In Silico Biology - Volume 7, issue 3

Authors: Rodin, Sergei N. | Kolchanov, Nikolay A.

Article Type: Other

Citation: In Silico Biology, vol. 7, no. 3, pp. 239-240, 2007

Authors: Orlov, Yuriy L. | Zhou, Jiangtao | Lipovich, Leonard | Shahab, Atif | Kuznetsov, Vladimir A.

Article Type: Research Article

Abstract: Careful analysis of microarray probe design should be an obligatory component of MicroArray Quality Control (MACQ) project [Patterson et al., 2006; Shi et al., 2006] initiated by the FDA (USA) in order to provide quality control tools to researchers of gene expression profiles and to translate the microarray technology from bench to bedside. The identification and filtering of unreliable probesets are important preprocessing steps before analysis of microarray data. These steps may result in an essential …improvement in the selection of differentially expressed genes, gene clustering and construction of co-regulatory expression networks. We revised genome localization of the Affymetrix U133A&B GeneChip initial (target) probe sequences, and evaluated the impact of erroneous and poorly annotated target sequences on the quality of gene expression data. We found about 25% of Affymetrix target sequences overlapping with interspersed repeats that could cause cross-hybridization effects. In total, discrepancies in target sequence annotation account for up to ∼30% of 44692 Affymetrix probesets. We introduce a novel quality control algorithm based on target sequence mapping onto genome and GeneChip expression data analysis. To validate the quality of probesets we used expression data from large, clinically and genetically distinct groups of breast cancers (249 samples). For the first time, we quantitatively evaluated the effect of repeats and other sources of inadequate probe design on the specificity, reliability and discrimination ability of Affymetrix probesets. We propose that only functionally reliable Affymetrix probesets that passed our quality control algorithm (∼ 86%) for gene expression analysis should be utilized. The target sequence annotation and filtering is available upon request. Show more

Keywords: U133 microarray, target sequences, noise signals, cross-hybridization, human genome, gene expression, sense-antisense gene pairs, interspersed repeats, breast cancer

Citation: In Silico Biology, vol. 7, no. 3, pp. 241-260, 2007

Authors: Lashin, Sergey A. | Suslov, Valentin V. | Kolchanov, Nikolay A. | Matushkin, Yury G.

Article Type: Research Article

Abstract: An original modeling tool called Evolutionary Constructor has been proposed and described. Evolutionary Constructor combines the advantages of both generalized and portrait modeling and, additionally, provides an option to modify a current model's structure. The evolution of communities comprising a trophic ring-like network with the horizontal transfer of metabolism genes occurring among the communities has been modeled and presented. It has been demonstrated that a prolonged increase in the fitness of any single population …that forms part of that trophic ring-like network of antagonistic communities will eventually lead that system to becoming absolutely dependent on environmental fluctuations. This result challenges the intuitive attitudes that the higher population fitness, the more stability is given to that population. Modeling of a system comprised by symbiotic communities has revealed that horizontal transfer confers a selective advantage not only on the acceptor population (which is up to expectations) but also on the donor population. It has therefore been demonstrated that horizontal transfer can be preserved by selection along evolution even without "selfish genes". Evolutionary Constructor can handle any phenotypic trait that is controlled genetically, epigenetically, etc., which extends the applicability of this tool to various processes of information transduction among populations, provided that these processes resemble horizontal gene transfer. Show more

Keywords: Ecosystem, trophic network, symbiotic community, antagonistic community, evolution of community, metabolic cul-de-sac, mathematical modeling, program package, mutation, horizontal gene transfer

Citation: In Silico Biology, vol. 7, no. 3, pp. 261-275, 2007

Authors: Bukin, Jury Sergeevich | Pudovkina, Tatyana Anatoljevna | Sherbakov, Dmitry Jurjevich | Sitnikova, Tatyana Jakovlevna

Article Type: Research Article

Abstract: In this work, we apply population dynamic approach enhanced with simulation of the fate of neutrally evolving "DNA sequences" included into each individual in the computer experiment to the case of the Baikalian endemic polychaetes Manayunkia. These animals inhabit a narrow littoral zone around whole the lake perimeter and are of very limited mobility. Accordingly, the general model was modified by addition of a "geographic barrier" of different isolating power and length of existence. Using this …model, we simulated the process of genetic differentiation of groups in this organism taking into account isolation by distance and geographical barriers. Wright's F_{st} test was used in order to estimate of genetic flow. Relevant sample sizes were estimated, which would produce most important population parameters of the precision required to describe micro-evolutionary processes in Manayunkia. Show more

Keywords: Population dynamic, DNA, Baikalian polychaetes, stochastic model, population genetics, geographical isolation

