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1.
Biol Direct ; 18(1): 45, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37568147

RESUMO

BACKGROUND: It is generally accepted that most evolutionary transformations at the phenotype level are associated either with rearrangements of genomic regulatory elements, which control the activity of gene networks, or with changes in the amino acid contents of proteins. Recently, evidence has accumulated that significant evolutionary transformations could also be associated with the loss/emergence of whole genes. The targeted identification of such genes is a challenging problem for both bioinformatics and evo-devo research. RESULTS: To solve this problem we propose the WINEGRET method, named after the first letters of the title. Its main idea is to search for genes that satisfy two requirements: first, the desired genes were lost/emerged at the same evolutionary stage at which the phenotypic trait of interest was lost/emerged, and second, the expression of these genes changes significantly during the development of the trait of interest in the model organism. To verify the first requirement, we do not use existing databases of orthologs, but rely purely on gene homology and local synteny by using some novel quickly computable conditions. Genes satisfying the second requirement are found by deep RNA sequencing. As a proof of principle, we used our method to find genes absent in extant amniotes (reptiles, birds, mammals) but present in anamniotes (fish and amphibians), in which these genes are involved in the regeneration of large body appendages. As a result, 57 genes were identified. For three of them, c-c motif chemokine 4, eotaxin-like, and a previously unknown gene called here sod4, essential roles for tail regeneration were demonstrated. Noteworthy, we established that the latter gene belongs to a novel family of Cu/Zn-superoxide dismutases lost by amniotes, SOD4. CONCLUSIONS: We present a method for targeted identification of genes whose loss/emergence in evolution could be associated with the loss/emergence of a phenotypic trait of interest. In a proof-of-principle study, we identified genes absent in amniotes that participate in body appendage regeneration in anamniotes. Our method provides a wide range of opportunities for studying the relationship between the loss/emergence of phenotypic traits and the loss/emergence of specific genes in evolution.


Assuntos
Mamíferos , Animais
2.
Life (Basel) ; 10(9)2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32927891

RESUMO

An original bioinformatics technique is developed to identify the protein-coding genes in rodents, lagomorphs and nonhuman primates that are pseudogenized in humans. The method is based on per-gene verification of local synteny, similarity of exon-intronic structures and orthology in a set of genomes. It is applicable to any genome set, even with the number of genomes exceeding 100, and efficiently implemented using fast computer software. Only 50 evolutionary recent human pseudogenes were predicted. Their functional homologs in model species are often associated with the immune system or digestion and mainly express in the testes. According to current evidence, knockout of most of these genes leads to an abnormal phenotype. Some genes were pseudogenized or lost independently in human and nonhuman hominoids.

3.
Biomed Res Int ; 2020: 3465380, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32025518

RESUMO

The lengths of intergenic regions between neighboring genes that are convergent, divergent, or unidirectional were calculated for plastids of the rhodophytic branch and complete archaeal and bacterial genomes. Statistically significant linear relationships between any pair of the medians of these three length types have been revealed in each genomic group. Exponential relationships between the optimal growth temperature and each of the three medians have been revealed as well. The leading coefficients of the regression equations relating all pairs of the medians as well as temperature and any of the medians have the same sign and order of magnitude. The results obtained for plastids, archaea, and bacteria are also similar at the qualitative level. For instance, the medians are always low at high temperatures. At low temperatures, the medians tend to statistically significant greater values and scattering. The original model was used to test our hypothesis that the intergenic distances are optimized in particular to decrease the competition of RNA polymerases within the locus that results in transcribing shortened RNAs. Overall, this points to an effect of temperature for both remote and close genomes.


Assuntos
Archaea/crescimento & desenvolvimento , Archaea/genética , Bactérias/crescimento & desenvolvimento , Bactérias/genética , Plastídeos/genética , Plastídeos/fisiologia , Temperatura , Archaea/metabolismo , Proteínas Arqueais/genética , Bactérias/metabolismo , Proteínas de Bactérias/genética , Técnicas de Cultura de Células , Proteínas de Cloroplastos/genética , Evolução Molecular , Genoma Arqueal , Genoma Bacteriano , Genomas de Plastídeos , Modelos Lineares , Plastídeos/metabolismo
4.
Oxid Med Cell Longev ; 2019: 2901057, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781330

