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 Novel generic models for differentiating stem cells reveal oscillatory mechanisms

2021 ◽  
Vol 18 (183) ◽  
Author(s):  
Saeed Farjami ◽  
Karen Camargo Sosa ◽  
Jonathan H. P. Dawes ◽  
Robert N. Kelsh ◽  
Andrea Rocco
Keyword(s):  
Cell Fate ◽  
Regulatory Networks ◽  
Oscillatory Process ◽  
Oscillatory Regime ◽  
Epigenetic Landscape ◽  
Generic Models ◽  
Gene Regulatory ◽  
Oscillatory Mechanisms ◽  
Gradual Variation ◽  
Standard Framework

Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddington’s epigenetic landscape. The models allow us to suggest two generic dynamical scenarios that describe the differentiation process. In the first scenario, gradual variation of a single control parameter is responsible for both entering and exiting the oscillatory regime. In the second scenario, two control parameters vary: one responsible for entering, and the other for exiting the oscillatory regime. We analyse the standard repressilator and four variants of it and show the dynamical behaviours associated with each scenario. We present a thorough analysis of the associated bifurcations and argue that gene regulatory networks with these repressilator-like characteristics are promising candidates to describe cell fate selection through an oscillatory process.

scholarly journals Evolution of gene regulatory networks by means of selection and random genetic drift

2018 ◽  
Author(s):  
Antonios Kioukis ◽  
Pavlos Pavlidis
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Genetic Drift ◽  
Regulatory Networks ◽  
Fitness Landscape ◽  
Random Genetic Drift ◽  
Maturation Period ◽  
Evolutionary Forces ◽  
Gene Regulatory

The evolution of a population by means of genetic drift and natural selection operating on a gene regulatory network (GRN) of an individual has not been scrutinized in depth. Thus, the relative importance of various evolutionary forces and processes on shaping genetic variability in GRNs is understudied. Furthermore, it is not known if existing tools that identify recent and strong positive selection from genomic sequences, in simple models of evolution, can detect recent positive selection when it operates on GRNs. Here, we propose a simulation framework, called EvoNET, that simulates forward-in-time the evolution of GRNs in a population. Since the population size is finite, random genetic drift is explicitly applied. The fitness of a mutation is not constant, but we evaluate the fitness of each individual by measuring its genetic distance from an optimal genotype. Mutations and recombination may take place from generation to generation, modifying the genotypic composition of the population. Each individual goes through a maturation period, where its GRN reaches equilibrium. At the next step, individuals compete to produce the next generation. As time progresses, the beneficial genotypes push the population higher in the fitness landscape. We examine properties of the GRN evolution such as robustness against the deleterious effect of mutations and the role of genetic drift. We confirm classical results from Andreas Wagner’s work that GRNs show robustness against mutations and we provide new results regarding the interplay between random genetic drift and natural selection.

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 Conceptual Confusion: The case of Epigenetics

2016 ◽  
Author(s):  
Angela Oliveira Pisco ◽  
Aymeric Fouquier d’Hérouël ◽  
Sui Huang
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Gene Activation ◽  
Epigenetic Landscape ◽  
The Past ◽  
Time Period ◽  
Formal Concepts ◽  
Gene Regulatory ◽  
Mathematical Foundations ◽  
Conceptual Confusion

ABSTRACTThe observations of phenotypic plasticity have stimulated the revival of ‘epigenetics’. Over the past 70 years the term has come in many colors and flavors, depending on the biological discipline and time period. The meanings span from Waddington’s “epigenotype” and “epigenetic landscape” to the molecular biologists’ “epigenetic marks” embodied by DNA methylation and histone modifications. Here we seek to quell the ambiguity of the name. First we place “epigenetics” in the various historical contexts. Then, by presenting the formal concepts of dynamical systems theory we show that the “epigenetic landscape” is more than a metaphor: it has specific mathematical foundations. The latter explains how gene regulatory networks produce multiple attractor states, the self-stabilizing patterns of gene activation across the genome that account for “epigenetic memory”. This network dynamics approach replaces the reductionist correspondence of molecular epigenetic modifications with concept of the epigenetic landscape, by providing a concrete and crisp correspondence.

