scholarly journals Independent Transposon Exaptation Is a Widespread Mechanism of Redundant Enhancer Evolution in the Mammalian Genome

2020 ◽  
Vol 12 (3) ◽  
pp. 1-17
Author(s):  
Nicolai K H Barth ◽  
Lifei Li ◽  
Leila Taher
Keyword(s):  
Convergent Evolution ◽  
Regulatory Networks ◽  
Tissue Specificity ◽  
Target Genes ◽  
Mouse Genome ◽  
Intrinsic Property ◽  
Mammalian Genome ◽  
Fine Tuning ◽  
Evolutionary Advantage ◽  
Species Specific

Abstract Many regulatory networks appear to involve partially redundant enhancers. Traditionally, such enhancers have been hypothesized to originate mainly by sequence duplication. An alternative model postulates that they arise independently, through convergent evolution. This mechanism appears to be counterintuitive to natural selection: Redundant sequences are expected to either diverge and acquire new functions or accumulate mutations and become nonfunctional. Nevertheless, we show that at least 31% of the redundant enhancer pairs in the human genome (and 17% in the mouse genome) indeed originated in this manner. Specifically, for virtually all transposon-derived redundant enhancer pairs, both enhancer partners have evolved independently, from the exaptation of two different transposons. In addition to conferring robustness to the system, redundant enhancers could provide an evolutionary advantage by fine-tuning gene expression. Consistent with this hypothesis, we observed that the target genes of redundant enhancers exhibit higher expression levels and tissue specificity as compared with other genes. Finally, we found that although enhancer redundancy appears to be an intrinsic property of certain mammalian regulatory networks, the corresponding enhancers are largely species-specific. In other words, the redundancy in these networks is most likely a result of convergent evolution.

scholarly journals Independent transposon exaptation is a widespread mechanism of shadow enhancer evolution in the mammalian genome

2019 ◽  
Author(s):  
Nicolai K. H. Barth ◽  
Lifei Li ◽  
Leila Taher
Keyword(s):  
Convergent Evolution ◽  
Regulatory Networks ◽  
Tissue Specificity ◽  
Regulatory Elements ◽  
Mammalian Genome ◽  
Alternative Mechanism ◽  
Human And Mouse ◽  
Enhancer Evolution

ABSTRACTMany regulatory networks involve (possibly partially) redundant cis-regulatory elements. These elements are commonly referred to as shadow enhancers and have been assumed to mainly originate by sequence duplication. An alternative mechanism that has not been examined involves the independent exaptation of transposons. Here, we identified 2,117 and 2,787 pairs of shadow enhancers in the human and mouse genomes, respectively, and found that 34% and 18% of these pairs derive from transposons. Moreover, we show that virtually all the enhancer partners of these transposon-derived shadow enhancer pairs are independent exaptations from different transposon types and hypothesize that the increase in the expression and tissue-specificity of their targets as compared to those of non-shadow enhancers facilitates their fixation in the genome. Finally, we provide evidence that the regulatory redundancy observed in many mammalian regulatory networks is predominantly driven by convergent evolution, since shadow enhancers are hardly ever conserved across species.

scholarly journals Genome-Wide microRNA Profiling Using Oligonucleotide Microarray Reveals Regulatory Networks of microRNAs in Nicotiana benthamiana During Beet Necrotic Yellow Vein Virus Infection

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 310 ◽  
Author(s):  
Junying Liu ◽  
Huiyan Fan ◽  
Ying Wang ◽  
Chenggui Han ◽  
Xianbing Wang ◽  
...  
Keyword(s):  
Nicotiana Benthamiana ◽  
Regulatory Networks ◽  
Target Genes ◽  
Tobacco Rattle Virus ◽  
Yellow Vein ◽  
Differentially Expressed ◽  
Virus Induced Gene Silencing ◽  
Developmental Defects ◽  
Differentially Expressed Mirnas ◽  
Species Specific

