Sample records for plausible evolutionary pathway

  1. Conditional iron and pH-dependent activity of a non-enzymatic glycolysis and pentose phosphate pathway.

    PubMed

    Keller, Markus A; Zylstra, Andre; Castro, Cecilia; Turchyn, Alexandra V; Griffin, Julian L; Ralser, Markus

    2016-01-01

    Little is known about the evolutionary origins of metabolism. However, key biochemical reactions of glycolysis and the pentose phosphate pathway (PPP), ancient metabolic pathways central to the metabolic network, have non-enzymatic pendants that occur in a prebiotically plausible reaction milieu reconstituted to contain Archean sediment metal components. These non-enzymatic reactions could have given rise to the origin of glycolysis and the PPP during early evolution. Using nuclear magnetic resonance spectroscopy and high-content metabolomics that allowed us to measure several thousand reaction mixtures, we experimentally address the chemical logic of a metabolism-like network constituted from these non-enzymatic reactions. Fe(II), the dominant transition metal component of Archean oceanic sediments, has binding affinity toward metabolic sugar phosphates and drives metabolism-like reactivity acting as both catalyst and cosubstrate. Iron and pH dependencies determine a metabolism-like network topology and comediate reaction rates over several orders of magnitude so that the network adopts conditional activity. Alkaline pH triggered the activity of the non-enzymatic PPP pendant, whereas gentle acidic or neutral conditions favored non-enzymatic glycolytic reactions. Fe(II)-sensitive glycolytic and PPP-like reactions thus form a chemical network mimicking structural features of extant carbon metabolism, including topology, pH dependency, and conditional reactivity. Chemical networks that obtain structure and catalysis on the basis of transition metals found in Archean sediments are hence plausible direct precursors of cellular metabolic networks.

  2. Conditional iron and pH-dependent activity of a non-enzymatic glycolysis and pentose phosphate pathway

    PubMed Central

    Keller, Markus A.; Zylstra, Andre; Castro, Cecilia; Turchyn, Alexandra V.; Griffin, Julian L.; Ralser, Markus

    2016-01-01

    Little is known about the evolutionary origins of metabolism. However, key biochemical reactions of glycolysis and the pentose phosphate pathway (PPP), ancient metabolic pathways central to the metabolic network, have non-enzymatic pendants that occur in a prebiotically plausible reaction milieu reconstituted to contain Archean sediment metal components. These non-enzymatic reactions could have given rise to the origin of glycolysis and the PPP during early evolution. Using nuclear magnetic resonance spectroscopy and high-content metabolomics that allowed us to measure several thousand reaction mixtures, we experimentally address the chemical logic of a metabolism-like network constituted from these non-enzymatic reactions. Fe(II), the dominant transition metal component of Archean oceanic sediments, has binding affinity toward metabolic sugar phosphates and drives metabolism-like reactivity acting as both catalyst and cosubstrate. Iron and pH dependencies determine a metabolism-like network topology and comediate reaction rates over several orders of magnitude so that the network adopts conditional activity. Alkaline pH triggered the activity of the non-enzymatic PPP pendant, whereas gentle acidic or neutral conditions favored non-enzymatic glycolytic reactions. Fe(II)-sensitive glycolytic and PPP-like reactions thus form a chemical network mimicking structural features of extant carbon metabolism, including topology, pH dependency, and conditional reactivity. Chemical networks that obtain structure and catalysis on the basis of transition metals found in Archean sediments are hence plausible direct precursors of cellular metabolic networks. PMID:26824074

  3. The emergence and early evolution of biological carbon-fixation.

    PubMed

    Braakman, Rogier; Smith, Eric

    2012-01-01

    The fixation of CO₂ into living matter sustains all life on Earth, and embeds the biosphere within geochemistry. The six known chemical pathways used by extant organisms for this function are recognized to have overlaps, but their evolution is incompletely understood. Here we reconstruct the complete early evolutionary history of biological carbon-fixation, relating all modern pathways to a single ancestral form. We find that innovations in carbon-fixation were the foundation for most major early divergences in the tree of life. These findings are based on a novel method that fully integrates metabolic and phylogenetic constraints. Comparing gene-profiles across the metabolic cores of deep-branching organisms and requiring that they are capable of synthesizing all their biomass components leads to the surprising conclusion that the most common form for deep-branching autotrophic carbon-fixation combines two disconnected sub-networks, each supplying carbon to distinct biomass components. One of these is a linear folate-based pathway of CO₂ reduction previously only recognized as a fixation route in the complete Wood-Ljungdahl pathway, but which more generally may exclude the final step of synthesizing acetyl-CoA. Using metabolic constraints we then reconstruct a "phylometabolic" tree with a high degree of parsimony that traces the evolution of complete carbon-fixation pathways, and has a clear structure down to the root. This tree requires few instances of lateral gene transfer or convergence, and instead suggests a simple evolutionary dynamic in which all divergences have primary environmental causes. Energy optimization and oxygen toxicity are the two strongest forces of selection. The root of this tree combines the reductive citric acid cycle and the Wood-Ljungdahl pathway into a single connected network. This linked network lacks the selective optimization of modern fixation pathways but its redundancy leads to a more robust topology, making it more plausible than any modern pathway as a primitive universal ancestral form.

  4. Evolutionary paths of streptococcal and staphylococcal superantigens

    PubMed Central

    2012-01-01

    Background Streptococcus pyogenes (GAS) harbors several superantigens (SAgs) in the prophage region of its genome, although speG and smez are not located in this region. The diversity of SAgs is thought to arise during horizontal transfer, but their evolutionary pathways have not yet been determined. We recently completed sequencing the entire genome of S. dysgalactiae subsp. equisimilis (SDSE), the closest relative of GAS. Although speG is the only SAg gene of SDSE, speG was present in only 50% of clinical SDSE strains and smez in none. In this study, we analyzed the evolutionary paths of streptococcal and staphylococcal SAgs. Results We compared the sequences of the 12–60 kb speG regions of nine SDSE strains, five speG+ and four speG–. We found that the synteny of this region was highly conserved, whether or not the speG gene was present. Synteny analyses based on genome-wide comparisons of GAS and SDSE indicated that speG is the direct descendant of a common ancestor of streptococcal SAgs, whereas smez was deleted from SDSE after SDSE and GAS split from a common ancestor. Cumulative nucleotide skew analysis of SDSE genomes suggested that speG was located outside segments of steeper slopes than the stable region in the genome, whereas the region flanking smez was unstable, as expected from the results of GAS. We also detected a previously undescribed staphylococcal SAg gene, selW, and a staphylococcal SAg -like gene, ssl, in the core genomes of all Staphylococcus aureus strains sequenced. Amino acid substitution analyses, based on dN/dS window analysis of the products encoded by speG, selW and ssl suggested that all three genes have been subjected to strong positive selection. Evolutionary analysis based on the Bayesian Markov chain Monte Carlo method showed that each clade included at least one direct descendant. Conclusions Our findings reveal a plausible model for the comprehensive evolutionary pathway of streptococcal and staphylococcal SAgs. PMID:22900646

  5. Marr's levels and the minimalist program.

    PubMed

    Johnson, Mark

    2017-02-01

    A simple change to a cognitive system at Marr's computational level may entail complex changes at the other levels of description of the system. The implementational level complexity of a change, rather than its computational level complexity, may be more closely related to the plausibility of a discrete evolutionary event causing that change. Thus the formal complexity of a change at the computational level may not be a good guide to the plausibility of an evolutionary event introducing that change. For example, while the Minimalist Program's Merge is a simple formal operation (Berwick & Chomsky, 2016), the computational mechanisms required to implement the language it generates (e.g., to parse the language) may be considerably more complex. This has implications for the theory of grammar: theories of grammar which involve several kinds of syntactic operations may be no less evolutionarily plausible than a theory of grammar that involves only one. A deeper understanding of human language at the algorithmic and implementational levels could strengthen Minimalist Program's account of the evolution of language.

  6. Coercion in the Evolution of Plant-Microbe Communication: A Perspective.

    PubMed

    Rowe, S L; Norman, J S; Friesen, M L

    2018-06-06

    Plants and microbes are dependent on chemical signals as a means of interkingdom communication. There are two predicted paths for the evolution of these signals. Ritualization is the oft-assumed pathway for the evolution of plant-microbe communication systems. In this process, chemical signals, which benefit both receiver and sender, evolve from chemical cues, which benefit only the receiver. However, plant-microbe signaling may evolve from coercive interactions as well, a process known as sensory manipulation. Here, we aim to highlight the prevalence of coercive interactions and discuss sensory manipulation in the context of plant-microbe interactions. We present two examples of stabilized coercion: microbial coercion of plants via the release of phytohormones and plant coercion of microbes via manipulation of quorum-sensing compounds. Furthermore, we provide an evolutionary framework for the emergence of signaling from coercive plant-microbe interactions through the process of sensory manipulation. We hope that researchers will recognize the relevance of coercive interactions in plant-microbe systems and consider sensory manipulation as a plausible evolutionary trajectory for the emergence of plant-microbe signaling.

  7. Biology Teachers' Conceptions of the Diversity of Life and the Historical Development of Evolutionary Concepts

    ERIC Educational Resources Information Center

    da Silva, Paloma Rodrigues; de Andrade, Mariana A. Bologna Soares; de Andrade Caldeira, Ana Maria

    2015-01-01

    Biology is a science that involves study of the diversity of living organisms. This diversity has always generated questions and has motivated cultures to seek plausible explanations for the differences and similarities between types of organisms. In biology teaching, these issues are addressed by adopting an evolutionary approach. The aim of this…

  8. Supersize me: how whole-genome sequencing and big data are transforming epidemiology.

    PubMed

    Kao, Rowland R; Haydon, Daniel T; Lycett, Samantha J; Murcia, Pablo R

    2014-05-01

    In epidemiology, the identification of 'who infected whom' allows us to quantify key characteristics such as incubation periods, heterogeneity in transmission rates, duration of infectiousness, and the existence of high-risk groups. Although invaluable, the existence of many plausible infection pathways makes this difficult, and epidemiological contact tracing either uncertain, logistically prohibitive, or both. The recent advent of next-generation sequencing technology allows the identification of traceable differences in the pathogen genome that are transforming our ability to understand high-resolution disease transmission, sometimes even down to the host-to-host scale. We review recent examples of the use of pathogen whole-genome sequencing for the purpose of forensic tracing of transmission pathways, focusing on the particular problems where evolutionary dynamics must be supplemented by epidemiological information on the most likely timing of events as well as possible transmission pathways. We also discuss potential pitfalls in the over-interpretation of these data, and highlight the manner in which a confluence of this technology with sophisticated mathematical and statistical approaches has the potential to produce a paradigm shift in our understanding of infectious disease transmission and control. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Testing co-evolutionary hypotheses over geological timescales: interactions between Mesozoic non-avian dinosaurs and cycads.

    PubMed

    Butler, Richard J; Barrett, Paul M; Kenrick, Paul; Penn, Malcolm G

    2009-02-01

    The significance of co-evolution over ecological timescales is well established, yet it remains unclear to what extent co-evolutionary processes contribute to driving large-scale evolutionary and ecological changes over geological timescales. Some of the most intriguing and pervasive long-term co-evolutionary hypotheses relate to proposed interactions between herbivorous non-avian dinosaurs and Mesozoic plants, including cycads. Dinosaurs have been proposed as key dispersers of cycad seeds during the Mesozoic, and temporal variation in cycad diversity and abundance has been linked to dinosaur faunal changes. Here we assess the evidence for proposed hypotheses of trophic and evolutionary interactions between these two groups using diversity analyses, a new database of Cretaceous dinosaur and plant co-occurrence data, and a geographical information system (GIS) as a visualisation tool. Phylogenetic evidence suggests that the origins of several key biological properties of cycads (e.g. toxins, bright-coloured seeds) likely predated the origin of dinosaurs. Direct evidence of dinosaur-cycad interactions is lacking, but evidence from extant ecosystems suggests that dinosaurs may plausibly have acted as seed dispersers for cycads, although it is likely that other vertebrate groups (e.g. birds, early mammals) also played a role. Although the Late Triassic radiations of dinosaurs and cycads appear to have been approximately contemporaneous, few significant changes in dinosaur faunas coincide with the late Early Cretaceous cycad decline. No significant spatiotemporal associations between particular dinosaur groups and cycads can be identified - GIS visualisation reveals disparities between the spatiotemporal distributions of some dinosaur groups (e.g. sauropodomorphs) and cycads that are inconsistent with co-evolutionary hypotheses. The available data provide no unequivocal support for any of the proposed co-evolutionary interactions between cycads and herbivorous dinosaurs - diffuse co-evolutionary scenarios that are proposed to operate over geological timescales are plausible, but such hypotheses need to be firmly grounded on direct evidence of interaction and may be difficult to support given the patchiness of the fossil record.

