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https://www.readbyqxmd.com/read/28525580/a-new-formulation-of-random-genetic-drift-and-its-application-to-the-evolution-of-cell-populations
#1
Yuxin Chen, Ding Tong, Chung-I Wu
Random genetic drift, or stochastic change in gene frequency, is a fundamental evolutionary force that is usually defined within the ideal Wright-Fisher (WF) population. However, as the theory is increasingly applied to populations that deviate strongly from the ideal model, a paradox of random drift has emerged. When drift is defined by the WF model, it becomes stronger as the population size, N, decreases. However, the intensity of competition decreases when N decreases and, hence, drift might become weaker...
May 19, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28523547/dna-methylation-in-major-depressive-disorder
#2
Ehsan Pishva, Bart P F Rutten, Daniel van den Hove
Epigenetic mechanisms regulate gene expression, influencing protein levels and ultimately shaping phenotypes during life. However, both stochastic epigenetic variations and environmental reprogramming of the epigenome might influence neurodevelopment and ageing, and this may contribute to the origins of mental ill-health. Studying the role of epigenetic mechanisms is challenging, as genotype-, tissue- and cell type-dependent epigenetic changes have to be taken into account, while the nature of mental disorders also poses significant challenges for linking them with biological profiles...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28522611/long-terminal-repeats-power-evolution-of-genes-and-gene-expression-programs-in-mammalian-oocytes-and-zygotes
#3
Vedran Franke, Sravya Ganesh, Rosa Karlic, Radek Malik, Josef Pasulka, Filip Horvat, Maja Kuzman, Helena Fulka, Marketa Cernohorska, Jana Urbanova, Eliska Svobodova, Jun Ma, Yutaka Suzuki, Fugaku Aoki, Richard M Schultz, Kristian Vlahovicek, Petr Svoboda
Retrotransposons are 'copy-and-paste' insertional mutagens that substantially contribute to mammalian genome content. Retrotransposons often carry long terminal repeats (LTRs) for retrovirus-like reverse transcription and integration into the genome. We report an extraordinary impact of a group of LTRs from the mammalian endogenous retrovirus-related ERVL retrotransposon class on gene expression in the germline and beyond. In mouse, we identified >800 LTRs from ORR1, MT, MT2, and MLT families, which resemble mobile gene-remodeling platforms that supply promoters and first exons...
May 18, 2017: Genome Research
https://www.readbyqxmd.com/read/28521011/translation-initiation-events-on-structured-eukaryotic-mrnas-generate-gene-expression-noise
#4
Estelle Dacheux, Naglis Malys, Xiang Meng, Vinoy Ramachandran, Pedro Mendes, John Eg McCarthy
Gene expression stochasticity plays a major role in biology, creating non-genetic cellular individuality and influencing multiple processes, including differentiation and stress responses. We have addressed the lack of knowledge about posttranscriptional contributions to noise by determining cell-to-cell variations in the abundance of mRNA and reporter protein in yeast. Two types of structural element, a stem-loop and a poly(G) motif, not only inhibit translation initiation when inserted into an mRNA 5΄ untranslated region, but also generate noise...
