A Persistence Detector for Metabolic Network Rewiring in an Animal

Bulcha, Jote; Giese, Gabrielle E.; Ali, M. Zulfikar; Lee, Yong-Uk; Walker, Melissa; Holdorf, Amy D.; Yılmaz, L. Şafak; Brewster, Robert C.; Walhout, Albertha J.M.

doi:10.1016/j.celrep.2018.12.064

Cited by 53 publications

(92 citation statements)

References 25 publications

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“…Many examples of memory, anticipation, contextdependent decision-making, and learning are exhibited by organisms from yeast and bacteria to plants and somatic cells [reviewed in (Lyon, 2006(Lyon, , 2015Baluška and Levin, 2016)]. This is even true of subcellular-level components, e.g., generegulatory networks can execute similar learning and computational properties as neural networks, as can cytoskeletal networks, cell signaling pathways, reaction-diffusion chemistry, and metabolic networks (Watson et al, 2010;Szabó et al, 2012;Stockwell et al, 2015;Prentice-Mott et al, 2016;Dent, 2017;Stovold and O'Keefe, 2017;Barvitenko et al, 2018;Gabalda-Sagarra et al, 2018;Bulcha et al, 2019). Single cells are very good at managing their morphology, behavior, and physiology as needed for survival, altering their motility, and metabolism in response to, and proactively in, changing environmental conditions.…”

Section: -Gautama Buddhamentioning

confidence: 99%

The Computational Boundary of a “Self”: Developmental Bioelectricity Drives Multicellularity and Scale-Free Cognition

2019

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All epistemic agents physically consist of parts that must somehow comprise an integrated cognitive self. Biological individuals consist of subunits (organs, cells, and molecular networks) that are themselves complex and competent in their own native contexts. How do coherent biological Individuals result from the activity of smaller sub-agents? To understand the evolution and function of metazoan creatures' bodies and minds, it is essential to conceptually explore the origin of multicellularity and the scaling of the basal cognition of individual cells into a coherent larger organism. In this article, I synthesize ideas in cognitive science, evolutionary biology, and developmental physiology toward a hypothesis about the origin of Individuality: "Scale-Free Cognition." I propose a fundamental definition of an Individual based on the ability to pursue goals at an appropriate level of scale and organization and suggest a formalism for defining and comparing the cognitive capacities of highly diverse types of agents. Any Self is demarcated by a computational surface -the spatio-temporal boundary of events that it can measure, model, and try to affect. This surface sets a functional boundarya cognitive "light cone" which defines the scale and limits of its cognition. I hypothesize that higher level goal-directed activity and agency, resulting in larger cognitive boundaries, evolve from the primal homeostatic drive of living things to reduce stress -the difference between current conditions and life-optimal conditions. The mechanisms of developmental bioelectricity -the ability of all cells to form electrical networks that process informationsuggest a plausible set of gradual evolutionary steps that naturally lead from physiological homeostasis in single cells to memory, prediction, and ultimately complex cognitive agents, via scale-up of the basic drive of infotaxis. Recent data on the molecular mechanisms of pre-neural bioelectricity suggest a model of how increasingly sophisticated cognitive functions emerge smoothly from cell-cell communication used to guide embryogenesis and regeneration. This set of hypotheses provides a novel perspective on numerous phenomena, such as cancer, and makes several unique, testable predictions for interdisciplinary research that have implications not only for evolutionary developmental biology but also for biomedicine and perhaps artificial intelligence and exobiology.

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Section: -Gautama Buddhamentioning

confidence: 99%

The Computational Boundary of a “Self”: Developmental Bioelectricity Drives Multicellularity and Scale-Free Cognition

2019

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“…In GRNs, transcription factors may activate or repress each other transcriptionally [32][33][34][35][36], or alternatively, they may interact at the post-transcriptional level. The latter includes indirect interactions, such as independent binding to the same promoters [37], or ligand-mediated interactions [38].…”

