Taking the Relational Turn: Biosemiotics and Some New Trends in Biology

A cluster of similar trends emerging in separate fields of science and philosophy points to new opportunities to apply biosemiotic ideas as tools for conceptual integration in theoretical biology. I characterize these developments as the outcome of a “relational turn” in these disciplines. They signal a shift of attention away from objects and things and towards relational structures and processes. Increasingly sophisticated research technologies of molecular biology have generated an enormous quantity of experimental data, sparking a need for relational approaches that could help to find recurrent patterns in the mass of data. Earlier conceptions of relational biology and cybernetics, once deemed too abstract and speculative, are now resurrected and applied by means of new computational and simulation tools. I think this receptivity should be extended to incorporate nets of semiotic relations as heuristic guides for discerning global patterns of interactions in living systems. In this article I review aspects of systems biology and new directions in evolutionary theory, focusing on the role of circular and downward causation in relational structures and dynamical networks. I also indicate promising avenues of integration of some ideas of biosemiotics with those emerging from these new currents in biology. Relational developments in biology bear a telling similarity to a parallel relational turn presently manifest in the philosophy of science, rooted in the philosophy of physics and mathematics and in different varieties of structural and informational realism. The recognition of the relational nature of reality within these disciplines entails a tacit repudiation of nominalistic biases in science that have hindered the reception of semitiotic conceptions in biology. In previous investigations I explored connections between two kinds of relational structures: the networks of self-referential circular loops that appear pervasively in living systems, and the triadic relational structures that Peircean semiotics places at the basis of all semiotic transactions. Current relational views in the sciences seem oblivious to the difference between dyadic and triadic relations. Incorporating this essential distinction from biosemiotics into other fields could be a first step in seizing the opportunities opened by the relational turn for a renewal of biology and of natural philosophy in general, across disciplinary boundaries.     

On the Semio-Mathematical Nature of Codes

The relational structure of RNA, DNA, and protein bears an interesting similarity to the determination problem in category theory. In this paper, we present this deep-structure similarity and use it as a springboard for discussing some abstract properties of coding in various systems. These abstract properties, in turn, may shed light on the evolution of the DNA world from a semiotic perspective. According to the perspective adopted in this paper, living systems are not information processing systems but “meaning-making” systems. Therefore, what flows in the genetic system is not “information” but “value.” We define meaning, meaning-making, and value and then use these terms to explain the abstract dynamics of coding, which can illuminate many forms of sign-mediated activities in biosystems.     

Confrontation of the Cybernetic Definition of a Living Individual with the Real World

The cybernetic definition of a living individual proposed previously (Korzeniewski, 2001) is very abstract and therefore describes the essence of life in a very formal and general way. In the present article this definition is reformulated in order to determine clearly the relation between life in general and a living individual in particular, and it is further explained and defended. Next, the cybernetic definition of a living individual is confronted with the real world. It is demonstrated that numerous restrictions imposed on the cybernetic definition of life by physical reality imply a number of particular properties of life that characterize present life on Earth, namely: (1) a living individual must be a dissipative structure (and therefore a low-entropy thermodynamic system out of the state of equilibrium); (2) spontaneously-originated life must be based on organic compounds; (3) evolutionarily stable self-dependent, free-living individuals must have some minimal level of complexity of structure and function; (4) a living individual must have a record of identity separated from an executive machinery; (5) the identity of living individuals must mutate and may evolve; (6) living individuals may collect and accumulate information in subsequent generations over very long periods of time; (7) the degree of complexity of a living individual reflects the degree of complexity of its environment (ecological niche) and (8) living individuals are capable of supple adaptation to varying environmental conditions. Thus, the cybernetic definition of a living individual, when confronted with the real physical world, generates most of the general properties of the present life on Earth.     

Multiscale Analysis of Biological Systems

It is argued that multiscale approaches are necessary for an explanatory modeling of biological systems. A first step, besides common to the multiscale modeling of physical and living systems, is a bottom-up integration based on the notions of effective parameters and minimal models. Top-down effects can be accounted for in terms of effective constraints and inputs. Biological systems are essentially characterized by an entanglement of bottom-up and top-down influences following from their evolutionary history. A self-consistent multiscale scheme is proposed to capture the ensuing circular causality. Its differences with standard mean-field self-consistent equations and slow-fast decompositions are discussed. As such, this scheme offers a way to unravel the multilevel architecture of living systems and their regulation. Two examples, genome functions and biofilms, are detailed.     

