bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chance and pleiotropy dominate genetic diversity in complex bacterial environments
Authors: Noda-Garcia Lianet , Davidi Dan , Korenblum Elisa , Elazar Assaf , Putintseva Ekaterina , Aharoni Asaph , Tawfik Dan S. 
Published: June 2018

AbstractHow does environmental complexity affect the evolution of single genes? Here, we measured the effects of a set of mutants ofBacillus subtilisglutamate dehydrogenase across 19 different environments - from homogenous single cell populations in liquid media to heterogeneous biofilms, plant roots and soil communities. The effects of individual gene mutations on organismal fitness were highly reproducible in liquid cultures. Strikingly, however, 84% of the tested alleles showed opposing fitness effects under different growth conditions (environmental pleiotropy). In biofilms and soil samples, different alleles dominated in parallel replica experiments. Accordingly, we found that in these heterogeneous cell communities the fate of mutations was dictated by a combination of selection and drift. The latter relates to programmed prophage excisions that occurred along biofilm development. Overall, per individual condition, by the combined action of selection, pleiotropy and chance, a wide range of glutamate dehydrogenase mutations persisted and sometimes fixated. However, across longer periods and multiple environments, nearly all this diversity would be lost - indeed, considering all environments and conditions we have tested, wild-type is the fittest allele.
Different SUMO Paralogs Determine the Fate of WT and Mutant CFTRs: Biogenesis vs. Degradation
Authors: Gong Xiaoyan , Liao Yong , Ahner Annette , Larsen Mads Breum , Wang Xiaohui , Bertrand Carol A. , Frizzell Raymond A. 
Published: June 2018

ABSTRACTA pathway for CFTR degradation is initiated by Hsp27 which cooperates with Ubc9 and binds to the common F508del mutant to modify it with SUMO-2/3. These SUMO paralogs form poly-chains, which are recognized by the ubiquitin ligase, RNF4, for proteosomal degradation. Here, protein array analysis identified the SUMO E3, PIAS4, which increased WT and F508del CFTR biogenesis in CFBE airway cells. PIAS4 increased immature CFTR three-fold and doubled expression of mature CFTR, detected by biochemical and functional assays. In cycloheximide chase assays, PIAS4 slowed immature F508del degradation 3-fold and stabilized mature WT CFTR at the PM. PIAS4 knockdown reduced WT and F508del CFTR expression by 40-50%, suggesting a physiological role in CFTR biogenesis. PIAS4 modified F508del CFTR with SUMO-1in vivoand reduced its conjugation to SUMO-2/3. These SUMO paralog specific effects of PIAS4 were reproducedin vitrousing purified F508del NBD1 and SUMOylation reaction components. PIAS4 reduced endogenous ubiquitin conjugation to F508del CFTR by ~50%, and blocked the impact of RNF4 on mutant CFTR disposal. These findings indicate that different SUMO paralogs determine the fates of WT and mutant CFTRs, and they suggest that a paralog switch during biogenesis can direct these proteins to different outcomes: biogenesis vs. degradation.
The genomic landscape of recombination rate variation inChlamydomonas reinhardtiireveals a pronounced effect of linked selection
Authors: Hasan Ahmed R. , Ness Rob W. 
Published: June 2018

AbstractRecombination confers a major evolutionary advantage by breaking up linkage disequilibrium (LD) between harmful and beneficial mutations and facilitating selection. Here, we use genome-wide patterns of LD to infer fine-scale recombination rate variation in the genome of the model green algaChlamydomonas reinhardtiiand estimate rates of LD decay across the entire genome. We observe recombination rate variation of up to two orders of magnitude, finding evidence of recombination hotspots playing a role in the genome. Recombination rate is highest just upstream of genic regions, suggesting the preferential targeting of recombination breakpoints in promoter regions. Furthermore, we observe a positive correlation between GC content and recombination rate, suggesting a role for GC-biased gene conversion or selection on base composition within the GC-rich genome ofC. reinhardtii. We also find a positive relationship between nucleotide diversity and recombination, consistent with widespread influence of linked selection in the genome. Finally, we use estimates of the effective rate of recombination to calculate the rate of sex that occurs in natural populations of this important model microbe, estimating a sexual cycle roughly every 770 generations. We argue that the relatively infrequent rate of sex and large effective population size creates an population genetic environment that increases the influence of linked selection on the genome.
Network Inference from Perturbation Time Course Data
Authors: Sarmah Deepraj , Smith Gregory R , Bouhaddou Mehdi , Stern Alan D. , Erskine James , Birtwistle Marc R 
Published: June 2018

