Advances in Life Science and Medicine
Volume 2 | Issue 2 | Pages 01-11
Freedom and Nontriviality of Information Function in The Time of Biological Development
Institute of Problems of Chemical Physics, 142432 Moscow Region, Chernogolovka
This paper focuses on freedom of information systems as a necessary factor of its progressive evolution. The freedom can be defined as an acceptable waiting time for the choice and the implementation of one of the numerous potentially achievable combinations of elements of the information system. A system emerged which gave rise to a completely new essence– information. Only two information systems in biological objects – genetic system of the cell and the human psyche are basic, i.e. system generated. Only they have the ability to search, memorize and implement the selected variants in viable forms. Creative impulses and new valuable information emerge from the bottom, that is, from the genetic system of the cell and in the human brain. The principle of supplementary, non–genetic information is formulated, which we can consider as the display of new biological determinism in ontogenesis (embryogenesis).
Information systems, Freedom and stability, Information, Biological organization, Supplementary determination.
Cite this article as: Mitrokhin, Y., 2016. Freedom and Nontriviality of Information Function in The Time of Biological Development. Advances in Life Science and Medicine 02 (02), 01-11.
Introduction and definitions
Living organisms have a property that has long been noticed consciously and intuitively felt by humans, that is, being in two states, which can be defined as stable being and unstable periods, or formation. Today this observation found its expression in a strictly scientific theory of complex systems and the principles of self-organization (Haken 1988; Chernavsky 2000; Prigogine and Stengers 2003). In this paper we want to show that in the process of biological evolution the formation of higher levels of organization begins from below, from the level of the genome of the cell, where new information is generated. Spontaneous emergence of a primary, basic genetic system or self-organization was the key event in the emergence of life. The most important feature of this simple information system is the principle of matrix-based, complementary reproduction of randomly generated nucleotide sequences and the freedom to combine elements of this structure. The term “self-organization” is not entirely correct if applied unconditionally to such processes as prebiological evolution, phylogenesis and embryogenesis. Self-organization is present in these three phenomena of the organic world to different extents. Apparently, using the term without any reservations would be correct only in respect of the stage of prebiotic evolution, when truly spontaneous first attempts were tentatively made at the synthesis of short oligonucleotides and peptides in the primary chaos of physico-chemical systems. These two classes of organic compounds were not yet associated with each other with prescriptive information relationships. But when such relationships emerged in the depths of the substrate and the structure of the peptides become determined by nucleotide sequences, this stage of self-organization acquired a new way to express itself. The time has come of the information-sensitive, or, in the terminology suggested by M. Barbieri (2012), “artifact” self-organization.
It is only possible to talk about self-organization in the process of embryogenesis in respect of its part that goes beyond the necessary, information-dependent events of intracellular structures reproduction. The fact that is of crucial importance for this type of development is that the whole process of embryogenesis is determined not only by the genetic information contained in the DNA of the cell lines of the germ. Self-organization at the level of interaction of differentiated cells is carried out in parallel with the supplementary, non-genetic information that is emerging in the system. This information reflects and records those configurations of the cell-to-cell interactions that lead to the formation of new structures at the organismic level. Apparently, this is the kind of information which is defined as structural (Battail 2009).
Finally, is “self-organization” actually present in phylogenesis? As one observes a series of objective consecutive events of ontogenesis of our days, which are the points of growth of the giant phylogenetic tree, one sometimes wonders what the term phylogenesis actually means, whether it exists as a kind of independent, tangible biological phenomenon, or it is just a figment of our imagination. But at the same time one has to admit the actual existence, both in the past and today, of those continuous lines of germ cells (“germplasm”), in whose genome elementary acts of phylogenesis take place. It is obvious that both biological phenomena – ontogenesis and phylogenesis, are conceptually and essentially inseparable. It is the genome rearrangements, together with the subsequent reproduction of organisms and their selection, that constitute those rare events of self-organization, because the process was accompanied with the emergence of new information and new biological characteristics. Thus, we see phylogeny as a dialectical unity of strictly determinate acts of saving the selected information in the subsequent generations and rare, randomly appearing new combinations of genetic elements. The entropy of the genomes increasing about and the associated theory of non-adaptive evolution in the context of low cleaning selection (McShea and Brandon 2010; Lynch and Conery 2003) originates from the same source with the idea that we recently expressed, on the information entropy in the genomes of the past generations as a factor which compensates anti-entropic processes in today’s organisms (Mitrokhin 2014). We regard the physical meaning of information entropy as a manifestation of another side of the total entropy process along with the thermodynamic entropy produced in any physicochemical system.
