On the physics of the symbol--matter problem in biological systems and the origin of life: affine Hilbert spaces model of the robustness of the internal quantum dynamics of biological systems

In the present paper, some physical considerations of the biological symbol-matter problem is exposed. First of all, the physical concept of quantum dynamical internal measuremental robustness is discussed. In this context, the significance of introducing affine molecular Hilbert spaces, the original (primordeal) internal quantum measurement, and the global constraining nature of time-inversion symmetry restoring, as a special restoration force, is discussed at some length. It is pointed out, as a summary, that global robustness of the internal dynamics of quantum measurements is due to two basic factors: on one hand, the global constraining nature of the chosen specific (symmetry-) restoring force, and on the other, the individual robustness of the discrete local internal measuremental interactions. The second condition is supposed to follow from a system-internalised ("objective") Bohr-type Copenhagen interpretation of quantum mechanics, corresponding, in an external context, to the Generalized Complementarity Principle of Bohr and Elsasser. It is not claimed, however, that this latter problem has been, as yet, satisfactorily settled physically. In fact, if it were, it would amount to a specifically biological quantum theory of internal measurement, which had to be rooted in the original primordeal global internal measurement, amounting to the origin of the genetic code.     

Appendix: Mathematical approaches to the evaluation of the flux of γ-aminobutyrate in brain tissue in vitro

In the preceding paper (Balázs, Machiyama, Hammond, Julian & Richter, 1970) the flux of gamma-aminobutyrate (GABA) was found, in guinea-pig brain-cortex slices incubated in glucose-saline medium, to represent about 10% of the total tricarboxylic acid cycle flux, as opposed to other estimates, which are as high as 40%. However, the latter value was deduced from experimental results by methods that made no allowance for the metabolic compartmentation of glutamate: a mathematical investigation was therefore undertaken to show that this omission necessarily leads to an overestimation of GABA flux. The magnitude of this over-estimation was shown by computer simulation methods to be of such an order as to bring the corrected value into agreement with the lower value. Computer simulation methods were also used to evaluate the GABA flux from the experimental results presented by Balázs et al. (1970) and a value of 0.0315mumol/min per g wet wt. was obtained. This value was also shown to be consistent, in the simulated system, with the experimentally observed time-courses for the radioactivity and quantity of aspartate. Since there is now evidence that GABA is itself a metabolically compartmented intermediate this possibility was considered mathematically, but it was found that in this case the assumption of compartmentation had little effect upon the value of GABA flux deduced on the basis of GABA homogeneity.     

A new savanna-like community of the sierra del rosario mountains,Cuba

This communication describes a new savanna-like community, theBletio purpureae-Andropogonetum gracilis Balátová-Tulá?ková etR. Capote ass. nov., found in the woodless eastern part of the Sierra del Rosario Mountains (western part of Cuba). From the phytosociological point of view, it belongs to the allianceAchlaenion piptostachyae Balátová-Tulá?ková all. nov., the orderAchlaenetalia piptostachyae Balátová-Tulá?ková ord. nov., and the classSclerio baldwinii-Andropogonetea gracilis Balátová-Tulá?ková cl. nov. In the area under study four subassociations were distinguished: theBletio-Andropogonetum typicum Balátová-Tulá?ková et.R. Capote subass. nov., theB.-A. rhynchosporetosum fascicularis Balátová-Tulá?ková etR. Capote subass. nov., theB.-A. cassietosum aeschynomenes Balátová-Tulá?ková etR. Capote subass. nov., and theB.-A. stenandrietosum droseroidis Balátová-Tulá?ková etR. Capote subass. nov.     

A concept of relation between physical and biological time in animals

A definition is proposed for biological ("internal") time tau(t) for a growing organism whose weight variation obeys the law w(t): tau(t) = 1/c(w) (t) = w(t)/w'(t), where t is physical ("external") time, w'(t) is weight increase rate, and c(w) (t) = w'(t)/w(t) is specific growth rate. Properties of functions tau(t) and w(tau) were studied for those cases when growth curves w(t) were described by Bertalanffy's or logistic equations.     