AbstractNetworks underlie much of biology from subcellular to ecological scales. Yet, understanding what experimental data are needed and how to use them for unambiguously identifying the structure of even small networks remains a broad challenge. Here, we integrate a dynamic least squares framework into established modular response analysis (DL-MRA), that specifies sufficient experimental perturbation time course data to robustly infer arbitrary two and three node networks. DL-MRA considers important network properties that current methods often struggle to capture: (i) edge sign and directionality; (ii) cycles with feedback or feedforward loops including self-regulation; (iii) dynamic network behavior; (iv) edges external to the network; and (v) robust performance with experimental noise. We evaluate the performance of and the extent to which the approach applies to cell state transition networks, intracellular signaling networks, and gene regulatory networks. Although signaling networks are often an application of network reconstruction methods, the results suggest that only under quite restricted conditions can they be robustly inferred. For gene regulatory networks, the results suggest that incomplete knockdown is often more informative than full knockout perturbation, which may change experimental strategies for gene regulatory network reconstruction. Overall, the results give a rational basis to experimental data requirements for network reconstruction and can be applied to any such problem where perturbation time course experiments are possible.
DivIVA concentrates mycobacterial cell envelope assembly for initiation and stabilization of polar growth
Authors: Melzer Emily S. , Sein Caralyn E. , Chambers James J. , Sloan Siegrist M. 
Published: June 2018

AbstractIn many model organisms, diffuse patterning of cell wall peptidoglycan synthesis by the actin homolog MreB enables the bacteria to maintain their characteristic rod shape. InCaulobacter crescentusandEscherichia coli, MreB is also required to sculpt this morphologyde novo. Mycobacteria are rod-shaped but expand their cell wall from discrete polar or sub-polar zones. In this genus, the tropomyosin-like protein DivIVA is required for the maintenance of cell morphology. DivIVA has also been proposed to direct peptidoglycan synthesis to the tips of the mycobacterial cell. The precise nature of this regulation is unclear, as is its role in creating rod shape from scratch. We find that DivIVA localizes nascent cell wall and covalently associated mycomembrane but is dispensable for the assembly process itself.Mycobacterium smegmatisrendered spherical by peptidoglycan digestion or by DivIVA depletion are able to regain rod shape at the population level in the presence of DivIVA. At the single cell level, there is a close spatiotemporal correlation between DivIVA foci, rod extrusion and concentrated cell wall synthesis. Thus, although the precise mechanistic details differ from other organisms,M. smegmatisalso establish and propagate rod shape by cytoskeleton-controlled patterning of peptidoglycan. Our data further support the emerging notion that morphology is a hardwired trait of bacterial cells.
Single olfactory receptors set odor detection thresholds
Authors: Dewan Adam , Cichy Annika , Zhang Jingji , Miguel Kayla , Feinstein Paul , Rinberg Dmitry , Bozza Thomas 
Published: June 2018

ABSTRACTIn many species, survival depends on olfaction, yet the mechanisms that underlie olfactory sensitivity are not well understood. Here, we examine how a conserved subset of olfactory receptors, the trace amine-associated receptors (TAARs) determine odor detection thresholds of mice to amines. We find that deleting all TAARs, or even single TAARs, results in significant odor detection deficits. This finding is not limited to TAARs, as the deletion of a canonical odorant receptor reduced behavioral sensitivity to its preferred ligand. Remarkably, behavioral threshold is set solely by the most sensitive receptor, with no contribution from other highly sensitive receptors. In addition, increasing the number of sensory neurons (and glomeruli) expressing a threshold-determining TAAR does not improve detection, indicating that sensitivity is not limited by the typical complement of sensory neurons. Our findings demonstrate that olfactory thresholds are set by the single highest affinity receptor, and suggest that TAARs are evolutionarily conserved because they determine the sensitivity to a class of biologically relevant chemicals.
Predicting clone genotypes from tumor bulk sequencing of multiple samples
Authors: Miura Sayaka , Gomez Karen , Murillo Oscar , Huuki Louise A , Vu Tracy , Buturla Tiffany , Kumar Sudhir 
Published: June 2018