Mechanisms of same/different concept learning in primates and avians

Mechanisms of same/different concept learning by rhesus monkeys, capuchin monkeys, and pigeons were studied in terms of how these species learned the task (e.g., item-specific learning versus relational learning) and how rapidly they learned the abstract concept, as the training set size was doubled. They had similar displays, training stimuli, test stimuli, and contingencies. The monkey species learned the abstract concept at similar rates and more rapidly than pigeons, thus showing a quantitative difference across species. All species eventually showed full concept learning (novel-stimulus transfer equivalent to baseline: 128-item set size for monkeys; 256-item set for pigeons), thus showing a qualitative similarity across species. Issues of stimulus regularity/symmetry, generalization from item pairs, and familiarity processing were not considered to be major factors in the final performances, converging on the conclusion that these species were increasingly controlled by the sample-test relationship (i.e., relational processing) leading to full abstract-concept learning.     

Abstract mathematical molecular biology: II some relational consequences of the “one gene-one enzyme” hypothesis

Following the program outlined in a previous paper (Bull. Math. Biophysics,23, 237–260, 1961), a further abstract study is made of some simple relational systems which possess some properties of living organisms. It is shown that the “one gene-one enzyme” hypothesis leads to the conclusion that either all genes are built of the same chemical building blocks, or that at least all genes have a number of building blocks in common. A consistent relational application of the “one gene-one enzyme” hypothesis leads moreover to the conclusion that replication is not an inherent property of a gene. Rather there must be a set of enzymes which “copy” the genes. The number of enzymes in this set must be less than the number of genes and therefore the activity of those “copying” enzymes cannot be absolutely specific.     

SIZE AND SHAPE TRANSFORMATIONS CORRELATED WITH OXIDATIVE PHOSPHORYLATION IN MITOCHONDRIA : II. Structural Changes in Mitochondrial Membrane Fragments

It has been demonstrated that the nature of the physical change in mitochondrial membrane fragments associated with the action of the respiratory enzymes is likely one of shape or symmetry rather than size. The findings suggest that in the state of decreased scattering the macromolecules may be present in an extended physical state. Conditions favorable for phosphorylation may give rise to a folding or contraction of the molecular complex to a more symmetrical structure. Since earlier studies have shown that there is a compulsory relationship between the integrity of systems operative in oxidative phosphorylation and scattering changes, experiments of this type may lead to values for the minimal size of a phosphorylating unit, which at present is estimated to be 2.1 x 10⁶ from light-scattering studies.     

Allostery in very large molecular assemblies

In contrast to small allosteric systems (like hemoglobin) those containing very large numbers (n) of binding sites never exhibit cooperativity (as measured by the Hill coefficient, nH) even approaching the potential limit, n. The reason for this appears to be that in such macromolecules the cooperative unit always represents some sub-structure of the entire structure. On the other hand, it is frequently observed that such sub-structures, when isolated, do not exhibit cooperativity at all. This paper describes studies of some molluscan hemocyanins that explore this apparent anomaly. It is concluded that it is the higher order structure of the molecule that provides a framework within which the sub-structures may exhibit their allosteric behavior.     

Surfactant Assemblies and their Various Possible Roles for the Origin(S) of Life

A large number of surfactants (surface active molecules) are chemically simple compounds that can be obtained by simple chemical reactions, in some cases even under presumably prebiotic conditions. Surfactant assemblies are self-organized polymolecular aggregates of surfactants, in the simplest case micelles, vesicles, hexagonal and cubic phases. It may be that these different types of surfactant assemblies have played various, so-far underestimated important roles in the processes that led to the formation of the first living systems.Although nucleic acids are key players in the formation of cells as we know them today (RNA world hypothesis), it is still unclear how RNA could have been formed under prebiotic conditions. Surfactants with their self-organizing properties may have assisted, controlled and compartimentalized some of the chemical reactions that eventually led to the formation of molecules like RNA. Therefore, surfactants were possibly very important in prebiotic times in the sense that they may have been involved in different physical and chemical processes that finally led to a transformation of non-living matter to the first cellular form(s) of life. This hypothesis is based on four main experimental observations: (i) Surfactant aggregation can lead to cell-like compartimentation (vesicles). (ii) Surfactant assemblies can provide local reaction conditions that are very different from the bulk medium, which may lead to a dramatic change in the rate of chemical reactions and to a change in reaction product distributions. (iii) The surface properties of surfactant assemblies that may be liquid- or solid-like, charged or neutral, and the elasticity and packing density of surfactant assemblies depend on the chemical structure of the surfactants, on the presence of other molecules, and on the overall environmental conditions (e. g. temperature). This wide range of surface characteristics of surfactant assemblies may allow a control of surface-bound chemical reactions not only by the charge or hydrophobicity of the surface but also by its “softness”. (iv) Chiral polymolecular assemblies (helices) may form from chiral surfactants.There are many examples that illustrate the different roles and potential roles of surfactant assemblies in different research areas outside of the field of the origin(s) of life, most importantly in investigations of contemporary living systems, in nanotechnology applications, and in the development of drug delivery systems. Concepts and ideas behind many of these applications may have relevance also in connection to the different unsolved problems in understanding the origin(s) of life.     

