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 Genomic analysis reveals major determinants of cis-regulatory variation in Capsella grandiflora

2015 ◽  
Author(s):  
Kim A. Steige ◽  
Benjamin Laenen ◽  
Johan Reimegård ◽  
Douglas Scofield ◽  
Tanja Slotte
Keyword(s):  
Evolutionary Biology ◽  
Genomic Analysis ◽  
Purifying Selection ◽  
Gene Body ◽  
Gene Body Methylation ◽  
Specific Expression ◽  
Regulatory Variation ◽  
Wide Range ◽  
Allele Specific ◽  
Selective Forces

Understanding the causes of cis-regulatory variation is a long-standing aim in evolutionary biology. Although cis-regulatory variation has long been considered important for adaptation, we still have a limited understanding of the selective importance and genomic determinants of standing cis-regulatory variation. To address these questions, we studied the prevalence, genomic determinants and selective forces shaping cis-regulatory variation in the outcrossing plant Capsella grandiflora. We first identified a set of 1,010 genes with common cis-regulatory variation using analyses of allele-specific expression (ASE). Population genomic analyses of whole-genome sequences from 32 individuals showed that genes with common cis-regulatory variation are 1) under weaker purifying selection and 2) undergo less frequent positive selection than other genes. We further identified genomic determinants of cis-regulatory variation. Gene-body methylation (gbM) was a major factor constraining cis-regulatory variation, whereas presence of nearby TEs and tissue specificity of expression increased the odds of ASE. Our results suggest that most common cis-regulatory variation in C. grandiflora is under weak purifying selection, and that gene-specific functional constraints are more important for the maintenance of cis-regulatory variation than genome-scale variation in the intensity of selection. Our results agree with previous findings that suggest TE silencing affects nearby gene expression, and provide novel evidence for a link between gbM and cis-regulatory constraint, possibly reflecting greater dosage-sensitivity of body-methylated genes. Given the extensive conservation of gene-body methylation in flowering plants, this suggests that gene-body methylation could be an important predictor of cis-regulatory variation in a wide range of plant species.

scholarly journals Constraint and divergence of global gene expression in the mammalian embryo

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Noah Spies ◽  
Cheryl L Smith ◽  
Jesse M Rodriguez ◽  
Julie C Baker ◽  
Serafim Batzoglou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Purifying Selection ◽  
Global Gene Expression ◽  
Mouse Strains ◽  
Specific Expression ◽  
Mammalian Embryo ◽  
Expression Phenotype ◽  
Gene Expression Phenotype ◽  
Allele Specific ◽  
Gene Regulatory

The effects of genetic variation on gene regulation in the developing mammalian embryo remain largely unexplored. To globally quantify these effects, we crossed two divergent mouse strains and asked how genotype of the mother or of the embryo drives gene expression phenotype genomewide. Embryonic expression of 331 genes depends on the genotype of the mother. Embryonic genotype controls allele-specific expression of 1594 genes and a highly overlapping set of cis-expression quantitative trait loci (eQTL). A marked paucity of trans-eQTL suggests that the widespread expression differences do not propagate through the embryonic gene regulatory network. The cis-eQTL genes exhibit lower-than-average evolutionary conservation and are depleted for developmental regulators, consistent with purifying selection acting on expression phenotype of pattern formation genes. The widespread effect of maternal and embryonic genotype in conjunction with the purifying selection we uncovered suggests that embryogenesis is an important and understudied reservoir of phenotypic variation.

scholarly journals Landscape and evolution of cis- and trans-regulation in chicken genome between two contrasted breeds analyzed in three tissues at one day of age

2019 ◽  
Author(s):  
Qiong Wang ◽  
Yaxiong Jia ◽  
Yuan Wang ◽  
Zhihua Jiang ◽  
Xiang Zhou ◽  
...  
Keyword(s):  
Chicken Genome ◽  
Reproductive Traits ◽  
Purifying Selection ◽  
Population Divergence ◽  
White Leghorn ◽  
Specific Expression ◽  
Regulatory Variation ◽  
Allele Specific ◽  
Trans Regulation ◽  
Cis And Trans

Abstract Background Gene expression variation is an important mechanism underlying phenotypic variation, and can occur via cis- and trans-regulation. In order to understand the role of cis- and trans-regulatory variation on population divergence of chicken, we developed reciprocal crosses of two chicken breeds, White Leghorn and Cornish Game, with major differences in size and reproductive traits, and used them to identify the degree of cis versus trans variation in brain, liver and muscle of both male and female samples at 1-day age. Results We provided a landscape about how the transcriptomes are regulated between two contrasted breeds by allele specific expression analysis. Our results showed that compared with the cis-regulated genes, trans-acted genes existed more extensively in the chicken genome. Furthermore, a widespread compensatory tendency exists in chicken genome. Most importantly, we found the evidence of stronger purifying selection for trans-regulatory variation than the cis-elements. Conclusions Our research performed the first study to describe the transcriptome regulation between White Leghorn and Cornish Game breeds and suggests that artificial selection associated with domestication in chicken may have more often acted on trans-regulatory variation.

scholarly journals Genomic analysis reveals major determinants ofcis-regulatory variation inCapsella grandiflora