AbstractMotivationAnalyses of data generated from bulk sequencing of tumors have revealed extensive genomic heterogeneity within patients. Many computational methods have been developed to enable the inference of genotypes of tumor cell populations (clones) from bulk sequencing data. However, the relative and absolute accuracy of available computational methods in estimating clone counts and clone genotypes is not yet known.ResultsWe have assessed the performance of nine methods, including eight previously-published and one new method (CloneFinder), by analyzing computer simulated datasets. CloneFinder, LICHeE, CITUP, and cloneHD inferred clone genotypes with low error (<5% per clone) for a majority of datasets in which the tumor samples contained evolutionarily-related clones. Computational methods did not perform well for datasets in which tumor samples contained mixtures of clones from different clonal lineages. Generally, the number of clones was underestimated by cloneHD and overestimated by Phy-loWGS, and BayClone2, Canopy, and Clomial required prior information regarding the number of clones. AncesTree and Canopy did not produce results for a large number of datasets.ConclusionsDeconvolution of clone genotypes from single nucleotide variant (SNV) frequency differences among tumor samples remains challenging, so there is a need to develop more accurate computational methods and robust software for clone genotype inference.Availability and ImplementationCloneFinder is implemented in Python and is available fromhttps://github.com/gstecher/CloneFinderAPI.Contacts.kumar@temple.eduSupplementary informationSupplementary data are available atBioinformaticsonline
Thermodynamic constraints on the regulation of metabolic fluxes
Authors: Dai Ziwei , Locasale Jason W. 
Published: June 2018

AbstractNutrition and metabolism are fundamental to cellular function in physiological and pathological contexts. Metabolic activity (i.e. rates, flow, or most commonly referred to as flux) is constrained by thermodynamics and regulated by the activity of enzymes. The general principles that relate biological and physical variables to metabolic control are incompletely understood. Using metabolic control analysis in several representative topological structures of metabolic pathways as models, we derive exact results and conduct computer simulations that define relationships between thermodynamics, enzyme activity, and flux control. We confirm that metabolic pathways that are very far from equilibrium are controlled by the activity of upstream enzymes. However, in general, metabolic pathways have a more adaptable pattern of regulation, controlled minimally by thermodynamics and not necessarily by the specific enzyme that generates the given reaction. These findings show how the control of metabolic pathways, which are rarely very far from equilibrium, is largely set by the overall flux through a pathway rather than by the enzyme which generates the flux or by thermodynamics.
How many, and when? Optimising targeted gene flow for a step change in the environment
Authors: Kelly E. , Phillips BL. 
Published: June 2018

AbstractTargeted gene flow is an emerging conservation strategy that involves translocating individuals with particular traits to places where they are of benefit, thereby increasing a population’s evolutionary resilience. While the idea can work in theory, questions remain as to how best to implement it. Here, we vary timing of introduction and size of the introduced cohort to maximise our objective – survival of the recipient population’s genome. We demonstrate our approach using the northern quoll, an Australian marsupial predator threatened by the toxic cane toad. We highlight a general trade-off between maintaining a local genome and reducing population extinction risk, but show that key management levers can optimise this so that 100% of the population’s genome is preserved. In our case, any action was better than not acting at all (even with strong outbreeding depression), but the size of the benefit was sensitive to timing and size of the introduction.
HERC2 promotes BLM and WRN to suppress G-quadruplex DNA
Authors: Wu Wenwen , Rokutanda Nana , Takeuchi Jun , Lai Yongqiang , Maruyama Reo , Togashi Yukiko , Nishikawa Hiroyuki , Arai Naoko , Miyoshi Yasuo , Suzuki Nao , Saeki Yasushi , Tanaka Keiji , Ohta Tomohiko 
Published: June 2018

