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Biomedical subjects

M V Volkenstein

Publications and source records attributed to M V Volkenstein.

At least 19 recordsLinked to original sources

Directionality of evolution at molecular and organismic levels.

The molecular evolution theories of Eigen and Kimura are compared and their difference is explained. In terms of Eigen's theory for the evolution of macromolecules, the selection of genotypes occurs directly. The physical meaning of the neutral theory is the degeneracy of the correlation between a phenotype and a genotype at the molecular level. A model theory of evolution on a fitness landscape is proposed. The theory shows that the constraints of selection determined by the structure and dynamics of previous evolution stages increases its rate strongly.

Biological Evolution

On the divergence of species.

Speciation may be considered as a kind of non-equilibrium phase transition which is caused by bifurcation at a critical point of instability. It can be shown that multiple branching of an evolutionary tree is highly improbable, since non-degenerate mathematical models describe only binary branchings.

Biological Evolution

Speciation and bifurcations.

The interrelations of physics and biology are discussed. It is shown that Darwin can be considered as one of the founders of the important field of contemporary physics called physics of dissipative structures or synergetics. The theories of gradual and punctual evolution are presented. The contradiction between these theories can be solved on the basis of molecular theory of evolution and on the basis of the phenomenological physical treatment. The general physical properties of living systems, considered as open systems being far from equilibrium, are listed and simple non-linear mathematical models describing gradual and punctual speciation are suggested. The usual pictures which present these two kinds of speciation can possess physico-mathematical sense. Punctuated speciation means bifurcation, a kind of non-equilibrium phase transition.

Biological Evolution

Statistical analysis of nucleotide runs in coding and noncoding DNA sequences.

A statistical analysis of the occurrence of particular nucleotide runs in DNA sequences of different species has been carried out. There are considerable differences of run distributions in DNA sequences of procaryotes, invertebrates and vertebrates. There is an abundance of short runs (1-2 nucleotides long) in the coding sequences and there is a deficiency of such runs in the noncoding regions. However, some interesting exceptions from this rule exist for the run distribution of adenine in procaryotes and for the arrangement of purine-pyrimidine runs in eucaryotes. The similarity in the distributions of such runs in the coding and noncoding regions may be due to some structural features of the DNA molecule as a whole. Runs of guanine (or cytosine) of three to six nucleotides occur predominantly in noncoding DNA regions in eucaryotes, especially in vertebrates.

Animals

Punctualism, non-adaptationism, neutralism and evolution.

In its further development the theory of evolution will incorporate molecular biology, synergetics and the theory of information. Using a simple model it is shown that speciation can be similar to phase transition. This is a thermodynamical statement which does not say anything concerning the sharpness and kinetic features of transition. Hence there is no contradiction between punctuated equilibrium and phyletic gradualism. The notion of punctualism can be used in the sense of phase transition. Evolution is directional because of constraints of natural selection due to the structure of organisms already existing and to the possible pathways of development. Correspondingly many characters are non-adaptative. Not only are the structures of proteins important for speciation but also the exact answers to the questions: "how much", "where" and "when"? These answers can be obtained as the results of regulation of genes, particularly of homeiotic regulation. The basis features of the structure of proteins are considered and the sense of the neutral theory is discussed in connection with degeneracy of correlation between the primary structure of a protein, its spatial structure and biological function. Informational aspects of evolution are discussed. Punctualism, non-adaptationism and neutralism form the triad of internally connected features of evolution. The Darwinian theory preserves its fundamental significance.

Adaptation, Biological

Protein structure and neutral theory of evolution.

The neutral theory of evolution is extended to the origin of protein molecules. Arguments are presented which suggest that the amino acid sequences of many globular proteins mainly represent "memorized" random sequences while biological evolution reduces to the "editing" these random sequences. Physical requirements for a functional globular protein are formulated and it is shown that many of these requirement do not involve strategical selection of amino acid sequences during biological evolution but are inherent also for typical random sequences. In particular, it is shown that random sequences of polar and amino acid residues can form alpha-helices and beta-strand with lengths and arrangement along the chain similar to those in real globular proteins. These alpha- and beta-regions in random sequences can form three-dimensional folding patterns also similar to those in proteins. The arguments are presented suggesting that even the tight packing of side groups inside protein core do not require very strong biological selection of amino acid sequences either. Thus many structural features of real proteins can exist also in random sequences and the biological selection is needed mainly for the creation of active site of protein and for their stability under physiological conditions.