  10. Endocannabinoid Signaling in Motivation, Reward, and Addiction: Influences on Mesocorticolimbic Dopamine Function.

    PubMed

    Sagheddu, Claudia; Muntoni, Anna Lisa; Pistis, Marco; Melis, Miriam

    2015-01-01

    Evidence suggests that the endocannabinoid system has been conserved in the animal kingdom for 500 million years, and this system influences many critical behavioral processes including associative learning, reward signaling, goal-directed behavior, motor skill learning, and action-habit transformation. Additionally, the neurotransmitter dopamine has long been recognized to play a critical role in the processing of natural rewards, as well as of motivation that regulates approach and avoidance behavior. This motivational role of dopamine neurons is also based upon the evidence provided by several studies investigating disorders of dopamine pathways such as drug addiction and Parkinson's disease. From an evolutionary point of view, individuals engage in behaviors aimed at maximizing and minimizing positive and aversive consequences, respectively. Accordingly, those with the greatest fitness have a better potential to survival. Hence, deviations from fitness can be viewed as a part of the evolutionary process by means of natural selection. Given the long evolutionary history of both the endocannabinoid and dopaminergic systems, it is plausible that they must serve as fundamental and basic modulators of physiological functions and needs. Notably, endocannabinoids regulate dopamine neuronal activity and its influence on behavioral output. The goal of this chapter is to examine the endocannabinoid influence on dopamine signaling specifically related to (i) those behavioral processes that allow us to successfully adapt to ever-changing environments (i.e., reward signaling and motivational processes) and (ii) derangements from behavioral flexibility that underpin drug addiction. © 2015 Elsevier Inc. All rights reserved.

  11. Evolution of a predator-induced, nonlinear reaction norm.

    PubMed

    Carter, Mauricio J; Lind, Martin I; Dennis, Stuart R; Hentley, William; Beckerman, Andrew P

    2017-08-30

    Inducible, anti-predator traits are a classic example of phenotypic plasticity. Their evolutionary dynamics depend on their genetic basis, the historical pattern of predation risk that populations have experienced and current selection gradients. When populations experience predators with contrasting hunting strategies and size preferences, theory suggests contrasting micro-evolutionary responses to selection. Daphnia pulex is an ideal species to explore the micro-evolutionary response of anti-predator traits because they face heterogeneous predation regimes, sometimes experiencing only invertebrate midge predators and other times experiencing vertebrate fish and invertebrate midge predators. We explored plausible patterns of adaptive evolution of a predator-induced morphological reaction norm. We combined estimates of selection gradients that characterize the various habitats that D. pulex experiences with detail on the quantitative genetic architecture of inducible morphological defences. Our data reveal a fine scale description of daphnid defensive reaction norms, and a strong covariance between the sensitivity to cues and the maximum response to cues. By analysing the response of the reaction norm to plausible, predator-specific selection gradients, we show how in the context of this covariance, micro-evolution may be more uniform than predicted from size-selective predation theory. Our results show how covariance between the sensitivity to cues and the maximum response to cues for morphological defence can shape the evolutionary trajectory of predator-induced defences in D. pulex . © 2017 The Authors.

  12. Estimating evolutionary rates in giant viruses using ancient genomes

    PubMed Central

    Duchêne, Sebastián

    2018-01-01

    Abstract Pithovirus sibericum is a giant (610 Kpb) double-stranded DNA virus discovered in a purportedly 30,000-year-old permafrost sample. A closely related virus, Pithovirus massiliensis, was recently isolated from a sewer in southern France. An initial comparison of these two virus genomes assumed that P. sibericum was directly ancestral to P. massiliensis and gave a maximum evolutionary rate of 2.60 × 10−5 nucleotide substitutions per site per year (subs/site/year). If correct, this would make pithoviruses among the fastest-evolving DNA viruses, with rates close to those seen in some RNA viruses. To help determine whether this unusually high rate is accurate we utilized the well-known negative association between evolutionary rate and genome size in DNA microbes. This revealed that a more plausible rate estimate for Pithovirus evolution is ∼2.23 × 10−6 subs/site/year, with even lower estimates obtained if evolutionary rates are assumed to be time-dependent. Hence, we estimate that Pithovirus has evolved at least an order of magnitude more slowly than previously suggested. We then used our new rate estimates to infer a time-scale for Pithovirus evolution. Strikingly, this suggests that these viruses could have diverged at least hundreds of thousands of years ago, and hence have evolved over longer time-scales than previously suggested. We propose that the evolutionary rate and time-scale of pithovirus evolution should be reconsidered in the light of these observations and that future estimates of the rate of giant virus evolution should be carefully examined in the context of their biological plausibility. PMID:29511572

  13. Concepts in solid tumor evolution.

    PubMed

    Sidow, Arend; Spies, Noah

    2015-04-01

    Evolutionary mechanisms in cancer progression give tumors their individuality. Cancer evolution is different from organismal evolution, however, and we discuss where concepts from evolutionary genetics are useful or limited in facilitating an understanding of cancer. Based on these concepts we construct and apply the simplest plausible model of tumor growth and progression. Simulations using this simple model illustrate the importance of stochastic events early in tumorigenesis, highlight the dominance of exponential growth over linear growth and differentiation, and explain the clonal substructure of tumors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. On the formation mechanisms of compact elliptical galaxies

    NASA Astrophysics Data System (ADS)

    Ferré-Mateu, Anna; Forbes, Duncan A.; Romanowsky, Aaron J.; Janz, Joachim; Dixon, Christopher

    2018-01-01

    In order to investigate the formation mechanisms of the rare compact elliptical (cE) galaxies, we have compiled a sample of 25 cEs with good SDSS spectra, covering a range of stellar masses, sizes and environments. They have been visually classified according to the interaction with their host, representing different evolutionary stages. We have included clearly disrupted galaxies, galaxies that despite not showing signs of interaction are located close to a massive neighbour (thus are good candidates for a stripping process), and cEs with no host nearby. For the latter, tidal stripping is less likely to have happened and instead they could simply represent the very low-mass, faint end of the ellipticals. We study a set of properties (structural parameters, stellar populations, star formation histories and mass ratios) that can be used to discriminate between an intrinsic or stripped origin. We find that one diagnostic tool alone is inconclusive for the majority of objects. However, if we combine all the tools a clear picture emerges. The most plausible origin, as well as the evolutionary stage and progenitor type, can be then determined. Our results favour the stripping mechanism for those galaxies in groups and clusters that have a plausible host nearby, but favours an intrinsic origin for those rare cEs without a plausible host and that are located in looser environments.

  15. Applied evolutionary theories for engineering of secondary metabolic pathways.

    PubMed

    Bachmann, Brian O

    2016-12-01

    An expanded definition of 'secondary metabolism' is emerging. Once the exclusive provenance of naturally occurring organisms, evolved over geological time scales, secondary metabolism increasingly encompasses molecules generated via human engineered biocatalysts and biosynthetic pathways. Many of the tools and strategies for enzyme and pathway engineering can find origins in evolutionary theories. This perspective presents an overview of selected proposed evolutionary strategies in the context of engineering secondary metabolism. In addition to the wealth of biocatalysts provided via secondary metabolic pathways, improving the understanding of biosynthetic pathway evolution will provide rich resources for methods to adapt to applied laboratory evolution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Acceptance of evolutionary explanations as they are applied to plants, animals, and humans

    NASA Astrophysics Data System (ADS)

    Thanukos, Anastasia

    In four investigations using Likert-scale questionnaires and think-aloud protocols with 173 university students in total, the willingness to accept evolutionary explanations regarding plant, animal, and human characteristics was examined. Participants were presented with evolutionary explanations for features and behaviors and were asked to rate how much they agreed with evolution as an explanation for each scenario. Some were also asked to explain their reasoning in think-aloud protocols or to discuss item ratings with one another. Overall, participants thought evolutionary explanations appropriate, with median ratings in the upper quarter of the rating scale. They were slightly more willing to ascribe evolutionary explanations to plant than to human phenomena; however, this general effect was mediated by more specific aspects of the evolutionary scenarios in question. Participants who were generally negative regarding evolution were particularly negative towards human evolution. Those who were positive or neutral towards evolution in general were more willing to accept human evolution, but were more likely to use evolution to explain similarities between humans and other species than to explain particular human adaptations. For example, they were more likely to agree that evolution is responsible for the DNA similarities between humans and chimpanzees than that evolution is responsible for human behavioral characteristics, such as the fight or flight response. Think-aloud protocols suggest that, while people are more familiar with human evolutionary relationships than plant evolutionary relationships, they may be less likely to see human characteristics as adaptively valuable. One plausible explanation for these patterns is that an evolutionary explanation is judged jointly by its availability in an individual's memory and its plausibility (i.e., its congruence with the individual's worldview). Popular media coverage, with its focus on controversy and litigation, makes it likely that awareness of human evolution is high, compared with plant evolution (which may not even "enter the radar screen" when most people think of evolution). Some aspects of human evolution, such as the basic relationship between all primates, may have become so pedestrian that they do not threaten many individuals' worldviews. However, even for those positively disposed towards evolution, extending the ramifications of human evolution by suggesting that evolution shapes our behaviors and physical traits may pose a threat to their sense of personal agency. This threat is not associated with plant evolution.

  17. Neuronal boost to evolutionary dynamics.

    PubMed

    de Vladar, Harold P; Szathmáry, Eörs

    2015-12-06

    Standard evolutionary dynamics is limited by the constraints of the genetic system. A central message of evolutionary neurodynamics is that evolutionary dynamics in the brain can happen in a neuronal niche in real time, despite the fact that neurons do not reproduce. We show that Hebbian learning and structural synaptic plasticity broaden the capacity for informational replication and guided variability provided a neuronally plausible mechanism of replication is in place. The synergy between learning and selection is more efficient than the equivalent search by mutation selection. We also consider asymmetric landscapes and show that the learning weights become correlated with the fitness gradient. That is, the neuronal complexes learn the local properties of the fitness landscape, resulting in the generation of variability directed towards the direction of fitness increase, as if mutations in a genetic pool were drawn such that they would increase reproductive success. Evolution might thus be more efficient within evolved brains than among organisms out in the wild.

  18. Evidence of evolutionary history and selective sweeps in the genome of Meishan pig reveals its genetic and phenotypic characterization.

    PubMed

    Zhao, Pengju; Yu, Ying; Feng, Wen; Du, Heng; Yu, Jian; Kang, Huimin; Zheng, Xianrui; Wang, Zhiquan; Liu, George E; Ernst, Catherine W; Ran, Xueqin; Wang, Jiafu; Liu, Jian-Feng

    2018-05-01

    Meishan is a pig breed indigenous to China and famous for its high fecundity. The traits of Meishan are strongly associated with its distinct evolutionary history and domestication. However, the genomic evidence linking the domestication of Meishan pigs with its unique features is still poorly understood. The goal of this study is to investigate the genomic signatures and evolutionary evidence related to the phenotypic traits of Meishan via large-scale sequencing. We found that the unique domestication of Meishan pigs occurred in the Taihu Basin area between the Majiabang and Liangzhu Cultures, during which 300 protein-coding genes have underwent positive selection. Notably, enrichment of the FoxO signaling pathway with significant enrichment signal and the harbored gene IGF1R were likely associated with the high fertility of Meishan pigs. Moreover, NFKB1 exhibited strong selective sweep signals and positively participated in hyaluronan biosynthesis as the key gene of NF-kB signaling, which may have resulted in the wrinkled skin and face of Meishan pigs. Particularly, three population-specific synonymous single-nucleotide variants occurred in PYROXD1, MC1R, and FAM83G genes; the T305C substitution in the MCIR gene explained the black coat of the Meishan pigs well. In addition, the shared haplotypes between Meishan and Duroc breeds confirmed the previous Asian-derived introgression and demonstrated the specific contribution of Meishan pigs. These findings will help us explain the unique genetic and phenotypic characteristics of Meishan pigs and offer a plausible method for their utilization of Meishan pigs as valuable genetic resources in pig breeding and as an animal model for human wrinkled skin disease research.