RESUMO

Cardiolipin interacts with many proteins of the mitochondrial inner membrane and, together with cytochrome C and creatine kinase, activates them. It can be considered as an integrating factor for components of the mitochondrial respiratory chain, which provides for an efficient transfer of electrons and protons. The major, if not the only, factor of cardiolipin maturation is tafazzin. Variations of isoform proportions of this enzyme can cause severe diseases such as Barth syndrome. Using bioinformatic methods, we have found conserved C-terminal regions in many tafazzin isoforms and identified new mammalian species that acquired exon 5 as well as rare occasions of intron retention between exons 8 and 9. The regions in the C-terminal part arise from frameshifts relative to the full-length TAZ transcript after skipping exon 9 or retention of the intron between exons 10 and 11. These modifications demonstrate specific distribution among the orders of mammals. The dependence of the species maximum lifespan, body weight, and mitochondrial metabolic rate on the modifications has been demonstrated. Arguably, unconventional tafazzin isoforms provide for the optimal balance between the increased biochemical activity of mitochondria (resulting from specific environmental or nutritional conditions) and lifespan maintenance; and the functional role of such isoforms is linked to the modification of the primary and secondary structures at their C-termini.


Assuntos
Síndrome de Barth/metabolismo , Cardiolipinas/metabolismo , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Fatores de Transcrição/metabolismo , Aciltransferases , Animais , Síndrome de Barth/genética , Síndrome de Barth/patologia , Cardiolipinas/genética , Transporte de Elétrons/genética , Humanos , Mitocôndrias/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Fatores de Transcrição/genética
5.
BioData Min ; 12: 20, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31728160

RESUMO

BACKGROUND: Gerontogenes include those that modulate life expectancy in various species and may be the actual longevity genes. We believe that a long (relative to body weight) lifespan in individual rodent and primate species can be due, among other things, to the loss of particular genes that are present in short-lived species of the same orders. These genes can also explain the widely different rates of aging among diverse species as well as why similarly sized rodents or primates sometimes have anomalous life expectancies (e.g., naked mole-rats and humans). Here, we consider the gene loss in the context of the prediction of Williams' theory that concerns the reallocation of physiological resources of an organism between active reproduction (r-strategy) and self-maintenance (K-strategy). We have identified such lost genes using an original computer-aided approach; the software considers the loss of a gene as disruptions in gene orthology, local gene synteny or both. RESULTS: A method and software identifying the genes that are absent from a predefined set of species but present in another predefined set of species are suggested. Examples of such pairs of sets include long-lived vs short-lived, homeothermic vs poikilothermic, amniotic vs anamniotic, aquatic vs terrestrial, and neotenic vs nonneotenic species, among others. Species are included in one of two sets according to the property of interest, such as longevity or homeothermy. The program is universal towards these pairs, i.e., towards the underlying property, although the sets should include species with quality genome assemblies. Here, the proposed method was applied to study the longevity of Euarchontoglires species. It largely predicted genes that are highly expressed in the testis, epididymis, uterus, mammary glands, and the vomeronasal and other reproduction-related organs. This agrees with Williams' theory that hypothesizes a species transition from r-strategy to K-strategy. For instance, the method predicts the mouse gene Smpd5, which has an expression level 20 times greater in the testis than in organs unrelated to reproduction as experimentally demonstrated elsewhere. At the same time, its paralog Smpd3 is not predicted by the program and is widely expressed in many organs not specifically related to reproduction. CONCLUSIONS: The method and program, which were applied here to screen for gene losses that can accompany increased lifespan, were also applied to study reduced regenerative capacity and development of the telencephalon, neoteny, etc. Some of these results have been carefully tested experimentally. Therefore, we assume that the method is widely applicable.

6.
Cell Rep ; 29(4): 1027-1040.e6, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31644900

RESUMO

The molecular basis of higher regenerative capacity of cold-blooded animals comparing to warm-blooded ones is poorly understood. Although this difference in regenerative capacities is commonly thought to be a result of restructuring of the same regulatory gene network, we hypothesized that it may be due to loss of some genes essential for regeneration. We describe here a bioinformatic method that allowed us to identify such genes. For investigation in depth we selected one of them encoding transmembrane protein, named "c-Answer." Using the Xenopus laevis frog as a model cold-blooded animal, we established that c-Answer regulates regeneration of body appendages and telencephalic development through binding to fibroblast growth factor receptors (FGFRs) and P2ry1 receptors and promoting MAPK/ERK and purinergic signaling. This suggests that elimination of c-answer in warm-blooded animals could lead to decreased activity of at least two signaling pathways, which in turn might contribute to changes in mechanisms regulating regeneration and telencephalic development.


