Epigenetics: reality or fiction? Phenotype determined by the genotype and genotype determined by the Phenotype.

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1 Epigenetics: reality or fiction? Genotype determines and it is determined. Phenotype determined by the genotype and genotype determined by the Phenotype. Personality characters which could inherit. Acquired cognitive brain structures could be inherited. How the environment modifies the personality, these changes are traduced in the molecular and genetic level, and then these changes can transmit genetically. Introduction The genes don t specify our behavior in a straight way, but they codify molecular products which built and guide our brain working through that it express our behavior. The brain development, brain activity and behavior, all depend on the genetics influences and so the environment, and there is a growing accumulation of evidence that the social influence could alter the genetic expression of the brain and the behavior. We will see some examples. From time ago, almost a century, we were taught, and many articles and books were written as scientific as divulgation, that the characteristics of the personality, as well as some acquired characters do not inherited. Well, after some published studies plus the use of common sense from the careful observation of some persons and their seed, I could guarantee without almost any doubt, that the personality characters, as well as another acquired characteristics, could be inherited, including certain immunity ways and the answers to some injuries/noxas.

2 It has thought the genoma was only a permanent structure its guide the entire body development and its processes. From some investigations, we assume that the genoma, far to seem static it is highly active, that it responds to a variety of stimulus associated to the social behavior. 1 Thereby, the social information can reach to changes in the brain and to the behavior through changes in the genoma, acquired. The question is if these changes in the genoma could inherit. It should exist a molecular and cellular process of the acquired characteristics during the long life of the person, with a structural and sustained anchorage, that it has to produce also a change in the structure of the DNA, so it could be inherited. Paul Kammerer was, in fact, in the beginning of XX century, who first say that the acquired features during the lifelong of some organism, could transmit to its descent. This cost to him a humiliation, personal and professional degradation, whereby it was said in those times that this was the cause of his suicide. So, without taking out the science history, we say that Kammerer was the founder of we now know as the epigenetics. 2 He would have got ahead many decades to Conrad Waddington, who described the first cases of this phenomenon and named it in Gene, proteins and behavior Somehow there are whole circuits, integral, between the genetic material and the molecular changes of the behavior, so with the personality characters, feed and feedback circuits which make our personal, human being, personality, behavior, thinking features integrate in some way into the genetic material, I mean the genoma. Also this would allow a fixed structure which determines our behavior day by day. I mean, the molecular changes would be anchored in some way. Because in the cellular dynamics, these changes would have been stables through time for assure that my learning and behaviors will continue to be the same during my entire life. Obviously, this can change and adjust with new learning. Otherwise, the cognitive structures one developed with the learning and persist with time, so with the main personality features, have a sustention in the genoma, which permit also 1 Robinson GE, Fernald RD, Clayton DF. Genes and social behavior. Science 2008 November 7 th ;322(5903): Pennisi E. The case of the midwife toad: fraud or epigenetics?. Science 325:1194 (2009).

3 that these structures can self remodel (or by external stimuli) and through time, and so repair in the case of damage. So, a reverse road of feedback should exist between proteins, RNA and DNA, allowing the gene knew what it is happening outside the cell. They have to receive information from the outer part of the cell membrane, not only the extracellular matrix, and then they could modify the genoma structure in order to change the proteins which conduct the mechanisms of our changing body and environment. And these changes in the genoma could be, or should be, inherited and be stable during the personal life and future generations. Why I m telling this? Because the offspring have personality and character features very similar to their parents. This is possible and due to the familiar and social environment which do it or may be exist a genetic load make it happened? That is to say there is an underlying molecular structure which predispose to certain personality or to certain character features. And this structure of the neural network is of course genetically determined. Nothing is built in the cell nor in any tissue without the genoma agreement. The reverse sequence of information flux would be: Proteins RNA DNA. This reversion of the classic synthesis way has been proposed by many authors, and some of them have demonstrated ergo that RNA can transcript in reverse way to DNA calling this copy of DNA (retrocopy) that would be functional segments of DNA These proteins act as neurotransmitters, neuromodulators, messengers, etc, it means, signals from outside the cell and these changes transmitted by the messenger o the proteins, if they stay in time, would place definitely inside of the cellular molecular structure and inside the tissue level too. In turn, these structures would determine changes in DNA for instance maintain the same structures inside and outside the cell, it means, in the successive cellular divisions. Of course, this would include the germinal cells, inheriting the descent the acquired changes. 3 Parker HG et al. An expressed Fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. Science August 2009; 325: Kaessmann H et al. Nat Rev Genet 10: 19 (2009). 5 Mc Carrey JR et al. Nature 326:501 (1987).

4 We mentioned the histic level because of the neuronal tridimensional morphology, as it is the brain tissue and it modifies in light of external changes like the learning, as the sensations which it produces in a repeated way and also in an isolated manner, for leaving in the memory of the body what it happened, as a way to leave printed for future generations the scaffolding for deciding behaviors or similar feelings. We repeat on the concept of the changes perdurability and these can see reflected in the underlying structure, in the molecular, cellular or histic level. I mean, the molecular changes settled in DNA, RNA and proteins can see reflected in cellular changes and in changes in the tridimensional structure of the tissues, adopting a special and unique conformation for the different situations, keeping embodied in fixed structures and stables for always. These structures I denomínate stables because really otherwise we could not have neither any permanent learning nor similar answers in front of similar situations, many of them far in time. For example, where is the muscular memory? Where is, in the molecular, cellular and histic level the smelling memory, the auditory sensor, or the feelings? The Darwin concepts Thereby Darwin planted the evolution idea (a brilliant idea) and the idea of no inherited of the acquired characters, this not only needs but it is reviewing in the light of the news findings of the structure and function of the DNA, so its interaction with the intracellular environment and with the outside too. This mechanism its called, for some authors, a paramutation ( escaping Mendel ), and says about epigenetecis modifications in the genoma that can be passed on to the next generation. 6 I mean, as the functions of the DNA are regulated producing more proteins depending on the inside and outside cell environment, also its regulated the actions and the interactions with the logical consequences that the environment establish over the human being. And not only the biological environment also the social environment, where the individual and social learning might apprehended in fixed structures but also malleable what permit modify as the social environment change (of course, is the opposite that we observe in the diary life, that the adult persons few times can change these cognitive structures, someone 6 Ehrard Jr KF et al. RNA polymerase IV functions in paramutations in Zea mays. Science 27 February 2009 (323):