  19. Adverse outcome pathway (AOP) development I: Strategies and principles

    EPA Science Inventory

    An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically-supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organizatio...

  20. Teaching the Toolkit: A Laboratory Series to Demonstrate the Evolutionary Conservation of Metazoan Cell Signaling Pathways

    ERIC Educational Resources Information Center

    LeClair, Elizabeth E.

    2008-01-01

    A major finding of comparative genomics and developmental genetics is that metazoans share certain conserved, embryonically deployed signaling pathways that instruct cells as to their ultimate fate. Because the DNA encoding these pathways predates the evolutionary split of most animal groups, it should in principle be possible to clone…

  1. An Evolutionary Comparison of the Handicap Principle and Hybrid Equilibrium Theories of Signaling.

    PubMed

    Kane, Patrick; Zollman, Kevin J S

    2015-01-01

    The handicap principle has come under significant challenge both from empirical studies and from theoretical work. As a result, a number of alternative explanations for honest signaling have been proposed. This paper compares the evolutionary plausibility of one such alternative, the "hybrid equilibrium," to the handicap principle. We utilize computer simulations to compare these two theories as they are instantiated in Maynard Smith's Sir Philip Sidney game. We conclude that, when both types of communication are possible, evolution is unlikely to lead to handicap signaling and is far more likely to result in the partially honest signaling predicted by hybrid equilibrium theory.

  2. Evolutionary and preservational constraints on origins of biologic groups: divergence times of eutherian mammals

    NASA Technical Reports Server (NTRS)

    Foote, M.; Hunter, J. P.; Janis, C. M.; Sepkoski, J. J. Jr

    1999-01-01

    Some molecular clock estimates of divergence times of taxonomic groups undergoing evolutionary radiation are much older than the groups' first observed fossil record. Mathematical models of branching evolution are used to estimate the maximal rate of fossil preservation consistent with a postulated missing history, given the sum of species durations implied by early origins under a range of species origination and extinction rates. The plausibility of postulated divergence times depends on origination, extinction, and preservation rates estimated from the fossil record. For eutherian mammals, this approach suggests that it is unlikely that many modern orders arose much earlier than their oldest fossil records.

  3. Oxidation of cefazolin by potassium permanganate: Transformation products and plausible pathways.

    PubMed

    Li, Liping; Wei, Dongbin; Wei, Guohua; Du, Yuguo

    2016-04-01

    Cefazolin was demonstrated to exert high reactivity toward permanganate (Mn(VII)), a common oxidant in water pre-oxidation treatment. In this study, five transformation products were found to be classified into three categories according to the contained characteristic functional groups: three (di-)sulfoxide products, one sulfone product and one di-ketone product. Products analyses showed that two kinds of reactions including oxidation of thioether and the cleavage of unsaturated CC double bond occurred during transformation of cefazolin by Mn(VII). Subsequently, the plausible transformation pathways under different pH conditions were proposed based on the identified products and chemical reaction principles. More importantly, the simulation with real surface water matrix indicated that the proposed transformation pathways of cefazolin could be replayed in real water treatment practices. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Fast and Frugal Heuristics Are Plausible Models of Cognition: Reply to Dougherty, Franco-Watkins, and Thomas (2008)

    ERIC Educational Resources Information Center

    Gigerenzer, Gerd; Hoffrage, Ulrich; Goldstein, Daniel G.

    2008-01-01

    M. R. Dougherty, A. M. Franco-Watkins, and R. Thomas (2008) conjectured that fast and frugal heuristics need an automatic frequency counter for ordering cues. In fact, only a few heuristics order cues, and these orderings can arise from evolutionary, social, or individual learning, none of which requires automatic frequency counting. The idea that…

  5. Neuronal boost to evolutionary dynamics

    PubMed Central

    de Vladar, Harold P.; Szathmáry, Eörs

    2015-01-01

    Standard evolutionary dynamics is limited by the constraints of the genetic system. A central message of evolutionary neurodynamics is that evolutionary dynamics in the brain can happen in a neuronal niche in real time, despite the fact that neurons do not reproduce. We show that Hebbian learning and structural synaptic plasticity broaden the capacity for informational replication and guided variability provided a neuronally plausible mechanism of replication is in place. The synergy between learning and selection is more efficient than the equivalent search by mutation selection. We also consider asymmetric landscapes and show that the learning weights become correlated with the fitness gradient. That is, the neuronal complexes learn the local properties of the fitness landscape, resulting in the generation of variability directed towards the direction of fitness increase, as if mutations in a genetic pool were drawn such that they would increase reproductive success. Evolution might thus be more efficient within evolved brains than among organisms out in the wild. PMID:26640653

  6. Consciousness and the natural method.

    PubMed

    Flanagan, O

    1995-09-01

    'Consciousness' is a superordinate term for a heterogeneous array of mental state types. The types share the property of 'being experienced' or 'being experiences'--'of there being something that it is like for the subject to be in one of these states.' I propose that we can only build a theory of consciousness by deploying 'the natural method' of coordinating all relevant informational resources at once, especially phenomenology, cognitive science, neuroscience and evolutionary biology. I'll provide two examples of the natural method in action in mental domains where an adaptationist evolutionary account seems plausible: (i) visual awareness and (ii) conscious event memory. Then I will discuss a case, (iii), dreaming, where I think no adaptationist evolutionary account exists. Beyond whatever interest the particular cases have, the examination will show why I think that a theory of mind, and the role conscious mentation plays in it, will need to be built domain-by-domain with no a priori expectation that there will be a unified account of the causal role or evolutionary history of different domains and competences.

  7. The evolution of a mechanism of cell suicide.

    PubMed

    Blackstone, N W; Green, D R

    1999-01-01

    In the vertebrates, programmed cell death or apoptosis frequently involves the relocalization of mitochondrial cytochrome c to the cytoplasm. This prominent role in the regulation of apoptosis is in addition to the primary function of cytochrome c in the mitochondrial electron transport chain. These seemingly divergent roles become plausible when considering the symbiotic origin of the mitochondrion. Symbiosis involves conflicts between levels of selection, in this case between the primitive host cell and the protomitochondria. In an aerobic environment, selection on the protomitochondria may have favored routine manipulations of the host cell's phenotype using products and by-products of oxidative phosphorylation, in particular reactive oxygen species (ROS). Blocking the mitochondrial electron transport chain by removing cytochrome c enhances the production of ROS; thus cytochrome c release by protomitochondria may have altered the host cell's phenotype via enhanced ROS production. Subsequently, this signaling pathway may have been refined by selection so that cytochrome c itself became the trigger for changes in the host's phenotype. A mechanism of apoptosis in metazoans may thus be a vestige of evolutionary conflicts within the eukaryotic cell.

  8. Complex Ancestries of Isoprenoid Synthesis in Dinoflagellates.

    PubMed

    Bentlage, Bastian; Rogers, Travis S; Bachvaroff, Tsvetan R; Delwiche, Charles F

    2016-01-01

    Isoprenoid metabolism occupies a central position in the anabolic metabolism of all living cells. In plastid-bearing organisms, two pathways may be present for de novo isoprenoid synthesis, the cytosolic mevalonate pathway (MVA) and nuclear-encoded, plastid-targeted nonmevalonate pathway (DOXP). Using transcriptomic data we find that dinoflagellates apparently make exclusive use of the DOXP pathway. Using phylogenetic analyses of all DOXP genes we inferred the evolutionary origins of DOXP genes in dinoflagellates. Plastid replacements led to a DOXP pathway of multiple evolutionary origins. Dinoflagellates commonly referred to as dinotoms due to their relatively recent acquisition of a diatom plastid, express two completely redundant DOXP pathways. Dinoflagellates with a tertiary plastid of haptophyte origin, by contrast, express a hybrid pathway of dual evolutionary origin. Here, changes in the targeting motif of signal/transit peptide likely allow for targeting the new plastid by the proteins of core isoprenoid metabolism proteins. Parasitic dinoflagellates of the Amoebophyra species complex appear to have lost the DOXP pathway, suggesting that they may rely on their host for sterol synthesis. © 2015 The Author(s) Journal of Eukaryotic Microbiology © 2015 International Society of Protistologists.

  9. Workshop on Self-Determination in Developing and Evolving Systems

    DTIC Science & Technology

    1994-02-18

    processes of duplication (e.g. gene duplication, cell duplication, structural enlargement), responses to selfish DNA (e.g. suppression of outlaw...direct their development, then the genes would need some form of environmental feedback. Are there any plausible mechanisms for such feedback? 3. What is...evolutionary innovation, what is the contribution of random mutations, directed mutation, gene conversion, symbiogenesis, fusion, jumping genes or other

  10. An Evolutionary Comparison of the Handicap Principle and Hybrid Equilibrium Theories of Signaling

    PubMed Central

    Kane, Patrick; Zollman, Kevin J. S.

    2015-01-01

    The handicap principle has come under significant challenge both from empirical studies and from theoretical work. As a result, a number of alternative explanations for honest signaling have been proposed. This paper compares the evolutionary plausibility of one such alternative, the “hybrid equilibrium,” to the handicap principle. We utilize computer simulations to compare these two theories as they are instantiated in Maynard Smith’s Sir Philip Sidney game. We conclude that, when both types of communication are possible, evolution is unlikely to lead to handicap signaling and is far more likely to result in the partially honest signaling predicted by hybrid equilibrium theory. PMID:26348617

  11. Convergent evolution at the pathway level: predictable regulatory changes during flower color transitions.

    PubMed

    Larter, Maximilian; Dunbar-Wallis, Amy; Berardi, Andrea E; Smith, Stacey D

    2018-06-07

    The predictability of evolution, or whether lineages repeatedly follow the same evolutionary trajectories during phenotypic convergence remains an open question of evolutionary biology. In this study, we investigate evolutionary convergence at the biochemical pathway level and test the predictability of evolution using floral anthocyanin pigmentation, a trait with a well-understood genetic and regulatory basis. We reconstructed the evolution of floral anthocyanin content across 28 species of the Andean clade Iochrominae (Solanaceae) and investigated how shifts in pigmentation are related to changes in expression of 7 key anthocyanin pathway genes. We used phylogenetic multivariate analysis of gene expression to test for phenotypic and developmental convergence at a macroevolutionary scale. Our results show that the four independent losses of the ancestral pigment delphinidin involved convergent losses of expression of the three late pathway genes (F3'5'h, Dfr and Ans). Transitions between pigment types affecting floral hue (e.g. blue to red) involve changes to the expression of branching genes F3'h and F3'5'h, while the expression levels of early steps of the pathway are strongly conserved in all species. These patterns support the idea that the macroevolution of floral pigmentation follows predictable evolutionary trajectories to reach convergent phenotype space, repeatedly involving regulatory changes. This is likely driven by constraints at the pathway level, such as pleiotropy and regulatory structure.

  12. Characterizing the roles of changing population size and selection on the evolution of flux control in metabolic pathways.

    PubMed

    Orlenko, Alena; Chi, Peter B; Liberles, David A

    2017-05-25

    Understanding the genotype-phenotype map is fundamental to our understanding of genomes. Genes do not function independently, but rather as part of networks or pathways. In the case of metabolic pathways, flux through the pathway is an important next layer of biological organization up from the individual gene or protein. Flux control in metabolic pathways, reflecting the importance of mutation to individual enzyme genes, may be evolutionarily variable due to the role of mutation-selection-drift balance. The evolutionary stability of rate limiting steps and the patterns of inter-molecular co-evolution were evaluated in a simulated pathway with a system out of equilibrium due to fluctuating selection, population size, or positive directional selection, to contrast with those under stabilizing selection. Depending upon the underlying population genetic regime, fluctuating population size was found to increase the evolutionary stability of rate limiting steps in some scenarios. This result was linked to patterns of local adaptation of the population. Further, during positive directional selection, as with more complex mutational scenarios, an increase in the observation of inter-molecular co-evolution was observed. Differences in patterns of evolution when systems are in and out of equilibrium, including during positive directional selection may lead to predictable differences in observed patterns for divergent evolutionary scenarios. In particular, this result might be harnessed to detect differences between compensatory processes and directional processes at the pathway level based upon evolutionary observations in individual proteins. Detecting functional shifts in pathways reflects an important milestone in predicting when changes in genotypes result in changes in phenotypes.

