Suggestion for a possible approach to molecular biology

A hypothetical “self-reproducing living molecule” has been recently frequently discussed in the literature. A physical theory of such a molecule is tentatively outlined. The relational, rather than the quantitative, aspects of the process are emphasized. The process of synthesis of such a molecule from its components is considered as a transition of a complex system between two quantum-mechanical states. The requirement that a “living molecule” should be able to multiply only by self-reproduction but not by a formationde novo leads to the conclusion that the above mentioned transition is a forbidden one. A constellation of conditions under which the forbiddenness is lifted by the presence of an already existing “living molecule” is suggested. The outlined mechanism leads to the conclusion that the property of self-reproduction does not so much reside in the self-reproducing molecule itself as in its relations to other molecules of a system.     

Self-reproduction and serial message transfer: Two related problems

For a certain class of physical machines, termed “structure-determined,” the problem of self-reproduction can be reduced to the problem of serial message reproduction. Serial message reproduction however presupposes a sort of “open system” constraint. This leads to the principle of pseudo, or exogenously standardized, respectively, self-reproduction. It seems to be consistent with both chemical and biological self-reproduction. It thus may reflect a general principle of biological design. The proposed principle is a physico chemical analog to Robert Rosen's abstract relational self-reproduction constraint.     

Mirror symmetry breaking in biochemical evolution

The problem of origination of molecular asymmetry in biochemical evolution is discussed. The theoretical analysis shows that chiral purity of biomolecules has the biological significance for self-reproduction of organisms. The models of spontaneous symmetry-breaking in molecular systems are given. The aspects of various stages of biochemical evolution associated with the development of chiral polarization are analysed.     

Mirror symmetry breaking in biochemical evolution.

The problem of origination of molecular asymmetry in biochemical evolution is discussed. The theoretical analysis shows that chiral purity of biomolecules has the biological significance for self-reproduction of organisms. The models of spontaneous symmetry-breaking in molecular systems are given. The aspects of various stages of biochemical evolution associated with the development of chiral polarization are analysed.     

Organismic sets: Outline of a general theory of biological and social organisms

The discussion as to whether societies are organisms andvice versa has been going on for a long time. The question is meaningless unless a clear definition of the term “organism” is made. Once such a definition is made, the question may be answered by studying whether there exists any relational isomorphism between what the biologist calls an organism and what the sociologist calls society. Such a study should also include animal societies studied by ecologists. Both human and animal societies are sets of individuals together with certain other objects which are the products of their activities. A multicellular organism is a set of cells together with some products of their activities. A cell itself may be regarded as a set of genes together with the products of their activities because every component of the cell is either directly or indirectly the result of the activities of the genes. Thus it is natural to define both biological and social organisms as special kinds of sets. A number of definitions are given in this paper which define what we call here organismic sets. Postulates are introduced which characterize such sets, and a number of conclusions are drawn. It is shown that an organismic set, as defined here, does represent some basic relational aspects of both biological organisms and societies. In particular a clarification and a sharpening of the Postulate of Relational Forces given previously (Bull. Math. Biophysics,28, 283–308, 1966) is presented. It is shown that from the basic definitions and postulates of the theory of organismic sets, it folows that only such elements of those sets will aggregate spontaneously, which are not completely “specialized” in the performance of only one activity. It is further shown that such “non-specialized” elements undergo a process of specialization, and as a result of it their spontaneous aggregation into organismic sets becomes impossible. This throws light on the problem of the origin of life on Earth and the present absence of the appearance of life by spontaneous generation. Some applications to problems of ontogenesis and philogenesis are made. Finally the relation between physics, biology, and sociology is discussed in the light of the theory of organismic sets.     

Self-replicating micelles — A chemical version of a minimal autopoietic system

Reverse micelles hosting the internal production of the surfactant are proposed as experimentally feasible models of simple (or minimal) autopoietic systems. We describe the conditions under which these may be formed and their possible biological implications. The micellar systems considered here turn out also to exhibit a capacity for self-reproduction through fragmentation under plausible conditions, thus constituting also a minimal experimental model for prebiotic self-reproduction.     

An axiomatic explanation of complete self-reproduction

A similarity between the concepts of reproduction and explanation is observed which implies a similarity between the less well understood concepts of complete self-reproduction and complete self-explanation. These latter concepts are shown to be independent from ordinary logical-mathematical-biological reasoning, and a special form of complete self-reproduction is shown to be axiomatizable. Involved is the question whether there exists a function that belongs to its own domain or range. Previously, Wittgenstein has argued, on intuitive grounds, that no function can be its own argument. Similarly, Rosen has argued that a paradox is implied by the notion of a function which is a member of its own range. Our result shows that such functions indeed are independent from ordinary logical-mathematical reasoning, but that they need not imply any inconsistencies. Instead such functions can be axiomatized, and in this sense they really do exist. Finally, the introduced notion of complete self-reproduction is compared with “self-reproduction” of ordinary biological language. It is pointed out that complete self-reproduction is primarily of interest in connection with formal theories of evolution.     

