Epigenetics Decouples Mutational from Environmental Robustness. Did It Also Facilitate Multicellularity?

Gombar, Saurabh; MacCarthy, Thomas; Bergman, Aviv

doi:10.1371/journal.pcbi.1003450

Cited by 22 publications

(25 citation statements)

References 53 publications

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“…Intriguingly, our results show a similar pattern in VSV, where the decoupling of genetic robustness and thermostability may be related to the evolution of antigenic variation. Others have proposed decoupling mechanisms that may be relevant for other systems, such as oligomerization [71] or epigenetic modification [72]. …”

Section: Discussionmentioning

confidence: 99%

Antigenic diversification is correlated with increased thermostability in a mammalian virus

et al. 2016

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The theory of plastogenetic congruence posits that ultimately, the pressure to maintain function in the face of biomolecular destabilization produces robustness. As temperature goes up so does destabilization. Thus, genetic robustness, defined as phenotypic constancy despite mutation, should correlate with survival during thermal challenge. We tested this hypothesis using vesicular stomatitis virus (VSV). We produced two sets of evolved strains after selection for higher thermostability by either preincubation at 37°C or by incubation at 40°C during infection. These VSV populations became more thermostable and also more fit in the absence of thermal selection, demonstrating an absence of tradeoffs. Eleven out of 12 evolved populations had a fixed, nonsynonymous substitution in the nucleocapsid (N) open reading frame. There was a partial correlation between thermostability and mutational robustness that was observed when the former was measured at 42°C, but not at 37°C. These results are consistent with our earlier work and suggest that the relationship between robustness and thermostability is complex. Surprisingly, many of the thermostable strains also showed increased resistance to monoclonal antibody and polyclonal sera, including sera from natural hosts. These data suggest that evolved thermostability may lead to antigenic diversification and an increased ability to escape immune surveillance in febrile hosts, and potentially to an improved robustness. These relationships have important implications not only in terms of viral pathogenesis, but also for the development of vaccine vectors and oncolytic agents.

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Section: Discussionmentioning

confidence: 99%

Antigenic diversification is correlated with increased thermostability in a mammalian virus

et al. 2016

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“…Their catalytic signatures are well-characterized; PRC2 trimethylates histone H3K27 into H3K27me3; this modified histone is bound by PRC1, which in turn ubiquitylates histone H2A. Extensive study on the evolution and conservation of PRC1 and PRC2 has suggested that expansion and diversification of PcG proteins contributed to the complexity of multicellular organisms (Trojer & Reinberg 2006;Whitcomb et al 2007;Köhler & Villar 2008;Gombar et al 2014).…”

Section: Blue Is Related To the Origin Of Multicellularitymentioning

confidence: 99%

“…The chromatin landscape consists of DNA, histones, and other associated proteins and RNAs, and plays a fundamental role in development, cellular memory, and integration of external signals. As a unique feature of the eukaryotic cell, it is closely tied to the evolution of eukaryotes, both regarding their origin and the major transition(s) to multicellularity (Newman 2005;Aravind et al 2014;Gombar et al 2014;Penny et al 2014;Miyamoto et al 2015;Sebé-Pedrós et al 2017). At a basic level, chromatin is responsible for maintenance, organization, and correct use of the genome.…”

Section: Introductionmentioning

confidence: 99%

“…From an evolutionary point of view, although prokaryotes have specialized proteins associated with their DNA, they do not share homology with eukaryotic CAPs (Luijsterburg et al 2008). In general, evolution of chromatin and diversification of epigenetic mechanisms are suggested to be tightly linked with eukaryotic evolution, from its origin to the transition to multicellularity (Newman 2005;Aravind et al 2014;Gombar et al 2014;Penny et al 2014;Miyamoto et al 2015;Sebé-Pedrós et al 2017). Indeed, the Last Eukaryotic Common Ancestor (LECA) is considered to possess the key components of eukaryotic epigenetics, including most histone modification enzymes and some histone mark readers (Aravind et al 2014).…”

Section: Introductionmentioning

confidence: 99%

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Evolution of theD. melanogasterchromatin landscape and its associated proteins