  13. The Role of ERK1/2 in the Progression of Anti-Androgen Resistance of mtDNA Deficient Prostate Cancer

    DTIC Science & Technology

    2012-05-01

    of PCa and BCa. Signaled by a metabolic-to-proto-oncogenic pathway, it is plausible that the mitoGPS is a ubiquitous (patho) physiological response to...extracellular environment. We are the first to directly establish the mitochondrion as a direct physiological source of hypoxia in an in vitro system. Our...mitochondrial genome. It is plausible that the mitoGPS is a ubiquitous (patho) physiological response to the etiology and/or progression of a broad spectrum of

  14. Identification of a missing link in the evolution of an enzyme into a transcriptional regulator.

    PubMed

    Durante-Rodríguez, Gonzalo; Mancheño, José Miguel; Rivas, Germán; Alfonso, Carlos; García, José Luis; Díaz, Eduardo; Carmona, Manuel

    2013-01-01

    The evolution of transcriptional regulators through the recruitment of DNA-binding domains by enzymes is a widely held notion. However, few experimental approaches have directly addressed this hypothesis. Here we report the reconstruction of a plausible pathway for the evolution of an enzyme into a transcriptional regulator. The BzdR protein is the prototype of a subfamily of prokaryotic transcriptional regulators that controls the expression of genes involved in the anaerobic degradation of benzoate. We have shown that BzdR consists of an N-terminal DNA-binding domain connected through a linker to a C-terminal effector-binding domain that shows significant identity to the shikimate kinase (SK). The construction of active synthetic BzdR-like regulators by fusing the DNA-binding domain of BzdR to the Escherichia coli SKI protein strongly supports the notion that an ancestral SK domain could have been involved in the evolutionary origin of BzdR. The loss of the enzymatic activity of the ancestral SK domain was essential for it to evolve as a regulatory domain in the current BzdR protein. This work also supports the view that enzymes precede the emergence of the regulatory systems that may control their expression.

  15. The natural selection of altruistic traits.

    PubMed

    Boehm, C

    1999-09-01

    Proponents of the standard evolutionary biology paradigm explain human "altruism" in terms of either nepotism or strict reciprocity. On that basis our underlying nature is reduced to a function of inclusive fitness: human nature has to be totally selfish or nepotistic. Proposed here are three possible paths to giving costly aid to nonrelatives, paths that are controversial because they involve assumed pleiotropic effects or group selection. One path is pleiotropic subsidies that help to extend nepotistic helping behavior from close family to nonrelatives. Another is "warfare"-if and only if warfare recurred in the Paleolithic. The third and most plausible hypothesis is based on the morally based egalitarian syndrome of prehistoric hunter-gatherers, which reduced phenotypic variation at the within-group level, increased it at the between-group level, and drastically curtailed the advantages of free riders. In an analysis consistent with the fundamental tenets of evolutionary biology, these three paths are evaluated as explanations for the evolutionary development of a rather complicated human social nature.

  16. Sex-Specific Pathways to Early Puberty, Sexual Debut, and Sexual Risk Taking: Tests of an Integrated Evolutionary-Developmental Model

    ERIC Educational Resources Information Center

    James, Jenee; Ellis, Bruce J.; Schlomer, Gabriel L.; Garber, Judy

    2012-01-01

    The current study tested sex-specific pathways to early puberty, sexual debut, and sexual risk taking, as specified by an integrated evolutionary-developmental model of adolescent sexual development and behavior. In a prospective study of 238 adolescents (n = 129 girls and n = 109 boys) followed from approximately 12-18 years of age, we tested for…

  17. SOME USES OF MODELS OF QUANTITATIVE GENETIC SELECTION IN SOCIAL SCIENCE.

    PubMed

    Weight, Michael D; Harpending, Henry

    2017-01-01

    The theory of selection of quantitative traits is widely used in evolutionary biology, agriculture and other related fields. The fundamental model known as the breeder's equation is simple, robust over short time scales, and it is often possible to estimate plausible parameters. In this paper it is suggested that the results of this model provide useful yardsticks for the description of social traits and the evaluation of transmission models. The differences on a standard personality test between samples of Old Order Amish and Indiana rural young men from the same county and the decline of homicide in Medieval Europe are used as illustrative examples of the overall approach. It is shown that the decline of homicide is unremarkable under a threshold model while the differences between rural Amish and non-Amish young men are too large to be a plausible outcome of simple genetic selection in which assortative mating by affiliation is equivalent to truncation selection.

  18. Multiple regimes of robust patterns between network structure and biodiversity

    NASA Astrophysics Data System (ADS)

    Jover, Luis F.; Flores, Cesar O.; Cortez, Michael H.; Weitz, Joshua S.

    2015-12-01

    Ecological networks such as plant-pollinator and host-parasite networks have structured interactions that define who interacts with whom. The structure of interactions also shapes ecological and evolutionary dynamics. Yet, there is significant ongoing debate as to whether certain structures, e.g., nestedness, contribute positively, negatively or not at all to biodiversity. We contend that examining variation in life history traits is key to disentangling the potential relationship between network structure and biodiversity. Here, we do so by analyzing a dynamic model of virus-bacteria interactions across a spectrum of network structures. Consistent with prior studies, we find plausible parameter domains exhibiting strong, positive relationships between nestedness and biodiversity. Yet, the same model can exhibit negative relationships between nestedness and biodiversity when examined in a distinct, plausible region of parameter space. We discuss steps towards identifying when network structure could, on its own, drive the resilience, sustainability, and even conservation of ecological communities.

  19. Multiple regimes of robust patterns between network structure and biodiversity

    PubMed Central

    Jover, Luis F.; Flores, Cesar O.; Cortez, Michael H.; Weitz, Joshua S.

    2015-01-01

    Ecological networks such as plant-pollinator and host-parasite networks have structured interactions that define who interacts with whom. The structure of interactions also shapes ecological and evolutionary dynamics. Yet, there is significant ongoing debate as to whether certain structures, e.g., nestedness, contribute positively, negatively or not at all to biodiversity. We contend that examining variation in life history traits is key to disentangling the potential relationship between network structure and biodiversity. Here, we do so by analyzing a dynamic model of virus-bacteria interactions across a spectrum of network structures. Consistent with prior studies, we find plausible parameter domains exhibiting strong, positive relationships between nestedness and biodiversity. Yet, the same model can exhibit negative relationships between nestedness and biodiversity when examined in a distinct, plausible region of parameter space. We discuss steps towards identifying when network structure could, on its own, drive the resilience, sustainability, and even conservation of ecological communities. PMID:26632996

  20. Molecular microenvironments: Solvent interactions with nucleic acid bases and ions

    NASA Technical Reports Server (NTRS)

    Macelroy, R. D.; Pohorille, A.

    1986-01-01

    The possibility of reconstructing plausible sequences of events in prebiotic molecular evolution is limited by the lack of fossil remains. However, with hindsight, one goal of molecular evolution was obvious: the development of molecular systems that became constituents of living systems. By understanding the interactions among molecules that are likely to have been present in the prebiotic environment, and that could have served as components in protobiotic molecular systems, plausible evolutionary sequences can be suggested. When stable aggregations of molecules form, a net decrease in free energy is observed in the system. Such changes occur when solvent molecules interact among themselves, as well as when they interact with organic species. A significant decrease in free energy, in systems of solvent and organic molecules, is due to entropy changes in the solvent. Entropy-driven interactioins played a major role in the organization of prebiotic systems, and understanding the energetics of them is essential to understanding molecular evolution.

  1. Match Fitness: Development, Evolution, and Behavior--Comment on Frankenhuis and Del Giudice (2012)

    ERIC Educational Resources Information Center

    Gluckman, Peter D.; Beedle, Alan S.

    2012-01-01

    The application of evolutionary thinking to human physical and psychological medicine suggests several pathways through which evolutionary processes affect risk of disease. Among these is the concept of mismatch between an individual and its environment, either because the environment has changed for the whole species ("evolutionary novelty") or…

  2. Modeling evolution of crosstalk in noisy signal transduction networks

    NASA Astrophysics Data System (ADS)

    Tareen, Ammar; Wingreen, Ned S.; Mukhopadhyay, Ranjan

    2018-02-01

    Signal transduction networks can form highly interconnected systems within cells due to crosstalk between constituent pathways. To better understand the evolutionary design principles underlying such networks, we study the evolution of crosstalk for two parallel signaling pathways that arise via gene duplication. We use a sequence-based evolutionary algorithm and evolve the network based on two physically motivated fitness functions related to information transmission. We find that one fitness function leads to a high degree of crosstalk while the other leads to pathway specificity. Our results offer insights on the relationship between network architecture and information transmission for noisy biomolecular networks.

  3. Evolution of complex life cycles in trophically transmitted helminths. I. Host incorporation and trophic ascent.

    PubMed

    Parker, G A; Ball, M A; Chubb, J C

    2015-02-01

    Links between parasites and food webs are evolutionarily ancient but dynamic: life history theory provides insights into helminth complex life cycle origins. Most adult helminths benefit by sexual reproduction in vertebrates, often high up food chains, but direct infection is commonly constrained by a trophic vacuum between free-living propagules and definitive hosts. Intermediate hosts fill this vacuum, facilitating transmission to definitive hosts. The central question concerns why sexual reproduction, and sometimes even larval growth, is suppressed in intermediate hosts, favouring growth arrest at larval maturity in intermediate hosts and reproductive suppression until transmission to definitive hosts? Increased longevity and higher growth in definitive hosts can generate selection for larger parasite body size and higher fecundity at sexual maturity. Life cycle length is increased by two evolutionary mechanisms, upward and downward incorporation, allowing simple (one-host) cycles to become complex (multihost). In downward incorporation, an intermediate host is added below the definitive host: models suggest that downward incorporation probably evolves only after ecological or evolutionary perturbations create a trophic vacuum. In upward incorporation, a new definitive host is added above the original definitive host, which subsequently becomes an intermediate host, again maintained by the trophic vacuum: theory suggests that this is plausible even under constant ecological/evolutionary conditions. The final cycle is similar irrespective of its origin (upward or downward). Insights about host incorporation are best gained by linking comparative phylogenetic analyses (describing evolutionary history) with evolutionary models (examining selective forces). Ascent of host trophic levels and evolution of optimal host taxa ranges are discussed. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  4. Climate Change Impacts on Agriculture and Food Security in 2050 under a Range of Plausible Socioeconomic and Emissions Scenarios

    NASA Astrophysics Data System (ADS)

    Wiebe, K.; Lotze-Campen, H.; Bodirsky, B.; Kavallari, A.; Mason-d'Croz, D.; van der Mensbrugghe, D.; Robinson, S.; Sands, R.; Tabeau, A.; Willenbockel, D.; Islam, S.; van Meijl, H.; Mueller, C.; Robertson, R.

    2014-12-01

    Previous studies have combined climate, crop and economic models to examine the impact of climate change on agricultural production and food security, but results have varied widely due to differences in models, scenarios and data. Recent work has examined (and narrowed) these differences through systematic model intercomparison using a high-emissions pathway to highlight the differences. New work extends that analysis to cover a range of plausible socioeconomic scenarios and emission pathways. Results from three general circulation models are combined with one crop model and five global economic models to examine the global and regional impacts of climate change on yields, area, production, prices and trade for coarse grains, rice, wheat, oilseeds and sugar to 2050. Results show that yield impacts vary with changes in population, income and technology as well as emissions, but are reduced in all cases by endogenous changes in prices and other variables.