5 change a little sometimes and a few persons change too much). But we can assure that these cognitive structures are determined in the developing period of the human being, it wasn t born with them, although some of them, as we are maintaining from the beginning of this lecture, are in the childbirth, because these same fixed and no mobile structures are rooted in the DNA, allowing the person maintain in the social way, with interactions in a determined way in front of the challenges that the changing life put in our route. I mean, the subject has behavioral patterns socially acquired but also has genetically acquired. So, if these cognitive structures have accompanied the person during the whole life, it would be fool to assure that are anchored in the DNA and this DNA has coded proteins and another substances through these structures, that they have played as messengers or straight efferents for determining different ways of behaviors. And if this is true, and it has compromised the germinal cells in this theory, thus there we could have the secure offspring of these personal characters. The ways of feelings, the tastes, the artistic inclinations, how do you explain the inheritance? It is not only the environment which exists around the person during the early stages of its development. I insist, it is not only that. It might be more. It has to have a genetic basement, structural, inherited. Of course, the environment is fundamental, but not all. Without one of them, the other would be very limited to explain the variability between motivations and vocations of many children from different families, whose has ornot many kids. How can we affront Darwin theory without offend him and the evolutionary science, without be a superb, or arrogant, refuting or trying to refute one of the most scientist of the history, who changed the way we were seeing the world, as Einstein did. But as always and Darwin said, so in science, the things, the scientific theories, the biological laws, evolve. I mean, the scientific theories are changing in light of the new discoveries or refusing some parts or the total one of them. Which is the molecular, genetic or cell substrate, or may all of them, of this concept of inherited personality characters? How does it produce? May be that the permanent secretion of neurotransmitters does that the cellular environment adapts to the permanent

6 manufacturing of this neurotransmitters, and this does a permanent manufacturing of RNA for these neurotransmitters, and this does that RNA needs the DNA activation with the subsequent transcription to RNA, and so and so. Another explanation is that the synapses, structural way, modify permanently, because they have reinforced its necessity of activation front of different stimulus or the same stimulus. And this structure, so keeping during time, would generate a favorable environment for the transmission of this tridimensional structure to other cells, as notice them that is functioning and that it should last during its time and in the inheritance. How can we demonstrate all this? Could we interview or we could observe the grandparents, parents and offspring trying to determine in a detailed way that the things we image as physical similar and some personal acquired characters through the social and parental environment. The language The speaking language phonetics modifies the anatomical structures of the phonetic apparatus from our childbirth and continues during the whole life, so could these changes passed to the next generation? Thus the phonetic apparatus is different according to the different languages and its phonetics, so we suppose that these specific anatomical structures could inherited if the descend speaks the same language, or may be facilitates the developing of some language and not other languages. Because of the migration of some persons to another phonetics language may be possible but will be not the same as the maternal one, we mean the language with the person was born. These traits could be inherited? In fact, we can assume that the social behavior could be inherited too, and the psycological one too, and so and so. The behavior The genes codify proteins, no behaviors. But identifying how the genomic variation modifies the neuronal circuits, we could understand better where these changes begin. Small differences in the production of any protein in a determined cerebral site will induce then changes sometimes deep changes in the behavior.

7 The behavioral phenotypes, or phenotypes of the behavior, are the result of a complex interaction between the nature (DNA) and the experience. Then it has to identify in a detailed manner, how affects the experience to the DNA. Because the genoma is not the destiny. 7 Another investigation that could base this theory is Vincent Harley y L. Hare, who have demonstrated a genetic variation in the transsexual from man to woman, who apparently during the gestation period or in the beginning of their life, would be subjected to a less influence of male sexual hormones due to a inhibitor mechanism of the receptor. The author talks about a minor or an incomplete masculinization of the brain during its development. Thus, the prenatal hormones would affect the sexual development without modifying the sexual organs. 8 Other investigations routes are showing in a steadily manner, that really could exist perdurable molecular changes (and some inherited) underlying to some behaviors that for some persons could be not normal. So the molecular changes that exist in some psychiatric diseases were investigated, also there are some research and theoretical lines (as mine) where pose that underlying of the behaviors that we could consider no between biological parameters of our specie, exist really their respective molecular changes. As with the metaboloma as with the proteoma, I mean the sum of routes and molecular changes that identify a human being as unique, it would exists also a molecular change and the subsequent underlying genoma change for any kind of behavior and personality trait. 7 Landis S, Insel TR. The Neuro in neurogenetics. Science 2008; th November:821 8 Hare L, Bernard P, Sánchez FJ, Baird PN, Vilain E, Kennedy T, Harley VR. Androgen receptor repeat length polymorphism associated with male-to-female transsexualism. Biol Psychiatry Jan 1;65(1):93-6. Epub 2008 Oct 28

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