Conservation versus parallel gains in intron evolution

Orthologous genes from distant eukaryotic species, e.g. animals and plants, share up to 25–30% intron positions. However, the relative contributions of evolutionary conservation and parallel gain of new introns into this pattern remain unknown. Here, the extent of independent insertion of introns in the same sites (parallel gain) in orthologous genes from phylogenetically distant eukaryotes is assessed within the framework of the protosplice site model. It is shown that protosplice sites are no more conserved during evolution of eukaryotic gene sequences than random sites. Simulation of intron insertion into protosplice sites with the observed protosplice site frequencies and intron densities shows that parallel gain can account but for a small fraction (5–10%) of shared intron positions in distantly related species. Thus, the presence of numerous introns in the same positions in orthologous genes from distant eukaryotes, such as animals, fungi and plants, appears to reflect mostly bona fide evolutionary conservation

Mutational hotspots in the TP53 gene and, possibly, other tumor suppressors evolve by positive selection

BACKGROUND: The mutation spectra of the TP53 gene and other tumor suppressors contain multiple hotspots, i.e., sites of non-random, frequent mutation in tumors and/or the germline. The origin of the hotspots remains unclear, the general view being that they represent highly mutable nucleotide contexts which likely reflect effects of different endogenous and exogenous factors shaping the mutation process in specific tissues. The origin of hotspots is of major importance because it has been suggested that mutable contexts could be used to infer mechanisms of mutagenesis contributing to tumorigenesis. RESULTS: Here we apply three independent tests, accounting for non-uniform base compositions in synonymous and non-synonymous sites, to test whether the hotspots emerge via selection or due to mutational bias. All three tests consistently indicate that the hotspots in the TP53 gene evolve, primarily, via positive selection. The results were robust to the elimination of the highly mutable CpG dinucleotides. By contrast, only one, the least conservative test reveals the signature of positive selection in BRCA1, BRCA2, and p16. Elucidation of the origin of the hotspots in these genes requires more data on somatic mutations in tumors. CONCLUSION: The results of this analysis seem to indicate that positive selection for gain-of-function in tumor suppressor genes is an important aspect of tumorigenesis, blurring the distinction between tumor suppressors and oncogenes. REVIEWERS: This article was reviewed by Sandor Pongor, Christopher Lee and Mikhail Blagosklonny

Evolutionary conservation suggests a regulatory function of AUG triplets in 50 -UTRs of eukaryotic genes

By comparing sequences of human, mouse and rat orthologous genes, we show that in 50 -untranslated regions (50 -UTRs) of mammalian cDNAs but not in 30 - UTRs or coding sequences, AUG is conserved to a significantly greater extent than any of the other 63 nt triplets. This effect is likely to reflect, primarily, bona fide evolutionary conservation, rather than cDNA annotation artifacts, because the excess of conserved upstream AUGs (uAUGs) is seen in 50 -UTRs containing stop codons in-frame with the start AUG and many of the conserved AUGs are found in different frames, consistent with the location in authentic non-coding sequences. Altogether, conserved uAUGs are present in at least 20–30% of mammalian genes. Qualitatively similar results were obtained by comparison of orthologous genes from different species of the yeast genus Saccharomyces. Together with the observation that mammalian and yeast 50 -UTRs are significantly depleted in overall AUG content, these findings suggest that AUG triplets in 50 -UTRs are subject to the pressure of purifying selection in two opposite directions: the uAUGs that have no specific function tend to be deleterious and get eliminated during evolution, whereas those uAUGs thatdoserveafunctionareconserved.Mostprobably, the principal role of the conserved uAUGs is attenuation of translation at the initiation stage, which is often additionally regulated by alternative splicing in the mammalian 50 -UTRs. Consistent with this hypothesis, we found that open reading frames starting from conserved uAUGs are significantly shorter than those starting from non-conserved uAUGs, possibly, owing to selection for optimization of the level of attenuation

Evolutionary conservation suggests a regulatory function of AUG triplets in 5′-UTRs of eukaryotic genes

