Gene family evolution: an in-depth theoretical and simulation analysis of non-linear birth-death-innovation models

BACKGROUND: The size distribution of gene families in a broad range of genomes is well approximated by a generalized Pareto function. Evolution of ensembles of gene families can be described with Birth, Death, and Innovation Models (BDIMs). Analysis of the properties of different versions of BDIMs has the potential of revealing important features of genome evolution. RESULTS: In this work, we extend our previous analysis of stochastic BDIMs. In addition to the previously examined rational BDIMs, we introduce potentially more realistic logistic BDIMs, in which birth/death rates are limited for the largest families, and show that their properties are similar to those of models that include no such limitation. We show that the mean time required for the formation of the largest gene families detected in eukaryotic genomes is limited by the mean number of duplications per gene and does not increase indefinitely with the model degree. Instead, this time reaches a minimum value, which corresponds to a non-linear rational BDIM with the degree of approximately 2.7. Even for this BDIM, the mean time of the largest family formation is orders of magnitude greater than any realistic estimates based on the timescale of life's evolution. We employed the embedding chains technique to estimate the expected number of elementary evolutionary events (gene duplications and deletions) preceding the formation of gene families of the observed size and found that the mean number of events exceeds the family size by orders of magnitude, suggesting a highly dynamic process of genome evolution. The variance of the time required for the formation of the largest families was found to be extremely large, with the coefficient of variation >> 1. This indicates that some gene families might grow much faster than the mean rate such that the minimal time required for family formation is more relevant for a realistic representation of genome evolution than the mean time. We determined this minimal time using Monte Carlo simulations of family growth from an ensemble of simultaneously evolving singletons. In these simulations, the time elapsed before the formation of the largest family was much shorter than the estimated mean time and was compatible with the timescale of evolution of eukaryotes. CONCLUSIONS: The analysis of stochastic BDIMs presented here shows that non-linear versions of such models can well approximate not only the size distribution of gene families but also the dynamics of their formation during genome evolution. The fact that only higher degree BDIMs are compatible with the observed characteristics of genome evolution suggests that the growth of gene families is self-accelerating, which might reflect differential selective pressure acting on different genes

Birth and death of protein domains: A simple model of evolution explains power law behavior

BACKGROUND: Power distributions appear in numerous biological, physical and other contexts, which appear to be fundamentally different. In biology, power laws have been claimed to describe the distributions of the connections of enzymes and metabolites in metabolic networks, the number of interactions partners of a given protein, the number of members in paralogous families, and other quantities. In network analysis, power laws imply evolution of the network with preferential attachment, i.e. a greater likelihood of nodes being added to pre-existing hubs. Exploration of different types of evolutionary models in an attempt to determine which of them lead to power law distributions has the potential of revealing non-trivial aspects of genome evolution. RESULTS: A simple model of evolution of the domain composition of proteomes was developed, with the following elementary processes: i) domain birth (duplication with divergence), ii) death (inactivation and/or deletion), and iii) innovation (emergence from non-coding or non-globular sequences or acquisition via horizontal gene transfer). This formalism can be described as a birth, death and innovation model (BDIM). The formulas for equilibrium frequencies of domain families of different size and the total number of families at equilibrium are derived for a general BDIM. All asymptotics of equilibrium frequencies of domain families possible for the given type of models are found and their appearance depending on model parameters is investigated. It is proved that the power law asymptotics appears if, and only if, the model is balanced, i.e. domain duplication and deletion rates are asymptotically equal up to the second order. It is further proved that any power asymptotic with the degree not equal to -1 can appear only if the hypothesis of independence of the duplication/deletion rates on the size of a domain family is rejected. Specific cases of BDIMs, namely simple, linear, polynomial and rational models, are considered in details and the distributions of the equilibrium frequencies of domain families of different size are determined for each case. We apply the BDIM formalism to the analysis of the domain family size distributions in prokaryotic and eukaryotic proteomes and show an excellent fit between these empirical data and a particular form of the model, the second-order balanced linear BDIM. Calculation of the parameters of these models suggests surprisingly high innovation rates, comparable to the total domain birth (duplication) and elimination rates, particularly for prokaryotic genomes. CONCLUSIONS: We show that a straightforward model of genome evolution, which does not explicitly include selection, is sufficient to explain the observed distributions of domain family sizes, in which power laws appear as asymptotic. However, for the model to be compatible with the data, there has to be a precise balance between domain birth, death and innovation rates, and this is likely to be maintained by selection. The developed approach is oriented at a mathematical description of evolution of domain composition of proteomes, but a simple reformulation could be applied to models of other evolving networks with preferential attachment

