scholarly journals Natural cryptic variation in epigenetic modulation of an embryonic gene regulatory network

2019 ◽  
Author(s):  
Chee Kiang Ewe ◽  
Yamila N. Torres Cleuren ◽  
Sagen E. Flowers ◽  
Geneva Alok ◽  
Russell G. Snell ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Phenotypic Diversity ◽  
Epigenetic Modification ◽  
Genomic Variation ◽  
Bzip Transcription Factor ◽  
Rnai Pathway ◽  
C Elegans ◽  
Cryptic Variation ◽  
Organ Systems ◽  
Gene Regulatory

AbstractGene regulatory networks (GRNs) that direct animal embryogenesis must respond to varying environmental and physiological conditions to ensure robust construction of organ systems. While GRNs are evolutionarily modified by natural genomic variation, the roles of epigenetic processes in shaping plasticity of GRN architecture are not well-understood. The endoderm GRN in C. elegans is initiated by the maternally supplied SKN-1/Nrf2 bZIP transcription factor; however, the requirement for SKN-1 in endoderm specification varies widely among distinct C. elegans wild isotypes owing to rapid developmental system drift driven by accumulation of cryptic genetic variants. We report here that heritable epigenetic factors that are stimulated by transient developmental diapause also underlie cryptic variation in the requirement for SKN-1 in endoderm development. This epigenetic memory is inherited from the maternal germline, apparently through a nuclear, rather than cytoplasmic, signal, resulting in a parent-of-origin effect (POE), in which the phenotype of the progeny resembles that of the maternal founder. The occurrence and persistence of POE varies between different parental pairs, perduring for at least ten generations in one pair. This long-perduring POE requires piwi-piRNA function and the germline nuclear RNAi pathway, as well as MET-2 and SET-32, which direct histone H3K9 trimethylation and drive heritable epigenetic modification. Such non-genetic cryptic variation may provide a resource of additional phenotypic diversity through which adaptation may facilitate evolutionary changes and shape developmental regulatory systems.

scholarly journals Natural cryptic variation in epigenetic modulation of an embryonic gene regulatory network

2020 ◽  
Vol 117 (24) ◽  
pp. 13637-13646 ◽  
Author(s):  
Chee Kiang Ewe ◽  
Yamila N. Torres Cleuren ◽  
Sagen E. Flowers ◽  
Geneva Alok ◽  
Russell G. Snell ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Phenotypic Diversity ◽  
Epigenetic Modification ◽  
Genomic Variation ◽  
Bzip Transcription Factor ◽  
Rnai Pathway ◽  
Cryptic Variation ◽  
Organ Systems ◽  
Gene Regulatory ◽  
Epigenetic Modulation

Gene regulatory networks (GRNs) that direct animal embryogenesis must respond to varying environmental and physiological conditions to ensure robust construction of organ systems. While GRNs are evolutionarily modified by natural genomic variation, the roles of epigenetic processes in shaping plasticity of GRN architecture are not well understood. The endoderm GRN inCaenorhabditis elegansis initiated by the maternally supplied SKN-1/Nrf2 bZIP transcription factor; however, the requirement for SKN-1 in endoderm specification varies widely among distinctC. eleganswild isotypes, owing to rapid developmental system drift driven by accumulation of cryptic genetic variants. We report here that heritable epigenetic factors that are stimulated by transient developmental diapause also underlie cryptic variation in the requirement for SKN-1 in endoderm development. This epigenetic memory is inherited from the maternal germline, apparently through a nuclear, rather than cytoplasmic, signal, resulting in a parent-of-origin effect (POE), in which the phenotype of the progeny resembles that of the maternal founder. The occurrence and persistence of POE varies between different parental pairs, perduring for at least 10 generations in one pair. This long-perduring POE requires piwi-interacting RNA (piRNA) function and the germline nuclear RNA interference (RNAi) pathway, as well as MET-2 and SET-32, which direct histone H3K9 trimethylation and drive heritable epigenetic modification. Such nongenetic cryptic variation may provide a resource of additional phenotypic diversity through which adaptation may facilitate evolutionary changes and shape developmental regulatory systems.

scholarly journals Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Yamila N Torres Cleuren ◽  
Chee Kiang Ewe ◽  
Kyle C Chipman ◽  
Emily R Mears ◽  
Cricket G Wood ◽  
...  
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Recombinant Inbred Lines ◽  
Single Species ◽  
C Elegans ◽  
Cryptic Variation ◽  
Absolute Requirement ◽  
Natural Isolates ◽  
Gene Regulatory ◽  
Metazoan Phylogeny