By comparing sequences of human, mouse and rat orthologous genes, we show that in 5′-untranslated regions (5′-UTRs) of mammalian cDNAs but not in 3′-UTRs or coding sequences, AUG is conserved to a significantly greater extent than any of the other 63 nt triplets. This effect is likely to reflect, primarily, bona fide evolutionary conservation, rather than cDNA annotation artifacts, because the excess of conserved upstream AUGs (uAUGs) is seen in 5′-UTRs containing stop codons in-frame with the start AUG and many of the conserved AUGs are found in different frames, consistent with the location in authentic non-coding sequences. Altogether, conserved uAUGs are present in at least 20–30% of mammalian genes. Qualitatively similar results were obtained by comparison of orthologous genes from different species of the yeast genus Saccharomyces. Together with the observation that mammalian and yeast 5′-UTRs are significantly depleted in overall AUG content, these findings suggest that AUG triplets in 5′-UTRs are subject to the pressure of purifying selection in two opposite directions: the uAUGs that have no specific function tend to be deleterious and get eliminated during evolution, whereas those uAUGs that do serve a function are conserved. Most probably, the principal role of the conserved uAUGs is attenuation of translation at the initiation stage, which is often additionally regulated by alternative splicing in the mammalian 5′-UTRs. Consistent with this hypothesis, we found that open reading frames starting from conserved uAUGs are significantly shorter than those starting from non-conserved uAUGs, possibly, owing to selection for optimization of the level of attenuation

Results of determining the agrotechnical indicators of a flat cutter for fine tillage

In modern conditions, most soils are exposed to erosion processes. In this regard, it is necessary to control the amount of dust particles in the surface layer of the soil. Fine tillage with flat-cutting working bodies solves this issue by creating a finely cloddy soil structure of the upper fertile layer. The article considers the developed original design of a flat cutter for fine tillage. The results of experimental studies on the determination of agrotechnical indicators for the treated background and untreated stubble background are presented. In the course of the research, such indicators were established as: the average actual working depth, the standard deviation of the working depth from the given one, the coefficient of variation in the working depth, crumbling of the soil by the working bodies, the moisture content inside the reservoir, the number of erosion-dangerous particles in the surface soil layer. As a result of the research, it was found that the flat cutter qualitatively performs the specified depth of tillage with an acceptable deviation, the ridge size is in the range of 3.6-3.9 cm, which is allowed by agrotechnical requirements, the number of lumps up to 25 mm in size after the passage of the working body is 82-85% . With shallow tillage with a flat cutter, the removal of wet layers to the soil surface is not observed. The flat cutter can function qualitatively on an untreated stubble background as part of a combined unit that is not equipped with disk working bodies

ПРЕЦИЗІЙНІ СИСТЕМИ АВТОМАТИЧНОГО РЕГУЛЮВАННЯ ТУРБОГЕНЕРАТОРНИХ УСТАНОВОК

The article is devoted research and working out of scientific and technical and standard methods and means of improvement of indicators of quality developed turbogenerators by installations of power stations and their finishing to level of operating international standards. In work questions of working out and introduction of new effective technical decisions are considered, essentially reduce all kinds of static and dynamic errors and, thereby, raise accuracy of regulation and quality of the made electric power. Methods of structurally-parametrical synthesis of regulators of frequency and capacity concern such methods and decisions turbogenerators installations on the basis of return problems of dynamics, in particular.Статья посвящена исследованию и разработке научно-технических и нормативных методов и средств улучшения показателей качества вырабатываемой турбогенераторными установками электростанций и доведение их до уровня действующих международных стандартов. В работе рассмотрены вопросы разработки и внедрения новых эффективных технических решений, существенно уменьшают все виды статических и динамических погрешностей и, тем самым, повышают точность регулирования и качество производимой электроэнергии. К таким методам и решениям относятся, в частности, методы структурно-параметрического синтеза регуляторов частоты и мощности турбогенераторных установок на основе обратных задач динамики.Статтю присвячено дослідженню та розробці науково-технічних і нормативних методів і засобів поліпшення показників якості електроенергії, що виробляється турбогенераторними установками електростанцій і доведення їх до рівня діючих міжнародних стандартів. В роботі розглянуті питання розробки і впровадження нових ефективних технічних рішень, що суттєво зменшують всі види статичних і динамічних похибок і, тим самим, підвищують точність регулювання і якість виробляємої електроенергії. До таких методів і рішень відносяться, зокрема, методи структурно-параметричного синтезу регуляторів частоти та потужності турбогенераторних установок на основі зворотних задач динаміки

Protein composition of interband regions in polytene and cell line chromosomes of Drosophila melanogaster