Assuntos
Encéfalo/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Neurogênese , Regeneração , Animais , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiologia , Biologia Computacional , Sistema de Sinalização das MAP Quinases , Receptores de Fatores de Crescimento de Fibroblastos/genética , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Receptores Purinérgicos P2Y1/genética , Receptores Purinérgicos P2Y1/metabolismo , Xenopus laevis
7.
Front Genet ; 10: 443, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31178892

RESUMO

Two enigmatic groups of morphologically simple parasites of invertebrates, the Dicyemida (syn. Rhombozoa) and the Orthonectida, since the 19th century have been usually considered as two classes of the phylum Mesozoa. Early molecular evidence suggested their relationship within the Spiralia (=Lophotrochozoa), however, high rates of dicyemid and orthonectid sequence evolution led to contradicting phylogeny reconstructions. Genomic data for orthonectids revealed that they are highly simplified spiralians and possess a reduced set of genes involved in metazoan development and body patterning. Acquiring genomic data for dicyemids, however, remains a challenge due to complex genome rearrangements including chromatin diminution and generation of extrachromosomal circular DNAs, which are reported to occur during the development of somatic cells. We performed genomic sequencing of one species of Dicyema, and obtained transcriptomic data for two Dicyema spp. Homeodomain (homeobox) transcription factors, G-protein-coupled receptors, and many other protein families have undergone a massive reduction in dicyemids compared to other animals. There is also apparent reduction of the bilaterian gene complements encoding components of the neuromuscular systems. We constructed and analyzed a large dataset of predicted orthologous proteins from three species of Dicyema and a set of spiralian animals including the newly sequenced genome of the orthonectid Intoshia linei. Bayesian analyses recovered the orthonectid lineage within the Annelida. In contrast, dicyemids form a separate clade with weak affinity to the Rouphozoa (Platyhelminthes plus Gastrotricha) or (Entoprocta plus Cycliophora) suggesting that the historically proposed Mesozoa is a polyphyletic taxon. Thus, dramatic simplification of body plans in dicyemids and orthonectids, as well as their intricate life cycles that combine metagenesis and heterogony, evolved independently in these two lineages.

8.
Life (Basel) ; 7(1)2017 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-28264444

RESUMO

Recent phylogenetic analyses are incorporating ultraconserved elements (UCEs) and highly conserved elements (HCEs). Models of evolution of the genome structure and HCEs initially faced considerable algorithmic challenges, which gave rise to (often unnatural) constraints on these models, even for conceptually simple tasks such as the calculation of distance between two structures or the identification of UCEs. In our recent works, these constraints have been addressed with fast and efficient solutions with no constraints on the underlying models. These approaches have led us to an unexpected result: for some organelles and taxa, the genome structure and HCE set, despite themselves containing relatively little information, still adequately resolve the evolution of species. We also used the HCE identification to search for promoters and regulatory elements that characterize the functional evolution of the genome.

9.
BMC Bioinformatics ; 17: 385, 2016 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-27645252

RESUMO

BACKGROUND: Perfectly or highly conserved DNA elements were found in vertebrates, invertebrates, and plants by various methods. However, little is known about such elements in protists. The evolutionary distance between apicomplexans can be very high, in particular, due to the positive selection pressure on them. This complicates the identification of highly conserved elements in alveolates, which is overcome by the proposed algorithm. RESULTS: A novel algorithm is developed to identify highly conserved DNA elements. It is based on the identification of dense subgraphs in a specially built multipartite graph (whose parts correspond to genomes). Specifically, the algorithm does not rely on genome alignments, nor pre-identified perfectly conserved elements; instead, it performs a fast search for pairs of words (in different genomes) of maximum length with the difference below the specified edit distance. Such pair defines an edge whose weight equals the maximum (or total) length of words assigned to its ends. The graph composed of these edges is then compacted by merging some of its edges and vertices. The dense subgraphs are identified by a cellular automaton-like algorithm; each subgraph defines a cluster composed of similar inextensible words from different genomes. Almost all clusters are considered as predicted highly conserved elements. The algorithm is applied to the nuclear genomes of the superphylum Alveolata, and the corresponding phylogenetic tree is built and discussed. CONCLUSION: We proposed an algorithm for the identification of highly conserved elements. The multitude of identified elements was used to infer the phylogeny of Alveolata.


