Origin and Evolution of the Brain

Modern biology has not yet come to terms with the presence of many organic codes in Nature, despite the fact that we can prove their existence. As a result, it has not yet accepted the idea that the great events of macroevolution were associated with the origin of new organic codes, despite the fact that this is the most parsimonious and logical explanation of those events. This is probably due to the fact that the existence of organic codes in all fundamental processes of life, and in all major transitions in the history of life, has enormous theoretical implications. It requires nothing less than a new theoretical framework, and that kind of change is inevitably slow. There are too many facts to reconsider, too many bits of history to weave together in a new mosaic. But this is what science is about, and the purpose of the present paper is to show that it can be done. More precisely, it is shown that the whole natural history of the brain can be revisited in the light of the organic codes. What is described here is only a bird’s-eye view of brain macroevolution, but it is hoped that the extraordinary potential of the organic codes can nevertheless come through. The paper contains also another message. The organic codes prove that life is based on semiosis, and are in fact the components of organic semiosis, the first and the most diffused form of semiosis on Earth, but not the only one. It will be shown that the evolution of the brain was accompanied by the development of two new types of sign processes. More precisely, it gave origin first to interpretive semiosis, mostly in vertebrates, and then to cultural semiosis, in our species.     

Three Types of Semiosis

The existence of different types of semiosis has been recognized, so far, in two ways. It has been pointed out that different semiotic features exist in different taxa and this has led to the distinction between zoosemiosis, phytosemiosis, mycosemiosis, bacterial semiosis and the like. Another type of diversity is due to the existence of different types of signs and has led to the distinction between iconic, indexical and symbolic semiosis. In all these cases, however, semiosis has been defined by the Peirce model, i.e., by the idea that the basic structure is a triad of ‘sign, object and interpretant’, and that interpretation is an essential component of semiosis. This model is undoubtedly applicable to animals, since it was precisely the discovery that animals are capable of interpretation that allowed Thomas Sebeok to conclude that they are also capable of semiosis. Unfortunately, however, it is not clear how far the Peirce model can be extended beyond the animal kingdom, and we already know that we cannot apply it to the cell. The rules of the genetic code have been virtually the same in all living systems and in all environments ever since the origin of life, which clearly shows that they do not depend on interpretation. Luckily, it has been pointed out that semiosis is not necessarily based on interpretation and can be defined exclusively in terms of coding. According to the ‘code model’, a semiotic system is made of signs, meanings and coding rules, all produced by the same codemaker, and in this form it is immediately applicable to the cell. The code model, furthermore, allows us to recognize the existence of many organic codes in living systems, and to divide them into two main types that here are referred to as manufacturing semiosis and signalling semiosis. The genetic code and the splicing codes, for example, take part in processes that actually manufacture biological objects, whereas signal transduction codes and compartment codes organize existing objects into functioning supramolecular structures. The organic codes of single cells appeared in the first three billion years of the history of life and were involved either in manufacturing semiosis or in signalling semiosis. With the origin of animals, however, a third type of semiosis came into being, a type that can be referred to as interpretive semiosis because it became closely involved with interpretation. We realize in this way that the contribution of semiosis to life was far greater than that predicted by the Peirce model, where semiosis is always a means of interpreting the world. Life is essentially about three things: (1) it is about manufacturing objects, (2) it is about organizing objects into functioning systems, and (3) it is about interpreting the world. The idea that these are all semiotic processes, tells us that life depends on semiosis much more deeply and extensively than we thought. We realize in this way that there are three distinct types of semiosis in Nature, and that they gave very different contributions to the origin and the evolution of life.     

Revisiting the Physico-Chemical Hypothesis of Code Origin: An Analysis Based on Code-Sequence Coevolution in a Finite Population

The origin of the genetic code marked a major transition from a plausible RNA world to the world of DNA and proteins and is an important milestone in our understanding of the origin of life. We examine the efficacy of the physico-chemical hypothesis of code origin by carrying out simulations of code-sequence coevolution in finite populations in stages, leading first to the emergence of ten amino acid code(s) and subsequently to 14 amino acid code(s). We explore two different scenarios of primordial code evolution. In one scenario, competition occurs between populations of equilibrated code-sequence sets while in another scenario; new codes compete with existing codes as they are gradually introduced into the population with a finite probability. In either case, we find that natural selection between competing codes distinguished by differences in the degree of physico-chemical optimization is unable to explain the structure of the standard genetic code. The code whose structure is most consistent with the standard genetic code is often not among the codes that have a high fixation probability. However, we find that the composition of the code population affects the code fixation probability. A physico-chemically optimized code gets fixed with a significantly higher probability if it competes against a set of randomly generated codes. Our results suggest that physico-chemical optimization may not be the sole driving force in ensuring the emergence of the standard genetic code.     

