scholarly journals Gene age predicts the transcriptional landscape of sexual morphogenesis in multicellular fungi

2021 ◽  
Author(s):  
Zsolt Merenyi ◽  
Mate Viragh ◽  
Emile Gluck-Thaler ◽  
Jason C. Slot ◽  
Brigitta Kiss ◽  
...  
Keyword(s):  
Gene Expression ◽  
Evolutionary Constraint ◽  
Regulatory Evolution ◽  
Specific Expression ◽  
Developmental Gene Expression ◽  
Evolutionary Changes ◽  
History Of ◽  
Allele Specific ◽  
Gene Age

Multicellularity has been one of the most important innovations in the history of life. The role of regulatory evolution in driving transitions to multicellularity is being increasingly recognized; however, patterns and drivers of transcriptome evolution are poorly known in many clades. We here reveal that allele-specific expression, natural antisense transcripts and developmental gene expression, but not RNA editing or a developmental hourglass act in concert to shape the transcriptome of complex multicellular fruiting bodies of fungi. We find that transcriptional patterns of genes are strongly predicted by their evolutionary age. Young genes showed more expression variation both in time and space, possibly because of weaker evolutionary constraint, calling for partially non-adaptive interpretations of evolutionary changes in the transcriptome of multicellular fungi. Gene age also correlated with function, allowing us to separate fruiting body gene expression related to simple sexual development from that potentially underlying complex morphogenesis. Our study highlighted a transcriptional complexity that provides multiple speeds for transcriptome evolution, but also that constraints associated with gene age shape transcriptomic patterns during transitions to complex multicellularity in fungi.

scholarly journals Gene Expression Networks Across Multiple Tissues Are Associated with Rates of Molecular Evolution in Wild House Mice

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 225 ◽  
Author(s):  
Katya Mack ◽  
Megan Phifer-Rixey ◽  
Bettina Harr ◽  
Michael Nachman
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Gene Evolution ◽  
Purifying Selection ◽  
Evolutionary Constraint ◽  
Mus Musculus Domesticus ◽  
Specific Expression ◽  
Regulatory Variation ◽  
Allele Specific ◽  
Wild House Mice

Interactions between genes can influence how selection acts on sequence variation. In gene regulatory networks, genes that affect the expression of many other genes may be under stronger evolutionary constraint than genes whose expression affects fewer partners. While this has been studied for individual tissue types, we know less about the effects of regulatory networks on gene evolution across different tissue types. We use RNA-sequencing and genomic data collected from Mus musculus domesticus to construct and compare gene co-expression networks for 10 tissue types. We identify tissue-specific expression and local regulatory variation, and we associate these components of gene expression variation with sequence polymorphism and divergence. We found that genes with higher connectivity across tissues and genes associated with a greater number of cross-tissue modules showed significantly lower genetic diversity and lower rates of protein evolution. Consistent with this pattern, “hub” genes across multiple tissues also showed evidence of greater evolutionary constraint. Using allele-specific expression, we found that genes with cis-regulatory variation had lower average connectivity and higher levels of tissue specificity. Taken together, these results are consistent with strong purifying selection acting on genes with high connectivity within and across tissues.

scholarly journals Behavior-dependent cis regulation reveals genes and pathways associated with bower building in cichlid fishes

2018 ◽  
Vol 115 (47) ◽  
pp. E11081-E11090 ◽  
Author(s):  
Ryan A. York ◽  
Chinar Patil ◽  
Kawther Abdilleh ◽  
Zachary V. Johnson ◽  
Matthew A. Conte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neural Plasticity ◽  
Genetic Basis ◽  
Specific Expression ◽  
Preferential Expression ◽  
Cichlid Fishes ◽  
Brain Gene Expression ◽  
Genome Wide ◽  
Allele Specific ◽  
Genomic Regions