  5. Arginine deiminase pathway enzymes: evolutionary history in metamonads and other eukaryotes.

    PubMed

    Novák, Lukáš; Zubáčová, Zuzana; Karnkowska, Anna; Kolisko, Martin; Hroudová, Miluše; Stairs, Courtney W; Simpson, Alastair G B; Keeling, Patrick J; Roger, Andrew J; Čepička, Ivan; Hampl, Vladimír

    2016-10-06

    Multiple prokaryotic lineages use the arginine deiminase (ADI) pathway for anaerobic energy production by arginine degradation. The distribution of this pathway among eukaryotes has been thought to be very limited, with only two specialized groups living in low oxygen environments (Parabasalia and Diplomonadida) known to possess the complete set of all three enzymes. We have performed an extensive survey of available sequence data in order to map the distribution of these enzymes among eukaryotes and to reconstruct their phylogenies. We have found genes for the complete pathway in almost all examined representatives of Metamonada, the anaerobic protist group that includes parabasalids and diplomonads. Phylogenetic analyses indicate the presence of the complete pathway in the last common ancestor of metamonads and heterologous transformation experiments suggest its cytosolic localization in the metamonad ancestor. Outside Metamonada, the complete pathway occurs rarely, nevertheless, it was found in representatives of most major eukaryotic clades. Phylogenetic relationships of complete pathways are consistent with the presence of the Archaea-derived ADI pathway in the last common ancestor of all eukaryotes, although other evolutionary scenarios remain possible. The presence of the incomplete set of enzymes is relatively common among eukaryotes and it may be related to the fact that these enzymes are involved in other cellular processes, such as the ornithine-urea cycle. Single protein phylogenies suggest that the evolutionary history of all three enzymes has been shaped by frequent gene losses and horizontal transfers, which may sometimes be connected with their diverse roles in cellular metabolism.

  6. A common evolutionary origin for the ON- and OFF-edge motion detection pathways of the Drosophila visual system

    PubMed Central

    Shinomiya, Kazunori; Takemura, Shin-ya; Rivlin, Patricia K.; Plaza, Stephen M.; Scheffer, Louis K.; Meinertzhagen, Ian A.

    2015-01-01

    Synaptic circuits for identified behaviors in the Drosophila brain have typically been considered from either a developmental or functional perspective without reference to how the circuits might have been inherited from ancestral forms. For example, two candidate pathways for ON- and OFF-edge motion detection in the visual system act via circuits that use respectively either T4 or T5, two cell types of the fourth neuropil, or lobula plate (LOP), that exhibit narrow-field direction-selective responses and provide input to wide-field tangential neurons. T4 or T5 both have four subtypes that terminate one each in the four strata of the LOP. Representatives are reported in a wide range of Diptera, and both cell types exhibit various similarities in: (1) the morphology of their dendritic arbors; (2) their four morphological and functional subtypes; (3) their cholinergic profile in Drosophila; (4) their input from the pathways of L3 cells in the first neuropil, or lamina (LA), and by one of a pair of LA cells, L1 (to the T4 pathway) and L2 (to the T5 pathway); and (5) their innervation by a single, wide-field contralateral tangential neuron from the central brain. Progenitors of both also express the gene atonal early in their proliferation from the inner anlage of the developing optic lobe, being alone among many other cell type progeny to do so. Yet T4 receives input in the second neuropil, or medulla (ME), and T5 in the third neuropil or lobula (LO). Here we suggest that these two cell types were originally one, that their ancestral cell population duplicated and split to innervate separate ME and LO neuropils, and that a fiber crossing—the internal chiasma—arose between the two neuropils. The split most plausibly occurred, we suggest, with the formation of the LO as a new neuropil that formed when it separated from its ancestral neuropil to leave the ME, suggesting additionally that ME input neurons to T4 and T5 may also have had a common origin. PMID:26217193

  7. Evolutionary perspectives on ageing.

    PubMed

    Reichard, Martin

    2017-10-01

    From an evolutionary perspective, ageing is a decrease in fitness with chronological age - expressed by an increase in mortality risk and/or decline in reproductive success and mediated by deterioration of functional performance. While this makes ageing intuitively paradoxical - detrimental to individual fitness - evolutionary theory offers answers as to why ageing has evolved. In this review, I first briefly examine the classic evolutionary theories of ageing and their empirical tests, and highlight recent findings that have advanced our understanding of the evolution of ageing (condition-dependent survival, positive pleiotropy). I then provide an overview of recent theoretical extensions and modifications that accommodate those new discoveries. I discuss the role of indeterminate (asymptotic) growth for lifetime increases in fecundity and ageing trajectories. I outline alternative views that challenge a universal existence of senescence - namely the lack of a germ-soma distinction and the ability of tissue replacement and retrogression to younger developmental stages in modular organisms. I argue that rejuvenation at the organismal level is plausible, but includes a return to a simple developmental stage. This may exempt a particular genotype from somatic defects but, correspondingly, removes any information acquired during development. A resolution of the question of whether a rejuvenated individual is the same entity is central to the recognition of whether current evolutionary theories of ageing, with their extensions and modifications, can explain the patterns of ageing across the Tree of Life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Counterfactuals and history: Contingency and convergence in histories of science and life.

    PubMed

    Hesketh, Ian

    2016-08-01

    This article examines a series of recent histories of science that have attempted to consider how science may have developed in slightly altered historical realities. These works have, moreover, been influenced by debates in evolutionary science about the opposing forces of contingency and convergence in regard to Stephen Jay Gould's notion of "replaying life's tape." The article argues that while the historians under analysis seem to embrace contingency in order to present their counterfactual narratives, for the sake of historical plausibility they are forced to accept a fairly weak role for contingency in shaping the development of science. It is therefore argued that Simon Conway Morris's theory of evolutionary convergence comes closer to describing the restrained counterfactual worlds imagined by these historians of science than does contingency. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Evolution of siderophore pathways in human pathogenic bacteria.

    PubMed

    Franke, Jakob; Ishida, Keishi; Hertweck, Christian

    2014-04-16

    Ornibactin and malleobactin are hydroxamate siderophores employed by human pathogenic bacteria belonging to the genus Burkholderia. Similarities in their structures and corresponding biosynthesis gene clusters strongly suggest an evolutionary relationship. Through gene coexpression and targeted gene manipulations, the malleobactin pathway was successfully morphed into an ornibactin assembly line. Such an evolutionary-guided approach has been unprecedented for nonribosomal peptide synthetases. Furthermore, the timing of amino acid acylation before peptide assembly, the absolute configuration of the ornibactin side chain, and the function of the acyl transferase were elucidated. Beyond providing a proof of principle for the rational design of siderophore pathways, a compelling model for the evolution of virulence traits is presented.

  10. An Automated Pipeline for Engineering Many-Enzyme Pathways: Computational Sequence Design, Pathway Expression-Flux Mapping, and Scalable Pathway Optimization.

    PubMed

    Halper, Sean M; Cetnar, Daniel P; Salis, Howard M

    2018-01-01

    Engineering many-enzyme metabolic pathways suffers from the design curse of dimensionality. There are an astronomical number of synonymous DNA sequence choices, though relatively few will express an evolutionary robust, maximally productive pathway without metabolic bottlenecks. To solve this challenge, we have developed an integrated, automated computational-experimental pipeline that identifies a pathway's optimal DNA sequence without high-throughput screening or many cycles of design-build-test. The first step applies our Operon Calculator algorithm to design a host-specific evolutionary robust bacterial operon sequence with maximally tunable enzyme expression levels. The second step applies our RBS Library Calculator algorithm to systematically vary enzyme expression levels with the smallest-sized library. After characterizing a small number of constructed pathway variants, measurements are supplied to our Pathway Map Calculator algorithm, which then parameterizes a kinetic metabolic model that ultimately predicts the pathway's optimal enzyme expression levels and DNA sequences. Altogether, our algorithms provide the ability to efficiently map the pathway's sequence-expression-activity space and predict DNA sequences with desired metabolic fluxes. Here, we provide a step-by-step guide to applying the Pathway Optimization Pipeline on a desired multi-enzyme pathway in a bacterial host.

  11. Ancient Origin of the Tryptophan Operon and the Dynamics of Evolutionary Change†

    PubMed Central

    Xie, Gary; Keyhani, Nemat O.; Bonner; Jensen, Roy A.

    2003-01-01

    The seven conserved enzymatic domains required for tryptophan (Trp) biosynthesis are encoded in seven genetic regions that are organized differently (whole-pathway operons, multiple partial-pathway operons, and dispersed genes) in prokaryotes. A comparative bioinformatics evaluation of the conservation and organization of the genes of Trp biosynthesis in prokaryotic operons should serve as an excellent model for assessing the feasibility of predicting the evolutionary histories of genes and operons associated with other biochemical pathways. These comparisons should provide a better understanding of possible explanations for differences in operon organization in different organisms at a genomics level. These analyses may also permit identification of some of the prevailing forces that dictated specific gene rearrangements during the course of evolution. Operons concerned with Trp biosynthesis in prokaryotes have been in a dynamic state of flux. Analysis of closely related organisms among the Bacteria at various phylogenetic nodes reveals many examples of operon scission, gene dispersal, gene fusion, gene scrambling, and gene loss from which the direction of evolutionary events can be deduced. Two milestone evolutionary events have been mapped to the 16S rRNA tree of Bacteria, one splitting the operon in two, and the other rejoining it by gene fusion. The Archaea, though less resolved due to a lesser genome representation, appear to exhibit more gene scrambling than the Bacteria. The trp operon appears to have been an ancient innovation; it was already present in the common ancestor of Bacteria and Archaea. Although the operon has been subjected, even in recent times, to dynamic changes in gene rearrangement, the ancestral gene order can be deduced with confidence. The evolutionary history of the genes of the pathway is discernible in rough outline as a vertical line of descent, with events of lateral gene transfer or paralogy enriching the analysis as interesting features that can be distinguished. As additional genomes are thoroughly analyzed, an increasingly refined resolution of the sequential evolutionary steps is clearly possible. These comparisons suggest that present-day trp operons that possess finely tuned regulatory features are under strong positive selection and are able to resist the disruptive evolutionary events that may be experienced by simpler, poorly regulated operons. PMID:12966138

  12. A DNA and morphology based phylogenetic framework of the ant genus Lasius with hypotheses for the evolution of social parasitism and fungiculture.

    PubMed

    Maruyama, Munetoshi; Steiner, Florian M; Stauffer, Christian; Akino, Toshiharu; Crozier, Ross H; Schlick-Steiner, Birgit C

    2008-08-19

    Ants of the genus Lasius are ecologically important and an important system for evolutionary research. Progress in evolutionary research has been hindered by the lack of a well-founded phylogeny of the subgenera, with three previous attempts disagreeing. Here we employed two mitochondrial genes (cytochrome c oxidase subunit I, 16S ribosomal RNA), comprising 1,265 bp, together with 64 morphological characters, to recover the phylogeny of Lasius by Bayesian and Maximum Parsimony inference after exploration of potential causes of phylogenetic distortion. We use the resulting framework to infer evolutionary pathways for social parasitism and fungiculture. We recovered two well supported major lineages. One includes Acanthomyops, Austrolasius, Chthonolasius, and Lasius pallitarsis, which we confirm to represent a seventh subgenus, the other clade contains Dendrolasius, and Lasius sensu stricto. The subgenus Cautolasius, displaying neither social parasitism nor fungiculture, probably belongs to the second clade, but its phylogenetic position is not resolved at the cutoff values of node support we apply. Possible causes for previous problems with reconstructing the Lasius phylogeny include use of other reconstruction techniques, possibly more prone to instabilities in some instances, and the inclusion of phylogenetically distorting characters. By establishing an updated phylogenetic framework, our study provides the basis for a later formal taxonomic revision of subgenera and for studying the evolution of various ecologically and sociobiologically relevant traits of Lasius, although there is need for future studies to include nuclear genes and additional samples from the Nearctic. Both social parasitism and fungiculture evolved twice in Lasius, once in each major lineage, which opens up new opportunities for comparative analyses. The repeated evolution of social parasitism has been established for other groups of ants, though not for temporary social parasitism as found in Lasius. For fungiculture, the independent emergence twice in a monophyletic group marks a novel scenario in ants. We present alternative hypotheses for the evolution of both traits, with one of each involving loss of the trait. Though less likely for both traits than later evolution without reversal, we consider reversal as sufficiently plausible to merit independent testing.

  13. Evolution of sparsity and modularity in a model of protein allostery

    NASA Astrophysics Data System (ADS)

    Hemery, Mathieu; Rivoire, Olivier

    2015-04-01

    The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary constraints may take is important to interpret the information in protein sequences. To study this problem, we introduce a simple but physical model of protein evolution where selection targets allostery, the functional coupling of distal sites on protein surfaces. This model shows how the geometrical organization of couplings between amino acids within a protein structure can depend crucially on its evolutionary history. In particular, two scenarios are found to generate a spatial concentration of functional constraints: high mutation rates and fluctuating selective pressures. This second scenario offers a plausible explanation for the high tolerance of natural proteins to mutations and for the spatial organization of their least tolerant amino acids, as revealed by sequence analysis and mutagenesis experiments. It also implies a faculty to adapt to new selective pressures that is consistent with observations. The model illustrates how several independent functional modules may emerge within the same protein structure, depending on the nature of past environmental fluctuations. Our model thus relates the evolutionary history of proteins to the geometry of their functional constraints, with implications for decoding and engineering protein sequences.