Genetic diversity and hierarchical population structure of a rare autotetraploid plant,Aster kantoensis (Asteraceae)

We sampled 17 populations of a rare autotetraploid Aster kantoensis (Asteraceae) from three river systems located in central Japan, and studied them for allelic variation at 22 enzyme loci. There was no significant correlation between the actual population size and three genetic diversity parameters, suggesting that the effective population size was very small even for the large populations, i.e., even large populations may still have a high probability of being of recent origin and remain influenced by the founder effect. Compared to other autotetraploid species, the total genetic variation of A. kantoensis is small. The number of alleles and gene diversity of a population were not significantly different among the river systems, although the percentage of polymorphic loci was different. Genetic differentiation among river systems was larger than between populations within the river systems, thereby indicating that gene flow between river systems is small, especially between the Kinu River system and Tama or Sagami River systems.     

Generation of valuable information and the problem of goal self-setting in living systems

The problem of origination of capacity for goal self-setting is discussed. It was shown that the definition "goal" in living systems differs from the definition "target function" in physical problems concerned with nonliving systems. It was also shown that the main goal of the elements of a system is the storage of information. In biology, this goal is the extension of the principle of struggle for existence. Conditions were determined that the dynamic system describing the goal self-setting process must satisfy. It was shown that living systems meet these conditions. In inorganic nature, such systems may also arise but only as a result of long-term evolution, after which they become living.     

Cotranslational Folding of a Pentarepeat β-Helix Protein

It is becoming increasingly clear that many proteins start to fold cotranslationally before the entire polypeptide chain has been synthesized on the ribosome. One class of proteins that a priori would seem particularly prone to cotranslational folding is repeat proteins, that is, proteins that are built from an array of nearly identical sequence repeats. However, while the folding of repeat proteins has been studied extensively in vitro with purified proteins, only a handful of studies have addressed the issue of cotranslational folding of repeat proteins. Here, we have determined the structure and studied the cotranslational folding of a β-helix pentarepeat protein from the human pathogen Clostridium botulinum—a homolog of the fluoroquinolone resistance protein MfpA—using an assay in which the SecM translational arrest peptide serves as a force sensor to detect folding events. We find that cotranslational folding of a segment corresponding to the first four of the eight β-helix coils in the protein produces enough force to release ribosome stalling and that folding starts when this unit is ~ 35 residues away from the P-site, near the distal end of the ribosome exit tunnel. An additional folding transition is seen when the whole PENT moiety emerges from the exit tunnel. The early cotranslational formation of a folded unit may be important to avoid misfolding events in vivo and may reflect the minimal size of a stable β-helix since it is structurally homologous to the smallest known β-helix protein, a four-coil protein that is stable in solution.     

Auditory Same/Different Concept Learning and Generalization in Black-Capped Chickadees (Poecile atricapillus)

Abstract concept learning was thought to be uniquely human, but has since been observed in many other species. Discriminating same from different is one abstract relation that has been studied frequently. In the current experiment, using operant conditioning, we tested whether black-capped chickadees (Poecile atricapillus) could discriminate sets of auditory stimuli based on whether all the sounds within a sequence were the same or different from one another. The chickadees were successful at solving this same/different relational task, and transferred their learning to same/different sequences involving novel combinations of training notes and novel notes within the range of pitches experienced during training. The chickadees showed limited transfer to pitches that was not used in training, suggesting that the processing of absolute pitch may constrain their relational performance. Our results indicate, for the first time, that black-capped chickadees readily form relational auditory same and different categories, adding to the list of perceptual, behavioural, and cognitive abilities that make this species an important comparative model for human language and cognition.     

Quantum entanglement in photoactive prebiotic systems

This paper contains the review of quantum entanglement investigations in living systems, and in the quantum mechanically modelled photoactive prebiotic kernel systems. We define our modelled self-assembled supramolecular photoactive centres, composed of one or more sensitizer molecules, precursors of fatty acids and a number of water molecules, as a photoactive prebiotic kernel systems. We propose that life first emerged in the form of such minimal photoactive prebiotic kernel systems and later in the process of evolution these photoactive prebiotic kernel systems would have produced fatty acids and covered themselves with fatty acid envelopes to become the minimal cells of the Fatty Acid World. Specifically, we model self-assembling of photoactive prebiotic systems with observed quantum entanglement phenomena. We address the idea that quantum entanglement was important in the first stages of origins of life and evolution of the biospheres because simultaneously excite two prebiotic kernels in the system by appearance of two additional quantum entangled excited states, leading to faster growth and self-replication of minimal living cells. The quantum mechanically modelled possibility of synthesizing artificial self-reproducing quantum entangled prebiotic kernel systems and minimal cells also impacts the possibility of the most probable path of emergence of protocells on the Earth or elsewhere. We also examine the quantum entangled logic gates discovered in the modelled systems composed of two prebiotic kernels. Such logic gates may have application in the destruction of cancer cells or becoming building blocks of new forms of artificial cells including magnetically active ones.     