As one observes the steady characteristics of intracellular structures and very long-term persistence of constant phenotypes of bacteria and archaea (Fox and Dose 1972), one may sometimes start thinking that in the process of evolution freedom is limited. The same idea is supported by the recent findings, which revealed extremely high conservatism and preservation of intragenic sequences of key genes for millions and even billions of years of evolution (Koonin 2009; Novichkov et al. 2009; Koonin 2012). One starts to believe that strict determinism dominates in the living nature. In this article we would like to use some well-known and firmly established facts of molecular and cell biology to show the balance between free choice and information-dependent one in natural information systems, which (balance) plays a decisive role in the formation and evolution of living systems. Our intuitive (but perfectly adequate) understanding of these categories in a human or social systems help us develop proper understanding about their role in the formation of new levels of biological organization. If the information comes from a kind of physical structure (or together with such structure) and becomes a factor that controls other structures, i.e., determines teleonomic behavior, it acts as a kind of “new force of nature.” Radical definition of information is given by W. Elsasser (1966): “Information can be viewed as a non-physical principle of the implementation of causal relationships in material objects.” M. Eigen (2000) also states that information is intangible. The notion of “information,” which we understand intuitively when the functioning of neural networks and genetic systems is described, can be rendered more concrete through meaningful insight into the structure. Structure is a fixed totality of realized choices of elementary acts of its matter formation.
The procedure for the choice of the next event in information-dependent processes can be defined in two fundamentally different ways. In the pre-biological systems, the freedom of elements that make up these systems is implemented through random interaction. The emergence of a new chemical structure, which is the consequence of a past series of relevant consecutive events, is accompanied by the production of structural information. The process is spontaneous and all the components of its events are random. Each elementary interaction takes place in accordance with the laws of physics and chemistry and in the specific environment where the system exists. The resulting sequence of random elementary interactions that occurred and the new structural information that emerged in the process cannot be used to reproduce the entire sequence of events in the neighboring areas. If the number of types of elements in the system is sufficiently large, then the period that is spent between the repetitions of the process is long. It is necessary to distinguish between two types of self-organization of biologically significant molecular structures. Pre-biological systems are characterized by probability, or true self-organization, whereas primary biological objects have prescribing, or information-dependent self-organization. Apparently, the second method for synthesize the new copies of oligonucleotides (replica formation) was present still in pre-biological systems. It is based on the principle of non-random complementary selection of the next monomer.
The situation changed dramatically when some fairly stable molecules capable of template-based reproduction emerge in the pre-biotic system. These are irregular polymers (nucleic acids constructed of four kinds of nucleotides). At the same time, there was a spontaneous process of the formation of polypeptides that are not capable of self-replication. Both these processes are usually seen as inherent to the initial stages of life. The populations of arising molecules have become the unique substrate for the emergence of the principle of digital encoding of information in nucleic acids. The molecular device of recoding a nucleotide sequence in the amino acid sequence should be considered the key event in the origin of life. The resulting system with the information-dependent determination of the structure of functionally active molecules (polypeptides) became the carrier of an infinite number of degrees of freedom and started its work as the generator which has been processing potential information into structural and symbolic information for more than ~ (3.5–4) × 109 years (Battail 2009). Information is not coming to the system from without. It comes into existence, becomes a reality in a primary physical-chemical systems. Contemporary scenarios of the molecular events of this period are the attempts of reconstruction of the so-called LUCA (Last Universal Common Ancestor). They develop the fruitful hypercycle concept (Eigen and Schuster, 1979). Most attractive is the idea of the noncellular but compartmentalized LUCA (Glansdorff et al. 2008; Koonin and Martin, 2005). This pre-biological system is supposed to have been a heterogeneous population of genetic elements, polymerizing and breeding in the network of inorganic cells constructed from zinc sulfide or iron. Most likely, such cells arose in the field of terrestrial hot springs and served as incubators suitable for primary metabolic reactions and spontaneous synthesis of primary biopolymers (Mulkidjanian et al., 2012). This scenario, like others, has a formidable logical limit, called Eigen’s threshold (Eigen, 1971). It is impossible to simultaneously increase the complexity of the genome, and to maintain the necessary precision of copying. However, in real life this threshold was overcome step by step with the help of small, evolutionarily beneficial deviations and achieving of minimum initial complications, which together triggered the Darwin—Eigen’s cycle (Koonin, 2012).