Beet necrotic yellow vein virus (BNYVV) infections induce stunting and leaf curling, as well as root and floral developmental defects and leaf senescence in Nicotiana benthamiana. A microarray analysis with probes capable of detecting 1596 candidate microRNAs (miRNAs) was conducted to investigate differentially expressed miRNAs and their targets upon BNYVV infection of N. benthamiana plants. Eight species-specific miRNAs of N. benthamiana were identified. Comprehensive characterization of the N. benthamiana microRNA profile in response to the BNYVV infection revealed that 129 miRNAs were altered, including four species-specific miRNAs. The targets of the differentially expressed miRNAs were predicted accordingly. The expressions of miR164, 160, and 393 were up-regulated by BNYVV infection, and those of their target genes, NAC21/22, ARF17/18, and TIR, were down-regulated. GRF1, which is a target of miR396, was also down-regulated. Further genetic analysis of GRF1, by Tobacco rattle virus-induced gene silencing, assay confirmed the involvement of GRF1 in the symptom development during BNYVV infection. BNYVV infection also induced the up-regulation of miR168 and miR398. The miR398 was predicted to target umecyanin, and silencing of umecyanin could enhance plant resistance against viruses, suggesting the activation of primary defense response to BNYVV infection in N. benthamiana. These results provide a global profile of miRNA changes induced by BNYVV infection and enhance our understanding of the mechanisms underlying BNYVV pathogenesis.

scholarly journals Evidence for convergent evolution of SINE-directed Staufen-mediated mRNA decay

2018 ◽  
Vol 115 (5) ◽  
pp. 968-973 ◽  
Author(s):  
Bronwyn A. Lucas ◽  
Eitan Lavi ◽  
Lily Shiue ◽  
Hana Cho ◽  
Sol Katzman ◽  
...  
Keyword(s):  
Convergent Evolution ◽  
Regulatory Networks ◽  
Parallel Evolution ◽  
Orthologous Gene ◽  
Control Networks ◽  
Short Interspersed Elements ◽  
Gene Pairs ◽  
Sine Insertion ◽  
Rapid Divergence ◽  
Species Specific

Primate-specific Alu short interspersed elements (SINEs) as well as rodent-specific B and ID (B/ID) SINEs can promote Staufen-mediated decay (SMD) when present in mRNA 3′-untranslated regions (3′-UTRs). The transposable nature of SINEs, their presence in long noncoding RNAs, their interactions with Staufen, and their rapid divergence in different evolutionary lineages suggest they could have generated substantial modification of posttranscriptional gene-control networks during mammalian evolution. Some of the variation in SMD regulation produced by SINE insertion might have had a similar regulatory effect in separate mammalian lineages, leading to parallel evolution of the Staufen network by independent expansion of lineage-specific SINEs. To explore this possibility, we searched for orthologous gene pairs, each carrying a species-specific 3′-UTR SINE and each regulated by SMD, by measuring changes in mRNA abundance after individual depletion of two SMD factors, Staufen1 (STAU1) and UPF1, in both human and mouse myoblasts. We identified and confirmed orthologous gene pairs with 3′-UTR SINEs that independently function in SMD control of myoblast metabolism. Expanding to other species, we demonstrated that SINE-directed SMD likely emerged in both primate and rodent lineages >20–25 million years ago. Our work reveals a mechanism for the convergent evolution of posttranscriptional gene regulatory networks in mammals by species-specific SINE transposition and SMD.

Evolution of miRNA binding sites and regulatory networks in cichlids

2021 ◽  
Author(s):  
Tarang K Mehta ◽  
Luca Penso-Dolfin ◽  
Will K Nash ◽  
Sushmita Roy ◽  
Federica Di Palma ◽  
...  
Keyword(s):  
Binding Site ◽  
Binding Sites ◽  
Regulatory Networks ◽  
Target Genes ◽  
Phenotypic Diversity ◽  
Regulatory Regions ◽  
Adaptive Trait ◽  
Regulatory Variants ◽  
Key Driver ◽  
Species Specific