May 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28514750/epigenome-wide-association-study-in-hepatocellular-carcinoma-identification-of-stochastic-epigenetic-mutations-through-an-innovative-statistical-approach
#5
REVIEW
Davide Gentilini, Stefania Scala, Germano Gaudenzi, Paolo Garagnani, Miriam Capri, Matteo Cescon, Gian Luca Grazi, Maria Giulia Bacalini, Serena Pisoni, Alessandra Dicitore, Luisa Circelli, Sara Santagata, Francesco Izzo, Anna Maria Di Blasio, Luca Persani, Claudio Franceschi, Giovanni Vitale
Hepatocellular carcinoma (HCC) results from accumulation of both genetic and epigenetic alterations. We investigated the genome-wide DNA methylation profile in 69 pairs of HCC and adjacent non-cancerous liver tissues using the Infinium HumanMethylation 450K BeadChip array. An innovative analytical approach has been adopted to identify Stochastic Epigenetic Mutations (SEMs) in HCC.HCC and peritumoral tissues showed a different epigenetic profile, mainly characterized by loss of DNA methylation in HCC. Total number of SEMs was significantly higher in HCC tumor (median: 77,370) than in peritumoral (median: 5,656) tissues and correlated with tumor grade...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514665/systems-analysis-reveals-high-genetic-and-antigen-driven-predetermination-of-antibody-repertoires-throughout-b-cell-development
#6
Victor Greiff, Ulrike Menzel, Enkelejda Miho, Cédric Weber, René Riedel, Skylar Cook, Atijeh Valai, Telma Lopes, Andreas Radbruch, Thomas H Winkler, Sai T Reddy
Antibody repertoire diversity and plasticity is crucial for broad protective immunity. Repertoires change in size and diversity across multiple B cell developmental stages and in response to antigen exposure. However, we still lack fundamental quantitative understanding of the extent to which repertoire diversity is predetermined. Therefore, we implemented a systems immunology framework for quantifying repertoire predetermination on three distinct levels: (1) B cell development (pre-B cell, naive B cell, plasma cell), (2) antigen exposure (three structurally different proteins), and (3) four antibody repertoire components (V-gene usage, clonal expansion, clonal diversity, repertoire size) extracted from antibody repertoire sequencing data (400 million reads)...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28511648/a-mathematical-model-of-mechanotransduction-reveals-how-mechanical-memory-regulates-mesenchymal-stem-cell-fate-decisions
#7
Tao Peng, Linan Liu, Adam L MacLean, Chi Wut Wong, Weian Zhao, Qing Nie
BACKGROUND: Mechanical and biophysical properties of the cellular microenvironment regulate cell fate decisions. Mesenchymal stem cell (MSC) fate is influenced by past mechanical dosing (memory), but the mechanisms underlying this process have not yet been well defined. We have yet to understand how memory affects specific cell fate decisions, such as the differentiation of MSCs into neurons, adipocytes, myocytes, and osteoblasts. RESULTS: We study a minimal gene regulatory network permissive of multi-lineage MSC differentiation into four cell fates...
May 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28505727/multiple-binding-sites-for-transcriptional-repressors-can-produce-regular-bursting-and-enhance-noise-suppression
#8
Iván M Lengyel, Luis G Morelli
Cells may control fluctuations in protein levels by means of negative autoregulation, where transcription factors bind DNA sites to repress their own production. Theoretical studies have assumed a single binding site for the repressor, while in most species it is found that multiple binding sites are arranged in clusters. We study a stochastic description of negative autoregulation with multiple binding sites for the repressor. We find that increasing the number of binding sites induces regular bursting of gene products...
April 2017: Physical Review. E
https://www.readbyqxmd.com/read/28502614/partially-compromised-specification-causes-stochastic-effects-on-gut-development-in-c-elegans
#9
Hailey Choi, Gina Broitman-Maduro, Morris F Maduro
The C. elegans gut descends from the E progenitor cell through a series of stereotyped cell divisions and morphogenetic events. Effects of perturbations of upstream cell specification on downstream organogenesis have not been extensively investigated. Here we have assembled an allelic series of strains that variably compromise specification of E by perturbing the activation of the gut-specifying end-1 and end-3 genes. Using a marker that allows identification of all E descendants regardless of fate, superimposed with markers that identify cells that have adopted a gut fate, we have examined the fate of E lineage descendants among hundreds of embryos...