Then the system can be reproduced due to division and evolve by the Darwinian mechanism. Therefore, it can not be considered as a pure software as G. Chaitin (2012) supposes which defines life as ‘evolving software’. The system evolves as a single whole including all the above cycle elements. Any spontaneous random changes in the primary nucleotide sequence are accompanied by changes followed in elements of the organized system and, hence, are materials for selection. The number of potential combinations of the elements of genetic information system which it can assume during the periods of its reorganization that expresses the freedom inherent to the system; this freedom increases with the size and complexity of the genome. Freedom is largely a philosophical category and cannot be measured with a value which would be permanently inherent to a given system. The presence of freedom in material objects is evident when we compare simple systems of inanimate nature with living organisms, which are based on information systems. It is a combination of freedom of information elements in the genomes that provides the emergence of new genes for the future biological functions or ways of regulating the activity of the existing genes. However, physical and chemical laws which form the basis for the strength of the material structure of DNA, as well as the enzymatic systems that support the accuracy of its copying are able to provide the steady state of the genome and the preservation of selected combinations of elements for a very long time in successive generations.
Based on the above, we suggest the following definitions: 1. Freedom of informationsystem can be defined as unity of the number of potentially achievable combinations of genetic elements andacceptable waiting time before transition to the one of the numerous new combinations of its information elements. In other words, that is the reasonable correlation of times between arising challenge in environment and creation of adequate adaptations.
The information in general view can be defined as a tool of realization one of the hardly probable and steady combination of information system’s elements. With regard to genetic systems, information can be defined even more specifically: it is memory about the realized acts of choices of the next monomer, which (memory) is recorded in the polynucleotide sequence of monomers. Information emerges in the system together with the formation (and reproduction) of the polynucleotide and determines through the encoding system the sequence of choices in respect of elementary events that form another structure — polypeptide.
This definition of information emphasizes its role as an active, dynamic principle, which is also reflected in the recently proposed concept of “prescriptive information” (PI) (Abel 2009). But the general concept of “information” has one more aspect to it, and this is not semantic; it is the degree of order (organization) in the completed material object (whether biological or inorganic) which is not capable of self-replication. This information is termed “descriptive information” (DI) (Abel 2009). Later on, we are going to refer to it as a source of the so-called subsidiary information which emerges in each newly formed structure and system of the developing embryo.
It is generally recognized that biological organization began its development as an information system; however, this assertion is challenged by the supporters of the concept of holism, who regard biological information and the whole system of its transmission as a process that cannot be decomposed (Maynard Smith 2000; Noble 2008; Shcherbakov 2012). This view is captivating due to its romantic charm, but it does not promote the desire to look inside living objects. The proponents of this concept argue that it is impossible to consider genomic DNA as the sole source of information that provides the formation of the complete set of characteristics of the descendants. This statement definitely cannot be challenged. Indeed, along with the prescriptive information in the chromosomal DNA, a new cell also receives all the structural information contained in enzymes, structural proteins, membranes and organic molecules of the cytoplasm. However, there is a fundamental difference between these two types of information. Structural information, which isn’t transferred anywhere, and the structures that carry it, cannot be reproduced without the information received from the genome. These are the terminal elements of the genetic information system. They are only able to perform their function and die. But most importantly, these structures cannot change the information they carry, they are incapable of evolution. The new form of these molecules, improved and adequate to the new conditions, can arise only through information-dependent formation of new molecules; e.g., via the genome of the DNA. A cell is definitely an integral whole, but it is worth trying to understand how the parts of this whole interact with each other. The proponents of holism and their opponents might well reach an agreement in respect of the roles of the nucleus and the cytoplasm as the factors of inheritance of traits related to the same cell, whereas the determination of the characteristics and structures of a multicellular organism is the subject that they would find difficult to agree about. We definitely should not abandon the fruitful molecular biological concept which tells us that natural, spontaneously developing biological information systems are organized by the modular method (in blocks). This structure allows its constituent elements (nucleotides of DNA, genes, or discrete states of neurons) change their position (combine) without destroying the whole.