Assuntos
Algoritmos , Alveolados/classificação , Alveolados/genética , Sequência Conservada , Análise de Sequência de DNA/métodos , Sequência de Bases , DNA/química , Evolução Molecular , Genoma , Filogenia
10.
Biol Direct ; 11(1): 20, 2016 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-27084079

RESUMO

Short leader genes usually do not encode stable proteins, although their importance in expression control of bacterial genomes is widely accepted. Such genes are often involved in the control of attenuation regulation. However, the abundance of leader genes suggests that their role in bacteria is not limited to regulation. Specifically, we hypothesize that leader genes increase the expression of protein-coding (structural) genes via ribosome reinitiation at the leader peptide in the case of a short distance between the stop codon of the leader gene and the start codon of the structural gene. For instance, in Actinobacteria, the frequency of leader genes at a distance of 10-11 bp is about 70 % higher than the mean frequency within the 1 to 65 bp range; and it gradually decreases as the range grows longer. A pronounced peak of this frequency-distance relationship is also observed in Proteobacteria, Bacteroidetes, Spirochaetales, Acidobacteria, the Deinococcus-Thermus group, and Planctomycetes. In contrast, this peak falls to the distance of 15-16 bp and is not very pronounced in Firmicutes; and no such peak is observed in cyanobacteria and tenericutes. Generally, this peak is typical for many bacteria. Some leader genes located close to a structural gene probably play a regulatory role as well.


Assuntos
Proteínas de Bactérias/metabolismo , Sinais Direcionadores de Proteínas/fisiologia , Ribossomos/metabolismo , Acidobacteria/metabolismo , Actinobacteria/metabolismo , Bacteroidetes/metabolismo , Spirochaetales/metabolismo
11.
Biomed Res Int ; 2015: 510598, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26114108

RESUMO

We report the database of plastid protein families from red algae, secondary and tertiary rhodophyte-derived plastids, and Apicomplexa constructed with the novel method to infer orthology. The families contain proteins with maximal sequence similarity and minimal paralogous content. The database contains 6509 protein entries, 513 families and 278 nonsingletons (from which 230 are paralog-free, and among the remaining 48, 46 contain at maximum two proteins per species, and 2 contain at maximum three proteins per species). The method is compared with other approaches. Expression regulation of the moeB gene is studied using this database and the model of RNA polymerase competition. An analogous database obtained for green algae and their symbiotic descendants, and applications based on it are published earlier.


Assuntos
Evolução Biológica , Proteínas de Cloroplastos/genética , Rodófitas/genética , Simbiose/genética , Apicomplexa/genética , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Proteínas de Cloroplastos/biossíntese , Bases de Dados de Proteínas , Regulação da Expressão Gênica , Filogenia , Plastídeos/genética
12.
Biomed Res Int ; 2015: 452958, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26114107

RESUMO

In general, the mechanism of protein translocation through the apicoplast membrane requires a specific extension of a functionally important region of the apicoplast-targeted proteins. The corresponding signal peptides were detected in many apicomplexans but not in the majority of apicoplast-targeted proteins in Toxoplasma gondii. In T. gondii signal peptides are either much diverged or their extension region is processed, which in either case makes the situation different from other studied apicomplexans. We propose a statistic method to compare extensions of the functionally important regions of apicoplast-targeted proteins. More specifically, we provide a comparison of extension lengths of orthologous apicoplast-targeted proteins in apicomplexan parasites. We focus on results obtained for the model species T. gondii, Neospora caninum, and Plasmodium falciparum. With our method, cross species comparisons demonstrate that, in average, apicoplast-targeted protein extensions in T. gondii are 1.5-fold longer than in N. caninum and 2-fold longer than in P. falciparum. Extensions in P. falciparum less than 87 residues in size are longer than the corresponding extensions in N. caninum and, reversely, are shorter if they exceed 88 residues.