May 11, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28498984/inheritance-of-vernalization-memory-at-flowering-locus-c-during-plant-regeneration
#10
Miyuki Nakamura, Lars Hennig
Specific gene states can be transmitted to subsequent cell generations through mitosis involving particular chromatin (epigenetic) states. During reproduction of plants and animals, however, most epigenetic states are reset to allow development to start anew. Flowering is one of the critical developmental steps by which plants acquire their reproductive capacity. This phase transition is controlled by environmental signals and autonomous regulation. The FLOWERING LOCUS C (FLC) gene is a flowering repressor that is epigenetically silenced after long-term exposure to cold, ensuring flowering in the spring season...
May 11, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28495919/alternative-tsss-are-co-regulated-in-single-cells-in-the-mouse-brain
#11
Kasper Karlsson, Peter Lönnerberg, Sten Linnarsson
Alternative transcription start sites (TSSs) have been extensively studied genome-wide for many cell types and have been shown to be important during development and to regulate transcript abundance between cell types. Likewise, single-cell gene expression has been extensively studied for many cell types. However, how single cells use TSSs has not yet been examined. In particular, it is unknown whether alternative TSSs are independently expressed, or whether they are co-activated or even mutually exclusive in single cells...
May 11, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28493880/identifying-stochastic-oscillations-in-single-cell-live-imaging-time-series-using-gaussian-processes
#12
Nick E Phillips, Cerys Manning, Nancy Papalopulu, Magnus Rattray
Multiple biological processes are driven by oscillatory gene expression at different time scales. Pulsatile dynamics are thought to be widespread, and single-cell live imaging of gene expression has lead to a surge of dynamic, possibly oscillatory, data for different gene networks. However, the regulation of gene expression at the level of an individual cell involves reactions between finite numbers of molecules, and this can result in inherent randomness in expression dynamics, which blurs the boundaries between aperiodic fluctuations and noisy oscillators...
May 11, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28493042/on-the-stochastic-evolution-of-finite-populations
#13
Fabio A C C Chalub, Max O Souza
This work is a systematic study of discrete Markov chains that are used to describe the evolution of a two-types population. Motivated by results valid for the well-known Moran (M) and Wright-Fisher (WF) processes, we define a general class of Markov chains models which we term the Kimura class. It comprises the majority of the models used in population genetics, and we show that many well-known results valid for M and WF processes are still valid in this class. In all Kimura processes, a mutant gene will either fixate or become extinct, and we present a necessary and sufficient condition for such processes to have the probability of fixation strictly increasing in the initial frequency of mutants...
May 10, 2017: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/28486496/phenotypic-heterogeneity-promotes-adaptive-evolution
#14
Zoltán Bódi, Zoltán Farkas, Dmitry Nevozhay, Dorottya Kalapis, Viktória Lázár, Bálint Csörgő, Ákos Nyerges, Béla Szamecz, Gergely Fekete, Balázs Papp, Hugo Araújo, José L Oliveira, Gabriela Moura, Manuel A S Santos, Tamás Székely, Gábor Balázsi, Csaba Pál
Genetically identical cells frequently display substantial heterogeneity in gene expression, cellular morphology and physiology. It has been suggested that by rapidly generating a subpopulation with novel phenotypic traits, phenotypic heterogeneity (or plasticity) accelerates the rate of adaptive evolution in populations facing extreme environmental challenges. This issue is important as cell-to-cell phenotypic heterogeneity may initiate key steps in microbial evolution of drug resistance and cancer progression...
May 2017: PLoS Biology
https://www.readbyqxmd.com/read/28483564/the-influence-of-nuclear-compartmentalisation-on-stochastic-dynamics-of-self-repressing-gene-expression
#15
Marc Sturrock, Shiyu Li, Vahid Shahrezaei
Gene expression is an inherently noisy process. This noise is generally thought to be deleterious as precise internal regulation of biochemical reactions is essential for cell growth and survival. Self-repression of gene expression, which is the simplest form of a negative feedback loop, is commonly believed to be employed by cellular systems to decrease the stochastic fluctuations in gene expression. When there is some delay in autoregulation, it is also believed that this system can generate oscillations...