  14. New understanding of adolescent brain development: relevance to transitional healthcare for young people with long term conditions.

    PubMed

    Colver, Allan; Longwell, Sarah

    2013-11-01

    Whether or not adolescence should be treated as a special period, there is now no doubt that the brain changes much during adolescence. From an evolutionary perspective, the idea of an under developed brain which is not fit for purpose until adulthood is illogical. Rather, the adolescent brain is likely to support the challenges specific to that period of life. New imaging techniques show striking changes in white and grey matter between 11 and 25 years of age, with increased connectivity between brain regions, and increased dopaminergic activity in the pre-frontal cortices, striatum and limbic system and the pathways linking them. The brain is dynamic, with some areas developing faster and becoming more dominant until other areas catch up. Plausible mechanisms link these changes to cognitive and behavioural features of adolescence. The changing brain may lead to abrupt behavioural change with attendant risks, but such a brain is flexible and can respond quickly and imaginatively. Society allows adolescent exuberance and creativity to be bounded and explored in relative safety. In healthcare settings these changes are especially relevant to young people with long term conditions as they move to young adult life; such young people need to learn to manage their health conditions with the support of their healthcare providers.

  15. Variable genetic architectures produce virtually identical molecules in bacterial symbionts of fungus-growing ants

    PubMed Central

    Sit, Clarissa S.; Ruzzini, Antonio C.; Van Arnam, Ethan B.; Ramadhar, Timothy R.; Currie, Cameron R.; Clardy, Jon

    2015-01-01

    Small molecules produced by Actinobacteria have played a prominent role in both drug discovery and organic chemistry. As part of a larger study of the actinobacterial symbionts of fungus-growing ants, we discovered a small family of three previously unreported piperazic acid-containing cyclic depsipeptides, gerumycins A–C. The gerumycins are slightly smaller versions of dentigerumycin, a cyclic depsipeptide that selectively inhibits a common fungal pathogen, Escovopsis. We had previously identified this molecule from a Pseudonocardia associated with Apterostigma dentigerum, and now we report the molecule from an associate of the more highly derived ant Trachymyrmex cornetzi. The three previously unidentified compounds, gerumycins A–C, have essentially identical structures and were produced by two different symbiotic Pseudonocardia spp. from ants in the genus Apterostigma found in both Panama and Costa Rica. To understand the similarities and differences in the biosynthetic pathways that produced these closely related molecules, the genomes of the three producing Pseudonocardia were sequenced and the biosynthetic gene clusters identified. This analysis revealed that dramatically different biosynthetic architectures, including genomic islands, a plasmid, and the use of spatially separated genetic loci, can lead to molecules with virtually identical core structures. A plausible evolutionary model that unifies these disparate architectures is presented. PMID:26438860

  16. Selective Bottlenecks Shape Evolutionary Pathways Taken during Mammalian Adaptation of a 1918-like Avian Influenza Virus.

    PubMed

    Moncla, Louise H; Zhong, Gongxun; Nelson, Chase W; Dinis, Jorge M; Mutschler, James; Hughes, Austin L; Watanabe, Tokiko; Kawaoka, Yoshihiro; Friedrich, Thomas C

    2016-02-10

    Avian influenza virus reassortants resembling the 1918 human pandemic virus can become transmissible among mammals by acquiring mutations in hemagglutinin (HA) and polymerase. Using the ferret model, we trace the evolutionary pathway by which an avian-like virus evolves the capacity for mammalian replication and airborne transmission. During initial infection, within-host HA diversity increased drastically. Then, airborne transmission fixed two polymerase mutations that do not confer a detectable replication advantage. In later transmissions, selection fixed advantageous HA1 variants. Transmission initially involved a "loose" bottleneck, which became strongly selective after additional HA mutations emerged. The stringency and evolutionary forces governing between-host bottlenecks may therefore change throughout host adaptation. Mutations occurred in multiple combinations in transmitted viruses, suggesting that mammalian transmissibility can evolve through multiple genetic pathways despite phenotypic constraints. Our data provide a glimpse into avian influenza virus adaptation in mammals, with broad implications for surveillance on potentially zoonotic viruses. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Lysosomal enzymes and their receptors in invertebrates: an evolutionary perspective.

    PubMed

    Kumar, Nadimpalli Siva; Bhamidimarri, Poorna M

    2015-01-01

    Lysosomal biogenesis is an important process in eukaryotic cells to maintain cellular homeostasis. The key components that are involved in the biogenesis such as the lysosomal enzymes, their modifications and the mannose 6-phosphate receptors have been well studied and their evolutionary conservation across mammalian and non-mammalian vertebrates is clearly established. Invertebrate lysosomal biogenesis pathway on the other hand is not well studied. Although, details on mannose 6-phosphate receptors and enzymes involved in lysosomal enzyme modifications were reported earlier, a clear cut pathway has not been established. Recent research on the invertebrate species involving biogenesis of lysosomal enzymes suggests a possible conserved pathway in invertebrates. This review presents certain observations based on these processes that include biochemical, immunological and functional studies. Major conclusions include conservation of MPR-dependent pathway in higher invertebrates and recent evidence suggests that MPR-independent pathway might have been more prominent among lower invertebrates. The possible components of MPR-independent pathway that may play a role in lysosomal enzyme targeting are also discussed here.

  18. Constructing phylogenetic trees using interacting pathways.

    PubMed

    Wan, Peng; Che, Dongsheng

    2013-01-01

    Phylogenetic trees are used to represent evolutionary relationships among biological species or organisms. The construction of phylogenetic trees is based on the similarities or differences of their physical or genetic features. Traditional approaches of constructing phylogenetic trees mainly focus on physical features. The recent advancement of high-throughput technologies has led to accumulation of huge amounts of biological data, which in turn changed the way of biological studies in various aspects. In this paper, we report our approach of building phylogenetic trees using the information of interacting pathways. We have applied hierarchical clustering on two domains of organisms-eukaryotes and prokaryotes. Our preliminary results have shown the effectiveness of using the interacting pathways in revealing evolutionary relationships.

  19. Fast Construction of Near Parsimonious Hybridization Networks for Multiple Phylogenetic Trees.

    PubMed

    Mirzaei, Sajad; Wu, Yufeng

    2016-01-01

    Hybridization networks represent plausible evolutionary histories of species that are affected by reticulate evolutionary processes. An established computational problem on hybridization networks is constructing the most parsimonious hybridization network such that each of the given phylogenetic trees (called gene trees) is "displayed" in the network. There have been several previous approaches, including an exact method and several heuristics, for this NP-hard problem. However, the exact method is only applicable to a limited range of data, and heuristic methods can be less accurate and also slow sometimes. In this paper, we develop a new algorithm for constructing near parsimonious networks for multiple binary gene trees. This method is more efficient for large numbers of gene trees than previous heuristics. This new method also produces more parsimonious results on many simulated datasets as well as a real biological dataset than a previous method. We also show that our method produces topologically more accurate networks for many datasets.

  20. Religious groups as adaptive units.

    PubMed

    Wilson, D S

    2001-01-01

    This essay provides a sketch of religion as a set of biologically and culturally evolved adaptations that enable human groups to function as adaptive units. Recent developments in evolutionary biology make such a group-level interpretation of religion more plausible than in the past. A brief survey of relevant concepts is followed by a relatively detailed interpretation of Calvinism as a religious system in which explicit behavioral prescriptions, beliefs about God and his relationship with people, and numerous social control mechanisms combined to change the city of Geneva from a collection of warring factions to a unified population.

  1. A race-specific interaction between vitamin K status and statin use

    USDA-ARS?s Scientific Manuscript database

    The oral anticoagulant warfarin is a vitamin K antagonist. Phylloquinone, the primary circulating form of vitamin K, is transported by triglyceride-rich lipoproteins and shares a metabolic pathway with cholesterol. Thus, there is biological plausibility for an interaction between serum phylloquinone...

  2. Selective α-arylation of α,β-unsaturated imides mediated by a visible light photoredox catalyst.

    PubMed

    Ando, Yuki; Kamatsuka, Takuto; Shinokubo, Hiroshi; Miyake, Yoshihiro

    2017-08-10

    Visible light-mediated α-arylation of α,β-unsaturated imides is achieved via aminium radicals generated from diarylalkylamines using a photoredox catalyst. On the basis of emission quenching experiments, a plausible pathway of the reaction is discussed.

  3. The evolution of plant virus transmission pathways.

    PubMed

    Hamelin, Frédéric M; Allen, Linda J S; Prendeville, Holly R; Hajimorad, M Reza; Jeger, Michael J

    2016-05-07

    The evolution of plant virus transmission pathways is studied through transmission via seed, pollen, or a vector. We address the questions: under what circumstances does vector transmission make pollen transmission redundant? Can evolution lead to the coexistence of multiple virus transmission pathways? We restrict the analysis to an annual plant population in which reproduction through seed is obligatory. A semi-discrete model with pollen, seed, and vector transmission is formulated to investigate these questions. We assume vector and pollen transmission rates are frequency-dependent and density-dependent, respectively. An ecological stability analysis is performed for the semi-discrete model and used to inform an evolutionary study of trade-offs between pollen and seed versus vector transmission. Evolutionary dynamics critically depend on the shape of the trade-off functions. Assuming a trade-off between pollen and vector transmission, evolution either leads to an evolutionarily stable mix of pollen and vector transmission (concave trade-off) or there is evolutionary bi-stability (convex trade-off); the presence of pollen transmission may prevent evolution of vector transmission. Considering a trade-off between seed and vector transmission, evolutionary branching and the subsequent coexistence of pollen-borne and vector-borne strains is possible. This study contributes to the theory behind the diversity of plant-virus transmission patterns observed in nature. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Applying Evolutionary Genetics to Developmental Toxicology and Risk Assessment

    PubMed Central

    Leung, Maxwell C. K.; Procter, Andrew C.; Goldstone, Jared V.; Foox, Jonathan; DeSalle, Robert; Mattingly, Carolyn J.; Siddall, Mark E.; Timme-Laragy, Alicia R.

    2018-01-01

    Evolutionary thinking continues to challenge our views on health and disease. Yet, there is a communication gap between evolutionary biologists and toxicologists in recognizing the connections among developmental pathways, high-throughput screening, and birth defects in humans. To increase our capability in identifying potential developmental toxicants in humans, we propose to apply evolutionary genetics to improve the experimental design and data interpretation with various in vitro and whole-organism models. We review five molecular systems of stress response and update 18 consensual cell-cell signaling pathways that are the hallmark for early development, organogenesis, and differentiation; and revisit the principles of teratology in light of recent advances in high-throughput screening, big data techniques, and systems toxicology. Multiscale systems modeling plays an integral role in the evolutionary approach to cross-species extrapolation. Phylogenetic analysis and comparative bioinformatics are both valuable tools in identifying and validating the molecular initiating events that account for adverse developmental outcomes in humans. The discordance of susceptibility between test species and humans (ontogeny) reflects their differences in evolutionary history (phylogeny). This synthesis not only can lead to novel applications in developmental toxicity and risk assessment, but also can pave the way for applying an evo-devo perspective to the study of developmental origins of health and disease. PMID:28267574

  5. Eco-evolutionary feedbacks, adaptive dynamics and evolutionary rescue theory

    PubMed Central

    Ferriere, Regis; Legendre, Stéphane

    2013-01-01

    Adaptive dynamics theory has been devised to account for feedbacks between ecological and evolutionary processes. Doing so opens new dimensions to and raises new challenges about evolutionary rescue. Adaptive dynamics theory predicts that successive trait substitutions driven by eco-evolutionary feedbacks can gradually erode population size or growth rate, thus potentially raising the extinction risk. Even a single trait substitution can suffice to degrade population viability drastically at once and cause ‘evolutionary suicide’. In a changing environment, a population may track a viable evolutionary attractor that leads to evolutionary suicide, a phenomenon called ‘evolutionary trapping’. Evolutionary trapping and suicide are commonly observed in adaptive dynamics models in which the smooth variation of traits causes catastrophic changes in ecological state. In the face of trapping and suicide, evolutionary rescue requires that the population overcome evolutionary threats generated by the adaptive process itself. Evolutionary repellors play an important role in determining how variation in environmental conditions correlates with the occurrence of evolutionary trapping and suicide, and what evolutionary pathways rescue may follow. In contrast with standard predictions of evolutionary rescue theory, low genetic variation may attenuate the threat of evolutionary suicide and small population sizes may facilitate escape from evolutionary traps. PMID:23209163

  6. Pathway-GPS and SIGORA: identifying relevant pathways based on the over-representation of their gene-pair signatures

    PubMed Central

    Foroushani, Amir B.K.; Brinkman, Fiona S.L.