Many behaviors are associated with heritable genetic variation [Kendler and Greenspan (2006) Am J Psychiatry 163:1683–1694]. Genetic mapping has revealed genomic regions or, in a few cases, specific genes explaining part of this variation [Bendesky and Bargmann (2011) Nat Rev Gen 12:809–820]. However, the genetic basis of behavioral evolution remains unclear. Here we investigate the evolution of an innate extended phenotype, bower building, among cichlid fishes of Lake Malawi. Males build bowers of two types, pits or castles, to attract females for mating. We performed comparative genome-wide analyses of 20 bower-building species and found that these phenotypes have evolved multiple times with thousands of genetic variants strongly associated with this behavior, suggesting a polygenic architecture. Remarkably, F1 hybrids of a pit-digging and a castle-building species perform sequential construction of first a pit and then a castle bower. Analysis of brain gene expression in these hybrids showed that genes near behavior-associated variants display behavior-dependent allele-specific expression with preferential expression of the pit-digging species allele during pit digging and of the castle-building species allele during castle building. These genes are highly enriched for functions related to neurodevelopment and neural plasticity. Our results suggest that natural behaviors are associated with complex genetic architectures that alter behavior via cis-regulatory differences whose effects on gene expression are specific to the behavior itself.

scholarly journals Genetic influences on cell type specific gene expression and splicing during neurogenesis elucidate regulatory mechanisms of brain traits

2020 ◽  
Author(s):  
Nil Aygün ◽  
Angela L. Elwell ◽  
Dan Liang ◽  
Michael J. Lafferty ◽  
Kerry E. Cheek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Elements ◽  
Regulatory Mechanisms ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Risk Variants ◽  
Allele Specific ◽  
Cell Type Specific ◽  
Regulatory Effects

SummaryInterpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing is mainly performed in bulk post-mortem adult tissue. However, genetic risk loci are enriched in regulatory elements of cells present during neocortical differentiation, and regulatory effects of risk variants may be masked by heterogeneity in bulk tissue. Here, we map e/sQTLs and allele specific expression in primary human neural progenitors (n=85) and their sorted neuronal progeny (n=74). Using colocalization and TWAS, we uncover cell-type specific regulatory mechanisms underlying risk for these traits.

Allele-Specific Expression and Evolution of Gene Regulation Underlying Acute Heat Stress Response and Local Adaptation in the Copepod Tigriopus californicus

2020 ◽  
Vol 111 (6) ◽  
pp. 539-547
Author(s):  
Sumaetee Tangwancharoen ◽  
Brice X Semmens ◽  
Ronald S Burton
Keyword(s):  
Gene Expression ◽  
Heat Stress ◽  
Stress Response ◽  
Local Adaptation ◽  
F1 Hybrids ◽  
Specific Expression ◽  
Heat Stress Response ◽  
Acute Heat Stress ◽  
Number Of Genes ◽  
Allele Specific

Abstract Geographic variation in environmental temperature can select for local adaptation among conspecific populations. Divergence in gene expression across the transcriptome is a key mechanism for evolution of local thermal adaptation in many systems, yet the genetic mechanisms underlying this regulatory evolution remain poorly understood. Here we examine gene expression in 2 locally adapted Tigriopus californicus populations (heat tolerant San Diego, SD, and less tolerant Santa Cruz, SC) and their F1 hybrids during acute heat stress response. Allele-specific expression (ASE) in F1 hybrids was used to determine cis-regulatory divergence. We found that the number of genes showing significant allelic imbalance increased under heat stress compared to unstressed controls. This suggests that there is significant population divergence in cis-regulatory elements underlying heat stress response. Specifically, the number of genes showing an excess of transcripts from the more thermal tolerant (SD) population increased with heat stress while that number of genes with an SC excess was similar in both treatments. Inheritance patterns of gene expression also revealed that genes displaying SD-dominant expression phenotypes increase in number in response to heat stress; that is, across loci, gene expression in F1’s following heat stress showed more similarity to SD than SC, a pattern that was absent in the control treatment. The observed patterns of ASE and inheritance of gene expression provide insight into the complex processes underlying local adaptation and thermal stress response.

scholarly journals The genetic basis of evolutionary change in gene expression levels

2010 ◽  
Vol 365 (1552) ◽  
pp. 2581-2590 ◽  
Author(s):  
J. J. Emerson ◽  
Wen-Hsiung Li
Keyword(s):  
Gene Expression ◽  
Genetic Basis ◽  
Regulation Of Gene Expression ◽  
Specific Expression ◽  
Genetic Changes ◽  
Expression Variation ◽  
Regulatory Variation ◽  
Global Mapping ◽  
History Of ◽  
Trait Locus