Barbieri’s Organic Codes Enable Error Correction of Genomes

Barbieri introduced and developed the concept of organic codes. The most basic of them is the genetic code, a set of correspondence rules between otherwise unrelated sequences: strings of nucleotides on the one hand, polypeptidic chains on the other hand. Barbieri noticed that it implies ‘coding by convention’ as arbitrary as the semantic relations a language establishes between words and outer objects. Moreover, the major transitions in life evolution originated in new organic codes similarly involving conventional rules. Independently, dealing with heredity as communication over time and relying on information theory, we asserted that the conservation of genomes over the ages demands that error-correcting codes make them resilient to casual errors. Moreover, the better conservation of very old parts of the genome demands that they result from combining successively established nested codes such that the older an information, the more numerous component codes protect it. Barbieri’s concept of organic code and that of genomic error-correcting code may seem unrelated. We show however that organic codes actually entail error-correcting properties. Error-correcting, in general, results from constraints being imposed on a set of sequences. Mathematical equalities are conveniently used in communication engineering for expressing constraints but error correction only needs that constraints exist. Biological sequences are similarly endowed with error-correcting ability by physical-chemical or linguistic constraints, thus defining ‘soft codes’. These constraints are moreover presumably efficient for correcting errors. Insofar as biological sequences are subjected to constraints, organic codes necessarily involve soft codes, and their successive onset results in the nested structure we hypothesized. Organic codes are generated and maintained by means of molecular ‘semantic feedback loops’. Each of these loops involves genes which code for proteins, the enzymatic action of which controls a function needed for the protein assembly. Taken together, thus, they control the assembly of their own structure as instructed by the genome and, once closed, these loops ensure their own conservation. However, the semantic feedback loops do not prevent the genome lengthening. It increases both the redundancy of the genome (as an error-correcting code) and the information quantity it bears, thus improving the genome reliability and the specificity of the enzymes, which enables further evolution.     

Is the “Histone Code” an Organic Code?

Post-translational histone modifications and their biological effects have been described as a ‘histone code’. Independently, Barbieri used the term ‘organic code’ to describe biological codes in addition to the genetic code. He also provided the defining criteria for an organic code, but to date the histone code has not been tested against these criteria. This paper therefore investigates whether the histone code is a bona fide organic code. After introducing the use of the term ‘code’ in biology, the criteria a putative organic code such as the histone code must conform to in order to be recognised as an organic code are described. Our current knowledge of histones and their major post-translational modifications, and the specific protein binding domains that recognise and translate these into specific biological effects, is then reviewed in detail. The histone modification system is then placed in the context of an organic code and it is concluded that it fulfils all the requirements of an organic code. The marks produced on histones by processes such as acetylation and methylation act as organic signs that are translated into unique biological effects, their biological meanings. These translations are accomplished by effector proteins that consist of a binding domain that recognises a specific histone mark and a regulatory domain that mediates the biological effect. Crucially, these domains can be experimentally interchanged between different effector proteins, thus altering the rules that specify the relationships between sign and meaning. The effector proteins therefore fulfil the role of adaptor molecules.     

Code Biology – A New Science of Life

Systems Biology and the Modern Synthesis are recent versions of two classical biological paradigms that are known as structuralism and functionalism, or internalism and externalism. According to functionalism (or externalism), living matter is a fundamentally passive entity that owes its organization to external forces (functions that shape organs) or to an external organizing agent (natural selection). Structuralism (or internalism), is the view that living matter is an intrinsically active entity that is capable of organizing itself from within, with purely internal processes that are based on mathematical principles and physical laws. At the molecular level, the basic mechanism of the Modern Synthesis is molecular copying, the process that leads in the short run to heredity and in the long run to natural selection. The basic mechanism of Systems Biology, instead, is self-assembly, the process by which many supramolecular structures are formed by the spontaneous aggregation of their components. In addition to molecular copying and self-assembly, however, molecular biology has uncovered also a third great mechanism at the heart of life. The existence of the genetic code and of many other organic codes in Nature tells us that molecular coding is a biological reality and we need therefore a framework that accounts for it. This framework is Code biology, the study of the codes of life, a new field of research that brings to light an entirely new dimension of the living world and gives us a completely new understanding of the origin and the evolution of life.     