Assuntos
Apicoplastos/metabolismo , Parasitos/metabolismo , Proteínas/genética , Toxoplasma/metabolismo , Sequência de Aminoácidos , Animais , Apicoplastos/genética , Humanos , Malária Falciparum/parasitologia , Neospora/metabolismo , Neospora/patogenicidade , Parasitos/genética , Plasmodium falciparum/metabolismo , Plasmodium falciparum/patogenicidade , Sinais Direcionadores de Proteínas/genética , Proteínas/metabolismo , Toxoplasma/patogenicidade
13.
Comput Biol Chem ; 49: 7-13, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24513779

RESUMO

The paper studies proteins with domains PF00480 or PF14340, as well as some other poorly characterized proteins, encoded by genes associated with leader peptide genes containing a tract of cysteine codons. Such proteins are hypothetically regulated with cysteine-dependent transcription attenuation, namely the Rho-dependent or classic transcription attenuation. Cysteine is an important structural amino acid in various proteins and is required for synthesis of many sulfur-containing compounds, such as methionine, thiamine, glutathione, taurine and the lipoic acid. Earlier a few species of mycobacteria were predicted by the authors to have cysteine-dependent regulation of operons containing the cysK gene. In Escherichia coli this regulation is absent, and the same operon is regulated by the CysB transcription activator. The paper also studies Rho-dependent and classic transcription regulations in all annotated genes of mycobacteria available in GenBank and their orthologs in Actinomycetales. We predict regulations for many genes involved in sulfur metabolism and transport of sulfur-containing compounds; these regulations differ considerably among species. On the basis of predictions, we assign a putative role to proteins encoded by the regulated genes with unknown function, and also describe the structure of corresponding regulons, predict the lack of such regulations for many genes. Thus, all proteins with the uncharacterized Pfam domains PF14340 and PF00480, as well as some others, are predicted to be involved in sulfur metabolism. We also surmise the affinity of some transporters to sulfur-containing compounds. The obtained results considerably extend earlier large-scale studies of Rho-dependent and classic transcription attenuations.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica/genética , Enxofre/metabolismo , Actinomycetales/química , Algoritmos , Sequência de Aminoácidos , Proteínas de Bactérias/química , Mycobacteriaceae/química , Estrutura Terciária de Proteína , Alinhamento de Sequência
14.
Biomed Res Int ; 2013: 413450, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24073405

RESUMO

This study considers transcription regulation of plastid genes involved in sulfate transport in the parasites of invertebrate (Helicosporidium sp.) and other species of the Viridiplantae. A one-box conserved motif with the consensus TAAWATGATT is found near promoters upstream the cysT and cysA genes in many species. In certain cases, the motif is repeated two or three times.


Assuntos
Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Plastídeos/genética , Sulfatos/metabolismo , Transcrição Gênica , Viridiplantae/genética , Viridiplantae/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Transporte Biológico/genética , Sequência Conservada/genética , Dados de Sequência Molecular , Motivos de Nucleotídeos/genética , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Estrutura Terciária de Proteína , Alinhamento de Sequência , Synechocystis/genética , Synechocystis/metabolismo
15.
Biol Direct ; 7: 26, 2012 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-22873568

RESUMO

BACKGROUND: In previous work, we introduced a concept, a mathematical model and its computer realization that describe the interaction between bacterial and phage type RNA polymerases, protein factors, DNA and RNA secondary structures during transcription, including transcription initiation and termination. The model accurately reproduces changes of gene transcription level observed in polymerase sigma-subunit knockout and heat shock experiments in plant plastids. The corresponding computer program and a user guide are available at http://lab6.iitp.ru/en/rivals. Here we apply the model to the analysis of transcription and (partially) translation processes in the mitochondria of frog, rat and human. Notably, mitochondria possess only phage-type polymerases. We consider the entire mitochondrial genome so that our model allows RNA polymerases to complete more than one circle on the DNA strand. RESULTS: Our model of RNA polymerase interaction during transcription initiation and elongation accurately reproduces experimental data obtained for plastids. Moreover, it also reproduces evidence on bulk RNA concentrations and RNA half-lives in the mitochondria of frog, human with or without the MELAS mutation, and rat with normal (euthyroid) or hyposecretion of thyroid hormone (hypothyroid). The transcription characteristics predicted by the model include: (i) the fraction of polymerases terminating at a protein-dependent terminator in both directions (the terminator polarization), (ii) the binding intensities of the regulatory protein factor (mTERF) with the termination site and, (iii) the transcription initiation intensities (initiation frequencies) of all promoters in all five conditions (frog, healthy human, human with MELAS syndrome, healthy rat, and hypothyroid rat with aberrant mtDNA methylation). Using the model, absolute levels of all gene transcription can be inferred from an arbitrary array of the three transcription characteristics, whereas, for selected genes only relative RNA concentrations have been experimentally determined. Conversely, these characteristics and absolute transcription levels can be obtained using relative RNA concentrations and RNA half-lives known from various experimental studies. In this case, the "inverse problem" is solved with multi-objective optimization. CONCLUSIONS: In this study, we demonstrate that our model accurately reproduces all relevant experimental data available for plant plastids, as well as the mitochondria of chordates. Using experimental data, the model is applied to estimate binding intensities of phage-type RNA polymerases to their promoters as well as predicting terminator characteristics, including polarization. In addition, one can predict characteristics of phage-type RNA polymerases and the transcription process that are difficult to measure directly, e.g., the association between the promoter's nucleotide composition and the intensity of polymerase binding. To illustrate the application of our model in functional predictions, we propose a possible mechanism for MELAS syndrome development in human involving a decrease of Phe-tRNA, Val-tRNA and rRNA concentrations in the cell. In addition, we describe how changes in methylation patterns of the mTERF binding site and three promoters in hypothyroid rat correlate with changes in intensities of the mTERF binding and transcription initiations. Finally, we introduce an auxiliary model to describe the interaction between polysomal mRNA and ribonucleases.