Особенности цитокинового профиля у детей с расстройством аутистического спектра

The aim of the study: to reveal the particularities of the concentration of cytokines IL4, IL6, IL10, IL17, IFNγ in blood serum in children with autism spectrum disorder (ASD).Materials and methods. The blood samples obtained from children of two study groups: children with autism spectrum disorder (n = 93) and clinically healthy children (n = 30), served as the material for the  study. Cytokine concentrations were determined in blood serum using the Bender Medsystems (Austria) kits  for IL17A and Vector-Best (Russia) kits for IL4, IL6, IL10, IFNγ. Serum cytokine concentrations were determined by enzyme immunoassay using kits for IL17A (Bender Medsystems, Austria), IL4, IL6, IL10, IFNγ (Vector-Best, Russia). Assessment of cognitive and psychophysiological indicators in children was performed using the  Autism Treatment Evaluation Checklist (ATEC).Results. The concentrations of IL17A (U = 54; p = 0,015) and IFNγ (U = 4.64; p = 0,006) were increased and the concentrations of IL6 (U = 327; p = 0.001) and IL4 (U = 177; p = 0.001) were decreased in children with ASD. The concentration of IL6 correlates with the concentration of IL4 (r = 0.68; p < 0.05). The concentration of IL17A correlates with the concentration of IFNγ (r = 0.41; p < 0.05), IL6 (r = 0.87; p < 0.05) and ATEC score (r = 0.24; p < 0.05) in the group of children with ASD.Conclusion. The cytokine disbalance in children with ADS, which was observed in our study, confirms the  hypothesis of their participation in the development of the disease and clearly shows the Th17  immunoregulation pathway in the pathogenesis of the autism spectrum disorder.Цель работы: выявить уровень концентрации цитокинов IL-4, I-L6, IL-10, IL-17, IFNγ в сыворотке крови у детей с расстройством аутистического спектра (РАС).Материалы и методы. Материалом исследования служили образцы крови, полученные от детей двух групп исследования: детей с расстройством аутистического спектра (n = 93) и клинически здоровых детей (n = 30). Средний возраст в обеих группах составил (7 ± 2) лет. В сыворотке крови методом иммуноферментного анализа определяли концентрацию цитокинов IL-17А (с применением набора Bender Medsystems, Австрия) и IL-4, IL-6, IL-10, IFNγ (Вектор-Бест, Россия). Оценку когнитивных и  психофизиологических показателей проводили с помощью анкеты Autism TreatmentEvaluation Checklist (АТЕС).Результаты. У детей с РАС повышены значения концентрации IL-17A (U = 54; p = 0,015) и IFNγ (U = 4,64; p = 0,006) и снижены – IL-6 (U = 327; p = 0,001) и IL-4 (U = 177; p = 0,001) по сравнению с этими показателями у детей в контрольной группе. Установлены корреляции между концентрацией IL-6 и IL-4 (r = 0,68; p < 0,05); между IL-17A и IFNγ (r = 0,41; p < 0,05), IL-6 (r = 0,87; p < 0,05), количеством баллов АТЕС (r = 0,24; p < 0,05) у детей с РАС.Заключение. Установленный нами дисбаланс цитокинов у детей с РАС подтверждает гипотезу его участия в развитии РАС и свидетельствует об Th17-направлении  иммунорегуляции в патогенезе расстройств аутистического спектра

