Publication: Genética y epigenética: yo soy yo y mi circunstancia
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2017
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Carlos Vicente Córdoba
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Abstract
En 1914 publicaba D. José Ortega y Gasset su libro “Meditaciones del Quijote” en el cual afirmaba: “Yo soy yo y mi circunstancia y si no la salvo a ella no me salvo yo”. El fondo científico del “yo soy yo y mi circunstancia” fue definido por Waddington al definir la Epigenética como el estudio de las interacciones causales entre los genes y sus productos que dan lugar al fenotipo. Dicho de otra forma, durante el desarrollo y el ciclo vital de cada individuo pueden darse cambios heredables en la función génica que se producen sin un cambio en la secuencia del DNA.
Estos cambios consisten en modificaciones del DNA, modificaciones de las histonas y producción de RNAs no mensajeros y, por tanto, no codificantes. Las modificaciones del DNA consisten en la metilación en el C5 de la citosina en las llamadas islas CpG, regiones genómicas de entre 300 y 3.000 pares de bases con alto contenido en citosina (C) y guanina (G) contiguas. Las islas metiladas, si permanecen, reclutan represores de la transcripción que, al unirse a ellas, impiden la transcripción del gen en anexo. Las islas metiladas también reclutan desacetilasas y metilasas de histonas, las cuales pueden regular a su vez la expresión genética. Las histonas que recubre el DNA pueden también sufrir modificaciones post-traduccionales consistentes en acetilación, metilación y fosforilación de histona H3 en su grupo -amino (no involucrado en el enlace peptídico) de un resto lisina localizado en las colas amino terminales. En este estado conformacional, la histona recubre al DNA haciéndolo inaccesible a la maquinaria de la transcripción. Por último, los sRNAs (“small RNA”) son pequeños RNAs no codificantes (ncRNAs) que actúan como RNAs de interferencia, silenciando la traducción de proteínas específicas.
Estas modificaciones, condicionadas por factores ambientales, son perdurables y transmisibles, y afectan al desarrollo emocional del individuo, al desarrollo de los centros cerebrales encargados de la percepción, la memoria, las relaciones causa-efecto y la gestión de las emociones. Por ello, la personalidad final de un individuo viene condicionada, no solo por su genoma, lo que anularía el libre albedrío, sino por las modificaciones epigenéticas de su genoma que acumula durante toda su vida. Hoy día se conocen muchos genes, implicados en el desarrollo del cerebro, sometidos a regulación epigenética, como los implicados en el tamaño de la corteza cerebral, en la vía apoptótica durante la proliferación neural, en las vías de señalización WNT, en la codificación para una proteína esencial en la organización de las estructuras anteriores durante el desarrollo cerebral, en el control del tamaño cerebral, y en la especificidad de las estructuras ventrales del sistema nervioso central, directamente implicadas en las gestión de la experiencia acumulada.
In 1914 Don Jose Ortega y Gasset published his book "Meditations of Don Quixote" in which he affirmed: "I am me and my circumstance and if I do not save her I do not save myself." The scientific background of "I am me and my circumstance" was defined by Waddington as Epigenetics, the study of causal interactions between genes and their products that give rise to the phenotype. In other words, during the development and the life cycle of each individual, there may be inheritable changes in gene function that occur without a change in DNA sequence. These changes consist of DNA modifications, histone modifications, and production of non-messenger RNAs and, therefore, non-coding RNAs. DNA modifications consist of cytosine C5-methylation in the so-called CpG islands, genomic regions composed by 300-3,000 base pairs with high content of contiguous cytosine (C) and guanine (G). Methylated islands, if they remain, recruit repressors of transcription, which, when joined, prevent the expression of the gene in annex. Methylated islands also recruit histone deacetylases and methylases, which in turn can regulate gene expression. The histones that overlap the DNA may also undergo post-translational modifications consisting of acetylation, methylation and phosphorylation of histone H3 in its -amino group (not involved in the peptide bond) of a lysine residue located in the amino terminal tails. In this conformational state, the histone overlies the DNA making it inaccessible to the transcription machinery. Finally, sRNAs (small RNAs) are small non-coding RNAs (ncRNAs) that act as interference RNAs, silencing the translation of specific proteins. These changes, conditioned by environmental factors, are endurable and transmissible, affecting the emotional development of the individual, the development of brain centers responsible for perception, memory, cause-effect relationships and the management of emotions. Therefore, the final personality of an individual is conditioned, not only by its genome, which would cancel its freedom, but by the epigenetic modifications of its genome that accumulate throughout his life. Many genes are now known to be involved in the development of the brain, undergoing epigenetic changes, such as those involved in cerebral cortex size, in the apoptotic pathway during neural proliferation, in WNT signaling pathways, in coding for an essential protein in the organization of anterior structures during brain development, in controlling brain size, and in the specificity of ventral structures of the central nervous system, directly involved in the management of accumulated experience.
In 1914 Don Jose Ortega y Gasset published his book "Meditations of Don Quixote" in which he affirmed: "I am me and my circumstance and if I do not save her I do not save myself." The scientific background of "I am me and my circumstance" was defined by Waddington as Epigenetics, the study of causal interactions between genes and their products that give rise to the phenotype. In other words, during the development and the life cycle of each individual, there may be inheritable changes in gene function that occur without a change in DNA sequence. These changes consist of DNA modifications, histone modifications, and production of non-messenger RNAs and, therefore, non-coding RNAs. DNA modifications consist of cytosine C5-methylation in the so-called CpG islands, genomic regions composed by 300-3,000 base pairs with high content of contiguous cytosine (C) and guanine (G). Methylated islands, if they remain, recruit repressors of transcription, which, when joined, prevent the expression of the gene in annex. Methylated islands also recruit histone deacetylases and methylases, which in turn can regulate gene expression. The histones that overlap the DNA may also undergo post-translational modifications consisting of acetylation, methylation and phosphorylation of histone H3 in its -amino group (not involved in the peptide bond) of a lysine residue located in the amino terminal tails. In this conformational state, the histone overlies the DNA making it inaccessible to the transcription machinery. Finally, sRNAs (small RNAs) are small non-coding RNAs (ncRNAs) that act as interference RNAs, silencing the translation of specific proteins. These changes, conditioned by environmental factors, are endurable and transmissible, affecting the emotional development of the individual, the development of brain centers responsible for perception, memory, cause-effect relationships and the management of emotions. Therefore, the final personality of an individual is conditioned, not only by its genome, which would cancel its freedom, but by the epigenetic modifications of its genome that accumulate throughout his life. Many genes are now known to be involved in the development of the brain, undergoing epigenetic changes, such as those involved in cerebral cortex size, in the apoptotic pathway during neural proliferation, in WNT signaling pathways, in coding for an essential protein in the organization of anterior structures during brain development, in controlling brain size, and in the specificity of ventral structures of the central nervous system, directly involved in the management of accumulated experience.