An Alternative Look at Code Evolution: Using Non-canonical Codes to Evaluate Adaptive and Historic Models for the Origin of the Genetic Code

The canonical code has been shown many times to be highly robust against point mutations; that is, mutations that change a single nucleotide tend to result in similar amino acids more often than expected by chance. There are two major types of models for the origin of the code, which explain how this sophisticated structure evolved. Adaptive models state that the primitive code was specifically selected for error minimization, while historic models hypothesize that the robustness of the code is an artifact or by-product of the mechanism of code evolution. In this paper, we evaluated the levels of robustness in existing non-canonical codes as well as codes that differ in only one codon assignment from the standard code. We found that the level of robustness of many of these codes is comparable or better than that of the standard code. Although these results do not preclude an adaptive origin of the genetic code, they suggest that the code was not selected for minimizing the effects of point mutations.     

Phenomenon of Life: Between Equilibrium and Non-Linearity

A model of ordering applicable to biological evolution is presented. It is shown that a steady state (more precisely approaching to a steady state) system of irreversible processes, under conditions of disproportionation of entropy, produces a lower-entropy product, that is, ordering. The ordering is defined as restricting of degrees of freedom: freedom of motion, interactions etc. The model differs from previous ones in that it relates the ordering to processes running not far from equilibrium, described in the linear field of non-equilibrium thermodynamics. It is shown that a system, which includes adenosine triphosphate (ATP) to adenosine diphosphate (ADP) conversion meets the demands of the physical model: it provides energy maintaining steady state conditions, and hydrolysis of ATP proceeding with consumption of water can be tightly conjugated with the most important reactions of synthesis of organic polymers (peptides, nucleotide chains etc.), which proceed with release of water. For these and other reasons ATP seems to be a key molecule of prebiotic evolution. It is argued that the elementary chemical reaction proceeding under control of an enzyme is not necessarily far from equilibrium. The experimental evidence supporting this idea, is presented. It is based on isotope data. Carbon isotope distribution in biochemical systems reveals regularity, which is inherent to steady state systems of chemical reactions, proceeding not far from equilibrium. In living organisms this feature appears at the statistical level, as many completely irreversible and non-linear processes occur in organisms. However not-far-from-equilibrium reactions are inherent to biochemical systems as a matter of principle. They are reconcilable with biochemical behavior. Extant organisms are highly evolved entities which, however, show in their basis the same features, as the simplest chemical systems must have had been involved in the origin of life. Some consequences following from the model, which may be significant for understanding the origin of life and the mechanism of biological evolution, are pointed out.     

生命起源的历程始于何处?--从化学进化到生物进化的探索

生命起源开始于从化学进化进入生物进化．然而,在原始细胞出现之前,已存在一个有蛋白质、核酸等生命要素的过渡期．那么,生命起源的历程究竞从何处开始?对这个未解之迹,进行了讨论．首先,从化学进化到生物进化要实现3个相变,即：从随机的有机化学反应相变为定向代谢途径;从消旋体环境相变为生物手性环境：从化学混沌状态相变为生命耗散结构．通过比较分析发现,由于前生命化学时期出现了丙酮酸．它的独特性质导致了这3种相变同步发生,其中起驱动作用的是定向代谢途径．它起源于以丙酮酸为基质的逆向糖酵解(糖生成途径)．     

The role of alternative genetic codes in viral evolution and emergence

Although the ‘universal’ genetic code is widespread among life-forms, a number of diverse lineages have evolved unique codon reassignments. The proteomes of these organisms and organelles must, by necessity, use the same codon assignments. Likewise, for an exogenous genetic element, such as an infecting viral genome, to be accurately and completely expressed with the host's translation system, it must employ the same genetic code. This raises a number of intriguing questions regarding the origin and evolution of viruses. In particular, it is extremely unlikely that viruses of hosts utilizing the universal genetic code would emerge, via cross-species transmission, in hosts utilizing alternative codes, and vice versa. Consequently, more parsimonious scenarios for the origins of such viruses include the prolonged co-evolution of viruses with cellular life, or the escape of genetic material from host genomes. Further, we raise the possibility that emerging viruses provide the selection pressure favoring the use of alternative codes in potential hosts, such that the evolution of a variant genetic code acts as a unique and powerful antiviral strategy. As such, in the face of new emerging viruses, hosts with codon reassignments would have a significant selective advantage compared to hosts utilizing the universal code.     