Amino Acid Sequence

A spin label study of conformational changes in cytochrome c.

Spin-labeled pig heart cytochromes c singly modified at Met-65, Tyr-74 and at one of the lysine residues, Lys-72 or Lys-73, were investigated by the ESR method under conditions of different ligand and redox states of the heme and at various pH values. Replacement of Met-80 by the external ligand, cyanide, was shown to produce a sharp increase in the mobility of all the three bound labels while reduction of the spin-labeled ferricytochromes c did not cause any marked changes in their ESR spectra. In the pH range 6-13, two conformational transitions in ferricytochrome c were observed which preceded its alkaline denaturation: the first with pK 9.3 registered by the spin label at the Met-65 position, and the second with pK 11.1 registered by the labels bound to Tyr-74 and Lys-72(73). The conformational changes in the 'left-hand part' of ferricytochrome c are most probably induced in both cases by the exchange of internal protein ligands at the sixth coordination site of the heme.

Animals

Comparative study of dynamic structure of pig and chicken aspartate aminotransferases by measuring the rotational correlation time.

The rotational correlation time of two homologous cytoplasmic aspartate aminotransferase molecules isolated from pig and chicken hearts was obtained by spin-labeling technique. The maleimide and iodoacetamide spin-labels modifying external SH-groups of a protein were used. In the interpretation of ESR spectra a rotational motion of nitroxide group relative to the protein molecule was taken into account. To determine the macromolecule rotational correlation time two methods of the immobilization of a protein molecule were used: 1) by means of increasing protein solution viscosity and 2) by fixation of the protein molecule on adsorbent. From comparison of experimental and theoretical values of rotational correlation time it was conclude that the both enzymes exhibits an intramolecular flexibility.

Animals

Circular dichroism anisotrophy of DNA with different modifications at N7 of guanine.

The complexex DNA-Ag1+, DNA-Cu1+, protonated DNA and DNA methylated at N7 of guanine were oriented by pumping the solutions through a multicapillary cell in the direction of a light beam. The CD components along the DNA axis, delta epsilon parallel, and normal to it, 2 delta epsilon perpendicular, were calculated from the CD spectra of the oriented samples by the method of Chung and Holzwarth, (1975) J. Mol. Biol. 92, 449--466. It was shown that in most cases, except that of the protonated DNA, the degree of orientation was only slightly less than that for pure DNA. This demonstrated the absence of aggregation and of appreciable denaturation. In all cases the modifications of DNA give rise to a negative component 2 delta epsilon perpendicular, whose magnitude increased as the extent of modification increased. From both the CD spectra of non-oriented samples and the absorption spectra, an inference is drawn that Ag1+ and Cu1+ are attached to the same site as CH3 groups i.e., to the N7 atom of guanine. Proton transfer along the H-bond from the N1 atom of G to the N3 atom of the complementary cytosine is suggested to be a result of the modifications, although the case of H+-DNA may differ from the others. Based on the CD spectra for the anisotropic components, delta epsilon parallel and 2 delta epsilon perpendicular, it is proposed that ligand binding is accompanied by winding of the DNA helix.

Animals

Equilibrium and kinetic aspects of protein-DNA recognition.

The specificity of regulatory protein binding to DNA is due to a complementarity between the sequence of reaction centres on the protein and the base pair sequence in the specific DNA site allowing the formation of a number of specific noncovalent bonds between the interacting entities. In the present communication the thermodynamic and kinetic aspects of these interactions are considered. The extent of binding specificity is shown to increase with an increase of the bond stability constants and with an increase in the number of ligand reaction centres. Kinetic analysis is carried out assuming that association process is very fast and that dissociation of nonspecific complexes is a rate-limiting step in the recognition of a specific binding site on DNA. The calculations show that a ligand can recognize its specific binding site on DNA within a reasonably limited time interval if the number of its reaction centres and the corresponding stability constants are strongly limited.

DNA