The divergence of regulatory regions and gene regulatory network (GRN) rewiring is a key driver of cichlid phenotypic diversity. However, the contribution of miRNA binding site turnover has yet to be linked to GRN evolution across cichlids. Here, we extend our previous studies by analysing the selective constraints driving evolution of miRNA and transcription factor (TF) binding sites of target genes, to infer instances of cichlid GRN rewiring associated with regulatory binding site turnover. Comparative analyses identified increased species-specific networks that are functionally associated to traits of cichlid phenotypic diversity. The evolutionary rewiring is associated with differential models of miRNA snd TF binding site turnover, driven by a high proportion of fast-evolving polymorphic sites in adaptive trait genes compared to subsets of random genes. Positive selection acting upon discrete mutations in these regulatory regions is likely to be an important mechanism in rewiring GRNs in rapidly radiating cichlids. Regulatory variants of functionally associated miRNA and TF binding sites of visual opsin genes differentially segregate according to phylogeny and ecology of Lake Malawi species, identifying both rewired e.g. clade-specific and conserved network motifs of adaptive trait associated GRNs. Our approach revealed several novel candidate regulators, regulatory regions and three-node motifs across cichlid genomes with previously reported associations to known adaptive evolutionary traits.

scholarly journals Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPS cells

2017 ◽  
Author(s):  
Kai Fu ◽  
Constantinos Chronis ◽  
Abdenour Soufi ◽  
Giancarlo Bonora ◽  
Miguel Edwards ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Target Genes ◽  
Human Fibroblasts ◽  
Mouse Cell ◽  
Binding Motifs ◽  
Reprogramming Factors ◽  
Early Mouse ◽  
Species Specific ◽  
Human And Mouse ◽  
Syntenic Regions

AbstractBoth human and mouse fibroblasts can be reprogrammed to pluripotency with Oct4, Sox2, Klf4, and c-Myc (OSKM) transcription factors. While both systems generate pluripotency, human reprogramming takes considerably longer than mouse. To assess additional similarities and differences, we sought to compare the binding of the reprogramming factors between the two systems. In human fibroblasts, the OSK factors initially target many more closed chromatin sites compared to mouse. Despite this difference, the intra- and intergenic distribution of target sites, target genes, primary binding motifs, and combinatorial binding patterns between the reprogramming factors are largely shared. However, while many OSKM binding events in early mouse cell reprogramming occur in syntenic regions, only a limited number is conserved in human. In summary, these findings suggest similar general effects of OSKM binding across these two species, even though the detailed regulatory networks have diverged significantly.

scholarly journals NfiS, a species-specific regulatory noncoding RNA of Pseudomonas stutzeri, enhances oxidative stress tolerance in Escherichia coli

AMB Express ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Guihua Hu ◽  
Tao Hu ◽  
Yuhua Zhan ◽  
Wei Lu ◽  
Min Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Escherichia Coli ◽  
Stress Responses ◽  
Noncoding Rna ◽  
Regulatory Networks ◽  
Target Genes ◽  
Pseudomonas Stutzeri ◽  
Bacterial Strains ◽  
E Coli ◽  
Species Specific

Abstract Noncoding RNAs (ncRNAs) can finely control the expression of target genes at the posttranscriptional level in prokaryotes. Regulatory small RNAs (sRNAs) designed to control target gene expression for applications in metabolic engineering and synthetic biology have been successfully developed and used. However, the effect on the heterologous expression of species- or strain-specific ncRNAs in other bacterial strains remains poorly understood. In this work, a Pseudomonas stutzeri species-specific regulatory ncRNA, NfiS, which has been shown to play an important role in the response to oxidative stress as well as osmotic stress in P. stutzeri A1501, was cloned and transferred to the Escherichia coli strain Trans10. Recombinant NfiS-expressing E. coli, namely, Trans10-nfiS, exhibited significant enhancement of tolerance to oxidative stress. To map the possible gene regulatory networks mediated by NfiS in E. coli under oxidative stress, a microarray assay was performed to delineate the transcriptomic differences between Trans10-nfiS and wild-type E. coli under H2O2 shock treatment conditions. In all, 1184 genes were found to be significantly altered, and these genes were divided into mainly five functional categories: stress response, regulation, metabolism related, transport or membrane protein and unknown function. Our results suggest that the P. stutzeri species-specific ncRNA NfiS acts as a regulator that integrates adaptation to H2O2 with other cellular stress responses and helps protect E. coli cells against oxidative damage.

scholarly journals Divergence of regulatory networks governed by the orthologous transcription factors FLC and PEP1 in Brassicaceae species