    2013-01-01

    Motivation. Predominant pathway analysis approaches treat pathways as collections of individual genes and consider all pathway members as equally informative. As a result, at times spurious and misleading pathways are inappropriately identified as statistically significant, solely due to components that they share with the more relevant pathways. Results. We introduce the concept of Pathway Gene-Pair Signatures (Pathway-GPS) as pairs of genes that, as a combination, are specific to a single pathway. We devised and implemented a novel approach to pathway analysis, Signature Over-representation Analysis (SIGORA), which focuses on the statistically significant enrichment of Pathway-GPS in a user-specified gene list of interest. In a comparative evaluation of several published datasets, SIGORA outperformed traditional methods by delivering biologically more plausible and relevant results. Availability. An efficient implementation of SIGORA, as an R package with precompiled GPS data for several human and mouse pathway repositories is available for download from http://sigora.googlecode.com/svn/. PMID:24432194

  7. Multiple selective events at the PRDM16 functional pathway shaped adaptation of western European populations to different climate conditions.

    PubMed

    Quagliarello, Andrea; De Fanti, Sara; Giuliani, Cristina; Abondio, Paolo; Serventi, Patrizia; Sarno, Stefania; Sazzini, Marco; Luiselli, Donata

    2017-12-30

    Several studies highlighted the role of climate in shaping many human evolutionary processes. This occurred even in relatively recent times, having affected various human phenotypic traits, among which metabolic processes that orchestrate absorption and accumulation of substances to maintain energy homeostasis, that is critical for the survival of individuals in high energy-expenditure environments. To date, most researches have focalized on detection of climatic influence on SNPs' frequency in populations exposed to extreme environmental conditions or by comparing variation patterns between populations from different continents. In this study, we instead explored the genetic background of distinct western European human groups at loci involved in nutritional and thermoregulation processes, to test whether patterns of differential local adaptation to environmental conditions could be appreciated also at a lower geographical scale. Taking advantage from the 1000 Genomes Project data, genetic information for 21 genes involved in nutritional and thermoregulation processes was analysed for three western European populations. The applied Anthropological Genetics methods pointed to appreciable differentiation between the examined groups especially for the PRDM16 gene. Moreover, several neutrality tests suggested that balancing selection has acted on different regions of the gene in people from Great Britain, as well as that more recent positive selection could have also targeted some PRDM16 SNPs in Finn and Italian populations. These series of adaptive footprints are plausibly related to climate variability in both ancient and relatively recent times. Since this locus is involved in thermoregulation mechanisms and adipogenesis, local adaptations mediated by a pathway related to the brown adipose tissue activity could have evolved in response to changing cold temperature exposures of such populations.

  8. Evolutionary trends and functional anatomy of the human expanded autophagy network

    PubMed Central

    Till, Andreas; Saito, Rintaro; Merkurjev, Daria; Liu, Jing-Jing; Syed, Gulam Hussain; Kolnik, Martin; Siddiqui, Aleem; Glas, Martin; Scheffler, Björn; Ideker, Trey; Subramani, Suresh

    2015-01-01

    All eukaryotic cells utilize autophagy for protein and organelle turnover, thus assuring subcellular quality control, homeostasis, and survival. In order to address recent advances in identification of human autophagy associated genes, and to describe autophagy on a system-wide level, we established an autophagy-centered gene interaction network by merging various primary data sets and by retrieving respective interaction data. The resulting network (‘AXAN’) was analyzed with respect to subnetworks, e.g. the prime gene subnetwork (including the core machinery, signaling pathways and autophagy receptors) and the transcription subnetwork. To describe aspects of evolution within this network, we assessed the presence of protein orthologs across 99 eukaryotic model organisms. We visualized evolutionary trends for prime gene categories and evolutionary tracks for selected AXAN genes. This analysis confirms the eukaryotic origin of autophagy core genes while it points to a diverse evolutionary history of autophagy receptors. Next, we used module identification to describe the functional anatomy of the network at the level of pathway modules. In addition to obvious pathways (e.g., lysosomal degradation, insulin signaling) our data unveil the existence of context-related modules such as Rho GTPase signaling. Last, we used a tripartite, image-based RNAi – screen to test candidate genes predicted to play a role in regulation of autophagy. We verified the Rho GTPase, CDC42, as a novel regulator of autophagy-related signaling. This study emphasizes the applicability of system-wide approaches to gain novel insights into a complex biological process and to describe the human autophagy pathway at a hitherto unprecedented level of detail. PMID:26103419

  9. Evolutionary perspectives on the links between mitochondrial genotype and disease phenotype.

    PubMed

    Dowling, Damian K

    2014-04-01

    Disorders of the mitochondrial respiratory chain are heterogeneous in their symptoms and underlying genetics. Simple links between candidate mutations and expression of disease phenotype typically do not exist. It thus remains unclear how the genetic variation in the mitochondrial genome contributes to the phenotypic expression of complex traits and disease phenotypes. I summarize the basic genetic processes known to underpin mitochondrial disease. I highlight other plausible processes, drawn from the evolutionary biological literature, whose contribution to mitochondrial disease expression remains largely empirically unexplored. I highlight recent advances to the field, and discuss common-ground and -goals shared by researchers across medical and evolutionary domains. Mitochondrial genetic variance is linked to phenotypic variance across a variety of traits (e.g. reproductive function, life expectancy) fundamental to the upkeep of good health. Evolutionary theory predicts that mitochondrial genomes are destined to accumulate male-harming (but female-friendly) mutations, and this prediction has received proof-of-principle support. Furthermore, mitochondrial effects on the phenotype are typically manifested via interactions between mitochondrial and nuclear genes. Thus, whether a mitochondrial mutation is pathogenic in effect can depend on the nuclear genotype in which is it expressed. Many disease phenotypes associated with OXPHOS malfunction might be determined by the outcomes of mitochondrial-nuclear interactions, and by the evolutionary forces that historically shaped mitochondrial DNA (mtDNA) sequences. Concepts and results drawn from the evolutionary sciences can have broad, but currently under-utilized, applicability to the medical sciences and provide new insights into understanding the complex genetics of mitochondrial disease. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research. Copyright © 2013. Published by Elsevier B.V.

  10. The Phylogeny of Rickettsia Using Different Evolutionary Signatures: How Tree-Like is Bacterial Evolution?

    PubMed Central

    Murray, Gemma G. R.; Weinert, Lucy A.; Rhule, Emma L.; Welch, John J.

    2016-01-01

    Rickettsia is a genus of intracellular bacteria whose hosts and transmission strategies are both impressively diverse, and this is reflected in a highly dynamic genome. Some previous studies have described the evolutionary history of Rickettsia as non-tree-like, due to incongruity between phylogenetic reconstructions using different portions of the genome. Here, we reconstruct the Rickettsia phylogeny using whole-genome data, including two new genomes from previously unsampled host groups. We find that a single topology, which is supported by multiple sources of phylogenetic signal, well describes the evolutionary history of the core genome. We do observe extensive incongruence between individual gene trees, but analyses of simulations over a single topology and interspersed partitions of sites show that this is more plausibly attributed to systematic error than to horizontal gene transfer. Some conflicting placements also result from phylogenetic analyses of accessory genome content (i.e., gene presence/absence), but we argue that these are also due to systematic error, stemming from convergent genome reduction, which cannot be accommodated by existing phylogenetic methods. Our results show that, even within a single genus, tests for gene exchange based on phylogenetic incongruence may be susceptible to false positives. PMID:26559010

  11. The cultural evolution of fertility decline

    PubMed Central

    Colleran, Heidi

    2016-01-01

    Cultural evolutionists have long been interested in the problem of why fertility declines as populations develop. By outlining plausible mechanistic links between individual decision-making, information flow in populations and competition between groups, models of cultural evolution offer a novel and powerful approach for integrating multiple levels of explanation of fertility transitions. However, only a modest number of models have been published. Their assumptions often differ from those in other evolutionary approaches to social behaviour, but their empirical predictions are often similar. Here I offer the first overview of cultural evolutionary research on demographic transition, critically compare it with approaches taken by other evolutionary researchers, identify gaps and overlaps, and highlight parallel debates in demography. I suggest that researchers divide their labour between three distinct phases of fertility decline—the origin, spread and maintenance of low fertility—each of which may be driven by different causal processes, at different scales, requiring different theoretical and empirical tools. A comparative, multi-level and mechanistic framework is essential for elucidating both the evolved aspects of our psychology that govern reproductive decision-making, and the social, ecological and cultural contingencies that precipitate and sustain fertility decline. PMID:27022079

  12. Experimental evolution reveals hidden diversity in evolutionary pathways.

    PubMed

    Lind, Peter A; Farr, Andrew D; Rainey, Paul B

    2015-03-25

    Replicate populations of natural and experimental organisms often show evidence of parallel genetic evolution, but the causes are unclear. The wrinkly spreader morph of Pseudomonas fluorescens arises repeatedly during experimental evolution. The mutational causes reside exclusively within three pathways. By eliminating these, 13 new mutational pathways were discovered with the newly arising WS types having fitnesses similar to those arising from the commonly passaged routes. Our findings show that parallel genetic evolution is strongly biased by constraints and we reveal the genetic bases. From such knowledge, and in instances where new phenotypes arise via gene activation, we suggest a set of principles: evolution proceeds firstly via pathways subject to negative regulation, then via promoter mutations and gene fusions, and finally via activation by intragenic gain-of-function mutations. These principles inform evolutionary forecasting and have relevance to interpreting the diverse array of mutations associated with clinically identical instances of disease in humans.

  13. Novel pathway of 3-hydroxyanthranilic acid formation in limazepine biosynthesis reveals evolutionary relation between phenazines and pyrrolobenzodiazepines.

    PubMed

    Pavlikova, Magdalena; Kamenik, Zdenek; Janata, Jiri; Kadlcik, Stanislav; Kuzma, Marek; Najmanova, Lucie

    2018-05-17

    Natural pyrrolobenzodiazepines (PBDs) form a large and structurally diverse group of antitumour microbial metabolites produced through complex pathways, which are encoded within biosynthetic gene clusters. We sequenced the gene cluster of limazepines and proposed their biosynthetic pathway based on comparison with five available gene clusters for the biosynthesis of other PBDs. Furthermore, we tested two recombinant proteins from limazepine biosynthesis, Lim5 and Lim6, with the expected substrates in vitro. The reactions monitored by LC-MS revealed that limazepine biosynthesis involves a new way of 3-hydroxyanthranilic acid formation, which we refer to as the chorismate/DHHA pathway and which represents an alternative to the kynurenine pathway employed for the formation of the same precursor in the biosynthesis of other PBDs. The chorismate/DHHA pathway is presumably also involved in the biosynthesis of PBD tilivalline, several natural products unrelated to PBDs, and its part is shared also with phenazine biosynthesis. The similarities between limazepine and phenazine biosynthesis indicate tight evolutionary links between these groups of compounds.

  14. Assessing Risks to Sea Otters and the Exxon Valdez Oil Spill: New Scenarios, Attributable Risk, and Recovery

    PubMed Central

    Harwell, Mark A.; Gentile, John H.