The regulation of gene expression is an important determinant of organismal phenotype and evolution. However, the widespread recognition of this fact occurred long after the synthesis of evolution and genetics. Here, we give a brief sketch of thoughts regarding gene regulation in the history of evolution and genetics. We then review the development of genome-wide studies of gene regulatory variation in the context of the location and mode of action of the causative genetic changes. In particular, we review mapping of the genetic basis of expression variation through expression quantitative trait locus studies and measuring the cis / trans component of expression variation in allele-specific expression studies. We conclude by proposing a systematic integration of ideas that combines global mapping studies, cis / trans tests and modern population genetics methodologies, in order to directly estimate the forces acting on regulatory variation within and between species.

scholarly journals Interactions between genetic variation and cellular environment in skeletal muscle gene expression

2017 ◽  
Author(s):  
D. Leland Taylor ◽  
David A. Knowles ◽  
Laura J. Scott ◽  
Andrea H. Ramirez ◽  
Franceso Paolo Casale ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Genetic Variation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Specific Expression ◽  
Muscle Gene Expression ◽  
Cellular Environment ◽  
Allele Specific ◽  
Muscle Gene

AbstractFrom whole organisms to individual cells, responses to environmental conditions are influenced by genetic makeup, where the effect of genetic variation on a trait depends on the environmental context. RNA-sequencing quantifies gene expression as a molecular trait, and is capable of capturing both genetic and environmental effects. In this study, we explore opportunities of using allele-specific expression (ASE) to discovercisacting genotype-environment interactions (GxE) - genetic effects on gene expression that depend on an environmental condition. Treating 17 common, clinical traits as approximations of the cellular environment of 267 skeletal muscle biopsies, we identify 10 candidate interaction quantitative trait loci (iQTLs) across 6 traits (12 unique gene-environment trait pairs; 10% FDR per trait) including sex, systolic blood pressure, and low-density lipoprotein cholesterol. Although using ASE is in principle a promising approach to detect GxE effects, replication of such signals can be challenging as validation requires harmonization of environmental traits across cohorts and a sufficient sampling of heterozygotes for a transcribed SNP. Comprehensive discovery and replication will require large human transcriptome datasets, or the integration of multiple transcribed SNPs, coupled with standardized clinical phenotyping.

scholarly journals Large structural variations in the haplotype-resolved African cassava genome.

2021 ◽  
Author(s):  
Ben N Mansfeld ◽  
Adam Boyher ◽  
Jeffrey C Berry ◽  
Mark Wilson ◽  
Shujun Ou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Load ◽  
Specific Gene ◽  
Stem Cuttings ◽  
Structural Variations ◽  
Manihot Esculenta Crantz ◽  
Specific Expression ◽  
Global Food Security ◽  
Allele Specific ◽  
Two Phases

Cassava (Manihot esculenta Crantz, 2n=36) is a global food security crop. Cassava has a highly heterozygous genome, high genetic load, and genotype-dependent asynchronous flowering. It is typically propagated by stem cuttings and any genetic variation between haplotypes, including large structural variations, is preserved by such clonal propagation. Traditional genome assembly approaches generate a collapsed haplotype representation of the genome. In highly heterozygous plants, this results in artifacts and an oversimplification of heterozygous regions. We used a combination of Pacific Biosciences (PacBio), Illumina, and Hi-C to resolve each haplotype of the genome of a farmer-preferred cassava line, TME7 (Oko-iyawo). PacBio reads were assembled using the FALCON suite. Phase switch errors were corrected using FALCON-Phase and Hi-C read data. The ultra-long-range information from Hi-C sequencing was also used for scaffolding. Comparison of the two phases revealed more than 5,000 large haplotype-specific structural variants affecting over 8 Mb, including insertions and deletions spanning thousands of base pairs. The potential of these variants to affect allele specific expression was further explored. RNA-seq data from 11 different tissue types were mapped against the scaffolded haploid assembly and gene expression data are incorporated into our existing easy-to-use web-based interface to facilitate use by the broader plant science community. These two assemblies provide an excellent means to study the effects of heterozygosity, haplotype-specific structural variation, gene hemizygosity, and allele specific gene expression contributing to important agricultural traits and further our understanding of the genetics and domestication of cassava.

scholarly journals Antiepileptic pharmacotherapy is the leading factor in the induced pathomorphosis of epilepsy