Flooded meadow communities an analysis of their productivity in a wet year

The productivity of three plant communities differeing in moisture conditions was studied in the river basin of the Dyje near the village of Lan?hot (Southern Moravia). The communities were as follows:Serratuleto-Festucetum commutatae Balátová-Tulá?ková 1963,Gratiola officinalis—Carex praecox-suzae subass.Galium boreale Balátová-Tulá?ková 1963, andGratiola officinalis—Carex praecox-suzae subass.Rorippa silvestris Balátová-Tulá?ková 1963. The associationGratiola officinalis—Carex praecox-suzae subass.Galium boreale appeared as the most productive one, its biomass maximum W=400 g . m^?2 and the maximum R=0.042 g . g^?1 . day^?1 C=4.84 g . m^?2 . day^?1. Owing to extreme moisture conditions in the year 1966, the associationSerratuleto-Festucetum commutatae was also highly productive, as it reached the following maximum of dry matter production: 240 g . m^?2, R=0.0388g . g^?1 . day^?1 C=4.64 g . m^?2 . day^?1. The maximum value of dry matter in the associationGratiola officinalis—Carex praecox-suzae subass.Rorippa silvestris was 220 g.m^?2. Changes in dry matter production of shoots were evaluated statistically. The dry matter in the underground parts of plants in 1 square metre, collected from the 0–25 cm layer varied from 1,000 to 2,000 g.m^?2. Together with records of the increasing dry matter in the shoots the author kept records of the properties of dead material.     

A possible circular RNA at the origin of life

The increasing volume of sequenced genomes and the recent techniques for performing in vitro molecular evolution have rekindled the interest for questions on the origin of life. Nevertheless, a gap continues to exist between the research on prebiotic chemistry and molecule generation, on one hand, and the study of molecular fossils preserved in genomes, on the other. Here we attempt to fill this gap by using some assumptions about the prebiotic scenario (including a strong stereochemical basis for the genetic code) to determine the RNA sequences more likely to appear and subsist. A set of minimal RNA rings is exhaustively determined; a subset of them is then selected through stability arguments, and a particular ring ("AL ring") is finally singled out as the most likely winner of this prebiotic game. The rings happen to have several structural and statistical properties of modern genes: a repeated AUG codon appears spontaneously (and is thus made available for becoming a start signal), the form AUG/STOP emerges, and frequency patterns resemble those of present genes. The whole set of rings was also compared to a database of tRNAs, considering the conserved positions (located in the free parts of the molecule, essentially the loops); the ring that most closely matched tRNA sequences-and matched, in fact, the consensus of tRNA at all the aligned positions-was AL, the same ring independently selected before. The unselected emergence of gene-like features through two simple selection steps and the close similarity between the finally selected ring and tRNA (including some remarkable features of the resulting alignment) suggest a possible link between the prebiotic world and the first biological molecules, which is amenable for experimental testing. Even if our scenario is partially wrong, the unlikely coincidences should provide useful hints for other efforts.     

Endoplasmic reticulum and mitochondria as elements of mechanism of intracellular signaling in neurons

The temporal and spatial characteristics of a transitory increase in free Ca2+ ("calcium signals") concentration were determined in various types of the mice and rat neurones. Intracellular structures: endoplasmatic reticulum and mitochondria, were shown to play a major part in formation of these signals, the structures being able to absorb the Ca2+ ions from cytosol and release them back. The contribution of these processes proves rather varying depending on internal organisation and functional assignment of a neurone.     

Dual functions of codons in the genetic code

The discovery of the genetic code provided one of the basic foundations of modern molecular biology. Most organisms use the same genetic language, but there are also well-documented variations representing codon reassignments within specific groups of organisms (such as ciliates and yeast) or organelles (such as plastids and mitochondria). In addition, duality in codon function is known in the use of AUG in translation initiation and methionine insertion into internal protein positions as well as in the case of selenocysteine and pyrrolysine insertion (encoded by UGA and UAG, respectively) in competition with translation termination. Ambiguous meaning of CUG in coding for serine and leucine is also known. However, a recent study revealed that codons in any position within the open reading frame can serve a dual function and that a change in codon meaning can be achieved by availability of a specific type of RNA stem-loop structure in the 3′-untranslated region. Thus, duality of codon function is a more widely used feature of the genetic code than previously known, and this observation raises the possibility that additional recoding events and additional novel features have evolved in the genetic code.     

Dissociable influences of auditory object vs. spatial attention on visual system oscillatory activity

Given that both auditory and visual systems have anatomically separate object identification ("what") and spatial ("where") pathways, it is of interest whether attention-driven cross-sensory modulations occur separately within these feature domains. Here, we investigated how auditory "what" vs. "where" attention tasks modulate activity in visual pathways using cortically constrained source estimates of magnetoencephalograpic (MEG) oscillatory activity. In the absence of visual stimuli or tasks, subjects were presented with a sequence of auditory-stimulus pairs and instructed to selectively attend to phonetic ("what") vs. spatial ("where") aspects of these sounds, or to listen passively. To investigate sustained modulatory effects, oscillatory power was estimated from time periods between sound-pair presentations. In comparison to attention to sound locations, phonetic auditory attention was associated with stronger alpha (7-13 Hz) power in several visual areas (primary visual cortex; lingual, fusiform, and inferior temporal gyri, lateral occipital cortex), as well as in higher-order visual/multisensory areas including lateral/medial parietal and retrosplenial cortices. Region-of-interest (ROI) analyses of dynamic changes, from which the sustained effects had been removed, suggested further power increases during Attend Phoneme vs. Location centered at the alpha range 400-600 ms after the onset of second sound of each stimulus pair. These results suggest distinct modulations of visual system oscillatory activity during auditory attention to sound object identity ("what") vs. sound location ("where"). The alpha modulations could be interpreted to reflect enhanced crossmodal inhibition of feature-specific visual pathways and adjacent audiovisual association areas during "what" vs. "where" auditory attention.     