2017 ◽  
Vol 114 (5) ◽  
pp. 1087-1092 ◽  
Author(s):  
Kim A. Steige ◽  
Benjamin Laenen ◽  
Johan Reimegård ◽  
Douglas G. Scofield ◽  
Tanja Slotte
Keyword(s):  
Evolutionary Biology ◽  
Genomic Analysis ◽  
Purifying Selection ◽  
Gene Body Methylation ◽  
Specific Expression ◽  
Regulatory Variation ◽  
Wide Range ◽  
Allele Specific ◽  
Selective Forces ◽  
Genome Scale

Understanding the causes ofcis-regulatory variation is a long-standing aim in evolutionary biology. Althoughcis-regulatory variation has long been considered important for adaptation, we still have a limited understanding of the selective importance and genomic determinants of standingcis-regulatory variation. To address these questions, we studied the prevalence, genomic determinants, and selective forces shapingcis-regulatory variation in the outcrossing plantCapsella grandiflora. We first identified a set of 1,010 genes with commoncis-regulatory variation using analyses of allele-specific expression (ASE). Population genomic analyses of whole-genome sequences from 32 individuals showed that genes with commoncis-regulatory variation (i) are under weaker purifying selection and (ii) undergo less frequent positive selection than other genes. We further identified genomic determinants ofcis-regulatory variation. Gene body methylation (gbM) was a major factor constrainingcis-regulatory variation, whereas presence of nearby transposable elements (TEs) and tissue specificity of expression increased the odds of ASE. Our results suggest that most commoncis-regulatory variation inC. grandiflorais under weak purifying selection, and that gene-specific functional constraints are more important for the maintenance ofcis-regulatory variation than genome-scale variation in the intensity of selection. Our results agree with previous findings that suggest TE silencing affects nearby gene expression, and provide evidence for a link between gbM andcis-regulatory constraint, possibly reflecting greater dosage sensitivity of body-methylated genes. Given the extensive conservation of gbM in flowering plants, this suggests that gbM could be an important predictor ofcis-regulatory variation in a wide range of plant species.

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 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 Gene Expression Networks in the Drosophila Genetic Reference Panel

2019 ◽  
Author(s):  
Logan J. Everett ◽  
Wen Huang ◽  
Shanshan Zhou ◽  
Mary Anna Carbone ◽  
Richard F. Lyman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transposable Elements ◽  
Dna Sequences ◽  
Quantitative Trait ◽  
Regulatory Networks ◽  
Target Genes ◽  
Reference Panel ◽  
Modern Biology ◽  
Specific Expression ◽  
Drosophila Genetic Reference Panel

SummaryA major challenge in modern biology is to understand how naturally occurring variation in DNA sequences affects complex organismal traits through networks of intermediate molecular phenotypes. Here, we performed deep RNA sequencing of 200 Drosophila Genetic Reference Panel inbred lines with complete genome sequences, and mapped expression quantitative trait loci for annotated genes, novel transcribed regions (most of which are long noncoding RNAs), transposable elements and microbial species. We identified host variants that affect expression of transposable elements, independent of their copy number, as well as microbiome composition. We constructed sex-specific expression quantitative trait locus regulatory networks. These networks are enriched for novel transcribed regions and target genes in heterochromatin and euchromatic regions of reduced recombination, and genes regulating transposable element expression. This study provides new insights regarding the role of natural genetic variation in regulating gene expression and generates testable hypotheses for future functional analyses.

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.

scholarly journals Landscape and evolution of cis- and trans-regulatory divergence in chicken genome between two contrasted breeds analyzed in three tissues at one day age

2019 ◽  
Author(s):  
Qiong Wang ◽  
Yaxiong Jia ◽  
Yuan Wang ◽  
Zhihua Jiang ◽  
Xiang Zhou ◽  
...  
Keyword(s):  
Chicken Genome ◽  
Reproductive Traits ◽  
Purifying Selection ◽  
Population Divergence ◽  
Specific Reference ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific ◽  
Trans Regulation ◽  
Cis And Trans

Abstract Background: Gene expression variation is an important mechanism underlying phenotypic variation, and can occur via cis- and trans-regulation. In order to understand the role of cis- and trans-regulatory variation on population divergence of chicken, we developed reciprocal crosses of two chicken breeds, White Leghorn and Cornish Game, with major differences in body size and reproductive traits, and used them to identify the degree of cis versus trans variation in brain, liver and muscle of both male and female samples at 1 day age. Results: We provided a landscape about how the transcriptomes are regulated in the hybrid progenies of two contrasted breeds by allele specific expression analysis. Our results showed that compared with the cis-regulatory divergence, trans-acted genes existed more extensively in the chicken genome. Furthermore, a widespread tendency of compensatory regulation exists in chicken genome. Most importantly, we found the evidence of stronger purifying selection on genes regulated by trans variations than the cis elements. Conclusions: We demonstrated a pipeline to explore the allele-specific expression in the hybrid progenies of inbred lines without specific reference genome. Our research performed the first study to describe the regulatory divergence between two contrasted breeds. The results suggested that artificial selection associated with domestication in chicken may have more often acted on trans-regulatory divergence than cis.

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