2018 ◽  
Vol 10 (2) ◽  
pp. 59-73
Author(s):  
M. G. Amirkhanian
Keyword(s):  
Focal Epilepsy ◽  
Rational Approach ◽  
Chi Square ◽  
Antiepileptic Therapy ◽  
Evolutionary Changes ◽  
G 21 ◽  
Chi Square Test ◽  
History Of

Aim– to elucidate the role of antiepileptic pharmacotherapy in pathomorphosis of focal epilepsy in adult patients.Materials and methods. We examined 91 patients with focal epilepsy (main group, G); among them, 37 (41%) men (M) and 54 (59%) women (W). At the time of the first visit, 82 (90%) of  them [33 (89%) M and 49 (91%) W] were under antiepileptic therapy. The age of patients ranged  from 18 to 78 years (average 37.5 years). The debut of epilepsy was observed at the ages from 4  to 71 years. The duration of the disease ranged from 1 to 52 years, with the average of 16.1 years. All patients were then followed up for 1 to 2.5 years. Clinical and neurological examinations were  conducted in all patients; laboratory and instrumental diagnostic tests were used if indicated. The  medical history of patients was analyzed from the onset of epilepsy; if needed, new therapies were  prescribed or the existing therapies were modified. The therapeutic efficacy was assessed  using the data from the daily-seizures diary. The differences between the groups were tested for  their significance using the Chi-square test or the exact Fisher test if there were less than five  observations in the group. Results.Only 47 (52%) patients of group G [21 (57%) M and 26 (48%) W] received an antiepileptic therapy from the debut of the disease; the therapy was then adjusted in 41 (45%)  cases [19 (51%) M and 22 (41%) W (р>0.05)]. Of the 82 patients receiving therapy at the time of  examination, 37 (45%) received the basic, 20 (24%) – the updated, and 24 (29%) – a  combination of the basic and updated AED; in about 2% of cases, a combination with the 1st  generation drugs was prescribed. Monotherapy was used in 45 (55%), and polytherapy – in 37  (45%) patients. Of the 19 patients taking KBZ as the starting monotherapy, 10 (52%) received the drug in the non-prolonged form, twice a day. Relapse after long-term remission (12 months or  more) in 80% of cases was associated with changes in the AED regimen. Side effects were  observed in 43 (52%) patients under the treatment [15 (45%) M and 28 (57%) W]. Among those,  who underwent MRI examination, structural epileptogenic changes were detected in 37 (54%)  patients [21 (72%) M and 16 (40%) W (p<0.05)]. Comorbidity and the associated co-therapy were detected in 88% M and 90% W who were >50 years old.Conclusion. Antiepileptic pharmacotherapy is a leading factor that induces evolutionary changes in the clinical and neurophysiological picture of epilepsy. With a timely and rational approach, the  use of AED allows for creating favorable development of pathomorphosis of the disease. Full  patients awareness of the AED therapeutic regimens and the associated risks may increases the  compliance, reduce the risk of decompensation and improve the prognosis of epilepsy.

scholarly journals RNA sequencing-based screen for reactivation of silenced alleles of autosomal genes

2021 ◽  
Author(s):  
Saumya Gupta ◽  
Denis L Lafontaine ◽  
Sebastien Vigneau ◽  
Asia Mendelevich ◽  
Svetlana Vinogradova ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rna Sequencing ◽  
Mammalian Cells ◽  
Allelic Imbalance ◽  
Dna Demethylation ◽  
Monoallelic Expression ◽  
Specific Expression ◽  
Allele Specific ◽  
Mechanistic Basis

Abstract In mammalian cells, maternal and paternal alleles usually have similar transcriptional activity. Epigenetic mechanisms such as X-chromosome inactivation (XCI) and imprinting were historically viewed as rare exceptions to this rule. Discovery of autosomal monoallelic expression (MAE) a decade ago revealed an additional allele-specific mode regulating thousands of mammalian genes. Despite MAE prevalence, its mechanistic basis remains unknown. Using an RNA sequencing-based screen for reactivation of silenced alleles, we identified DNA methylation as key mechanism of MAE mitotic maintenance. In contrast with the all-or-nothing allelic choice in XCI, allele-specific expression in MAE loci is tunable, with exact allelic imbalance dependent on the extent of DNA methylation. In a subset of MAE genes, allelic imbalance was insensitive to DNA demethylation, implicating additional mechanisms in MAE maintenance in these loci. Our findings identify a key mechanism of MAE maintenance and provide basis for understanding the biological role of MAE.

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