The Systemic Concept of the Gene

Nucleic acid molecules may be taken as mere physical entities, very interesting in themselves, especially due to their ability for the templating of replicas, but this property is not exclusive to them. Being a gene is a very different attribute, derived from the embedment of nucleic acid molecules in a biotic system where, besides replication, they can template for the synthesis of proteins through a code.

If this were the only process involved in their participation in the bio-world, the outcome would be dispersive: functions of the proteins would conduct mostly to interactions with the outer environment. Our investigation of the process of formation of the code is rooted on the perspective that protein functions should also feed back positively upon the nucleic acids, thereby providing for a double link between genes and proteins, and both links being of equal weight. When RNAs were demonstrated to be better candidates for the primeval nucleic acids, instead of the intrinsically more stable DNA molecules, the definition of the principal function of early proteins could be pinpointed to stabilization of the RNA.

These processes involving molecular affinities, replication and differential physical stability should be considered in the realm of the self-organization of systems (see the categorization of systemic approaches by Di Giulio (2005) ). The extension of the Darwinian concept of natural selection to the molecular world in the origins of life only adds confusion; it should be reserved for the definitely biologic process of differential reproduction of cells and organisms. In the present context, it is sufficient to say that self-stabilizing and self-constructive systems grow faster and remain longer, or the term "molecular selection" should be adequately quoted.

In fact, we succeeded in showing that the genetic code organization presents clear signs of the relevance of the mechanism of RNA stabilization by proteins for fixation of the early attributions. This process established a stable nucleus (fixation of the GPS group of amino acids) around which the whole system could have developed. The temporal order of the stages in the model indicates the order of fixation of the paired boxes considering their final configuration in the code. The perspective of starting with a core, which grows outwards in all directions, differs from many of the technological models, attempting to sequentially lengthen and branch the chains of reactions in the clean test-tube chemistry. The process obviously includes the minimization of deviations from chemical norms or specificities, possibly starting with less specific and advancing to more specific catalysts, and may be modeled through the engineering optimization principles.

We would like to consider that the process of formation of the RNP genetic system as modeled here may be called self-cognitive, the term describing the reflexive and stimulatory association of the protein products to exactly the same RNAs involved with their production. The term cognition is derived from human communication affairs, among themselves or between humans and the environment, and spread into the realm of zoology. However, a correlate of it is frequently used by biochemists, relative to the molecular specificities of interaction, when saying that a substrate with high affinity to an enzyme, and this, are cognate to each other. When the binding of a stable protein occurred to a noncognate RNA - which did not participate in its synthesis - a self-maintaining system would not be formed. So, cognition is indicated to be at the basis of the productive and positive consequence or result of an interaction.

When we said (Pardini and Guimaraes, 1992) that "the system defines the gene," still based on observation of the large amount of evidence of the ambiguity of genetic sequences, we were duly asked (J. D. Watson, 1995) to clarify the workings of the system. We can now offer some molecular details. The genes are defined by the two-way processes that construct the genetic system: they produce proteins that are meaningful to them, that is, when the proteins help them to become stable and to be integrated in a system. The nucleoprotein system is constructed by the circular or reflexive association, through the coding (digital, letter by letter) and through the stabilizing connections (analogic, based on sequence patterns), and both are important to the same degree.

It happens as if the nucleic acids were, surprised, telling to the proteins - "you are my life!" - at the same time when the proteins were, equally surprised, telling to the nucleic acids - "you are my genes!" The definition of the producer by the product, in the present case, of the genotype (memory with code) by the phenotype (meaningful product), is just one specific case of a general process. For instance, in the building of some sentences in human languages, words are added sequentially but the precise meaning of the sentence is only reached when the last words are known; the last words are needed so that the first may be adequately chosen and correctly understood. The connections between the initial and final segments are multiple, simultaneous, and entangled in the circular configuration.

The former protein-first "or" nucleic acid-first hypotheses are now changed into proteins "and" genes together. When asking about the formation of systems, the question of which component came first is not relevant. The intelligent question is how the components became associated and integrated in a system. A piece of nucleic acid may be a gene for the systems that are able to accept it productively, but not for those where that piece is not productive, due to deficiencies in any of the processes of the circular associations. So, the definition of the gene is relative to its belonging in a system, not absolute to a piece of nucleic acid.

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