Biological information systems can be defined as linearly organized sequences of molecular structural elements (for a genetic system) or as dynamic sequences of discrete states of brain neurons and their synapses, which are able to be transformed into new combinations and thereby generate new information during the periods of their instability. These combinations of elements return to the stable state, which provides one of the most important properties of these information systems — memory. Another important feature is their ability to use code relationships to determine the structure of the functional elements of biological objects (enzymes, complex functional systems, etc.), or the semantic content of the sounds and written characters which humans, as conscious beings, operate with
2. Biological organization is a system whose elements are connected to each other with information relations; reproduction, sustainable functioning and development (evolution) which are carried out through the implementation of the available degrees of freedom that exist in the information subsystem of the organization.
In the phylogenesisly continuous line of germ cells the waiting time before a significant rearrangement of the genome and the selection of a new, evolutionarily significant variant of a nucleotide sequence, genes and gene complexes in the genome substantially exceeds the time of the unstable state of the system. The maintenance of an optimal balance of time between these states is a crucial task of the molecular-genetic system of the cell.
Amazingly, the time of the steady state for most species is so long that before the first evolution theories people regarded the world of animals and plants as completely unchanged. And even today this property of living nature affects our imagination so much that some authors even have some tempting ideas: “The goal of evolution is the cessation of evolution” (Shcherbakov 2005). It may seem that determining whether living matter is based on freedom or necessity is just a matter of taste.
Below we will show that the actual organizing principle in the biological systems that establishes a functioning, viable organization (at the level of cell and organism) is the genetic information system. This system, which develops spontaneously, may go into the state of instability and has the freedom without which evolution and improvement of the emerging organizations would be impossible. We will try to identify the actual role of freedom not only in the process of phylogenesis, but even in such seemingly rigidly determined process as embryogenesis.
Freedom and the principle of supplementary determination in the formation of biological structures
The relatively obscure nature of elementary events occurring in the genetic systems and the long-term existence of stable forms and processes in the world of living organisms have had a certain influence on the evaluation of the importance of freedom in the establishment and improvement of the levels of biological organization. This is reflected in the views of a number of researchers on the limitation of freedom at lower levels and the control exercised over them by the higher levels in the process of biological evolution. Thus, E.H. Merser (1981) formulates his idea of the formation of an organization as follows: “Each level of the hierarchy is limited to its own organizational relationships and further limited (or controlled) by a higher level.” Similar ideas were developed by E.M. Galimov (2001): “The inanimate nature is dominated by the desire for freedom. Life is related to the restriction of freedom,” and G.A. Zavarzin (2006): “What sets the ‘target’, prescribes the properties of the varieties of organisms? The answer is obvious: the system of the higher rank.” There is an edge of doubt about the adequacy of genetic programs and the belief that it is necessary to assess the role of causality coming from the top, a higher level, in the statements of D. Noble (2008). The conclusions on the limitation of freedom arise from the mixing of the levels of observation, which might be unintentional. On the one hand, these are the events occurring in the cell genome during those quite short period of instability, i.e., in the formation periods, when freedom is implemented and reveals itself. These periods escape the attention of the observer, because this is the molecular level. On the other hand, there is stable continuity of existence of species on the evolutionary time scale.
We believe that the above statements which tell us that a higher level of hierarchically organized systems affects the subordinate levels in some mysterious way are somewhat artificial and illogical.
The freedom that an information system has is an abstract concept; it is a space of possibilities that can be realized by the system. The place where the degrees of freedom of the genetic system are implemented is the very first, basic level of biological organization, that is, the interconnected system of polynucleotides (DNA and RNA) and polypeptides (proteins). They can be implemented in a particular material system, which includes, apart from the polynucleotide information carrier (gene), the whole metabolic infrastructure that supports the processes of genetic material replication, transcription, and translation. The understanding of the informational aspect of elementary events in the genetic systems at different stages of their evolution allows us to formulate the principle of supplementary determination in the formation of biological structures.