SUMMARYBLM and WRN are RecQ DNA helicases essential for genomic stability. Here we demonstrate that HERC2, a HECT E3 ligase, is critical for their functions to suppress G-quadruplex (G4) DNA. HERC2 interacts with BLM, WRN, and replication protein A (RPA) complexes during S-phase of the cell cycle. Depletion of HERC2 dissociates RPA from BLM and WRN complexes and significantly increases G4 formation. Triple depletion revealed that HERC2 has an epistatic relationship with BLM and WRN in their G4- suppressing function.In vitro, HERC2 releases RPA onto single-stranded DNA (ssDNA), rather than anchoring onto RPA-coated ssDNA. CRISPR/Cas9-mediated deletion of the catalytic ubiquitin-binding site of HERC2 causes RPA accumulation in the helicase complexes and increases G4, indicating an essential role for E3 activity in G4 suppression. Both HERC2 depletion and E3 inactivation sensitize cells to the G4-interacting compounds, telomestatin and pyridostatin. Overall, HERC2 is a master regulator of G4 suppression and affects the sensitivity of cells to G4 stabilizers.
Male pheromone composition depends on larval but not adult diet in Heliconius melpomene
Authors: Darragh Kathy , Byers Kelsey J.R.P. , Merrill Richard M. , Owen McMillan W. , Schulz Stefan , Jiggins Chris D. 
Published: June 2018

AbstractCondition-dependent traits can act as honest signals of mate quality, with fitter individuals able to display preferred phenotypes. Nutrition is known to be an important determinant of individual condition, with diet known to affect many secondary sexual traits. In Heliconius butterflies, male chemical signalling plays an important role in female mate choice. Heliconius pheromones are sexually dimorphic, found only in mature males, but it is unclear what information they convey to the female. Here, we manipulate both the larval and adult diet of male Heliconius melpomene rosina to test for environmental effects on wing and genital pheromone production. We find no evidence that adult pollen consumption affects pheromone production in the first ten days after eclosion. We also find strong overlap in the chemical profiles of individuals reared on different larval host plants. However, individual compounds were found in different amounts between host plant treatments. Further electrophysiological and behavioural experiments will be needed to determine the biological significance of these differences.
Blue-green opponency and trichromatic vision in the greenhouse whitefly (Trialeurodes vaporariorum)
Authors: Stukenberg Niklas , Poehling Hans-Michael 
Published: June 2018

AbstractVisual orientation in the greenhouse whitefly (Trialeurodes vaporariorum Westwood, Hemiptera: Aleyrodidae) is the result of ‘wavelength-specific behaviours’. Green-yellow elicits ‘settling behaviour’ while ultraviolet (UV) radiation initiates ‘migratory behaviour’. Electroretinograms of the photoreceptors’ spectral efficiency showed peaks in the green and the UV range and whitefly vision was said to be dichromatic.In order to study the visual behaviour of T. vaporariorum, nineteen narrow-bandwidth LEDs covering the UV-A and visible range were used in combination with light scattering acrylic glass screens in a small-scale choice arena under greenhouse conditions. Multiple-choice and dual-choice assays were performed, resulting in LED-based behavioural action spectra of settling (green) and migratory behaviour (UV). A potential inhibitory blue-green chromatic mechanism was studied by combining yellow with different blueish LEDs. Intensity dependencies were illustrated by changing LED intensities.Regarding the ‘settling response’, highest attraction was achieved by a green LED with a centroid wavelength of 550 nm, while a blue LED with 469 nm proved to be most inhibitory. Behaviour was distinctly intensity dependent. ‘Migratory behaviour’ was elicited the most by the UV LED with the shortest available wavelength of 373 nm. The results clearly prove the presence of a green and a yet undescribed blue sensitive photoreceptor and a blue-green opponent mechanism. Furthermore, empirical colour choice models were built and receptor peaks were estimated around 510 - 520 nm (green), 480 - 490 nm (blue) and 340 - 370 nm (UV). Consequently, Trialeurodes vaporariorum possesses a trichromatic receptor setup.Summary statementLED based choice experiments and empirical colour choice models reveal a yet undescribed blue sensitive photoreceptor and an inhibitory interaction with a green sensitive receptor.
The interspecific fungal hybrid Verticillium longisporum displays sub-genome-specific gene expression
Authors: Depotter Jasper R.L. , van Beveren Fabian , Rodriguez-Moreno Luis , Kramer H. Martin , Chavarro Carrero Edgar A. , Fiorin Gabriel L. , van den Berg Grardy C.M. , Wood Thomas A. , Thomma Bart P.H.J. , Seidl Michael F. 
Published: June 2018