Innovations in metazoan development arise from evolutionary modification of gene regulatory networks (GRNs). We report widespread cryptic variation in the requirement for two key regulatory inputs, SKN-1/Nrf2 and MOM-2/Wnt, into the C. elegans endoderm GRN. While some natural isolates show a nearly absolute requirement for these two regulators, in others, most embryos differentiate endoderm in their absence. GWAS and analysis of recombinant inbred lines reveal multiple genetic regions underlying this broad phenotypic variation. We observe a reciprocal trend, in which genomic variants, or knockdown of endoderm regulatory genes, that result in a high SKN-1 requirement often show low MOM-2/Wnt requirement and vice-versa, suggesting that cryptic variation in the endoderm GRN may be tuned by opposing requirements for these two key regulatory inputs. These findings reveal that while the downstream components in the endoderm GRN are common across metazoan phylogeny, initiating regulatory inputs are remarkably plastic even within a single species.

scholarly journals Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network

2019 ◽  
Author(s):  
Yamila N. Torres Cleuren ◽  
Chee Kiang Ewe ◽  
Kyle C. Chipman ◽  
Emily Mears ◽  
Cricket G. Wood ◽  
...  
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Recombinant Inbred Lines ◽  
Single Species ◽  
C Elegans ◽  
Cryptic Variation ◽  
Absolute Requirement ◽  
Natural Variants ◽  
Gene Regulatory ◽  
Metazoan Phylogeny

ABSTRACTInnovations in metazoan development arise from evolutionary modification of gene regulatory networks (GRNs). We report widespread cryptic variation in the requirement for two key regulatory inputs, SKN-1/Nrf2 and MOM-2/Wnt, into the C. elegans endoderm GRN. While some natural variants show a nearly absolute requirement for these two regulators, in others, most embryos differentiate endoderm in their absence. GWAS and analysis of recombinant inbred lines reveal multiple genetic regions underlying this broad phenotypic variation. We observe a reciprocal trend, in which genomic variants, or knockdown of endoderm regulatory genes, that result in a high SKN-1 requirement often show low MOM-2/Wnt requirement and vice-versa, suggesting that cryptic variation in the endoderm GRN may be tuned by opposing requirements for these two key regulatory inputs. These findings reveal that while the downstream components in the endoderm GRN are common across metazoan phylogeny, initiating regulatory inputs are remarkably plastic even within a single species.

scholarly journals Integration of Metabolic and Gene Regulatory Networks Modulates the C. elegans Dietary Response

Cell ◽  
2013 ◽  
Vol 153 (6) ◽  
pp. 1406-1407
Author(s):  
Emma Watson ◽  
Lesley T. MacNeil ◽  
H. Efsun Arda ◽  
Lihua Julie Zhu ◽  
Albertha J.M. Walhout
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
C Elegans ◽  
Gene Regulatory

scholarly journals Disruption in A-to-I editing levels affects C. elegans development more than a complete lack of editing

2018 ◽  
Author(s):  
Nabeel S. Ganem ◽  
Noa Ben-Asher ◽  
Aidan C. Manning ◽  
Sarah N. Deffit ◽  
Michael C. Washburn ◽  
...  
Keyword(s):  
Rna Editing ◽  
Phenotypic Diversity ◽  
Abnormal Development ◽  
C Elegans ◽  
Protein Levels ◽  
Stage Of Development ◽  
Extended Lifespan ◽  
Gene Regulatory ◽  
Adar Gene ◽  
Editing Process

SummaryA-to-I RNA editing is widespread in eukaryotic transcriptomes and plays an essential role in the creation of proteomic and phenotypic diversity. Loss of ADARs, the proteins responsible for A-to-I editing, results in lethality in mammals. In C. elegans, knocking out both ADARs, ADR-1 and ADR-2, results in aberrant behavior and abnormal development. Studies have shown that ADR-2 can actively deaminate dsRNA while ADR-1 cannot. However, as most studies of C. elegans ADARs were performed on worms mutated in both ADAR genes, the effects observed cannot be attributed to a single ADAR or to the interactions between ADAR genes. Therefore, we set to study the effects of each C. elegans ADAR on RNA editing, gene expression, protein levels and the contribution of each of ADAR to the phenotypes observed in worms mutated in both genes, in order to elucidate their distinct functions. We found significant differences in the phenotypes observed in worms mutated in a single ADAR gene. Worms harboring adr-1 mutations have a significant reduction in their lifespan, while worms harboring adr-2 mutations have extended lifespan. We also observed severe abnormalities in vulva formation in adr-1 mutants, and we suggest that these phenotypes are a result of an RNA editing independent function of ADR-1. Mutations in each ADAR resulted in expressional changes in hundreds of genes, and a significant downregulation of edited genes. However, very few changes in the protein levels were observed. In addition, we found that ADR-1 binds many edited genes and primarily promotes editing at the L4 stage of development. While editing still occurs in the absence of ADR-1, most of the editing occurs in genes that are edited in wildtype worms, suggesting that ADR-1 does not prevent editing by binding to and protecting the RNA but rather enhances or promotes editing. Our results suggest that ADR-1 plays a significant role in the RNA editing process and by altering editing levels it causes the severe phenotypes that we observed. In contrast, a complete lack of RNA editing is less harmful to the worms. Furthermore, our results indicate that the effect of RNA editing on the protein content in the cell is minor and probably the main purpose of these modifications is to antagonize or enhance other gene regulatory mechanisms that act on RNA.