1. At the stage of pre-biological systems, this principle is reflected in the fact that the formation of more complex organic compounds which is carried out as a series of random events in the physical-chemical system is replaced by irregular polymers (such as polynucleotides) that spontaneously emerge in this system. These polymers became the substrate from the depths of which the principle of supplementarity grew. A structure emerged that was capable of complementary reproduction, and at the same time a molecular mechanism emerged that implemented the collinear correspondence between the sequences of the two types of polymers (proteins and nucleic acids). The physical meaning (or, as well as possible, nonphysical) of the principle of supplementary determination is that the formation of irregular polymers with a biologically significant (selected) sequence of monomers was carried out in an information dependent manner, which superseded the original, spontaneous process of random formation of polymer sequences and other biological molecules based exclusively on the physical and chemical laws. The latter was superseded, but not completely replaced. And, in particular, in respect of the whole spectrum of organic molecules of the metabolic system which are not related to information polymers. It just changed the speed of their formation. This is true for the structure of the enzymes synthesizing these molecules, but not for the structure of their products. The structure of the latter is determined exclusively by the laws of physics and chemistry and carries fossilized, not genetic, structural information, according to the terminology suggested by G. Battail (2009).
2. At the stage of established biological objects (cells), a supplementary driving force in the formation of biologically active protein molecules is the laws of molecular statistics and physics of polymers. Apart from the mandatory prescriptive information that determines the sequence of amino acids in the polypeptide which is synthesized, the process requires supplementary information that is implemented through the action of physical laws. C. Anfinsen (1973) was the first to point to this circumstance. He postulated and experimentally proved that the proteins are capable of taking their final functional form spontaneously (folding). Although formally protein folding is not a step of transmitting genetic information, but actually, according to E. Koonin (2012): “folding involves the flow of information from one-dimensional sequence of amino acids in the polypeptide to a three-dimensional structure of the protein”. At this final stage, the molecule assumes its final, most likely configuration that has the desired activity. Here the supplementary source of determination for the formation of polypeptides is not the information- dependent principle (it creates the initial conditions), but a purely physical process which consists of achieving a structure with the minimum level of energy.
3. Apparently, the principle of supplementary determination can be also applied to a more adequate description of the process of embryogenesis, which we will discuss in more detail further on.
Thus, in the biological objects belonging to different levels of the organization we observe a combination of two complementary principles of structure determination. The new information dependent mechanism, which arose in the depths of the primary pre-biotic system, becomes, along with the physical and chemical laws, one of the supplementary factors that determine the formation of a biological structure. The core essence of the new biological determinism is the opportunity to choose and retain one of the available combinations of the information elements of the system. The implementation of more and more new features in the genetic system, together with the selection of viable combinations, leads to an increase of the information on the selected groups of organisms and the decrease of entropy.
In this paper, we advocate the view that higher levels of biological organization, which are controlled by the genetics, are the derivatives of the latter. They do not, and cannot, impose any restrictions upon the basic level. As they are the consequence, they cannot be the cause. The fact is that none of the higher levels of organization (except neural networks, which will be discussed further on) has any material substrate which is capable of acting as a carrier and expressing the activity of such levels, nor has any features of an information system.
Sources of supplementary information in embryogenesis
It is literally before our eyes that one of the most intriguing phenomena in the living world takes place, and that is the process of the formation of a multicellular organism — embryogenesis. It connects the two worlds, two different scales of time manifestations of life. On the one end of the spectrum, there is a long phylogenetic development of the substrate of the molecular genetic level of the organization based on the express condition of the freedom of choice of new genetic combinations that have not been tested yet. The understanding of this process develops our brain solely due to the imagination. On the other end, there is the world of countless enchanting flashes of individual Metazoa organisms. Embryogenesis is a peculiar kind of theater, where the familiar piece from the information sheet of the genome is played over and over again.
The journey from the hypothetical Eigen’s polynucleotide to the modern genomes took ~ (3.5–4) × 109 years. Such a great time was required to create the genetic information contained in the genome of germ cells of any modern highly organized animal. Most animals have the time of embryonic development ranging between 14 hours and 12 months; this is really a short moment in which one cell transforms into a complex multicellular organism. At the same time, it is generally agreed that the amount of information in the adult body is much larger than in the zygote, i.e., new information emerges. This idea was clearly formulated by J. Monod (1971). It was assumed that new information is not the genetic information contained in the DNA of a single cell. He suggested using the formation of three-dimensional protein structure (folding) as a model of epigenetic development. Genetic information implemented in the amino acid sequence reaches its final expression in the active structure of the protein globule only through the initial stage of the set of conditions (pH, temperature, ionic composition, etc.). It is at this stage where information grows incrementally as a result of the choices made, efforts to place the elements in the polypeptide chain in the optimal way. Only some of all the possible structures that can be implemented with the use of the original genetic information are actually implemented. It cannot be ruled out that the principle underlying the process of protein folding can be implemented in embryogenesis, but the elements that are used to form new structures (tissues, organs and entire system) in this case are clones of competent cells, each of which contains the same information as the original zygote. Ultimately, the mainspring of ontogenetic development is the original genetic information contained in the DNA structure. This thought used to dominate the discussion of the embryogenesis events for quite a long time (Raff and Kaufman 1983).