Complex adaptation and system structure

The structural organization of biological systems is one of nature’s most fascinating aspects, but its origin and functional role is not yet fully understood. For instance, basic adaptational mechanisms like genetic mutation and Hebbian adaptation seem to be generic and invariant across many species and are, on their own, fairly well investigated and understood. However, it is the organism’s structure – the representations these mechanisms act upon – that bears the complex functional effects of these mechanisms. While typical technical approaches to system design require detailed problem models and suffer from the need to explicitly take care of all possible cases, the organization of biological systems seems to induce inherent adaptability, flexibility and robustness. In this discussion paper we address the concept of structured variability, particularly the role of system structure as implementing a certain representation on which basic variational mechanisms act on. The functional adaptability (or search distribution) depends crucially on this representation.     

Replication in abstract and natural systems

Real reproducing systems are contrasted with cellular automata-based models of self-reproduction. It is argued that the reproduction described by the latter is trivial compared to its biological counterpart. The paper explores a few reasons and consequences of this situation, along with a discussion on different forms of the basic reproduction (and construction) process.     

Robustness as a non‐localizable relational phenomenon

A current challenge in neuroscience, systems and theoretical biology is to understand what properties allow organisms to exhibit and sustain behaviours despite perturbations (behavioural robustness). Indeed, there are still significant theoretical difficulties in this endeavour due to the context‐dependent nature of the problem. Contrary to the common view of biological robustness as a phenomenon that emerges internally, this article discusses the hypothesis that behavioural robustness is rooted in dynamical processes that distribute between internal controls, the organism body and the environment. This review highlights the varied perspectives and how they have led to the current focus on robustness as a relational phenomenon. A new perspective is proposed in which robustness is better understood in the context of agent‐environment dynamical couplings, in which such couplings are not always the full determinants of robustness. The challenges and limitations of the proposed approach are identified.     

Genetic variation: molecular mechanisms and impact on microbial evolution

On the basis of established knowledge of microbial genetics one can distinguish three major natural strategies in the spontaneous generation of genetic variations in bacteria. These strategies are: (1) small local changes in the nucleotide sequence of the genome, (2) intragenomic reshuffling of segments of genomic sequences and (3) the acquisition of DNA sequences from another organism. The three general strategies differ in the quality of their contribution to microbial evolution. Besides a number of non-genetic factors, various specific gene products are involved in the generation of genetic variation and in the modulation of the frequency of genetic variation. The underlying genes are called evolution genes. They act for the benefit of the biological evolution of populations as opposed to the action of housekeeping genes and accessory genes which are for the benefit of individuals. Examples of evolution genes acting as variation generators are found in the transposition of mobile genetic elements and in so-called site-specific recombination systems. DNA repair systems and restriction-modification systems are examples of modulators of the frequency of genetic variation. The involvement of bacterial viruses and of plasmids in DNA reshuffling and in horizontal gene transfer is a hint for their evolutionary functions. Evolution genes are thought to undergo biological evolution themselves, but natural selection for their functions is indirect, at the level of populations, and is called second-order selection. In spite of an involvement of gene products in the generation of genetic variations, evolution genes do not programmatically direct evolution towards a specific goal. Rather, a steady interplay between natural selection and mixed populations of genetic variants gives microbial evolution its direction.     

Bootstrapping on the adaptive landscape.

Different versions of a gene or of a multigenic system may be essentially equivalent so far as the specific function of the structures which they code for or control is concerned, but very different with respect to their amenability to evolution. The structural features which increase evolutionary amenability are a disadvantage to the organism in terms of energy. Nevertheless, they accumulate in the course of evolution as a consequence of hitchhiking along with the desirable traits whose evolution they make possible. This is the bootstrap principle of evolutionary adaptability. In terms of the adaptive landscape bootstrapping corresponds to populations evolving in such a way that they occupy regions of the landscape which are more amenable to evolutionary hill climbing. The bootstrapping idea has implications for structure-function relations in a number of complex biological information processing systems, including biochemical systems, the immune system, and the brain. Bootstrapping is also discussed in connection with the origin of information processing (the origin of life) and in connection with possible designs for macromolecular computing systems.     

Multiple relational equilibria: Polymorphism,metamorphosis and other possibly similar phenomena

In a preceding paper (Rashevsky, 1969. “Outline of a Unified Approach to Physics, Biology and Sociology.”Bulletin of Mathematical Biophysics,31, 159–198) certain isomorphisms between biological and social systems on the one hand and physical systems on the other were studied. The notion or relational forces, of which ordinary physical forces are a particular case, was introduced. In the present paper an attempt is made to establish analogies between stable equilibria in physical systems, equilibria due to physical forces, and stable equilibria in biological and social systems which are due to purely relational forces. The notion of relational forces causing multiple equilibria similar to multiple equilibria in some physical systems is studied, and it is outlined how this notion may possibly help the understanding of such phenomena as polymorphism, metamorphosis and the existence of rudimentary organs or rudimentary functions.     