The Origin of Cellular Life and Biosemiotics

Recent successes of systems biology clarified that biological functionality is multilevel. We point out that this fact makes it necessary to revise popular views about macromolecular functions and distinguish between local, physico-chemical and global, biological functions. Our analysis shows that physico-chemical functions are merely tools of biological functionality. This result sheds new light on the origin of cellular life, indicating that in evolutionary history, assignment of biological functions to cellular ingredients plays a crucial role. In this wider picture, even if aggregation of chance mutations of replicator molecules and spontaneously self-assembled proteins led to the formation of a system identical with a living cell in all physical respects but devoid of biological functions, it would remain an inanimate physical system, a pseudo-cell or a zombie-cell but not a viable cell. In the origin of life scenarios, a fundamental circularity arises, since if cells are the minimal units of life, it is apparent that assignments of cellular functions require the presence of cells and vice versa. Resolution of this dilemma requires distinguishing between physico-chemical and biological symbols as well as between physico-chemical and biological information. Our analysis of the concepts of symbol, rule and code suggests that they all rely implicitly on biological laws or principles. We show that the problem is how to establish physico-chemically arbitrary rules assigning biological functions without the presence of living organisms. We propose a solution to that problem with the help of a generalized action principle and biological harnessing of quantum uncertainties. By our proposal, biology is an autonomous science having its own fundamental principle. The biological principle ought not to be regarded as an emergent phenomenon. It can guide chemical evolution towards the biological one, progressively assigning greater complexity and functionality to macromolecules and systems of macromolecules at all levels of organization. This solution explains some perplexing facts and posits a new context for thinking about the problems of the origin of life and mind.     

Bootstrapping model of the origin of life

The origin of life is analyzed in terms of the self-facilitating aspect of evolution. According to the self-facilitation (or bootstrap) principle the structure of biological systems becomes increasingly suited to effective evolutionary search through the process of evolution. The principle may be extended to primitive collections of polymers with catalytic properties. The origin of the code may be based on a form of bootstrapping evolution. Once a primitive code appeared it could become more sophisticated through a multi-coding mechanism together with classical Darwinian mechanisms. The bootstrapping principle is also formulated in terms of the fluctuation-instability framework of Prigogine, Nicolis, and Babloyantz. Primitive collections of polymers accumulate evolution-enhancing redundancies which tend to reduce the extent to which they change when destabilized by fluctuation, but which increase the chances that these changes will lead to new predominant regimes. We show that the bootstrapping of evolutionary amenability is accompanied by the accumulation of a thermodynamic load, that is, a free energy cost which reduces the mechanistic efficiency. The bootstrapping effect suggests that the origin of life is most fruitfully approached as a long process during which the capacity to evolve facilitates itself in a step by step fashion rather than as a series of low probability events.     

Quantum microbiology

During his famous 1943 lecture series at Trinity College Dublin, the reknown physicist Erwin Schrodinger discussed the failure and challenges of interpreting life by classical physics alone and that a new approach, rooted in Quantum principles, must be involved. Quantum events are simply a level of organization below the molecular level. This includes the atomic and subatomic makeup of matter in microbial metabolism and structures, as well as the organic, genetic information code of DNA and RNA. Quantum events at this time do not elucidate, for example, how specific genetic instructions were first encoded in an organic genetic code in microbial cells capable of growth and division, and its subsequent evolution over 3.6 to 4 billion years. However, due to recent technological advances, biologists and physicists are starting to demonstrate linkages between various quantum principles like quantum tunneling, entanglement and coherence in biological processes illustrating that nature has exerted some level quantum control to optimize various processes in living organisms. In this article we explore the role of quantum events in microbial processes and endeavor to show that after nearly 67 years, Schr?dinger was prophetic and visionary in his view of quantum theory and its connection with some of the fundamental mechanisms of life.     

Physicochemical Optimization in the Genetic Code Origin as the Number of Codified Amino Acids Increases

We have assumed that the coevolution theory of genetic code origin (Wong JT, Proc Natl Acad Sci USA 72:1909–1912, 1975) is essentially correct. This theory makes it possible to identify at least 10 evolutionary stages through which genetic code organization might have passed prior to reaching its current form. The calculation of the minimization level of all these evolutionary stages leads to the following conclusions. (1) The minimization percentages increased linearly with the number of amino acids codified in the codes of the various evolutionary stages when only the sense changes are considered in the analysis. This seems to favor the physicochemical theory of genetic code origin even if, as discussed in the paper, this observation is also compatible with the coevolution theory. (2) For the first seven evolutionary stages of the genetic code, this trend is less clear and indeed is inverted when we consider the global optimisation of the codes due to both sense changes and synonymous changes. This inverse correlation between minimization percentages and the number of amino acids codified in the codes of the intermediate stages seems to favor neither the physicochemical nor the stereochemical theories of genetic code origin, as it is in the early and intermediate stages of code development that these theories would expect minimization to have played a crucial role, and this does not seem to be the case. However, these results are in agreement with the coevolution theory, which attributes a role to the physicochemical properties of amino acids that, while important, is nevertheless subordinate to the mechanism which concedes codons from the precursor amino acids to the product amino acids as the primary factor determining the evolutionary structuring of the genetic code. The results are therefore discussed in the context of the various theories proposed to explain genetic code origin. Received: 25 October 1998 / Accepted: 19 February 1999     