Quantifying the roles of space and stochasticity in computer simulations for cell biology and cellular biochemistry

Most of the fascinating phenomena studied in cell biology emerge from interactions among highly organized multimolecular structures embedded into complex and frequently dynamic cellular morphologies. For the exploration of such systems, computer simulation has proved to be an invaluable tool, and many researchers in this field have developed sophisticated computational models for application to specific cell biological questions. However, it is often difficult to reconcile conflicting computational results that use different approaches to describe the same phenomenon. To address this issue systematically, we have defined a series of computational test cases ranging from very simple to moderately complex, varying key features of dimensionality, reaction type, reaction speed, crowding, and cell size. We then quantified how explicit spatial and/or stochastic implementations alter outcomes, even when all methods use the same reaction network, rates, and concentrations. For simple cases, we generally find minor differences in solutions of the same problem. However, we observe increasing discordance as the effects of localization, dimensionality reduction, and irreversible enzymatic reactions are combined. We discuss the strengths and limitations of commonly used computational approaches for exploring cell biological questions and provide a framework for decision making by researchers developing new models. As computational power and speed continue to increase at a remarkable rate, the dream of a fully comprehensive computational model of a living cell may be drawing closer to reality, but our analysis demonstrates that it will be crucial to evaluate the accuracy of such models critically and systematically.     

Optimal choice of species and size class for transplanting coral community

Transplantation of sessile organisms living in a planned destruction site to a safe site is an important means of restoration to mitigate biodiversity loss following anthropogenic developments. In particular, corals, which play fundamental roles in the coral reef ecosystem and contribute to biodiversity, are good candidates for transplantation. In this study, we investigate the optimal choice of species and size class to be used for coral transplantation. We first studied a case in which the objective function to evaluate the success of transplantation is the maximum total coverage. The optimal strategy is to choose the species and size class with higher net coverage gain per unit handling effort. It is often recommended to transplant only one or a few species and neglect others, even if the original community consists of many species. This may achieve high coverage in the restored coral community but cause loss of species diversity. To overcome this problem, we next study a case in which the objective of the transplantation operation is to maximize the “prosperity index”, defined as the product of total coverage and species diversity. In this case, the optimal strategy depends on the species property, population size, and the limitation of total cost allowed for transplantation, but it tends to recommend more species to be transplanted than what is recommended by the coverage maximization criterion. We conclude that maximization of the prosperity index is a better criterion for transplantation than simple coverage maximization.     

Structures in systems biology

Oil and water do not normally mix, and apparently structural biology and systems biology look like two different universes. It can be argued that structural biology could play a very important role in systems biology. Although at the final stage of understanding a signal transduction pathway, a cell, an organ or a living system, structures could be obviated, we need them to be able to reach that stage. Structures of macromolecules, especially molecular machines, could provide quantitative parameters, help to elucidate functional networks or enable rational designed perturbation experiments for reverse engineering. The role of structural biology in systems biology should be to provide enough understanding so that macromolecules can be translated into dots or even into equations devoid of atoms.     

Life,information theory,probability, and physics

A purely information-theoretical approach to the problem of self-replication of elementary living units implies that pure chance is the determining factor in the formation of the first living unit. The probability of such a spontaneous formation can be calculated from the minimum amount of information which an organism must possess in order to replicate itself. An estimation of this amount of information is made here by two different methods. First by a “paper and pencil experiment” which indicates the minimum amount of information needed on a printed page in order that with given tools the page could be reproduced. Second—by an analytical consideration of some hypothetical molecular mechanisms. A general method for handling such problems is suggested. On the basis of estimated information contents it is shown that under most favorable conditions the probability of a spontaneous generation by pure chance during the lifetime of the earth is vanishingly small. It is concluded that dynamic factors, which may reduce tremendously the information content, must play a role in the genesis of life on earth.     

Aquatic insect larvae as indicators of limiting minimal contents of dissolved oxygen

Minimal concentrations of oxygen are limiting factors for limnic biocenoses. It should therefore be possible to use biocenose structure to infer minimal oxygen concentrations that have occured, provided the tolerance of the organisms concerned is known. A simple apparatus used to measure LC₅₀ of oxygen for aquatic insect larvae with tracheal gills is described. Lethal concentrations found in some Ephemeroptera differ between species. Usually, they are strongly temperature dependent. In the species so far studied, confidence intervals are very small and suggest that such insect larvae could be used as bioindicators of minimal oxygen concentrations (even of short term ones), especially in thermically stable waters.