scholarly journals From epigenetic landscape to phenotypic fitness landscape: evolutionary effect of pathogens on host traits

2016 ◽  
Author(s):  
Mark Jayson V. Cortez ◽  
Jomar F. Rabajante ◽  
Jerrold M. Tubay ◽  
Ariel L. Babierra
Keyword(s):  
Regulatory Networks ◽  
Fitness Landscape ◽  
Phenotypic Diversity ◽  
Oscillatory Behavior ◽  
Epigenetic Landscape ◽  
Negative Frequency Dependent Selection ◽  
Gene Regulatory ◽  
Epigenetic Gene Regulation ◽  
Phenotypic Fitness ◽  
The Red Queen

AbstractThe epigenetic landscape illustrates how cells differentiate into different types through the control of gene regulatory networks. Numerous studies have investigated epigenetic gene regulation but there are limited studies on how the epigenetic landscape and the presence of pathogens influence the evolution of host traits. Here we formulate a multistable decision-switch model involving many possible phenotypes with the antagonistic influence of parasitism. As expected, pathogens can drive dominant (common) phenotypes to become inferior, such as through negative frequency-dependent selection. Furthermore, novel predictions of our model show that parasitism can steer the dynamics of phenotype specification from multistable equilibrium convergence to oscillations. This oscillatory behavior could explain pathogen-mediated epimutations and excessive phenotypic plasticity. The Red Queen dynamics also occur in certain parameter space of the model, which demonstrates winnerless cyclic phenotype-switching in hosts and in pathogens. The results of our simulations elucidate how epigenetic landscape is associated with the phenotypic fitness landscape and how parasitism facilitates non-genetic phenotypic diversity.

scholarly journals Nuclear Transfer Arrest Embryos Show Massive Dysregulation of Genes Involved in Transcription Pathways

2021 ◽  
Vol 22 (15) ◽  
pp. 8187
Author(s):  
Chunshen Long ◽  
Hanshuang Li ◽  
Xinru Li ◽  
Wuritu Yang ◽  
Yongchun Zuo
Keyword(s):  
Gene Regulatory Networks ◽  
Nuclear Transfer ◽  
Regulatory Networks ◽  
Target Genes ◽  
Epigenetic Modification ◽  
Cell Nuclei ◽  
Activation Of Transcription ◽  
Gene Regulatory ◽  
Catabolic Process

Somatic cell nuclear transfer (SCNT) technology can reprogram terminally differentiated cell nuclei into a totipotent state. However, the underlying molecular barriers of SCNT embryo development remain incompletely elucidated. Here, we observed that transcription-related pathways were incompletely activated in nuclear transfer arrest (NTA) embryos compared to normal SCNT embryos and in vivo fertilized (WT) embryos, which hinders the development of SCNT embryos. We further revealed the transcription pathway associated gene regulatory networks (GRNs) and found the aberrant transcription pathways can lead to the massive dysregulation of genes in NTA embryos. The predicted target genes of transcription pathways contain a series of crucial factors in WT embryos, which play an important role in catabolic process, pluripotency regulation, epigenetic modification and signal transduction. In NTA embryos, however, these genes were varying degrees of inhibition and show a defect in synergy. Overall, our research found that the incomplete activation of transcription pathways is another potential molecular barrier for SCNT embryos besides the incomplete reprogramming of epigenetic modifications, broadening the understanding of molecular mechanism of SCNT embryonic development.