Responses of grapevine genotypes to abiotic stress

Background. Salt stress reduces water supply and causes ionic imbalance in the plant, eventually leading to a decrease in plant growth, functional activity, and productivity. Variable salinity levels in the field make it difficult to select salt-tolerant cultivars, so a need for other testing methods arises.   Materials and methods. The plant material consisted of two own-rooted Vitis vinifera (L.) genotypes: cv. ‘Asma’, and hybrid M. No. 8-08-8-4 (‘Kok Pandas’ × ‘Zeibel 6357’). Salt stress was simulated by treating with NaCl at 0, 50, 80, 100, and 120 mM concentrations. Water status was measured by the leaf water potential (Ψ) using a pressure chamber. Changes in the leaf areaand total root length were assessed in vitro.   Results. Salt stress affected growth characteristics and yield structure of both own-rooted vines, but hybrid M. No. 8-08-8-4 was more sensitive. The hybrid showed greater yield reduction (38.6 %) than cv. ‘Asma’ (28.4 %), while the mass concentration of sugars was higher in ‘Asma’. The greatest differences in the predawn leaf water potential were observed for ‘Asma’ and M. No. 8-08-8-4 on the 45th day of irrigation with water containing different NaCl concentrations. The root length of the more salt-tolerant cultivar reduced in vitro to a greater extent.   Conclusion. The functional abilities of a cultivar depend on the level of salinization and the genotype. Cv. ‘Asma’ demonstrated higher salt tolerance compared to hybrid M. No. 8-08-8-4. Leaf water potentials characterizing the water status of plants were measured. The responses to salinization were the same in the vines grown in vivo and in vitro, so it is possible to perform testing for salt tolerance in vitro

Вектор пространственного развития регионов Енисейской Сибири: Красноярский край, Республика Хакасия, Республика Тыва

This article provides a comprehensive assessment of the natural resource potential of the Krasnoyarsk Territory, the Republics of Khakassia and Tuva as part of implementing the «Yenisei Siberia» project. In the introductory section of the article, the authors set out the goals and objectives of the study of the quantitative and qualitative characteristics of the socio-economic potential of the Krasnoyarsk Territory, Republic of Khakassia, Republic of Tuva and examine the role of implementing particularly important Yenisei Siberia investment projects in the economic development of the territories. The body of the article starts with the overall review in the form of economic and statistical analysis of the socio-economic conditions in the regions examined. It is followed by an attempt at a statistical measurement of the influence of particularly important investment projects («Southern Cluster», «Construction of the railway Elegest - Kyzyl - Kuragino», «Construction of the timber processing complex in the Boguchansky district of the Krasnoyarsk Territory» and «Agro-industrial Park «Siberia») on a summarizing indicator of the economic activity of the regions - gross regional product (GRP). The investment projects were examined using open data sources and official statistical information. By comparing the available information from various sources, the authors assessed the adequacy of the obtained results to the current situation and challenges of the new economy.В статье дана комплексная характеристика природно-ресурсного потенциала Красноярского края, республик Хакасия и Тыва в условиях реализации проекта «Енисейская Сибирь». В вводной части публикации формулируются цель и задачи выполненного исследования по количественно-качественной характеристике социально-экономического потенциала Красноярского края, Республики Хакасия, Республики Тыва и оценке роли реализации отдельных значимых инвестиционных проектов «Енисейская Сибирь» на развитие экономики территорий. В основной части статьи после общего обзора в формате экономико-статистического анализа социально-экономического положения рассматриваемых регионов предпринята попытка статистического измерения влияния отдельных значимых инвестиционных проектов («Южный кластер», «Строительство железнодорожной линии Элегест - Кызыл - Курагино», «Строительство лесопромышленного комплекса на территории Богучанского района Красноярского края» и «Агропромышленный парк «Сибирь») на обобщающий показатель экономической деятельности регионов - валовой региональный продукт (ВРП). Инвестиционные проекты рассмотрены с использованием данных открытых информационных ресурсов и официальной статистической информации. На основе сопоставления имеющейся информации из различных источников проведена оценка адекватности полученных результатов сложившимся реалиям и вызовам современной экономики