AbstractHybridization is an important evolutionary mechanism that can enable organisms to adapt to environmental challenges. It has previously been shown that the fungal allodiploid species Verticillium longisporum, causal agent of Verticillium stem striping in rape seed, has originated from at least three independent hybridization events between two haploid Verticillium species. To reveal the impact of genome duplication as a consequence of the hybridization, we studied the genome and transcriptome dynamics upon two independent V. longisporum hybridization events, represented by the hybrid lineages “A1/D1” and “A1/D3”. We show that the V. longisporum genomes are characterized by extensive chromosomal rearrangements, including between parental chromosomal sets. V. longisporum hybrids display signs of evolutionary dynamics that are typically associated with the aftermath of allodiploidization, such as haploidization and a more relaxed gene evolution. Expression patterns of the two sub-genomes within the two hybrid lineages are more similar than those of the shared A1 parent between the two lineages, showing that expression patterns of the parental genomes homogenized within a lineage. However, as genes that display differential parental expression in planta do not typically display the same pattern in vitro, we conclude that sub-genome-specific responses occur in both lineages. Overall, our study uncovers the genomic and transcriptomic plasticity during evolution of the filamentous fungal hybrid V. longisporum and illustrate its adaptive potential.ImportanceVerticillium is a genus of plant-associated fungi that include a handful of plant pathogens that collectively affect a wide range of hosts. On several occasions, haploid Verticillium species hybridized into the stable allodiploid species Verticillium longisporum, which is, in contrast to haploid Verticillium species, a Brassicaceae specialist. Here, we studied the evolutionary genome and transcriptome dynamics of V. longisporum and the impact of the hybridization. V. longisporum genomes display a mosaic structure due do genomic rearrangements between the parental chromosome sets. Similar to other allopolyploid hybrids, V. longisporum displays an ongoing loss of heterozygosity and a more relaxed gene evolution. Also, differential parental gene expression is observed, with an enrichment for genes that encode secreted proteins. Intriguingly, the majority of these genes displays sub-genome-specific responses under differential growth conditions. In conclusion, hybridization has incited the genomic and transcriptomic plasticity that enables adaptation to environmental changes in a parental allele-specific fashion.
Pervasive positive and negative feedback regulation of insulin-like signaling inCaenorhabditis elegans
Authors: Maxwell Colin S. , Kaplan Rebecca E. W. , Codd Nicole Kurhanewicz , Baugh L. Ryan 
Published: June 2018

AbstractTheC. elegansinsulin-like signaling network supports homeostasis and developmental plasticity. The genome encodes 40 insulin-like peptides and one receptor. Feedback regulation has been reported, but the extent of feedback and its effect on signaling dynamics during a state transition has not been determined. We measured mRNA expression for each insulin-like peptide, the receptordaf-2, components of the PI3K pathway, and its transcriptional effectorsdaf-16/FoxO andskn-1/Nrf at high temporal resolution during transition from a starved, quiescent state to a fed, growing state in wild type and mutants affectingdaf-2/InsR anddaf-16/FoxO. We also analyzed the effect of temperature on insulin-like gene expression. We found that numerous PI3K pathway components and insulin-like peptides are affected by signaling activity, revealing pervasive positive and negative feedback regulation. Reporter gene analysis demonstrated that thedaf-2/InsR agonistdaf-28positively regulates its own expression and that other agonists cross-regulatedaf-28transcription through feedback. Our results show that feedback regulation of insulin-like signaling is widespread, suggesting a critical role of feedback in signaling dynamics in this endocrine network and likely others.