Lessons and Challenges

2014 ◽  
Author(s):  
Günter P. Wagner
Keyword(s):  
Empirical Data ◽  
Population Biology ◽  
Regulatory Networks ◽  
Cell Types ◽  
Theory Of Evolution ◽  
Developmental Evolution ◽  
Hard Time ◽  
Organ Systems ◽  
Gene Regulatory ◽  
Biological Entities

This book has argued for the reality of a class of biological entities that have a hard time finding their place in a theory of evolution based on genetics and population biology. These entities, or developmental types, include cell types, homologs, and body plans. The book has also provided examples that already have empirical data to see whether such ideas are contradicted by known facts about certain well-studied organ systems, like limbs, skin appendages, and flowers. This concluding chapter summarizes the book's central claims about homology, characters and character identity, and cooperativity in gene regulatory networks. It also discusses some of the lessons derived from reviewing the literature on these paradigms of devo-evo research as well as the challenges inherent in this perspective of developmental evolution.

scholarly journals The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator of C. elegans spermatogenesis

2020 ◽  
Author(s):  
James Matthew Ragle ◽  
Abigail L. Aita ◽  
Kayleigh N. Morrison ◽  
Raquel Martinez-Mendez ◽  
Hannah N. Saeger ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Nuclear Hormone Receptor ◽  
Model Systems ◽  
Residual Body ◽  
Major Sperm Protein ◽  
C Elegans ◽  
Summary Statement ◽  
Gene Regulatory ◽  
Established Role

AbstractIn sexually reproducing metazoans, spermatogenesis is the process by which uncommitted germ cells give rise to haploid sperm. Work in model systems has revealed mechanisms controlling commitment to the sperm fate, but how this fate is subsequently executed remains less clear. While studying the well-established role of the conserved nuclear hormone receptor transcription factor, NHR-23/NR1F1, in regulation of C. elegans molting, we discovered NHR-23/NR1F1 is also constitutively expressed in developing 1° spermatocytes and is a critical regulator of spermatogenesis. In this novel role, NHR-23/NR1F1 functions downstream of the canonical sex determination pathway. Degron-mediated depletion of NHR-23/NR1F1 within hermaphrodite or male germlines causes sterility due to an absence of functional sperm as depleted animals produce arrested primary spermatocytes rather than haploid sperm. These spermatocytes arrest in prometaphase I and fail to either progress to anaphase or attempt spermatid-residual body partitioning. They make sperm-specific membranous organelles (MOs) but fail to assemble their major sperm protein into fibrous bodies. NHR-23/NR1F1 appears to function independently of the known SPE-44 gene regulatory network, revealing the existence of an NHR-23/NR1F1-mediated module that regulates the spermatogenesis program.Summary StatementA well-characterized regulator of C. elegans molting also unexpectedly controls the spermatogenesis program; our work provides insights into the gene regulatory networks controlling spermatogenesis.

scholarly journals MarR Family Transcription Factors fromBurkholderiaSpecies: Hidden Clues to Control of Virulence-Associated Genes

2018 ◽  
Vol 83 (1) ◽  
Author(s):  
Ashish Gupta ◽  
Anuja Pande ◽  
Afsana Sabrin ◽  
Sudarshan S. Thapa ◽  
Brennan W. Gioe ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Environmental Changes ◽  
Phenotypic Diversity ◽  
Regulation Of Gene Expression ◽  
Virulence Determinants ◽  
Human Pathogens ◽  
Plant Host ◽  
Gene Regulatory

SUMMARYSpecies within the genusBurkholderiaexhibit remarkable phenotypic diversity. Genomic plasticity, including genome reduction and horizontal gene transfer, has been correlated with virulence traits in several species. However, the conservation of virulence genes in species otherwise considered to have limited potential for infection suggests that phenotypic diversity may not be explained solely on the basis of genetic diversity. Instead, differential organization and control of gene regulatory networks may underlie many phenotypic differences. In this review, we evaluate how regulation of gene expression by members of the multiple antibiotic resistance regulator (MarR) family of transcription factors may contribute to shaping the physiological diversity ofBurkholderiaspecies, with a focus on the clinically relevant human pathogens. AllBurkholderiaspecies encode a relatively large number of MarR proteins, a feature common to bacteria that must respond to environmental changes such as those associated with host invasion. However, evolution of gene regulatory networks has likely resulted in orthologous transcription factors controlling disparate sets of genes. Adaptation to, and survival in, diverse habitats, including a human or plant host, is key to the success ofBurkholderiaspecies as (opportunistic) pathogens, and recent reports suggest that control of virulence-associated genes by MarR proteins features prominently among the survival strategies employed by these species. We suggest that identification of MarR regulons will contribute significantly to clarification of virulence determinants and phenotypic diversity.

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