The problem of ontogenetical self-organization primarily concerns finding a plausible explanation to the question where in the developing embryo there emerges subsidiary information which, along with the genetic information in each cell, determines the structure formation in a multicellular organism. In this question it is implicitly supposed that the information contained in the genes is insufficient for this process. And this seems to be true. Indeed, it seems quite obvious that an adult body contains much more information than the DNA sequence of a zygote. In principle, a straightforward comparison of the amount of information in the zygote and contrasting it with the amount of information in a multicellular organism is not entirely correct. But the phenomenon requires an explanation. A competent approach in this case would be examining to the situation from the point of view of simpler systems, for example, protein folding and assembly of the ribosomes subunits. It is probably in a similar way that genetic information determines all the visible phenomena in embryogenesis, attracting relevant sources of subsidiary, non-genetic information, which arises as a result of the interaction of competent cells. But this information lives in a structure which is not intended for transfer and reproduction in the new system. This is a non-reusable substance. It is possible that the subsidiary information which clearly accumulates in the process of ontogenetic development of the organism matches perfectly the contents of the concept of descriptive information (DI), recently proposed by (Abel and Trevors 2005; Abel and Trevors 2006; Abel 2009). It is optional in the sense that it determines the elements and features of the organization of the developing organism which cannot be determined directly, through nucleotide and corresponding amino acid sequences, i.e., through the channel of prescriptive information (PI). Thus, DI here acts as a naturally determining factor that emerges in the course of interaction between relevant competent cell elements. It is not fixed to any sequence of information elements and is not converted into another sequence. It serves only as a means of maintaining some forming structure. This subsidiary information is not intended for the transfer (succession) with the material carrier. In the next generation, it will occur again at all stages of embryogenesis together with the developing cell lines. Thus, we can assume that during embryogenesis the self-organization of differentiating cells occurs either with the use of genetically inherited information contained in the genes or via a more general mechanism defined by the relevant information that emerges and determines the relative location of cells in the tissues.
We face even more difficulties, however, when we are trying to understand how purely individual features of the organism, inherited from parents, are determined: gait, gestures, smile, personality traits, etc. Here, it is not possible to engage that mysterious time-related information which helps form impersonal enzyme activity or a muscle in an arm. This cannot be done without specific inherited genes, although it is not clear how they control the process. There is a saying, which is difficult to prove, that the quantity of known individual genes cannot determine all the details of the structure, shape, and individual features, and that the increase in their numbers would be too costly for the body. Such extreme overvaluation of the “expensive” mechanism of determination of the whole complex of individual features may be quite acceptable, if the modulating effect of epigenetic mechanisms for alternative splicing is used, which is typical for the majority of mammalian genes. It may well form the basis for the wide variety of synthesized proteins (Blencowe 2006; Wang et al. 2008).
Apparently, the most plausible model is the one in which the basic genetic information that specifies the amino acid sequences of the cellular proteins and RNA is only a small part of all the information required for full determination of all species-specific and individual features of multicellular organisms. The transition to multicellular forms and the further evolution of these forms in the phylogenesis, as well as the phenomenon of embryonic development, could become a reality only due to the emergence of a new principle of information support for the formation of completely specific traits of a multicellular organism in the framework of the mechanism of functioning of the genome of early eukaryotes. This poses the question what element (principle) is firmly fixed in the structure, whereas the genes, both structural and regulatory, as well as the stretches of DNA of unknown function, are stirred continuously during gametogenesis (Koonin 2009; Koonin and Wolf 2010; Koonin 2012)? And then there is a very philosophical question: how freedom, which is one of the cornerstones of the genetic information system, gets on in the depths of its substrate with its exact opposite—necessity—during phylogeny? At the same time, I am not inclined to think that necessity denies freedom, as it is interpreted in the classical dialectics. Freedom continues to be a major characteristic of the level where it first appeared in his new role — in the system of informational macromolecules that emerged. It was the pre-condition for the birth of genetic information, its evolution and implementation in new biological forms.