Assuntos
RNA Polimerases Dirigidas por DNA/metabolismo , Mitocôndrias/enzimologia , Modelos Moleculares , Regiões Promotoras Genéticas , Animais , Anuros/genética , Anuros/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Sítios de Ligação , Chaperonina 60/genética , Chaperonina 60/metabolismo , Metilação de DNA , RNA Polimerases Dirigidas por DNA/genética , Genoma Mitocondrial , Meia-Vida , Humanos , Hipotireoidismo/enzimologia , Hipotireoidismo/genética , Síndrome MELAS/enzimologia , Síndrome MELAS/genética , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Polirribossomos/enzimologia , Polirribossomos/genética , Mapeamento de Interação de Proteínas/métodos , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Ratos , Reprodutibilidade dos Testes , Transcrição Gênica
16.
Biol Direct ; 6: 3, 2011 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-21255416

RESUMO

BACKGROUND: Modeling of a complex biological process can explain the results of experimental studies and help predict its characteristics. Among such processes is transcription in the presence of competing RNA polymerases. This process involves RNA polymerases collision followed by transcription termination. RESULTS: A mathematical and computer simulation model is developed to describe the competition of RNA polymerases during genes transcription on complementary DNA strands. E.g., in the barley Hordeum vulgare the polymerase competition occurs in the locus containing plastome genes psbA, rpl23, rpl2 and four bacterial type promoters. In heat shock experiments on isolated chloroplasts, a twofold decrease of psbA transcripts and even larger increase of rpl23-rpl2 transcripts were observed, which is well reproduced in the model. The model predictions are in good agreement with virtually all relevant experimental data (knockout, heat shock, chromatogram data, etc.). The model allows to hypothesize a mechanism of cell response to knockout and heat shock, as well as a mechanism of gene expression regulation in presence of RNA polymerase competition. The model is implemented for multiprocessor platforms with MPI and supported on Linux and MS Windows. The source code written in C++ is available under the GNU General Public License from the laboratory website. A user-friendly GUI version is also provided at http://lab6.iitp.ru/en/rivals. CONCLUSIONS: The developed model is in good agreement with virtually all relevant experimental data. The model can be applied to estimate intensities of binding of the holoenzyme and phage type RNA polymerase to their promoters using data on gene transcription levels, as well as to predict characteristics of RNA polymerases and the transcription process that are difficult to measure directly, e.g., the intensity (frequency) of holoenzyme binding to the promoter in correlation to its nucleotide composition and the type of σ-subunit, the amount of transcription initiation aborts, etc. The model can be used to make functional predictions, e.g., heat shock response in isolated chloroplasts and changes of gene transcription levels under knockout of different σ-subunits or RNA polymerases or due to gene expression regulation.


Assuntos
RNA Polimerases Dirigidas por DNA/metabolismo , Regulação da Expressão Gênica de Plantas , Técnicas de Silenciamento de Genes , Resposta ao Choque Térmico/genética , Modelos Genéticos , Fator sigma/genética , Transcrição Gênica , Algoritmos , Arabidopsis/fisiologia , Cloroplastos/fisiologia , Simulação por Computador , DNA/metabolismo , RNA Polimerases Dirigidas por DNA/química , RNA Polimerases Dirigidas por DNA/deficiência , RNA Polimerases Dirigidas por DNA/genética , Hordeum/fisiologia , Internet , Regiões Promotoras Genéticas , Ligação Proteica/genética , Software
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