Citation: In Silico Biology, vol. 7, no. 3, pp. 277-284, 2007

Authors: Rubanov, Lev | Lyubetsky, Vassily

Article Type: Research Article

Abstract: RNAmodel web server was recently established at the IITP RAS to implement our previously proposed model of the classic attenuation regulation of gene expression in bacteria. This new model is based on the concept of resonant-like interaction between RNA polymerase and hairpins of RNA secondary structure formed during transcription. Our modeling relies on standard Monte Carlo procedures and covers all essential stages of the process, including initiation and elongation of transcription and translation; the deceleration of …ribosome on regulatory codons, which depends on the concentration of charged amino acyl-tRNA; the polymerase shifting delay caused by secondary structure folded into the mRNA segment between ribosome and polymerase; and, ultimately, either transcription terminating prematurely or polymerase reaching a region of structural genes (antitermination). By means of Monte Carlo simulation we build a function p(c) which expresses the probability of termination (i.e., an enzyme activity) vs. the concentration of charged amino acyl-tRNA or of amino acid itself, measured in actual or relative units. Show more

Keywords: Classic attenuation, transcription regulation, mathematic modeling, web server implementation

Citation: In Silico Biology, vol. 7, no. 3, pp. 285-308, 2007

Authors: Rodin, Andrei S. | Rodin, Sergei N.

Article Type: Research Article

Abstract: The updated structural and phylogenetic analyses of tRNA pairs with complementary anticodons provide independent support for our earlier finding, namely that these tRNA pairs concertedly show complementary second bases in the acceptor stem. Two implications immediately follow: first, that a tRNA molecule gained its present, complete, cloverleaf shape via duplication(s) of a shorter precursor. Second, that common ancestry is shared by two major components of the genetic code within the tRNA molecule – the classic code …per se embodied in anticodon triplets, and the operational code of aminoacylation embodied primarily in the first three base pairs of the acceptor stems. In this communication we show that it might have been a double, sense-antisense, in-frame translation of the very first protein-encoding genes that directed the code's earliest expansion, thus preserving this fundamental dual-complementary link between acceptors and anticodons. Furthermore, the dual complementarity appears to be consistent with two mirror-symmetrical modes by which class I and II aminoacyl-tRNA synthetases recognize the cognate tRNAs – from the minor and major groove side of the acceptor stem, respectively. Show more

Keywords: RNA world, genetic code, double-strand coding, tRNA, aminoacyl-tRNA synthetase, aaRS

Citation: In Silico Biology, vol. 7, no. 3, pp. 309-318, 2007

Authors: Pintus, Sergey S. | Fomin, Eduard S. | Oshurkov, Ivan S. | Ivanisenko, Vladimir A.

Article Type: Research Article

Abstract: Proteins of the relative families p53 and p63/p73 are transcriptional factors that are involved in the signaling pathway in cells. The wide spectrum of their functions includes cell cycle arrest and apoptosis in response to DNA damage. The p53 protein also participates in development of particular tissues during embryogenesis. Thus, it is of high importance to establish the relation between structure, function and evolution of these proteins. In the current computational study, the evolutionary …mode of the p63/p73 protein family is investigated. Search for the adaptive branches of the phylogenetic tree and the adaptive codons in the nucleotide sequences was performed using the codeml program from the PAML package, version 3.14. The results obtained were compared with those of our previous phylogenetic analysis of the p53 protein. Evidence was obtained that the evolutionary history of the p63/p73 proteins has been under positive selection. An attempt is made to associate the current evidence with the previous for positive selection in the p53 family. Recently the G245C substitution has been assumed to result in formation of a novel Zn^{2+} -binding site in the p53 protein. The molecular mechanics simulations were performed to estimate energy of zinc binding to its site in two dominant-negative p53 mutants – G245C and R175H – in comparison with the wild-type p53. The results of the estimation provided evidence of the novel Zn^{2+} -binding site functionality in G245C mutant form. Show more

Keywords: p53, p63/p73, phylogenetic analysis, multiple alignment, positive selection, purifying selection

Citation: In Silico Biology, vol. 7, no. 3, pp. 319-332, 2007

Authors: Gunbin, Konstantin V. | Afonnikov, Dmitrij A. | Kolchanov, Nikolay A.

Article Type: Research Article

Abstract: Positive selection of genes that comprise signaling cascades and play the paramount role in the development of multicellular organisms is critical to our understanding of the reasons for the evolution of embryonic development. In this work, we analyze the evolution of 9 genes involved in the function of the Hh signaling cascade. We demonstrated that positive selection is a characteristic feature of the protein domains, encoded by gene regions, whose functions are related to the molecular …mechanisms of development. We also found that the positive selection of Hh-signaling cascade transcription factors, morphogens, their development-related receptors and intracellular signal transduction factors are related to the divergence of the Bilateria taxonomic types. Show more

Keywords: Hh-signaling cascade, positive selection, Bilateria, compensatory changes

Citation: In Silico Biology, vol. 7, no. 3, pp. 333-354, 2007