2017 ◽  
Vol 114 (51) ◽  
pp. E11037-E11046 ◽  
Author(s):  
Julieta L. Mateos ◽  
Vicky Tilmes ◽  
Pedro Madrigal ◽  
Edouard Severing ◽  
René Richter ◽  
...  
Keyword(s):  
Stress Responses ◽  
Regulatory Networks ◽  
Target Genes ◽  
Gene Transcript ◽  
Mads Box ◽  
Core Motif ◽  
The Core ◽  
Brassicaceae Species ◽  
Carg Box ◽  
Species Specific

Genome-wide landscapes of transcription factor (TF) binding sites (BSs) diverge during evolution, conferring species-specific transcriptional patterns. The rate of divergence varies in different metazoan lineages but has not been widely studied in plants. We identified the BSs and assessed the effects on transcription of FLOWERING LOCUS C (FLC) and PERPETUAL FLOWERING 1 (PEP1), two orthologous MADS-box TFs that repress flowering and confer vernalization requirement in the Brassicaceae species Arabidopsis thaliana and Arabis alpina, respectively. We found that only 14% of their BSs were conserved in both species and that these contained a CArG-box that is recognized by MADS-box TFs. The CArG-box consensus at conserved BSs was extended compared with the core motif. By contrast, species-specific BSs usually lacked the CArG-box in the other species. Flowering-time genes were highly overrepresented among conserved targets, and their CArG-boxes were widely conserved among Brassicaceae species. Cold-regulated (COR) genes were also overrepresented among targets, but the cognate BSs and the identity of the regulated genes were usually different in each species. In cold, COR gene transcript levels were increased in flc and pep1-1 mutants compared with WT, and this correlated with reduced growth in pep1-1. Therefore, FLC orthologs regulate a set of conserved target genes mainly involved in reproductive development and were later independently recruited to modulate stress responses in different Brassicaceae lineages. Analysis of TF BSs in these lineages thus distinguishes widely conserved targets representing the core function of the TF from those that were recruited later in evolution.

scholarly journals EPEN-21. IMPAIRED NEURONAL-GLIAL FATE SPECIFICATION IN PEDIATRIC EPENDYMOMA REVEALED BY SINGLE-CELL RNA-SEQ

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii311-iii312
Author(s):  
Bernhard Englinger ◽  
Johannes Gojo ◽  
Li Jiang ◽  
Jens M Hübner ◽  
McKenzie L Shaw ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Single Cell ◽  
Regulatory Networks ◽  
Target Genes ◽  
Target Identification ◽  
Rna Seq ◽  
Cell Models ◽  
Pediatric Ependymoma ◽  
Glial Fate ◽  
Anatomic Locations

Abstract Ependymoma represents a heterogeneous disease affecting the entire neuraxis. Extensive molecular profiling efforts have identified molecular ependymoma subgroups based on DNA methylation. However, the intratumoral heterogeneity and developmental origins of these groups are only partially understood, and effective treatments are still lacking for about 50% of patients with high-risk tumors. We interrogated the cellular architecture of ependymoma using single cell/nucleus RNA-sequencing to analyze 24 tumor specimens across major molecular subgroups and anatomic locations. We additionally analyzed ten patient-derived ependymoma cell models and two patient-derived xenografts (PDXs). Interestingly, we identified an analogous cellular hierarchy across all ependymoma groups, originating from undifferentiated neural stem cell-like populations towards different degrees of impaired differentiation states comprising neuronal precursor-like, astro-glial-like, and ependymal-like tumor cells. While prognostically favorable ependymoma groups predominantly harbored differentiated cell populations, aggressive groups were enriched for undifferentiated subpopulations. Projection of transcriptomic signatures onto an independent bulk RNA-seq cohort stratified patient survival even within known molecular groups, thus refining the prognostic power of DNA methylation-based profiling. Furthermore, we identified novel potentially druggable targets including IGF- and FGF-signaling within poorly prognostic transcriptional programs. Ependymoma-derived cell models/PDXs widely recapitulated the transcriptional programs identified within fresh tumors and are leveraged to validate identified target genes in functional follow-up analyses. Taken together, our analyses reveal a developmental hierarchy and transcriptomic context underlying the biologically and clinically distinct behavior of ependymoma groups. The newly characterized cellular states and underlying regulatory networks could serve as basis for future therapeutic target identification and reveal biomarkers for clinical trials.

