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Entropia semiótica do genoma: as mutações e os desequilíbrios epigenéticos resultando em câncer

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Entropia semiótica do genoma: as mutações e os desequilíbrios epigenéticos resultando em câncer




segunda-feira, janeiro 21, 2013




Entropy 2013, 15(1), 234-261; doi:10.3390/e15010234


Concept Paper


Biosemiotic Entropy of the Genome: Mutations and Epigenetic Imbalances Resulting in Cancer


Berkley E. Gryder 1,* , Chase W. Nelson 2 and Samuel S. Shepard 3


1 School of Chemistry and Biochemistry, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA


2 Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA


3 Centers for Disease Control and Prevention, Influenza Division, Atlanta, GA 30333, USA


* Author to whom correspondence should be addressed.


Received: 1 November 2012; in revised form: 30 December 2012 / Accepted: 11 January 2013 / Published: 16 January 2013


(This article belongs to the Special Issue Biosemiotic Entropy: Disorder, Disease, and Mortality)





Abstract:


Biosemiotic entropy involves the deterioration of biological sign systems. The genome is a coded sign system that is connected to phenotypic outputs through the interpretive functions of the tRNA/ribosome machinery. This symbolic sign system (semiosis) at the core of all biology has been termed “biosemiosis”. Layers of biosemiosis and cellular information management are analogous in varying degrees to the semiotics of computer programming, spoken, and written human languages. Biosemiotic entropy — an error or deviation from a healthy state — results from errors in copying functional information (mutations) and errors in the appropriate context or quantity of gene expres​sion(epigenetic imbalance). The concept of biosemiotic entropy is a deeply imbedded assumption in the study of cancer biology. Cells have a homeostatic, preprogrammed, ideal or healthy state that is rooted in genomics, strictly orchestrated by epigenetic regulation, and maintained by DNA repair mechanisms. Cancer is an eminent illustration of biosemiotic entropy, in which the corrosion of genetic information via substitutions, deletions, insertions, fusions, and aberrant regulation results in malignant phenotypes. However, little attention has been given to explicitly outlining the paradigm of biosemiotic entropy in the context of cancer. Herein we distill semiotic theory (from the familiar and well understood spheres of human language and computer code) to draw analogies useful for understanding the operation of biological semiosis at the genetic level. We propose that the myriad checkpoints, error correcting mechanisms, and immunities are all systems whose primary role is to defend against the constant pressure of biosemiotic entropy, which malignancy must shut down in order to achieve advanced stages. In lieu of the narrower tumor suppressor/oncogene model, characterization of oncogenesis into the biosemiotic framework of sign, index, or object entropy may allow for more effective explanatory hypotheses for cancer diagnosis, with consequence in improving profiling and bettering therapeutic outcomes.


Keywords: genetics; epigenetics; semiotics; cancer; biosemiotic entropy; homeostasis; gene mutations; population genetics; chromatin architecture; encode


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Entropia semiótica do genoma: as mutações e os desequilíbrios epigenéticos resultando em câncer



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