project description:Gene expression evolution can be caused by changes in cis- or trans-regulatory elements or both. As cis and trans regulation operate through different molecular mechanisms, cis and trans mutations may show different inheritance patterns and may be subjected to different selective constraints. To investigate these issues, we obtained and analyzed gene expression data from two Saccharomyces cerevisiae strains and their hybrid, using high-throughput sequencing. Our data indicate that compared to other types of genes, those with antagonistic cis-trans interactions are more likely to exhibit over- or under-dominant inheritance of expression level. Moreover, in accordance with previous studies, genes with trans variants tend to have a dominant inheritance pattern while cis variants are enriched for additive inheritance. In addition, cis regulatory differences contribute more to expression differences between species than within species, whereas trans regulatory differences show a stronger association between divergence and polymorphism. Our data indicate that in the trans component of gene expression differences genes subjected to weaker selective constraints tend to have an excess of polymorphism over divergence compared to those subjected to stronger selective constraints. In contrast, in the cis component, this difference between genes under stronger and weaker selective constraint is mostly absent. To explain these observations, we propose that purifying selection more strongly shapes trans polymorphism than cis polymorphism.
2013-11-10 | GSE46838 | GEO
Project description:Modification of cis regulatory elements to produce differences in gene expression level, localization, and timing is an important mechanism by which organisms evolve divergent adaptations. To examine gene regulatory change during the domestication of maize from its wild progenitor, teosinte, we assessed allele-specific expression in a collection of maize and teosinte inbreds and their F1 hybrids using three tissues from different developmental stages. Our use of F1 hybrids represents the first study in a domesticated crop and wild progenitor that dissects cis and trans regulatory effects to examine characteristics of genes under various cis and trans regulatory regimes. We find evidence for consistent cis regulatory divergence that differentiates maize from teosinte in approximately 4% of genes. These genes are significantly correlated with genes under selection during domestication and crop improvement, suggesting an important role for cis regulatory elements in maize evolution. We assayed genome-wide cis and trans regulatory differences between maize and its wild progenitor, teosinte, using deep RNA sequencing in F1 hybrid and parent inbred lines for three tissue types (ear, leaf and stem) followed by assessment of allele-specific gene expression.
2014-11-06 | E-GEOD-61810 | biostudies-arrayexpress
Project description:Background: Genomic instability is a hallmark of cancer and is frequently reflected in the DNA copy number profile and the expression profile of genes. Methodology is needed to compare array-CGH data and microarray expression data in order to unveil effects of DNA copy number alterations of a gene on the expression of the gene itself (in-cis effects) and on other genes (in-trans effects). Results: We present a method for detection of gene dosage effects on gene expression that first searches for genome-wide in-cis associations between copy number and expression, and then investigates in-trans effects of these genes. A key element of the method is a correction step to eliminate potential confounding effects of in-cis associations when searching for in-trans associations. This facilitates reliable detection of local in-trans associations (i.e. associations within a chromosome) and alleviates the problem of co-occurring copy number aberrations across the genome. Applying the method to data collected from breast carcinomas from 20 women, we found 422 genes with expression levels that are highly correlated to DNA copy number (in-cis) in certain regions of the genome. Of these, 109 (26%) had significant trans-correlation with the expression levels of a large number of genes (20 or more). The strongest trans-regulators were also differentially expressed in subgroups that were found on the basis of expression data by classification of the tumors to previously defined breast cancer subtypes. A study of the most significant in-trans correlated genes yields significant enrichment of certain cancer related pathways and GO terms. Conclusions: We introduce a method for the joint comparative analysis of expression and copy number profiles for the discovery and investigation of in-cis and in-trans regulatory mechanisms. Using data from 20 primary human breast cancers, a number of significant in-trans regulatory genes were found and their biological relevance indicated, calling for the application of the methods on larger data sets. Keywords: Correlations between copy number and gene expression, breast cancer
2010-07-01 | GSE10583 | GEO