V. V. Suslov

Molecular evolution of cyclin proteins in animals and fungi

BackgroundThe passage through the cell cycle is controlled by complexes of cyclins, the regulatory units, with cyclin-dependent kinases, the catalytic units. It is also known that cyclins form several families, which differ considerably in primary structure from one eukaryotic organism to another. Despite these lines of evidence, the relationship between the evolution of cyclins and their function is an open issue. Here we present the results of our study on the molecular evolution of A-, B-, D-, E-type cyclin proteins in animals and fungi.ResultsWe constructed phylogenetic trees for these proteins, their ancestral sequences and analyzed patterns of amino acid replacements. The analysis of infrequently fixed atypical amino acid replacements in cyclins evidenced that accelerated evolution proceeded predominantly during paralog duplication or after it in animals and fungi and that it was related to aromorphic changes in animals. It was shown also that evolutionary flexibility of cyclin function may be provided by consequential reorganization of regions on protein surface remote from CDK binding sites in animal and fungal cyclins and by functional differentiation of paralogous cyclins formed in animal evolution.ConclusionsThe results suggested that changes in the number and/or nature of cyclin-binding proteins may underlie the evolutionary role of the alterations in the molecular structure of cyclins and their involvement in diverse molecular-genetic events.

TATA box polymorphisms in genes of commercial and laboratory animals and plants associated with selectively valuable traits

Most of more than 11 million experimentally established polymorphisms, accumulated in dbSNP, were identified in the intergenic spacers or coding DNA regions. This fact enables interpretation of the former polymorphisms as neutral, while the latter makes clear the biological sense of the associated mutant phenotypes, “the defect of certain proteins”. The association of polymorphisms in regulatory DNA regions with mutant phenotypes is poorly studied. Specifically, the defects in certain DNA/protein binding sites were identified in less than 500 cases. In TATA-containing genes of eukaryotes the TATA box, the TBP (TATA-binding protein) binding site, is located about 30 bp upstream from the transcription start site. Interaction between DNA and TBP triggers assemblage of the preinitiation complex. For 38 TATA box polymorphisms in the genes of commercial and laboratory animals and plants, the effect on TBP-binding activity was evaluated using the equilibrium equation for the four subsequent steps of TBP/TATA box binding (nonspecific binding ↔ sliding ↔ recognition ↔ stabilization). According to the GenBank data, these 38 polymorphisms were associated with the change in a number of selectively valuable traits. Statistically significant congruence of in silico analysis performed with mutant phenotypes (α < 0.05, binomial law) provides suggestion of the mechanism of phenotypic manifestation of these polymorphisms (changing of the TBP-binding activity), as well a validates the possibility of developing the universal test system for experimental-computer prediction of the effects of TATA box mutations in specified genes on selectively valuable traits of the species, varieties, and breeds.

A precise equation of equilibrium of four steps of TBP binding with the TATA box for prognosis of phenotypic manifestation of mutations

Among the central events of transcription initiation of TATA-containing genes in eukaryotes are the recognition and binding of the TATA box by the TATA-binding protein (TBP) to start the preinitiation complex formation on nucleosomal DNA. Using the equation of equilibrium for step-by-step TBP/TATA binding, we have analyzed 69 experimental datasets for the characteristics of biologically important features altered by TATA-box mutations. Among these features, the TBP/TATA-complex parameters, the transcription level, the activity of gene products, yeast colony growth at a dose of growth inhibitor (phenotype), and the heterogeneity of the response of a population to unspecific environmental stress have been described. Significant correlations were found between in silico prediction for TBP/TATA affinity and experimental data for in vivo and in vitro test systems based on 15 cell types of 19 species, RNA polymerases II and III, and natural, recombinant or mutant TBP. Such an invariant impact of the step-by-step TBP/TATA binding on the biological activity of complex systems, from a molecule to a population, might be due to the fact that TBP/TATA-complex formation precedes specific steps of transcription machinery assembly, which provide the multivariant jigsaw puzzle according to the expression pattern of each eukaryotic gene.

Identification of the relationship between the variability of the expression of signaling pathway genes in the human brain and the affinity of TATA-binding protein to their promoters

Variations in gene expression are the subject of a wide range of research aimed at the reconstruction of regulatory protein binding sites on DNA, regulatory gene regions, gene networks, signaling pathways, and many other entities that are able to modify gene expression. Pearson’s coefficient of variation (Cv, the ratio of the standard deviation to the mean) is the measure of variations in gene expression that is the most used in the fields of intense biomedical and breeding research. In turn, only one common genomic regulatory signal has been identified in all eukaryotes, namely, the TATA box, together with three other, less conservative, obligatory elements of core promoters accompanying it: DPE, BPE, and INR. We applied the equation for TATA box Binding Protein (TBP) affinity to TATA boxes deduced from our experimental data to the analysis of high-throughput sequencing data on 35609 mRNAs in 946 human brain segments taken from the Allen Brain Atlas. The analysis revealed a significant correlation between the affinity of TBP binding to promoters of signaling pathways genes and in silico estimates of Pearson’s Cv of the expression of these genes. This finding may help scientists analyze high-throughput sequencing data in order to identify more candidate factors modifying gene expression.

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.

Molecular-genetic systems of development: Functional dynamics and molecular evolution

This work for the first time compares results obtained with studies of parametric robustness of the Hh-and Dpp/BMP signal cascades responsible for morphogenesis and molecular evolution of the Hh-and Dpp/BMP cascade genes. There is a link between adaptive evolution of genes and those changes in kinetic parameters of the signal cascade models, which are critical for normal functioning of these cascades. Special attention is paid to events of the molecular evolution of the Hh-and Dpp/BMP cascade genes that matched with the emergence of the major taxonomic types and classes of Bilateria.

Phylogenetic analysis of housekeeping Archaeal proteins and early stages of Archaea evolution

The most probable horizontal gene transfer events in the evolution of Archaea are reconstructed based on the comparison of phylogenetic trees of housekeeping orthologous protein families with consensus phylogenies of Archaea. The existence of these phenomena suggests that the common ancestor of Archaea was of methanogenic and hyperthermophilic nature and dwelt in communities with a high level of ecological integration.

Genome features and GC content in prokaryotic genomes in connection with environmental evolution

The GC content and genome size are integral genomic characteristics limiting potential range of licenses (environments) of prokaryotic taxa. In silico, associations of these characteristics and taxa deviating from the general trend are revealed. Relationships with ecology and early prokaryotic evolution are discussed.

Par force evolution as a mechanism for rapid adaptation

An important task is to reduce the cost of natural selection. The stress provides a short-term non-specific resistance to a number of factors (cross resistance); however, in the long term, it is harmful (distress). In a small population, it is more expedient to change the stress flow (prolonging the phase of cross resistance, neutralizing distress) by natural selection within a small group of stress genes than to test all mutations of genome in a search for preadaptations. This process can provoke allo- or aromorphosis.