scholarly journals Comparative transcriptome analysis reveals key genes associated with pigmentation in radish (Raphanus sativus L.) skin and flesh

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jifang Zhang ◽  
Jian Zhao ◽  
Qunyun Tan ◽  
Xiaojun Qiu ◽  
Shiyong Mei
Keyword(s):  
Transcription Factors ◽  
Raphanus Sativus ◽  
Regulatory Networks ◽  
Anthocyanin Biosynthesis ◽  
Comparative Transcriptome ◽  
Structural Genes ◽  
Key Genes ◽  
Transcript Profiles ◽  
Species Specific ◽  
Anthocyanin Biosynthetic Genes

AbstractRadish (Raphanus sativus) is an important vegetable worldwide that exhibits different flesh and skin colors. The anthocyanins responsible for the red and purple coloring in radishes possess nutritional value and pharmaceutical potential. To explore the structural and regulatory networks related to anthocyanin biosynthesis and identify key genes, we performed comparative transcriptome analyses of the skin and flesh of six colored radish accessions. The transcript profiles showed that each accession had a species-specific transcript profile. For radish pigmentation accumulation, the expression levels of anthocyanin biosynthetic genes (RsTT4, RsC4H, RsTT7, RsCCOAMT, RsDFR, and RsLDOX) were significantly upregulated in the red- and purple-colored accessions, but were downregulated or absent in the white and black accessions. The correlation test, combined with metabolome (PCC > 0.95), revealed five structural genes (RsTT4, RsDFR, RsCCOAMT, RsF3H, and RsBG8L) and three transcription factors (RsTT8-1, RsTT8-2, and RsPAR1) to be significantly correlated with flavonoids in the skin of the taproot. Four structural genes (RsBG8L, RsDFR, RsCCOAMT, and RsLDOX) and nine transcription factors (RsTT8-1, RsTT8-2, RsMYB24L, RsbHLH57, RsPAR2L, RsbHLH113L, RsOGR3L, RsMYB24, and RsMYB34L) were found to be significantly correlated with metabolites in the flesh of the taproot. This study provides a foundation for future studies on the gene functions and genetic diversity of radish pigmentation and should aid in the cultivation of new valuable radish varieties.

scholarly journals Convergent evolution in Arabidopsis halleri and Arabidopsis arenosa on calamine metalliferous soils

2018 ◽  
Author(s):  
Veronica Preite ◽  
Christian Sailer ◽  
Lara Syllwasschy ◽  
Sian Bray ◽  
Ute Krämer ◽  
...  
Keyword(s):  
Convergent Evolution ◽  
Arabidopsis Halleri ◽  
Individual Genome ◽  
Genetic Changes ◽  
Association Analyses ◽  
Systematic Testing ◽  
Related Plant ◽  
Arabidopsis Arenosa ◽  
Species Specific ◽  
Degree Of Convergence

AbstractIt is a plausible hypothesis that parallel adaptation events to the same environmental challenge should result in genetic changes of similar or identical effects, depending on the underlying fitness landscapes. However, systematic testing of this is scarce. Here we examine this hypothesis in two closely related plant species, Arabidopsis halleri and Arabidopsis arenosa, which co-occur at two calamine metalliferous sites harbouring toxic levels of the heavy metals zinc and cadmium. We conduct individual genome resequencing alongside soil elemental analysis for 64 plants from 8 populations on metalliferous and non-metalliferous soils, and identify genomic footprints of selection and local adaptation. Selective sweep and environmental association analyses indicate a modest degree of gene as well as functional network convergence, whereby the proximal molecular factors mediating this convergence mostly differ between site pairs and species. Notably, we observe repeated selection on identical SNPs in several A. halleri genes at two independently colonized metalliferous sites. Our data suggest that species-specific metal handling and other biological features could explain a low degree of convergence between species. The parallel establishment of plant populations on calamine metalliferous soils involves convergent evolution, which will likely be more pervasive across sites purposely chosen for maximal similarity in soil composition.

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