scholarly journals Cis- and Trans-Regulatory Variations in the Domestication of the Chili Pepper Fruit

2020 ◽  
Vol 37 (6) ◽  
pp. 1593-1603 ◽  
Author(s):  
Erik Díaz-Valenzuela ◽  
Ruairidh H Sawers ◽  
Angélica Cibrián-Jaramillo
Keyword(s):  
Gene Expression ◽  
Chili Pepper ◽  
Loss Of Function ◽  
Morphological Transformation ◽  
Specific Expression ◽  
Network Analyses ◽  
Regulatory Variants ◽  
Regulatory Cascades ◽  
In The Wild ◽  
Cis And Trans

Abstract The process of domestication requires the rapid transformation of the wild morphology into the cultivated forms that humans select for. This process often takes place through changes in the regulation of genes, yet, there is no definite pattern on the role of cis- and trans-acting regulatory variations in the domestication of the fruit among crops. Using allele-specific expression and network analyses, we characterized the regulatory patterns and the inheritance of gene expression in wild and cultivated accessions of chili pepper, a crop with remarkable fruit morphological variation. We propose that gene expression differences associated to the cultivated form are best explained by cis-regulatory hubs acting through trans-regulatory cascades. We show that in cultivated chili, the expression of genes associated with fruit morphology is partially recessive with respect to those in the wild relative, consistent with the hybrid fruit phenotype. Decreased expression of fruit maturation and growth genes in cultivated chili suggest that selection for loss-of-function took place in its domestication. Trans-regulatory changes underlie the majority of the genes showing regulatory divergence and had larger effect sizes on gene expression than cis-regulatory variants. Network analysis of selected cis-regulated genes, including ARP9 and MED25, indicated their interaction with many transcription factors involved in organ growth and fruit ripening. Differentially expressed genes linked to cis-regulatory variants and their interactions with downstream trans-acting genes have the potential to drive the morphological differences observed between wild and cultivated fruits and provide an attractive mechanism of morphological transformation during the domestication of the chili pepper.

scholarly journals Measurement of selective constraint on human gene expression

2018 ◽  
Author(s):  
Emily C Glassberg ◽  
Ziyue Gao ◽  
Arbel Harpak ◽  
Xun Lant ◽  
Jonathan K Pritchard
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Complex Traits ◽  
Stabilizing Selection ◽  
Common Variants ◽  
Loss Of Function ◽  
Specific Expression ◽  
Expression Levels ◽  
Expression Variation ◽  
Regulatory Variants

Gene expression variation is a major contributor to phenotypic variation in human complex traits. Selection on complex traits may therefore be reflected in constraint on gene expression levels. Here, we explore the effects of stabilizing selection on cis-regulatory genetic variation in humans. We analyze patterns of expression variation at copy number variants and find evidence for selection against large increases in gene expression. Using allele-specific expression (ASE) data, we further show evidence of selection against smaller-effect variants. We estimate that, across all genes, singletons in a sample of 122 individuals have approximately 2.5 × greater effects on expression variance than common variants. Despite their increased effect sizes relative to common variants, we estimate that singletons in the sample studied explain, on average, only 5% of the heritability of gene expression from cis-regulatory variants. Finally, we show that genes depleted for loss-of-function variants are also depleted for cis-eQTLs and have low levels of allelic imbalance, confirming tighter constraint on the expression levels of these genes. We conclude that constraint on gene expression is present, but has relatively weak effects on most cis-regulatory variants, thus permitting high levels of gene-regulatory genetic variation.

scholarly journals Auxin methylation is required for differential growth inArabidopsis

2018 ◽  
Vol 115 (26) ◽  
pp. 6864-6869 ◽  
Author(s):  
Mohamad Abbas ◽  
Jorge Hernández-García ◽  
Stephan Pollmann ◽  
Sophia L. Samodelov ◽  
Martina Kolb ◽  
...  
Keyword(s):  
Gene Expression ◽  
Auxin Transport ◽  
Polar Auxin Transport ◽  
Asymmetric Distribution ◽  
Loss Of Function ◽  
Differential Growth ◽  
Specific Expression ◽  
Auxin Homeostasis ◽  
Auxin Distribution ◽  
Gene Expression Levels