Optimization Models and the Structure of the Genetic Code

The codon assignment of the quasi-universal genetic code can be assumed to have resulted from the evolutionary pressures that prevailed when the code was still evolving. Here, we review studies of the structure of the genetic code based on optimization models. We also review studies that, from the structure of the code, attempt to derive aspects of the primordial circumstances in which the genetic code froze. Different rationales are summarized, compared with experimental data, discussed in the context of the transition from a RNA world to a DNA-protein world, and linked to the emergence of the last universal common ancestor.     

Recent evidence for evolution of the genetic code.

The genetic code, formerly thought to be frozen, is now known to be in a state of evolution. This was first shown in 1979 by Barrell et al. (G. Barrell, A. T. Bankier, and J. Drouin, Nature [London] 282:189-194, 1979), who found that the universal codons AUA (isoleucine) and UGA (stop) coded for methionine and tryptophan, respectively, in human mitochondria. Subsequent studies have shown that UGA codes for tryptophan in Mycoplasma spp. and in all nonplant mitochondria that have been examined. Universal stop codons UAA and UAG code for glutamine in ciliated protozoa (except Euplotes octacarinatus) and in a green alga, Acetabularia. E. octacarinatus uses UAA for stop and UGA for cysteine. Candida species, which are yeasts, use CUG (leucine) for serine. Other departures from the universal code, all in nonplant mitochondria, are CUN (leucine) for threonine (in yeasts), AAA (lysine) for asparagine (in platyhelminths and echinoderms), UAA (stop) for tyrosine (in planaria), and AGR (arginine) for serine (in several animal orders) and for stop (in vertebrates). We propose that the changes are typically preceded by loss of a codon from all coding sequences in an organism or organelle, often as a result of directional mutation pressure, accompanied by loss of the tRNA that translates the codon. The codon reappears later by conversion of another codon and emergence of a tRNA that translates the reappeared codon with a different assignment. Changes in release factors also contribute to these revised assignments. We also discuss the use of UGA (stop) as a selenocysteine codon and the early history of the code.     

Evolution of the genetic code.

Comparative path lengths in amino acid biosynthesis and other molecular indicators of the timing of codon assignment were examined to reconstruct the main stages of code evolution. The codon tree obtained was rooted in the 4 N-fixing amino acids (Asp, Glu, Asn, Gln) and 16 triplets of the NAN set. This small, locally phased (commaless) code evidently arose from ambiguous translation on a poly(A) collector strand, in a surface reaction network. Copolymerisation of these amino acids yields polyanionic peptide chains, which could anchor uncharged amide residues to a positively charged mineral surface. From RNA virus structure and replication in vitro, the first genes seemed to be RNA segments spliced into tRNA. Expansion of the code reduced the risk of mutation to an unreadable codon. This step was conditional on initiation at the 5'-codon of a translated sequence. Incorporation of increasingly hydrophobic amino acids accompanied expansion. As codons of the NUN set were assigned most slowly, they received the most nonpolar amino acids. The origin of ferredoxin and Gln synthetase was traced to mid-expansion phase. Surface metabolism ceased by the end of code expansion, as cells bounded by a proteo-phospholipid membrane, with a protoATPase, had emerged. Incorporation of positively charged and aromatic amino acids followed. They entered the post-expansion code by codon capture. Synthesis of efficient enzymes with acid-base catalysis was then possible. Both types of aminoacyl-tRNA synthetases were attributed to this stage. tRNA sequence diversity and error rates in RNA replication indicate the code evolved within 20 million yr in the preIsuan era. These findings on the genetic code provide empirical evidence, from a contemporaneous source, that a surface reaction network, centred on C-fixing autocatalytic cycles, rapidly led to cellular life on Earth.     