Parey

Crombach

2018

Preprint

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240w, max 250w)In the nucleus of eukaryotic cells, genomic DNA associates with numerous protein complexes and RNAs, forming the chromatin landscape. Through a genome-wide study of chromatinassociated proteins in Drosophila cells, five major chromatin types were identified as a refinement of the traditional binary division into hetero-and euchromatin. These five types were given colour names in reference to the Greek word chroma. They are defined by distinct but overlapping combinations of proteins and differ in biological and biochemical properties, including transcriptional activity, replication timing, and histone modifications. In this work, we assess the evolutionary relationships of chromatin-associated proteins and present an integrated view of the evolution and conservation of the fruit fly D. melanogaster chromatin landscape. We combine homology prediction across a wide range of species with gene age inference methods to determine the origin of each chromatin-associated protein. This provides insight into the evolution of the different chromatin types. Our results indicate that for the euchromatic types, YELLOW and RED, young associated proteins are more specialized than old ones. And for genes found in either chromatin type, intron/exon structure is lineagespecific. Next, we provide evidence that a subset of GREEN-associated proteins is involved in a centromere drive in D. melanogaster. Our results on BLUE chromatin support the hypothesis that the emergence of Polycomb Group proteins is linked to eukaryotic multicellularity. In light of these results, we discuss how the regulatory complexification of chromatin links to the origins of eukaryotic multicellularity.

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“…Currently, there is no definitive method for introducing the epigenetic process because the precise molecular process of histone modification is difficult to implement in a model with gene expression dynamics. However, it is possible to model the influence of the epigenetic process on expression dynamics phenomenologically [34][35][36][37][38]. The epigenetic process tends to fix the expression state; for example, when a given gene is expressed for a given period, its expression tends to become fixed, and when it is not expressed for a given period, it remains silenced.…”

Section: Differentiation From the Pluripotent State With Epigenetic Mmentioning

confidence: 99%

Pluripotency, Differentiation, and Reprogramming: A Gene Expression Dynamics Model with Epigenetic Feedback Regulation

Miyamoto

Furusawa²,

Kaneko

2015

PLoS Comput Biol

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Embryonic stem cells exhibit pluripotency: they can differentiate into all types of somatic cells. Pluripotent genes such as Oct4 and Nanog are activated in the pluripotent state, and their expression decreases during cell differentiation. Inversely, expression of differentiation genes such as Gata6 and Gata4 is promoted during differentiation. The gene regulatory network controlling the expression of these genes has been described, and slower-scale epigenetic modifications have been uncovered. Although the differentiation of pluripotent stem cells is normally irreversible, reprogramming of cells can be experimentally manipulated to regain pluripotency via overexpression of certain genes. Despite these experimental advances, the dynamics and mechanisms of differentiation and reprogramming are not yet fully understood. Based on recent experimental findings, we constructed a simple gene regulatory network including pluripotent and differentiation genes, and we demonstrated the existence of pluripotent and differentiated states from the resultant dynamical-systems model. Two differentiation mechanisms, interaction-induced switching from an expression oscillatory state and noise-assisted transition between bistable stationary states, were tested in the model. The former was found to be relevant to the differentiation process. We also introduced variables representing epigenetic modifications, which controlled the threshold for gene expression. By assuming positive feedback between expression levels and the epigenetic variables, we observed differentiation in expression dynamics. Additionally, with numerical reprogramming experiments for differentiated cells, we showed that pluripotency was recovered in cells by imposing overexpression of two pluripotent genes and external factors to control expression of differentiation genes. Interestingly, these factors were consistent with the four Yamanaka factors, Oct4, Sox2, Klf4, and Myc, which were necessary for the establishment of induced pluripotent stem cells. These results, based on a gene regulatory network and expression dynamics, contribute to our wider understanding of pluripotency, differentiation, and reprogramming of cells, and they provide a fresh viewpoint on robustness and control during development.

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Epigenetics Decouples Mutational from Environmental Robustness. Did It Also Facilitate Multicellularity?

Cited by 22 publications

References 53 publications

Antigenic diversification is correlated with increased thermostability in a mammalian virus

Antigenic diversification is correlated with increased thermostability in a mammalian virus

Evolution of theD. melanogasterchromatin landscape and its associated proteins

Pluripotency, Differentiation, and Reprogramming: A Gene Expression Dynamics Model with Epigenetic Feedback Regulation

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