<p>Abstract</p> <p>Background</p> <p>Despite many efforts, little is known about distribution and interactions of chromatin proteins which contribute to the specificity of chromomeric organization of interphase chromosomes. To address this issue, we used publicly available datasets from several recent Drosophila genome-wide mapping and annotation projects, in particular, those from modENCODE project, and compared molecular organization of 13 interband regions which were accurately mapped previously.</p> <p>Results</p> <p>Here we demonstrate that in interphase chromosomes of <it>Drosophila </it>cell lines, the interband regions are enriched for a specific set of proteins generally characteristic of the "open" chromatin (RNA polymerase II, CHRIZ (CHRO), BEAF-32, BRE1, dMI-2, GAF, NURF301, WDS and TRX). These regions also display reduced nucleosome density, histone H1 depletion and pronounced enrichment for ORC2, a pre-replication complex component. Within the 13 interband regions analyzed, most were around 3-4 kb long, particularly those where many of said protein features were present. We estimate there are about 3500 regions with similar properties in chromosomes of <it>D. melanogaster </it>cell lines, which fits quite well the number of cytologically observed interbands in salivary gland polytene chromosomes.</p> <p>Conclusions</p> <p>Our observations suggest strikingly similar organization of interband chromatin in polytene chromosomes and in chromosomes from cell lines thereby reflecting the existence of a universal principle of interphase chromosome organization.</p

Paucity and preferential suppression of transgenes in late replication domains of the D. melanogaster genome

<p>Abstract</p> <p>Background</p> <p>Eukaryotic genomes are organized in extended domains with distinct features intimately linking genome structure, replication pattern and chromatin state. Recently we identified a set of long late replicating euchromatic regions that are underreplicated in salivary gland polytene chromosomes of <it>D. melanogaster</it>.</p> <p>Results</p> <p>Here we demonstrate that these underreplicated regions (URs) have a low density of <it>P</it>-<it>element </it>and <it>piggyBac </it>insertions compared to the genome average or neighboring regions. In contrast, <it>Minos</it>-based transposons show no paucity in URs but have a strong bias to testis-specific genes. We estimated the suppression level in 2,852 stocks carrying a single <it>P</it>-<it>element </it>by analysis of eye color determined by the mini-<it>white </it>marker gene and demonstrate that the proportion of suppressed transgenes in URs is more than three times higher than in the flanking regions or the genomic average. The suppressed transgenes reside in intergenic, genic or promoter regions of the annotated genes. We speculate that the low insertion frequency of <it>P-elemen</it>ts and <it>piggyBac</it>s in URs partially results from suppression of transgenes that potentially could prevent identification of transgenes due to complete suppression of the marker gene. In a similar manner, the proportion of suppressed transgenes is higher in loci replicating late or very late in Kc cells and these loci have a lower density of <it>P-elements </it>and <it>piggyBac </it>insertions. In transgenes with two marker genes suppression of mini-<it>white </it>gene in eye coincides with suppression of <it>yellow </it>gene in bristles.</p> <p>Conclusions</p> <p>Our results suggest that the late replication domains have a high inactivation potential apparently linked to the silenced or closed chromatin state in these regions, and that such inactivation potential is largely maintained in different tissues.</p

ОПРЕДЕЛЕНИЕ ОПТИМАЛЬНОГО РАСХОДА ЦИРКУЛЯЦИОННОЙ ВОДЫ В КОНДЕНСАТОРАХ ТЕПЛОВЫХ И АТОМНЫХ ЭЛЕКТРОСТАНЦИЙ

В статье рассмотрены подходы к решению важной технической задачи в тепловой и атомной энергетике относительно определения оптимального расхода циркуляционной воды в конденсаторах станций. Определены критерии оптимальности и приведены основные аналитические зависимости, которые определяют оптимальный расход

ДОСВІД ЗАСТОСУВАННЯ АКТИВАТОРА ГОРІННЯ «АР-ГЕН-Ф» НА БЛОЦІ 200 МВТ ЗМІЇВСЬКОЇ ТЕС

In the article practical experience of application of activator of burning of «AR-GEN-F» is considered on a block 200 MVt Zmievskoy TES. Descriptions of work of caldron of block are rotined 200 MVt of s/bez activator in the different modes of loadings, influence of activator is certain on the process of burning and positive effect of his use. On the basis of tests conclusions are done about practical application of activator of burning of «AR-GEN-F».В статье рассмотрен практический опыт применения активатора горения «АР-ГЕН-Ф» на блоке 200 МВт Змиевской ТЭС. Показаны характеристики работы котла блока 200 МВт с/без активатора в различных режимах нагрузок, определено влияние активатора на процесс горения и положительный эффект его использования. На основе испытаний сделаны выводы о практическом применении активатора горения «АР-ГЕН-Ф».У статті розглянуто практичний досвід застосування активатора горіння «АР-ГЕН-Ф» на блоці 200 МВт Зміївської ТЕС. Показано характеристики роботи котла блоку 200 МВт з/без активатора в різних режимах навантажень, визначено вплив активатора на процес горіння й позитивний ефект його використання. На основі випробувань зроблено висновки щодо практичного застосування активатора горіння «АР-ГЕН-Ф»