Section: Nhr-40 and Nhr-1 Interact Post-transcriptionallymentioning

confidence: 99%

Conserved nuclear hormone receptors controlling a novel plastic trait target fast-evolving genes expressed in a single cell

et al. 2020

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Environment shapes development through a phenomenon called developmental plasticity. Deciphering its genetic basis has potential to shed light on the origin of novel traits and adaptation to environmental change. However, molecular studies are scarce, and little is known about molecular mechanisms associated with plasticity. We investigated the gene regulatory network controlling predatory vs. non-predatory dimorphism in the nematode Pristionchus pacificus and found that it consists of genes of extremely different age classes. We isolated mutants in the conserved nuclear hormone receptor nhr-1 with previously unseen phenotypic effects. They disrupt mouth-form determination and result in animals combining features of both wild-type morphs. In contrast, mutants in another conserved nuclear hormone receptor nhr-40 display altered morph ratios, but no intermediate morphology. Despite divergent modes of control, NHR-1 and NHR-40 share transcriptional targets, which encode extracellular proteins that have no orthologs in Caenorhabditis elegans and result from lineage-specific expansions. An array of transcriptional reporters revealed co-expression of all tested targets in the same pharyngeal gland cell. Major morphological changes in this gland cell accompanied the evolution of teeth and predation, linking rapid gene turnover with morphological innovations. Thus, the origin of feeding plasticity involved novelty at the level of genes, cells and behavior. Author summaryRather than following a pre-determined genetic "blueprint", organisms can adjust their development when they perceive relevant environmental signals-a phenomenon called plasticity. This improves performance in changing environment and may also affect how species evolve. To learn how plasticity works on the mechanistic genetic level, we investigated the roundworm Pristionchus pacificus. It may develop either as a toothed predator or as a narrow-mouthed microbe-eater depending on food source and population density, an ability that evolved less than 100 million years ago. Previous studies identified switch PLOS GENETICS PLOS Genetics | https://doi.

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“…After the discovery of RNA interference (RNAi) (Fire et al 1998), multiple RNAi libraries were developed for performing genome-wide knockdown screens (Kamath et al 2003;Rual et al 2004). Gene expression profiling studies using microarrays or RNA-seq have compared gene expression in sex-specific, developmental/aging-related, specific gene deletion, tissue-specific, and dietary or stressrelated animal conditions (Reinke et al 2000;Hillier et al 2005;Baugh et al 2009;Oliveira et al 2009;Deng et al 2011;Schwarz et al 2012;Bulcha et al 2019). While GO has been used extensively to analyze C. elegans gene expression profiling data, it has several limitations.…”

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confidence: 99%

WormCat: An Online Tool for Annotation and Visualization of Caenorhabditis elegans Genome-Scale Data

et al. 2020

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The emergence of large gene expression datasets has revealed the need for improved tools to identify enriched gene categories and visualize enrichment patterns. While gene ontogeny (GO) provides a valuable tool for gene set enrichment analysis, it has several limitations. First, it is difficult to graph multiple GO analyses for comparison. Second, genes from some model systems are not well represented. For example, ∼30% of Caenorhabditis elegans genes are missing from the analysis in commonly used databases. To allow categorization and visualization of enriched C. elegans gene sets in different types of genome-scale data, we developed WormCat, a web-based tool that uses a near-complete annotation of the C. elegans genome to identify coexpressed gene sets and scaled heat map for enrichment visualization. We tested the performance of WormCat using a variety of published transcriptomic datasets, and show that it reproduces major categories identified by GO. Importantly, we also found previously unidentified categories that are informative for interpreting phenotypes or predicting biological function. For example, we analyzed published RNA-seq data from C. elegans treated with combinations of lifespan-extending drugs, where one combination paradoxically shortened lifespan. Using WormCat, we identified sterol metabolism as a category that was not enriched in the single or double combinations, but emerged in a triple combination along with the lifespan shortening. Thus, WormCat identified a gene set with potential. phenotypic relevance not found with previous GO analysis. In conclusion, WormCat provides a powerful tool for the analysis and visualization of gene set enrichment in different types of C. elegans datasets.

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A Persistence Detector for Metabolic Network Rewiring in an Animal

Cited by 53 publications

References 25 publications

The Computational Boundary of a “Self”: Developmental Bioelectricity Drives Multicellularity and Scale-Free Cognition

The Computational Boundary of a “Self”: Developmental Bioelectricity Drives Multicellularity and Scale-Free Cognition

Conserved nuclear hormone receptors controlling a novel plastic trait target fast-evolving genes expressed in a single cell

WormCat: An Online Tool for Annotation and Visualization of Caenorhabditis elegans Genome-Scale Data

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