May 5, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28481360/a-chronic-low-dose-of-%C3%AE-9-tetrahydrocannabinol-thc-restores-cognitive-function-in-old-mice
#16
Andras Bilkei-Gorzo, Onder Albayram, Astrid Draffehn, Kerstin Michel, Anastasia Piyanova, Hannah Oppenheimer, Mona Dvir-Ginzberg, Ildiko Rácz, Thomas Ulas, Sophie Imbeault, Itai Bab, Joachim L Schultze, Andreas Zimmer
The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes underlying aging. The activity of the ECS declines during aging, as CB1 receptor expression and coupling to G proteins are reduced in the brain tissues of older animals and the levels of the major endocannabinoid 2-arachidonoylglycerol (2-AG) are lower...
May 8, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28469006/shaping-development-by-stochasticity-and-dynamics-in-gene-regulation
#17
REVIEW
Peng Dong, Zhe Liu
Animal development is orchestrated by spatio-temporal gene expression programmes that drive precise lineage commitment, proliferation and migration events at the single-cell level, collectively leading to large-scale morphological change and functional specification in the whole organism. Efforts over decades have uncovered two 'seemingly contradictory' mechanisms in gene regulation governing these intricate processes: (i) stochasticity at individual gene regulatory steps in single cells and (ii) highly coordinated gene expression dynamics in the embryo...
May 2017: Open Biology
https://www.readbyqxmd.com/read/28463205/aggregation-for-computing-multi-modal-stationary-distributions-in-1-d-gene-regulatory-networks
#18
Neslihan Avcu, Nihal Pekergin, Ferhan Pekergin, Cuneyt Guzelis
This paper proposes aggregation-based, three-stage algorithms to overcome the numerical problems encountered in computing stationary distributions and mean first passage times for multi-modal birth-death processes of large state space sizes. The considered birth-death processes which are defined by Chemical Master Equations are used in modeling stochastic behavior of gene regulatory networks. Computing stationary probabilities for a multi-modal distribution from Chemical Master Equations is subject to have numerical problems due to the probability values running out of the representation range of the standard programming languages with the increasing size of the state space...
April 27, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28457659/estimation-of-the-influence-of-sequencing-errors-and-distribution-of-random-sequence-tags-on-quantitative-sequencing
#19
Tatsuhiko Hoshino, Yohei Hamada
To simultaneously sequence and quantify target DNA, quantitative sequencing (qSeq) employs stochastic labeling of target DNA molecules with random-sequence tags (RSTs). This recently developed approach allows parallel quantification of hundreds of microorganisms in natural habitats in a single sequencing run. Yet, no study has addressed to what extent sequencing errors affect quantification and how many sequence reads are needed for quantification. Here, we addressed those issues by using numerical simulations and experimental data from second-generation sequencing of various RSTs...
April 28, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28455349/a-notch-positive-feedback-in-the-intestinal-stem-cell-niche-is-essential-for-stem-cell-self-renewal
#20
Kai-Yuan Chen, Tara Srinivasan, Kuei-Ling Tung, Julio M Belmonte, Lihua Wang, Preetish Kadur Lakshminarasimha Murthy, Jiahn Choi, Nikolai Rakhilin, Sarah King, Anastasia Kristine Varanko, Mavee Witherspoon, Nozomi Nishimura, James A Glazier, Steven M Lipkin, Pengcheng Bu, Xiling Shen
The intestinal epithelium is the fastest regenerative tissue in the body, fueled by fast-cycling stem cells. The number and identity of these dividing and migrating stem cells are maintained by a mosaic pattern at the base of the crypt. How the underlying regulatory scheme manages this dynamic stem cell niche is not entirely clear. We stimulated intestinal organoids with Notch ligands and inhibitors and discovered that intestinal stem cells employ a positive feedback mechanism via direct Notch binding to the second intron of the Notch1 gene...
April 28, 2017: Molecular Systems Biology
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