No accident: genetic codes freeze in error-correcting patterns of the standard genetic code

The standard genetic code poses a challenge in understanding the evolution of information processing at a fundamental level of biological organization. Genetic codes are generally coadapted with, or 'frozen' by, the protein-coding genes that they translate, and so cannot easily change by natural selection. Yet the standard code has a significantly non-random pattern that corrects common errors in the transmission of information in protein-coding genes. Because of the freezing effect and for other reasons, this pattern has been proposed not to be due to selection but rather to be incidental to other evolutionary forces or even entirely accidental. We present results from a deterministic population genetic model of code-message coevolution. We explicitly represent the freezing effect of genes on genetic codes and the perturbative effect of changes in genetic codes on genes. We incorporate characteristic patterns of mutation and translational error, namely, transition bias and positional asymmetry, respectively. Repeated selection over small successive changes produces genetic codes that are substantially, but not optimally, error correcting. In particular, our model reproduces the error-correcting patterns of the standard genetic code. Aspects of our model and results may be applicable to the general problem of adaptation to error in other natural information-processing systems.     

Prions: an evolutionary perspective.

Studies in both prion-due diseases in mammals and some non-Mendelian hereditary processes in yeasts have demonstrated that certain proteins are able to transmit structural information and self-replication. This induces the corresponding conformational changes in other proteins with identical or similar sequences. This ability of proteins may have been very useful during prebiotic chemical evolution, prior to the establishment of the genetic code. During this stage, proteins (proteinoids) must have molded and selected their structural folding units through direct interaction with the environment. The proteinoids that acquired the ability to propagate their conformations (which we refer to as conformons) would have acted as reservoirs and transmitters of a given structural information and hence could have acted as selectors for conformational changes. Despite the great advantage that arose from the establishment of the genetic code, the ability to propagate conformational changes did not necessarily disappear. Depending on the degree of involvement of this capacity in biological evolution, we propose two not mutually exclusive hypotheses: (i) extant prions could be an atavism of ancestral conformons, which would have co-evolved with cells, and (ii) the evolution of conformons would have produced cellular proteins, able to transmit structural information, and, in some cases, participating in certain processes of regulation and epigenesis. Therefore, prions could also be seen as conformons of a conventional infectious agent (or one that co-evolved with it independently) that, after a longer or shorter adaptive period, would have interacted with conformons from the host cells.     

Symmetry preservation in the evolution of the genetic code

The standard genetic code is found to exhibit an exact symmetry under a finite group of order 4 known in mathematics as the Klein group. The same symmetry is also present in almost all non-standard codes, mitochondrial as well as nuclear. Analysis of the phylogenetic tree for the evolution of the mitochondrial codes reveals that all changes along the main line of evolution preserve this symmetry, with a tendency towards symmetry enhancement. In the side branches of the evolutionary tree, the majority of changes also respect the symmetry. The few exceptional cases where it is broken correspond to reassignments that appear to be unstable or incomplete. Since the Klein group emerges naturally from the symplectic model for the prebiotic evolution that has led to the standard code, we interpret these results as lending support to the hypothesis that this symmetry has been selected during the evolution of the genetic code, not only before but also after establishment of the standard code.     

Thermodynamics in the present progressive mode and its role in the context of the origin of life.

The origin and evolution of biological organizations proceeding on Earth are put in a nonequilibrium thermodynamic framework within a cosmological context. The dynamic process responsible for chemical evolution leading to the origin of biological being depends upon consumer-dominating thermodynamics, in which the heat sink is taken to be active in extracting heat energy from a body at a higher temperature. Consumer-dominating thermodynamics follows from the fact that when a small hot body contacts a cold heat sink, it decreases the temperature at the possible fastest rate. The fastest temperature drop, when applied to chemical products being synthesized through the energy supplied from an external heat source, is selective in keeping only those products that can decrease the temperature at the fastest rate among the available alternatives. Synthesis of small organic molecules in the small ice grains in interstellar diffuse clouds irradiated by ultraviolet radiation is a representative case of consumer-dominating thermodynamics, in which diffuse clouds serve as cold heat sinks in the cosmological context. Another case of consumer-dominating thermodynamics predominant on Earth especially in the perspective of the origin and evolution of life is with submarine hydrothermal vents, in which the surrounding cold seawater constantly serves as the cold heat sink.