Asymmetric auxin distribution is instrumental for the differential growth that causes organ bending on tropic stimuli and curvatures during plant development. Local differences in auxin concentrations are achieved mainly by polarized cellular distribution of PIN auxin transporters, but whether other mechanisms involving auxin homeostasis are also relevant for the formation of auxin gradients is not clear. Here we show that auxin methylation is required for asymmetric auxin distribution across the hypocotyl, particularly during its response to gravity. We found that loss-of-function mutants inArabidopsis IAA CARBOXYL METHYLTRANSFERASE1(IAMT1) prematurely unfold the apical hook, and that their hypocotyls are impaired in gravitropic reorientation. This defect is linked to an auxin-dependent increase inPINgene expression, leading to an increased polar auxin transport and lack of asymmetric distribution of PIN3 in theiamt1mutant. Gravitropic reorientation in theiamt1mutant could be restored with either endodermis-specific expression ofIAMT1or partial inhibition of polar auxin transport, which also results in normalPINgene expression levels. We propose that IAA methylation is necessary in gravity-sensing cells to restrict polar auxin transport within the range of auxin levels that allow for differential responses.

scholarly journals Chromatin three-dimensional interactions mediate genetic effects on gene expression

Science ◽  
2019 ◽  
Vol 364 (6439) ◽  
pp. eaat8266 ◽  
Author(s):  
O. Delaneau ◽  
M. Zazhytska ◽  
C. Borel ◽  
G. Giannuzzi ◽  
G. Rey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Three Dimensional ◽  
Cell Types ◽  
Regulatory Elements ◽  
Genetic Effects ◽  
Chromatin Organization ◽  
Regulatory Domains ◽  
Regulatory Variants ◽  
Cis And Trans

Studying the genetic basis of gene expression and chromatin organization is key to characterizing the effect of genetic variability on the function and structure of the human genome. Here we unravel how genetic variation perturbs gene regulation using a dataset combining activity of regulatory elements, gene expression, and genetic variants across 317 individuals and two cell types. We show that variability in regulatory activity is structured at the intra- and interchromosomal levels within 12,583 cis-regulatory domains and 30 trans-regulatory hubs that highly reflect the local (that is, topologically associating domains) and global (that is, open and closed chromatin compartments) nuclear chromatin organization. These structures delimit cell type–specific regulatory networks that control gene expression and coexpression and mediate the genetic effects of cis- and trans-acting regulatory variants on genes.

scholarly journals Putative bovine topological association domains and CTCF binding motifs can reduce the search space for causative regulatory variants of complex traits

2018 ◽  
Author(s):  
Min Wang ◽  
Timothy P Hancock ◽  
Amanda J. Chamberlain ◽  
Christy J. Vander Jagt ◽  
Jennie E Pryce ◽  
...  
Keyword(s):  
Gene Expression ◽  
Complex Traits ◽  
Bovine Genome ◽  
Search Space ◽  
Ctcf Binding ◽  
P Value ◽  
Trna Genes ◽  
Specific Expression ◽  
Binding Motifs ◽  
Regulatory Variants

AbstractBackgroundTopological association domains (TADs) are chromosomal domains characterised by frequent internal DNA-DNA interactions. The transcription factor CTCF binds to conserved DNA sequence patterns called CTCF binding motifs to either prohibit or facilitate chromosomal interactions. TADs and CTCF binding motifs control gene expression, but they are not yet well defined in the bovine genome. In this paper, we sought to improve the annotation of bovine TADs and CTCF binding motifs, and assess whether the new annotation can reduce the search space for cis-regulatory variants.ResultsWe used genomic synteny to map TADs and CTCF binding motifs from humans, mice, dogs and macaques to the bovine genome. We found that our mapped TADs exhibited the same hallmark properties of those sourced from experimental data, such as housekeeping gene, tRNA genes, CTCF binding motifs, SINEs, H3K4me3 and H3K27ac. Then we showed that runs of genes with the same pattern of allele-specific expression (ASE) (either favouring paternal or maternal allele) were often located in the same TAD or between the same conserved CTCF binding motifs. Analyses of variance showed that when averaged across all bovine tissues tested, TADs explained 14% of ASE variation (standard deviation, SD: 0.056), while CTCF explained 27% (SD: 0.078). Furthermore, we showed that the quantitative trait loci (QTLs) associated with gene expression variation (eQTLs) or ASE variation (aseQTLs), which were identified from mRNA transcripts from 141 lactating cows’ white blood and milk cells, were highly enriched at putative bovine CTCF binding motifs. The most significant aseQTL and eQTL for each genic target were located within the same TAD as the gene more often than expected (Chi-Squared test P-value ≤ 0.001).ConclusionsOur results suggest that genomic synteny can be used to functionally annotate conserved transcriptional components, and provides a tool to reduce the search space for causative regulatory variants in the bovine genome.