On the origin and evolution of the genetic code I. Wobbling and its potential significance

In this paper several properties of the genetic code are interpreted by assuming that wobbling or some remnant of wobbling has originally been a common phenomenon also in the first nucleotide of each codon, and not only in the third nucleotide. Some of the last steps in the evolution of the genetic code are described on the basis of this interpretation of genetic code features.An attempt to outline some of the earlier steps in the evolution of the genetic code is based on the assumption that at an earlier stage wobbling may also have been common in the central nucleotide of each codon.In the last part of the paper the possibility is considered that the pairing rules which characterize wobbling may have been much more common in the past not only in codon-anticodon pairing but also in polymer copying. The advantages of a freer purine-pyrimidine pairing like the one characteristic of wobbling in a primitive (or prebiologic) environment in which nucleotide production was not entirely (or not at all) under biologic control are stressed.This paper is based exclusively on the “Frozen accident” interpretation of the genetic code (Crick, 1968) with a few modifications introduced or implied in the text. No stereochemical codon interpretations and only a minimum of chemical considerations are involved.     

Hidden symmetry of peptide and protein primary structures]

The internal symmetry of peptide chains was considered. To identify symmetrically located equivalent amino acids, the signatures method and the code of amino acid codon roots were applied. There was revealed the hidden symmetry of amino acid sequences of peptides and proteins as well as of their active centres. Amino acids having common codon roots in primary (and supposedly in the spatial "biologically active") molecular structures, are located symmetrically. Definition of local symmetry of peptide chains was proposed to use as one of the elements of complex analysis to determine location of molecular active centres.     

The possible role of assignment catalysts in the origin of the genetic code

A model is presented for the emergence of a primitive genetic code through the selection of a family of proteins capable of executing the code and catalyzing their own formation from polynucleotide templates. These proteins are assignment catalysts capable of modulating the rate of incorporation of different amino acids at the position of different codons. The starting point of the model is a polynucleotide based polypeptide construction process which maintains colinearity between template and product, but may not maintain a coded relationship between amino acids and codons. Among the primitive proteins made are assumed to be assignment catalysts characterized by structural and functional parameters which are used to formulate the production kinetics of these catalysts from available templates. Application of the model to the simple case of two letter codon and amino acid alphabets has been analyzed in detail. As the structural, functional, and kinetic parameters are varied, the dynamics undergoes many bifurcations, allowing an initially ambiguous system of catalysts to evolve to a coded, self-reproductive system. The proposed selective pressure of this evolution is the efficiency of utilization of monomers and energy. The model also simulates the qualitative features of suppression, in which a deleterious mutation is partly corrected by the introduction of translational error.     

Physico-chemical basis of the genetic code origin: stereochemical analysis of interactions of amino acids and nucleotides based on the progene hypothesis

A progene hypothesis has been proposed earlier to explain the mechanism of origin of the self-reproducing genetic system. Progenes (precursors of the genetic system) are mixed anhydrides of an amino acid and deoxyribotrinucleotide at the 3'-gamma-terminal phosphate (NpNpNppp-AA); they are produced from dinucleotides (NpNp) and 3'-gamma-aminoacylnucleotidylates (Nppp-AA) as a result of specific interaction between amino acid and dinucleotide. The postulated mechanism of progene formation accounts for the selection of substances, including chirality, the origin of the genetic code as well as for the mechanisms of formation, self-reproduction and evolution of the simpliest genetic system ("gene--polypeptide"). A stereochemical analysis of the progene formation mechanism has allowed us to support the main statements of the hypothesis that relate to the origin of the genetic code and to selection of substances. Atomic groups that could be responsible for the specificity of interaction between dinucleotides and amino acids in progene formation have been revealed. Stereochemical evidence for the physicochemical basis of the origin of the existing genetic code have been produced: 1) a special role of the second nucleotide in the codon is demonstrated in amino acid coding by the progene hypothesis principle; 2) an advantage of T against U in such coding is demonstrated; 3) for 16 amino acids out of 20 an agreement has been obtained between the optimal dinucleotide as revealed by the stereochemical analysis and the codon dinucleotides; 4) an explanation for the third nucleotide selection mechanism is offered. A restoration of the prebiotic code, based on these results, has indicated that the code contains 32 codons, is statistical and group-wise. It encodes 7 groups of isofunctional amino acids: 3 overlapping groups of non-polar amino acids 1) medium-size hydrophobic amino acids (chiefly Val, n-Val and a-But), 2) small and medium-size non-polar amino acids (chiefly Ala Val, n-Val a-But and Gly), 3) small non-polar amino acids (Gly, Ala, a-But) and 4 groups of polar amino acids--1) hydroxy--+dicarbonic (Asp, Glu, Ser and Thr), 2) dicarbonic (Asp and Glu), 3) hydroxy (Ser and Thr) and 4) basic (Arg and Lys). The code includes about 20 amino acids among which are 15-17 canonical and a few common non-canonical. The prebiotic code explains many properties of the existing genetic code and is capable of evolving into the latter by way of a gradual replacement of the physicochemical coding mechanism by the enzymatic coding mechanism.