Somatic pathology and imbalance of sex hormone levels in men

The paper features materials from both Russian and foreign literature, describing the effects of sex hormones on the emergence and development of internal pathology in men. It also describes interconnections between causes and effects.В работе представлены материалы отечественной и зарубежной литературы по вопросам влияния половых гормонов на возникновение и развитие внутренней патологии у мужчин. Описаны причинно-следственные связи

How the other half lives: CRISPR-Cas's influence on bacteriophages

CRISPR-Cas is a genetic adaptive immune system unique to prokaryotic cells used to combat phage and plasmid threats. The host cell adapts by incorporating DNA sequences from invading phages or plasmids into its CRISPR locus as spacers. These spacers are expressed as mobile surveillance RNAs that direct CRISPR-associated (Cas) proteins to protect against subsequent attack by the same phages or plasmids. The threat from mobile genetic elements inevitably shapes the CRISPR loci of archaea and bacteria, and simultaneously the CRISPR-Cas immune system drives evolution of these invaders. Here we highlight our recent work, as well as that of others, that seeks to understand phage mechanisms of CRISPR-Cas evasion and conditions for population coexistence of phages with CRISPR-protected prokaryotes.Comment: 24 pages, 8 figure

MODIFICATION OF THE STRUCTURE OF CORROSION-RESISTANT STEEL BY ION NITRIDING

Исследовали четыре марки аустенитных коррозионно-стойких сталей 02Х16Н10М2, 08Х15АГ10Д2, 06Х15АГ9НМ2 и 09Х15АГ9НД2 после холодной пластической деформации и закалки от 1050 С в воде и последующей имплантации ионами N+ с разной дозой облучения. Путем имплантации ионов N+ с высокой дозой облучения на 50–60 % повысилась твердость исследованных сталей. Повышение прочности до 20 % получено в стали с исходно низким содержанием азота 02Х16Н10М2.Four marks of austenitic corrosion-resistant steels 02H16N10M2, 08H15AG10D2, 06X15AG9NM2 and 09X15AG9ND2 after cold plastic deformation and quenching from 1050 °C in water and subsequent implantation with N+ ions with different radiation dose were investigated. By implanting N+ ions with a high irradiation dose by 50–60 %, the hardness of the investigated steels has increased. The increase in strength up to 20 % is obtained in steel with an initially low nitrogen content of 02H16N10M2

Comparative web search questions

We analyze comparative questions, i.e., questions asking to compare different items, that were submitted to Yandex in 2012. Responses to such questions might be quite different from the simple “ten blue links” and could, for example, aggregate pros and cons of the different options as direct answers. However, changing the result presentation is an intricate decision such that the classification of comparative questions forms a highly precision-oriented task. From a year-long Yandex log, we annotate a random sample of 50,000 questions; 2.8% of which are comparative. For these annotated questions, we develop a precision-oriented classifier by combining carefully hand-crafted lexico-syntactic rules with feature-based and neural approaches—achieving a recall of 0.6 at a perfect precision of 1.0. After running the classifier on the full year log (on average, there is at least one comparative question per second), we analyze 6,250 comparative questions using more fine-grained subclasses (e.g., should the answer be a “simple” fact or rather a more verbose argument) for which individual classifiers are trained. An important insight is that more than 65% of the comparative questions demand argumentation and opinions, i.e., reliable direct answers to comparative questions require more than the facts from a search engine’s knowledge graph. In addition, we present a qualitative analysis of the underlying comparative information needs (separated into 14 categories like consumer electronics or health), their seasonal dynamics, and possible answers from community question answering platforms. © 2020 Copyright held by the owner/author(s).This work has been partially supported by the DFG through the project “ACQuA: Answering Comparative Questions with Arguments” (grants BI 1544/7-1 and HA 5851/2-1) as part of the priority program “RATIO: Robust Argumentation Machines” (SPP 1999). We thank Yandex and Mail.Ru for granting access to the data. The study was partially conducted during Pavel Braslavski’s research stay at the Bauhaus-Universität Weimar in 2018 supported by the DAAD. We also thank Ekaterina Shirshakova and Valentin Dittmar for their help in question annotation