scholarly journals Spatially varying cis-regulatory divergence inDrosophilaembryos elucidates cis-regulatory logic

2017 ◽  
Author(s):  
Peter A. Combs ◽  
Hunter B. Fraser
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Raw Material ◽  
Spatial Patterning ◽  
Rna Seq ◽  
Specific Expression ◽  
Complex Interactions ◽  
Allele Specific ◽  
Spatially Varying ◽  
Cis And Trans

AbstractSpatial patterning of gene expression is a key process in development—responsible for the incredible diversity of animal body plans—yet how it evolves is still poorly understood. Both cis- and trans-acting changes could accumulate and participate in complex interactions, so to isolate the cis-regulatory component of patterning evolution, we measured allele-specific spatial gene expression patterns inD. melanogaster×D. simulanshybrid embryos. RNA-seq of cryosectioned slices revealed 55 genes with strong spatially varying allele-specific expression, and several hundred more with weaker but significant spatial divergence. For example, we found thathunchback (hb), a major regulator of developmental patterning, had reduced expression specifically in the anterior tip ofD. simulansembryos. Mathematical modeling ofhbcis-regulation suggested that a mutation in a Bicoid binding site was responsible, which we verified using CRISPR-Cas9 genome editing. In sum, even comparing morphologically near-identical species we identified a substantial amount of spatial variation in gene expression, suggesting that development is robust to many such changes, but also that natural selection may have ample raw material for evolving new body plans via cis-regulatory divergence.

scholarly journals Transcriptome Sequencing Reveals Widespread Gene-Gene and Gene-Environment Interactions

2014 ◽  
Author(s):  
Alfonso Buil ◽  
Andrew A Brown ◽  
Tuuli Lappalainen ◽  
Ana Viñuela ◽  
Matthew N Davies ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Architecture ◽  
Intermediate Step ◽  
Specific Expression ◽  
Relative Contribution ◽  
Regulatory Variants ◽  
Gene Environment ◽  
Genetic And Environmental Factors ◽  
Proper Estimation ◽  
In Cis

Understanding the genetic architecture of gene expression is an intermediate step to understand the genetic architecture of complex diseases. RNA-seq technologies have improved the quantification of gene expression and allow to measure allelic specific expression (ASE)1-3. ASE is hypothesized to result from the direct effect of cis regulatory variants, but a proper estimation of the causes of ASE has not been performed to date. In this study we take advantage of a sample of twins to measure the relative contribution of genetic and environmental effects on ASE and we found substantial effects of gene x gene (GxG) and gene x environment (GxE) interactions. We propose a model where ASE requires genetic variability in cis, a difference in the sequence of both alleles, but the magnitude of the ASE effect depends on trans genetic and environmental factors that interact with the cis genetic variants. We uncover large GxG and GxE effects on gene expression and likely complex phenotypes that currently remain elusive.

scholarly journals Cis-regulatory variants affect gene expression dynamics in yeast

2021 ◽  
Author(s):  
Ching-Hua Shih ◽  
Justin C. Fay
Keyword(s):  
Gene Expression ◽  
Gene Activation ◽  
Regulatory Sequences ◽  
Diauxic Shift ◽  
Promoter Regions ◽  
Specific Expression ◽  
Cis Acting ◽  
Regulatory Variants ◽  
Endogenous Expression ◽  
Gene Expression Dynamics

