Sunday, June 2, 2024

A Model for the organization of DNA in living organisms


This model was proposed in the 1970s

I must first remind the reader that the model I intend to postulate is purely speculative and is open to whatever criticisms and modifications that time and hard scientific evidence might demand. It seems to me that the basic strength of the scientific perspective is the use of the paradigm and the willing openness to allow empirical data to decide the ultimate usefulness of any conceptual model.

However, science like any other modern human institution has the tendency to become rigid in its outlook. I believe that at the present time there is a strong tendency to take a narrow and unbending stand concerning the evolution of life on the planet earth. No one who accepts the basic premise of scientific investigation is about to deny the existence of DNA, its inherent structure, and the role it plays in heredity. Also it is quite apparent that we as human beings coexist on the planet with a vast variety of living things each with its unique structures and adaptations. Various theories of evolution have attempted to explain the mechanism by which these forms have come into existence. Darwin, Mendel, and the brilliant work of modern molecular geneticists have elucidated the molecular structure and function of the actual genetic material. It has been clearly demonstrated how DNA by the very nature of its structure is capable of holding the biochemical information necessary for life; how it conserves this information, and how living things are able to call upon this information to organize the functions that are the definitive prerequisites for life. These mechanisms are not open to dispute since they represent hard data demonstrated over and over again.

However, it is my intention to show that there are certain explanations of phenomena that are strongly held but in fact rely on tenuous proofs. It is currently held that evolution has proceeded on planet earth through a process of spontaneous mutation of genetic material in which the resulting changes in characteristics of living forms are either rejected or reinforced by natural selection pressures. Allow me to give some examples. There exists now a variety of bacteria, Neisseria gonorrhoeae, that is the causative agent for the disease referred to as gonorrhea in humans that has become immune to penicillin. The argument to explain this event would be the following: a fortuitous mutation of the genetic material in this organism produced the ability to negate the effect of the antibiotic. This event was independent of the presence of penicillin in the environment of the organism. With this new characteristic the particular strain of bacteria that held the immunity of course would survive where its cohorts would perish. Hence the new natural condition selected for the organism with the immunity. This same rationale has been extended to encompass the entire evolution of living organisms on planet earth.

The contemporary view is that the information contained in the DNA is carefully conserved and fixed and is not generally subject to alteration by its environment except in the limited area of fortuitous mutational events. In my estimation A rigid model forbidding any sort of adaptive mechanism in the genetic material itself and if living structures actually adhered to such a model the planet earth would be probably be devoid of the richness and variety of the life that it in fact supports.

This perspective is not an original view of mine.  It is conceivable that within the organization of DNA there exists an inherent mechanism to allow for a non-random interaction between the environment and the structure of the information store.  It is with this thought in mind that I propose the following model:

1 -that there is a portion of the DNA that is rigidly fixed in information content in what is now referred to as genes in general and in the so-called introns in particular. Billions of years in the biosphere have established this information as being essential for life and substantial changes in this structure can prove deleterious.

2-there is a large portion of the DNA in organisms that has no apparent information content by nature of its seeming random and repetitive sequences. This DNA is far from trivial and some of this structure represents the basic language store from which the genetic material responds to environmental signals; allow me to elaborate.

Proteins, especially enzymes, are the intermediaries between the information stored in the DNA and the expression of this information into discrete characteristics. In point of fact discrete genes hold the information for the structure of discrete proteins. The genetic code has of course been definitely worked out. It is these proteins that act on the cellular environment of living things. Enzymes are specialized proteins and are responsible for the catalysis of all the diverse chemical reactions taking place within each and every living cell. Enzymes mediate cellular activity.

3 -The model I am proposing predicts the existence of quite another mechanism operating within the genetic material. The specificity of enzymes for their substrates has been well established. This specificity cannot be accidental but must rely on discrete and well-established chemical laws. In other words, there exists a particular relationship between amino acid sequences of enzymes and the exact structure of a particular enzyme allowing it to act upon a particular substrate, and also establishes the nature of that reactivity i.e. whether oxidative cleavage, reduction, synthesis etc.

This relationship will be found to be quite simple - computer analysis of amino acid sequences of different categories of enzymes i.e. proteases and oxidases as an example will reveal certain relationships. It is my prediction that it will eventually be shown that there exists particular patterns, arrangement and spacings of amino acids that give rise to certain classes of enzymes and that these patterns since they occur in proteins will be represented in the DNA of the gene having the information for the synthesis of that enzyme as is already understand.

It is my contention that the exact structure of a particular substrate contains enough information for the synthesis of a protein that can interact with it - there are only a limited number of ways cellular enzymatic systems can chemically modify substrates in its environment.  Examples of these are pathways for synthesis, degradation, oxidation or reduction, cleavage, methylation etc.  It is my contention that DNA sequences that correspond to the relationships between amino acid sequence and enzymatic activity are pre-existing within the seemingly random array of sequences within the genome that have no known purpose.   

Such arrays can be mobilized and activated by the appearance of new substrates in the cellular environment. Such a mechanism proposes the de-novo synthesis of a novel gene that has the information to create a novel enzyme to interact with the new substrate presented to the cellular environment.  This particular aspect of the model as of yet cannot fully explain the relationship between environmental change, the appearance of new substrates and enzymatic populations as related to gross characteristics. In multicellular organisms the degree of complexity is exceedingly high.

The above model describes a transient mechanism for adaptive change in genetic material .  In addition, I propose that there exists a mechanism for transferring these de-novo genes to the conserved population of DNA in other words into inheritable genes. If the environmental change persists then the new messenger RNA containing the information for the protein designed to interact with the novel substrate will exist over a prolonged time frame and therefore allowing reverse transcriptases the opportunity to integrate this new sequence within the genome.  It is at this stage that selection pressures play a significant role.

  • The following is a modification in part three of my proposition - dated July 19, 1982

Within the intervening sequences, the exons are composed of sequences of DNA that code for pieces of the primary sequence of proteins that are essential for determining the overall three-dimensional configuration of the resulting protein which in the case of an enzyme such as cytochrome P-450 or an antibody will also determine its specificity. Although these essential pieces can be fit together in innumerable ways there are only a finite number of mini sequences of amino acids probably containing highly conserved hydrophobic residues that produce configurational patterns resulting in active proteins.

The most essential feature of this model as I see it is that the capacity to respond to any new environmentally introduced signal i.e. to produce a novel protein with the required specificity that relies upon the existence of preformed genetic units, exons, that with the appropriate environmental signal can be recombined to allow for the synthesis of a de-novo protein. The advantage of this model is that it allows for more than merely a random selection process for the evolution of new biological activity.

The weakness of this model however lies with the fact that it rests upon the assumption that there exists a pre-existing mechanism that can be activated upon the appearance of a novel substrate and that can ultimately lead to the production of a particular sequence of amino acids and therefore into reproducible 3 dimensional configurations with discrete specificities that can bind to the new substrate.

However the existence or non-existence of such a mechanism is experimentally accessible either by direct synthesis of model sequences or sophisticated computer analysis of the many, many proteins in which both the three-dimensional configurations and primary sequences are already known. If such a language were indeed uncovered the possibilities would be endless for it would then be plausible to synthesize a protein de-novo with novel and predictable activity which in collaboration with genetic engineering could lead to the production of novel synthetic genes.