Recently, some convincing experimental data were received that significantly enhanced our understanding of the contribution of both genetic and epigenetic factors to the development of the embryo from the zygote. This area, to a certain extent, is a continuation to a long-standing vivid interest in the relative contribution of the nucleus and the cytoplasm to the inheritance of the differentiated state of cells in embryogenesis. Real progress in this direction became possible due to the advances in the study of the structure of chromosomes of various eukaryotes and identification of the significant arsenal of enzymatic systems and recruited factors of protein nature, as well as small non-coding RNAs (Sanchez-Eisner et al. 2006). These factors modify the chromatin structure in the way that some genes go to the “silent” state, while the other genes become an active, whereas the DNA sequence remains unaffected. It remains unclear how the sites are selected for chromatin modification in vivo. How do molecular mechanisms of chromatin matrix preparation for the transcription that are known today continue to have effect after the next division of the cell? (Felsenfeld 2007). We suggest considering epigenetic phenomena (including those during embryogenesis) as auxiliary enzyme systems of the cell intended for selective acceptance of genetic information.In other words, in this case, by undergoing the full cycle of the transcription apparatus, the source of information (a gene, a chromosome) becomes the receiver of the information, and its infrastructure is adjusted without any changes to the original DNA sequence, i.e., it appears in the role of phenotype.
The molecular mechanisms responsible for this process include post-translational histone modifications (methylation and acetylation); chromatin remodeling that alters nucleosome structure; dynamic insertion of new variants of histones in nucleosomes; DNA methylation; small non-coding RNAs (Baxter et al. 2004; Henikoff 2005; Ringrose and Paro 2004; Matzke and Birchler 2005; Sontheimer 2005; Rosenfeld 2010).
It may seem that the brilliant achievements of embryologists we mentioned above give the answer to our obsession with finding the source of the missing information needed for the formation of an adult organism from a zygote. It is implemented from the genes that are not active in the zygote. As shown in experiments on C. elegans, in each subsequent elementary act of intercellular interaction a new piece of such information is born, and it replaces the previous one. (Bischoff and Schnabel 2006). But these acts of configurations emergence that occur only once could only occur in a unique, necessary sequence, so that the final result was pre-determined. Its most likely source is some hypothetical way to capture and implement the required subsidiary information through signaling proteins such as Wnt/betacatenin-cascade and Hox-genes activity in the cells of developing differentiated clones. (Kawakami et al. 2006).
Today we know much more than we used to about the formation of differentiated cells due to the impressive success of epigenetic research (Youngson 2008), whereas the outcomes in respect of organogenesis and morphogenesis are not so impressive and sometimes contradictory (Anway et al. 2005; Masse et al. 2009; Rosenfeld 2010).
Thus, we may be fairly certain that the determinism we see in biological objects is significantly different from the determinism in physical systems. Elementary events that make up simple physical or chemical systems are quite monotonous in their manifestations, i.e., they have a small number of available degrees of freedom.
Quite a different situation is observed in living systems, and it has been like that since they first emerged. As it was noted above, their evolution apparently began with the emergence of the primary information system of hypercycle type, which was the foundation for future protocells (Eigen 1971). It is likely that spontaneous reproduction of the polynucleotide information carrier acquired real biological meaning only in case of the simultaneous formation of the molecular recoding device (the prototype of the future ribosome). The carrier of the function cannot be reproduced without it. This was a key step in the development of a full value information system capable of generating genetic information, storing it, transferring it to the next generation and determining the structure of specific proteins, the carriers of the function.
The new biological determinism appeared in the primary physical-chemical system, in which completely new entity was born – information.
A system of irregular information polymers became the substrate with a new, practically infinite scope of the degrees of freedom to choose the options of nucleotide sequences. There also emerged molecular mechanisms that ensure a high probability of physical implementation of these degrees of freedom. The evolution of the matter, starting with the origin of life and the gradual progressive development of this system in the phylogenetic series of generations of individuals will lead to the birth of one more non-physical reality – human consciousness. Thus, the Age of Life and Freedom, which the material world entered, was the time when two new non-physical realities emerged: information and consciousness.
This work was funded by Institute of Problems of Chemical Physics of Russian Academy of sciences.
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