Evolution of cis-regulatory sequences depends on how they effect gene expression and motivates both the identification and prediction of cis-regulatory variants responsible for expression differences within and between species. While much progress has been made in relating cis-regulatory variants to expression levels, the timing of gene activation and repression may also be important to the evolution of cis-regulatory sequences. We investigated allele-specific expression (ASE) dynamics within and between Saccharomyces species during the diauxic shift and found appreciable cis-acting variation in gene expression dynamics. Within species ASE is associated with intergenic variants, but ASE dynamics are more strongly associated with insertions and deletions than ASE levels. To refine these associations we used a high-throughput reporter assay to test promoter regions and individual variants. Within the subset of regions that recapitulated endogenous expression we identified and characterized cis-regulatory variants that affect expression dynamics. Between species, chimeric promoter regions generate novel patterns and indicate constraints on the evolution of gene expression dynamics. We conclude that changes in cis-regulatory sequences can tune gene expression dynamics and that the interplay between expression dynamics and other aspects expression are relevant to the evolution of cis-regulatory sequences.

scholarly journals Impact of the X chromosome and sex on regulatory variation

2015 ◽  
Author(s):  
Kimberly R Kukurba ◽  
Princy Parsana ◽  
Kevin S Smith ◽  
Zachary Zappala ◽  
David A Knowles ◽  
...  
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Molecular Mechanisms ◽  
Genome Wide Association Study ◽  
Specific Gene ◽  
Specific Expression ◽  
Regulatory Variation ◽  
Regulatory Variants ◽  
Genome Wide ◽  
The Impact

The X chromosome, with its unique mode of inheritance, contributes to differences between the sexes at a molecular level, including sex-specific gene expression and sex-specific impact of genetic variation. We have conducted an analysis of the impact of both sex and the X chromosome on patterns of gene expression identified through transcriptome sequencing of whole blood from 922 individuals. We identified that genes on the X chromosome are more likely to have sex-specific expression compared to the autosomal genes. Furthermore, we identified a depletion of regulatory variants on the X chromosome, especially among genes under high selective constraint. In contrast, we discovered an enrichment of sex-specific regulatory variants on the X chromosome. To resolve the molecular mechanisms underlying such effects, we generated and connected sex-specific chromatin accessibility to sex-specific expression and regulatory variation. As sex-specific regulatory variants can inform sex differences in genetic disease prevalence, we have integrated our data with genome-wide association study data for multiple immune traits and to identify traits with significant sex biases. Together, our study provides genome-wide insight into how the X chromosome and sex shape human gene regulation and disease.

scholarly journals Cis-regulatory variants affect gene expression dynamics in yeast

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ching-Hua Shih ◽  
Justin Fay
Keyword(s):  
Gene Expression ◽  
Gene Activation ◽  
Regulatory Sequences ◽  
Diauxic Shift ◽  
Promoter Regions ◽  
Specific Expression ◽  
Regulatory Variants ◽  
Endogenous Expression ◽  
Gene Expression Dynamics ◽  
Affect Gene Expression

Evolution of cis-regulatory sequences depends on how they affect gene expression and motivates both the identification and prediction of cis-regulatory variants responsible for expression differences within and between species. While much progress has been made in relating cis-regulatory variants to expression levels, the timing of gene activation and repression may also be important to the evolution of cis-regulatory sequences. We investigated allele-specific expression (ASE) dynamics within and between Saccharomyces species during the diauxic shift and found appreciable cis-acting variation in gene expression dynamics. Within species ASE is associated with intergenic variants, and ASE dynamics are more strongly associated with insertions and deletions than ASE levels. To refine these associations we used a high-throughput reporter assay to test promoter regions and individual variants. Within the subset of regions that recapitulated endogenous expression we identified and characterized cis-regulatory variants that affect expression dynamics. Between species, chimeric promoter regions generate novel patterns and indicate constraints on the evolution of gene expression dynamics. We conclude that changes in cis-regulatory sequences can tune gene expression dynamics and that the interplay between expression dynamics and other aspects expression are relevant to the evolution of cis-regulatory sequences.

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