[Theories of biological evolution from the viewpoint of the modern systemic biology].

Theories of biological evolution advanced in the last 200 years are reviewed from the viewpoint of advances of modern genetics. The theory of gene networks as a key direction of systemic biology is a link connecting different evolutionary theories.

[Evolutionary trends in the prokaryotic community and prokaryotic community-phage systems].

The Evolutionary Constructor software has been used for computer simulation of the life and evolution of communities of unicellular haploid organisms (prokaryotic cells). Opposite trends of the community evolution (simplification and complication of the genome) have been studied. It has been demonstrated that species with reduced genomes tend to replace genetically and metabolically rich species under highly favorable environmental conditions. Under unfavorable conditions, the opposite tendency is observed. It has also been shown that introduction of phages capable of killing the cells into the system may radically change the current evolutionary trend.

[Correlation of codon biases and potential secondary structures with mRNA translation efficiency in unicellular organisms].

UNLABELLED: Gene expression is known to correlate with degree of codon bias in many unicellular organisms. However, such correlation is absent in some organisms. Recently we demonstrated that inverted complementary repeats within coding DNA sequence must be considered for proper estimation of translation efficiency, since they may form secondary structures that obstruct ribosome movement. We have developed a program for estimation of potential coding DNA sequence expression in defined unicellular organism using its genome sequence. The program computes elongation efficiency index. Computation is based on estimation of coding DNA sequence elongation efficiency, taking into account three key factors: codon bias, average number of inverted complementary repeats, and free energy of potential stem-loop structures formed by the repeats. The influence of these factors on translation is numerically estimated. An optimal proportion of these factors is computed for each organism individually. Quantitative translational characteristics of 384 unicellular organisms (351 bacteria, 28 archaea, 5 eukaryota) have been computed using their annotated genomes from NCBI GenBank. Five potential evolutionary strategies of translational optimization have been determined among studied organisms. A considerable difference of preferred translational strategies between Bacteria and Archaea has been revealed. Significant correlations between elongation efficiency index and gene expression levels have been shown for two organisms (S. cerevisiae and H. pylori) using available microarray data. The proposed method allows to estimate numerically the coding DNA sequence translation efficiency and to optimize nucleotide composition of heterologous genes in unicellular organisms. AVAILABILITY: http://www.mgs.bionet.nsc.ru/mgs/programs/eei-calculator/.

[On connection of a graph of a gene network with qualitative modes of function]. / O sviazi grafa genno seti s kachestvennymi rezhimami ee funktsionirovaniia.

Theoretical investigation of properties of assumed gene networks constructed from elementary units of two types, genetic elements and control links, was carried out. A test was formulated for a subclass of such networks with cyclic structure called S(n,k)-networks allowing calculation-free prediction of the network limiting properties (the presence/absence and number of stationery and/or cyclic functioning modes) from a graph of the network structure. The obtained data can be useful for constructing gene networks with predefined properties.

[A generalized chemical-kinetic method for modeling gene networks]. / Obobshchennyi khimiko-kineticheskii metod modelirovaniia gennykh setei.

Development of methods for mathematical simulation of biological systems and building specific simulations is an important trend of bioinformatics development. Here we describe the method of generalized chemokinetic simulation generating flexible and adequate simulations of various biological systems. Adequate simulations of complex nonlinear gene networks--control system of cholesterol by synthesis in the cell and erythrocyte differentiation and maturation--are given as the examples. The simulations were expressed in terms of unit processes--biochemical reactions. Optimal sets of parameters were determined and the systems were numerically simulated under various conditions. The simulations allow us to study possible functional conditions of these gene networks, calculate consequences of mutations, and define optimal strategies for their correction including therapeutic ones. Graphical user interface for these simulations is available at http://wwwmgs.bionet.nsc.ru/systems/MGL/GeneNet/.

[Alpha-helix retention in prion proteins]. / Sokhranenie al'fa-spiralei v prionovykh belkakh.

Prion diseases belong to a group of neurodegenerative disorders caused by conformational changes--destroying the alpha-helices--in prion proteins (PrP). We performed a phylogenetic analysis of 32 PrP sequences and restored the most probable evolutionary spectrum of amino acid substitutions. Although prion proteins are not too conserved judging from the evolutionary rates, conserved substitutions leading only to amino acids with similar physical and chemical parameters occurred in evolution within the putative helical PrP regions. Those substitutions that destroy alpha-helices primarily arose in prion proteins as was demonstrated by the methods of prediction of protein secondary structure used for analysis of the complete spectrum of single-step substitutions in human PrP sequences. The data obtained support a suggestion that prion diseases result from changes in PrP conformation manifested in destroying the alpha-helices and formation of beta-structures.

[Identification of polygenes in the system achaete-scute in Drosophila melanogaster using cluster analysis]. / Identifikatsiia poligenov v sisteme achaete-scute u Drosophila melanogaster metodami klasternogo analiza.

Data on location of mobile elements mdg1, Dm412, copia, and B104 in 33 isogenic lines of Drosophila melanogaster has been processed by means of cluster analysis to reveal the relationship between the penetrance for bristle reduction and the distribution of mobile elements. The presence of two groups of sites specific for lines with contrasting penetrance levels have been demonstrated. The specificity suggests that the sites can be associated with the location of corresponding polygenes, affecting the penetrance level in mutant lines.

[Features of cytochrome P450 evolution]. / Osobennosti évoliutsii tsitokhromov P450.

It is shown that the process of mutation in the CYP2 family of the superfamily of P450 cytochromes is species-specific (man, rat, and mouse). It is also shown that, within one species (rat), different families (CYP2 and CYP11) have different mutation spectra, indicating a high specificity of the mutation process for the families of cytochrome genes. A similar specificity was demonstrated for five families (CYP1, CYP2, CYP6, CYP7, CYP11) as compared with globins and prions. The analysis of the evolutionary mutation pattern, and the pattern of pseudogenes and damaged alleles of the CYP21 family (found in patients with congenital adrenal hyperplasia) does not confirm the widely accepted hypothesis that mutations arising in pseudogenes are transduced to normal alleles of the CYP21 gene through gene conversion.

[The coevolutionary aspects of the genome and mobile elements]. / Nekotorye aspekty koévoliustii genoma i mobil'nykh élementov.

Under investigation is congruent variation of movable elements, the "genome parasites" (GP), and genome proper, as the "host". Several differential equations are studied that describe the following situations. 1. GP is able to insert in free sites only, existing in autonomous stage (outside of the genome) limited time only. 2. GP inserts in free sites only, being able to exist autonomously relatively long time. 3. GP inserts in both free and occupied sites ("molecular memory"), existing autonomously relatively short time, its prototype being Alu-like repetitions in mammals. 4. GP inserts in both free and occupied sites, and is able to live autonomously, its prototype being retrovirus. In is presumed that the genome is tolerant to "selfish" breeding of GP as long as proportion of invaded sites does not exceed some critical value. It is shown that co-evolutionary complication of GP--from the simplest one that is able to insert in free sites only, through acquiring terminal repetitions ("molecular memory"), up to complicated entities existing outside of genome--accompanied by alteration of selective co-evolutionary limitations on genome size: limitations from above--no limitations--limitations from below. Thus, genetical movable elements can be considered as intrinsic factor of progressive, co-evolutionary stipulated complication of the genome.