生物鲁棒性的研究进展

生物鲁棒性是指在受到外部扰动或内部参数摄动等不确定因素干扰时,生物系统保持其结构和功能稳定的一种特性。目前已经发现生物鲁棒性普遍存在于生物系统整体、器官、细胞、分子等各种层次,如细菌趋化、细胞周期、细胞信号通讯、基因突变、生物发育、基因网络等等。产生生物鲁棒性的作用机制主要是生物系统的反馈、冗余、模块和结构稳定等。稳定鲁棒性和品质鲁棒性是生物鲁棒性研究的两个重要命题,数学模型是生物鲁棒性研究的重要手段。认识生物鲁棒性对癌症、MDS、糖尿病等疾病的发生、发展和治疗有重要意义。丈章从上述几个方面综述了生物鲁棒性的研究进展。     

Genes, genome and Gestalt

According to Gestalt thinking, biological systems cannot be viewed as the sum of their elements, but as processes of the whole. To understand organisms we must start from the whole, observing how the various parts are related. In genetics, we must observe the genome over and above the sum of its genes. Either loss or addition of one gene in a genome can change the function of the organism. Genomes are organized in networks of genes, which need to be well integrated. In the case of genetically modified organisms (GMOs), for example, soybeans, rats, Anopheles mosquitoes, and pigs, the insertion of an exogenous gene into a receptive organism generally causes disturbance in the networks, resulting in the breakdown of gene interactions. In these cases, genetic modification increased the genetic load of the GMO and consequently decreased its adaptability (fitness). Therefore, it is hard to claim that the production of such organisms with an increased genetic load does not have ethical implications.     

Cancer as an emergent phenomenon in systems radiation biology

Radiation-induced DNA damage elicits dramatic cell signaling transitions, some of which are directed towards deciding the fate of that particular cell, while others lead to signaling to other cells. Each irradiated cell type and tissue has a characteristic pattern of radiation-induced gene expression, distinct from that of the unirradiated tissue and different from that of other irradiated tissues. It is the sum of such events, highly modulated by genotype that sometimes leads to cancer. The challenge is to determine as to which of these phenomena have persistent effect that should be incorporated into models of how radiation increases the risk of developing cancer. The application of systems biology to radiation effects may help to identify which biological responses are significant players in radiation carcinogenesis. In contrast to the radiation biology paradigm that focuses on genomic changes, systems biology seeks to integrate responses at multiple scales (e.g. molecular, cellular, organ, and organism). A key property of a system is that some phenomenon emerges as a property of the system rather than of the parts. Here, the idea that cancer in an organism can be considered as an emergent phenomenon of a perturbed system is discussed. Given the current research goal to determine the consequences of high and low radiation exposures, broadening the scope of radiation studies to include systems biology concepts should benefit risk modeling of radiation carcinogenesis. Presented at the First International Workshop on Systems Radiation Biology, February 14–16 2007, GSF-Research Centre, Neuherberg, Germany.     

Macromolecular Synthesis and Thymineless Death in Mycoplasma laidlawii B

The relationships between macromolecular synthesis and viability have been studied in the pleuropneumonia-like organism Mycoplasma laidlawii B adapted to a semidefined grwoth medium. This organism exhibited an absolute growth requirement for the nucleosides uridine and thymidine, a partial requirement for guanosine and deoxyguanosine, but no requirement for adenosine, deoxyadenosine, cytosine, and deoxycytosine. Cytosine and deoxycytosine partially satisfied the requirement for uridine. Loss in viability resulted from thymidine deprivation, but not from a deficiency in other growth requirements. This phenomenon of thymineless death in a mycoplasma is similar in many respects to that reported in other bacterial systems. Chloramphenicol specifically inhibited protein synthesis and allowed deoxyribonucleic acid synthesis to proceed to only about 40% of that normally produced per generation period, while causing less inhibition of ribonucleic acid synthesis. Protein synthesis inhibition permitted thymineless death to a survival level of less than 0.5%, but ribonucleic acid synthesis inhibition resulted in a higher (10%) survival level. These results are consistent with previously noted aspects of thymineless death in Escherichia coli strains, which suggest that thymineless death is coupled to ribonucleic acid synthesis.     

Cell shape: taking the heat

Preservation of cell architecture under physically stressful conditions is a basic requirement for many biological processes and is critical for mechanosensory systems built to translate subtle changes in cell shape into changes in organism behaviour. A new study reveals how an extracellular protein--Spam--helps mechanosensory organs in the fruit fly to withstand the effects of the water loss that accompanies heat shock.