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.

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 A family of fitness landscapes modeled through gene regulatory networks

2021 ◽  
Author(s):  
Chia-Hung Yang ◽  
Samuel V. Scarpino
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Evolutionary Dynamics ◽  
Fitness Landscape ◽  
Fitness Function ◽  
Fitness Landscapes ◽  
Relative Fitness ◽  
Landscape Models ◽  
Fitness Value ◽  
Gene Regulatory

AbstractOver 100 years, Fitness landscapes have been a powerful metaphor for understanding the evolution of biological systems. These landscapes describe how genotypes are connected to each other and are related according to relative fitness. Despite the high dimensionality of such real-world landscapes, empirical studies are often limited in their ability to quantify the fitness of different genotypes beyond point mutations, while theoretical works attempt statistical/mechanistic models to reason the overall landscape structure. However, most classical fitness landscape models overlook an instinctive constraint that genotypes leading to the same phenotype almost certainly share the same fitness value, since the information of genotype-phenotype mapping is rarely incorporated. Here, we investigate fitness landscape models through the lens of Gene Regulatory Networks (GRNs), where the regulatory products are computed from multiple genes and collectively treated as the phenotypes. With the assumption that regulatory mediators/products exhibit binary states, we prove topographical features of GRN fitness landscape models such as accessibility and connectivity insensitive to the choice of the fitness function. Furthermore, using graph theory, we deduce a mesoscopic structure underlying GRN fitness landscape models that retains necessary information for evolutionary dynamics with minimal complexity. We also propose an algorithm to construct such a mesoscopic backbone which is more efficient than the brute-force approach. Combined, this work provides mathematical implications for fitness landscape models with high-dimensional genotype-phenotype mapping, yielding the potential to elucidate empirical landscapes and their resulting evolutionary processes in a manner complementary to existing computational studies.

scholarly journals Hopf bifurcation in a gene regulatory network model: Molecular movement causes oscillations

2015 ◽  
Vol 25 (06) ◽  
pp. 1179-1215 ◽  
Author(s):  
Mark Chaplain ◽  
Mariya Ptashnyk ◽  
Marc Sturrock
Keyword(s):  
Hopf Bifurcation ◽  
Heat Shock ◽  
Gene Regulatory Network ◽  
Negative Feedback ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Oscillatory Behavior ◽  
Feedback Systems ◽  
Linearized Stability ◽  
Gene Regulatory

Gene regulatory networks, i.e. DNA segments in a cell which interact with each other indirectly through their RNA and protein products, lie at the heart of many important intracellular signal transduction processes. In this paper, we analyze a mathematical model of a canonical gene regulatory network consisting of a single negative feedback loop between a protein and its mRNA (e.g. the Hes1 transcription factor system). The model consists of two partial differential equations describing the spatio-temporal interactions between the protein and its mRNA in a one-dimensional domain. Such intracellular negative feedback systems are known to exhibit oscillatory behavior and this is the case for our model, shown initially via computational simulations. In order to investigate this behavior more deeply, we undertake a linearized stability analysis of the steady states of the model. Our results show that the diffusion coefficient of the protein/mRNA acts as a bifurcation parameter and gives rise to a Hopf bifurcation. This shows that the spatial movement of the mRNA and protein molecules alone is sufficient to cause the oscillations. Our result has implications for transcription factors such as p53, NF-κB and heat shock proteins which are involved in regulating important cellular processes such as inflammation, meiosis, apoptosis and the heat shock response, and are linked to diseases such as arthritis and cancer.

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

2017 ◽  
Vol 51 ◽  
pp. 245-254 ◽  
Author(s):  
Mark Jayson V. Cortez ◽  
Jomar F. Rabajante ◽  
Jerrold M. Tubay ◽  
Ariel L. Babierra
Keyword(s):  
Fitness Landscape ◽  
Epigenetic Landscape ◽  
Evolutionary Effect ◽  
Phenotypic Fitness
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