    2014-01-01

    The Exxon Valdez oil spill occurred more than two decades ago, and the Prince William Sound ecosystem has essentially recovered. Nevertheless, discussion continues on whether or not localized effects persist on sea otters (Enhydra lutris) at northern Knight Island (NKI) and, if so, what are the associated attributable risks. A recent study estimated new rates of sea otter encounters with subsurface oil residues (SSOR) from the oil spill. We previously demonstrated that a potential pathway existed for exposures to polycyclic aromatic hydrocarbons (PAHs) and conducted a quantitative ecological risk assessment using an individual-based model that simulated this and other plausible exposure pathways. Here we quantitatively update the potential for this exposure pathway to constitute an ongoing risk to sea otters using the new estimates of SSOR encounters. Our conservative model predicted that the assimilated doses of PAHs to the 1-in-1000th most-exposed sea otters would remain 1–2 orders of magnitude below the chronic effects thresholds. We re-examine the baseline estimates, post-spill surveys, recovery status, and attributable risks for this subpopulation. We conclude that the new estimated frequencies of encountering SSOR do not constitute a plausible risk for sea otters at NKI and these sea otters have fully recovered from the oil spill. PMID:24587690

  15. Structure versus time in the evolutionary diversification of avian carotenoid metabolic networks.

    PubMed

    Morrison, Erin S; Badyaev, Alexander V

    2018-05-01

    Historical associations of genes and proteins are thought to delineate pathways available to subsequent evolution; however, the effects of past functional involvements on contemporary evolution are rarely quantified. Here, we examined the extent to which the structure of a carotenoid enzymatic network persists in avian evolution. Specifically, we tested whether the evolution of carotenoid networks was most concordant with phylogenetically structured expansion from core reactions of common ancestors or with subsampling of biochemical pathway modules from an ancestral network. We compared structural and historical associations in 467 carotenoid networks of extant and ancestral species and uncovered the overwhelming effect of pre-existing metabolic network structure on carotenoid diversification over the last 50 million years of avian evolution. Over evolutionary time, birds repeatedly subsampled and recombined conserved biochemical modules, which likely maintained the overall structure of the carotenoid metabolic network during avian evolution. These findings explain the recurrent convergence of evolutionary distant species in carotenoid metabolism and weak phylogenetic signal in avian carotenoid evolution. Remarkable retention of an ancient metabolic structure throughout extensive and prolonged ecological diversification in avian carotenoid metabolism illustrates a fundamental requirement of organismal evolution - historical continuity of a deterministic network that links past and present functional associations of its components. © 2018 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2018 European Society For Evolutionary Biology.

  16. Finding a common path: predicting gene function using inferred evolutionary trees.

    PubMed

    Reynolds, Kimberly A

    2014-07-14

    Reporting in Cell, Li and colleagues (2014) describe an innovative method to functionally classify genes using evolutionary information. This approach demonstrates broad utility for eukaryotic gene annotation and suggests an intriguing new decomposition of pathways and complexes into evolutionarily conserved modules. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Computational Identification Raises a Riddle for Distribution of Putative NACHT NTPases in the Genome of Early Green Plants.

    PubMed

    Arya, Preeti; Acharya, Vishal

    2016-01-01

    NACHT NTPases and AP-ATPases belongs to STAND (signal transduction ATPases with numerous domain) P-loop NTPase class, which are known to be involved in defense signaling pathways and apoptosis regulation. The AP-ATPases (also known as NB-ARC) and NACHT NTPases are widely spread throughout all kingdoms of life except in plants, where only AP-ATPases have been extensively studied in the scenario of plant defense response against pathogen invasion and in hypersensitive response (HR). In the present study, we have employed a genome-wide survey (using stringent computational analysis) of 67 diverse organisms viz., archaebacteria, cyanobacteria, fungi, animalia and plantae to revisit the evolutionary history of these two STAND P-loop NTPases. This analysis divulged the presence of NACHT NTPases in the early green plants (green algae and the lycophyte) which had not been previously reported. These NACHT NTPases were known to be involved in diverse functional activities such as transcription regulation in addition to the defense signaling cascades depending on the domain association. In Chalmydomonas reinhardtii, a green algae, WD40 repeats found to be at the carboxyl-terminus of NACHT NTPases suggest probable role in apoptosis regulation. Moreover, the genome of Selaginella moellendorffii, an extant lycophyte, intriguingly shows the considerable number of both AP-ATPases and NACHT NTPases in contrast to a large repertoire of AP-ATPases in plants and emerge as an important node in the evolutionary tree of life. The large complement of AP-ATPases overtakes the function of NACHT NTPases and plausible reason behind the absence of the later in the plant lineages. The presence of NACHT NTPases in the early green plants and phyletic patterns results from this study raises a quandary for the distribution of this STAND P-loop NTPase with the apparent horizontal gene transfer from cyanobacteria.

  18. Evolutionary innovation and diversification of carotenoid-based pigmentation in finches.

    PubMed

    Ligon, Russell A; Simpson, Richard K; Mason, Nicholas A; Hill, Geoffrey E; McGraw, Kevin J

    2016-12-01

    The ornaments used by animals to mediate social interactions are diverse, and by reconstructing their evolutionary pathways we can gain new insights into the mechanisms underlying ornamental innovation and variability. Here, we examine variation in plumage carotenoids among the true finches (Aves: Fringillidae) using biochemical and comparative phylogenetic analyses to reconstruct the evolutionary history of carotenoid states and evaluate competing models of carotenoid evolution. Our comparative analyses reveal that the most likely ancestor of finches used dietary carotenoids as yellow plumage colorants, and that the ability to metabolically modify dietary carotenoids into more complex pigments arose secondarily once finches began to use modified carotenoids to create red plumage. Following the evolutionary "innovation" that enabled modified red carotenoid pigments to be deposited as plumage colorants, many finch species subsequently modified carotenoid biochemical pathways to create yellow plumage. However, no reversions to dietary carotenoids were observed. The finding that ornaments and their underlying mechanisms may be operating under different selection regimes-where ornamental trait colors undergo frequent reversions (e.g., between red and yellow plumage) while carotenoid metabolization mechanisms are more conserved-supports a growing empirical framework suggesting different evolutionary patterns for ornaments and the mechanistic innovations that facilitate their diversification. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

  19. Comparative genomics explains the evolutionary success of reef-forming corals.

    PubMed

    Bhattacharya, Debashish; Agrawal, Shobhit; Aranda, Manuel; Baumgarten, Sebastian; Belcaid, Mahdi; Drake, Jeana L; Erwin, Douglas; Foret, Sylvian; Gates, Ruth D; Gruber, David F; Kamel, Bishoy; Lesser, Michael P; Levy, Oren; Liew, Yi Jin; MacManes, Matthew; Mass, Tali; Medina, Monica; Mehr, Shaadi; Meyer, Eli; Price, Dana C; Putnam, Hollie M; Qiu, Huan; Shinzato, Chuya; Shoguchi, Eiichi; Stokes, Alexander J; Tambutté, Sylvie; Tchernov, Dan; Voolstra, Christian R; Wagner, Nicole; Walker, Charles W; Weber, Andreas Pm; Weis, Virginia; Zelzion, Ehud; Zoccola, Didier; Falkowski, Paul G

    2016-05-24

    Transcriptome and genome data from twenty stony coral species and a selection of reference bilaterians were studied to elucidate coral evolutionary history. We identified genes that encode the proteins responsible for the precipitation and aggregation of the aragonite skeleton on which the organisms live, and revealed a network of environmental sensors that coordinate responses of the host animals to temperature, light, and pH. Furthermore, we describe a variety of stress-related pathways, including apoptotic pathways that allow the host animals to detoxify reactive oxygen and nitrogen species that are generated by their intracellular photosynthetic symbionts, and determine the fate of corals under environmental stress. Some of these genes arose through horizontal gene transfer and comprise at least 0.2% of the animal gene inventory. Our analysis elucidates the evolutionary strategies that have allowed symbiotic corals to adapt and thrive for hundreds of millions of years.

  20. Reduced graphene oxide as an effective adsorbent for removal of malachite green dye: Plausible adsorption pathways.

    PubMed

    Gupta, Kanika; Khatri, Om P

    2017-09-01

    Efficient removal of malachite green (MG) dye from simulated wastewater is demonstrated using high surface area reduced graphene oxide (rGO). The plausible interaction pathways between MG dye and rGO are deduced from nanostructural features (HRTEM) of rGO and spectroscopic analyses (FTIR and Raman). The high surface area (931m 2 ⋅gm -1 ) of rGO, π-π interaction between the aromatic rings of MG dye and graphitic skeleton, and electrostatic interaction of cationic centre of MG dye with π-electron clouds and negatively charged residual oxygen functionalities of rGO collectively facilitate the adsorption of MG dye on the rGO. The rGO displays adsorption capacity as high as 476.2mg⋅g -1 for MG dye. The thermodynamic parameters calculated from the temperature dependent isotherms suggested that the adsorption was a spontaneous and endothermic process. These results promise the potential of high surface area rGO for efficient removal of cationic dyes for wastewater treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. The structure of the cyanobactin domain of unknown function from PatG in the patellamide gene cluster

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mann, Greg; Koehnke, Jesko; Bent, Andrew F.

    The highly conserved domain of unknown function in the cyanobactin superfamily has a novel fold. The protein does not appear to bind the most plausible substrates, leaving questions as to its role. Patellamides are members of the cyanobactin family of ribosomally synthesized and post-translationally modified cyclic peptide natural products, many of which, including some patellamides, are biologically active. A detailed mechanistic understanding of the biosynthetic pathway would enable the construction of a biotechnological ‘toolkit’ to make novel analogues of patellamides that are not found in nature. All but two of the protein domains involved in patellamide biosynthesis have been characterized.more » The two domains of unknown function (DUFs) are homologous to each other and are found at the C-termini of the multi-domain proteins PatA and PatG. The domain sequence is found in all cyanobactin-biosynthetic pathways characterized to date, implying a functional role in cyanobactin biosynthesis. Here, the crystal structure of the PatG DUF domain is reported and its binding interactions with plausible substrates are investigated.« less

  2. Insights on the evolution of metabolic networks of unicellular translationally biased organisms from transcriptomic data and sequence analysis.

    PubMed

    Carbone, Alessandra; Madden, Richard

    2005-10-01

    Codon bias is related to metabolic functions in translationally biased organisms, and two facts are argued about. First, genes with high codon bias describe in meaningful ways the metabolic characteristics of the organism; important metabolic pathways corresponding to crucial characteristics of the lifestyle of an organism, such as photosynthesis, nitrification, anaerobic versus aerobic respiration, sulfate reduction, methanogenesis, and others, happen to involve especially biased genes. Second, gene transcriptional levels of sets of experiments representing a significant variation of biological conditions strikingly confirm, in the case of Saccharomyces cerevisiae, that metabolic preferences are detectable by purely statistical analysis: the high metabolic activity of yeast during fermentation is encoded in the high bias of enzymes involved in the associated pathways, suggesting that this genome was affected by a strong evolutionary pressure that favored a predominantly fermentative metabolism of yeast in the wild. The ensemble of metabolic pathways involving enzymes with high codon bias is rather well defined and remains consistent across many species, even those that have not been considered as translationally biased, such as Helicobacter pylori, for instance, reveal some weak form of translational bias for this genome. We provide numerical evidence, supported by experimental data, of these facts and conclude that the metabolic networks of translationally biased genomes, observable today as projections of eons of evolutionary pressure, can be analyzed numerically and predictions of the role of specific pathways during evolution can be derived. The new concepts of Comparative Pathway Index, used to compare organisms with respect to their metabolic networks, and Evolutionary Pathway Index, used to detect evolutionarily meaningful bias in the genetic code from transcriptional data, are introduced.

  3. The role of biotic forces in driving macroevolution: beyond the Red Queen

    PubMed Central

    Voje, Kjetil L.; Holen, Øistein H.; Liow, Lee Hsiang; Stenseth, Nils Chr.

    2015-01-01

    A multitude of hypotheses claim that abiotic factors are the main drivers of macroevolutionary change. By contrast, Van Valen's Red Queen hypothesis is often put forward as the sole representative of the view that biotic forcing is the main evolutionary driver. This imbalance of hypotheses does not reflect our current knowledge: theoretical work demonstrates the plausibility of biotically driven long-term evolution, whereas empirical work suggests a central role for biotic forcing in macroevolution. We call for a more pluralistic view of how biotic forces may drive long-term evolution that is compatible with both phenotypic stasis in the fossil record and with non-constant extinction rates. Promising avenues of research include contrasting predictions from relevant theories within ecology and macroevolution, as well as embracing both abiotic and biotic proxies while modelling long-term evolutionary data. By fitting models describing hypotheses of biotically driven macroevolution to data, we could dissect their predictions and transcend beyond pattern description, possibly narrowing the divide between our current understanding of micro- and macroevolution. PMID:25948685

  4. Assessment of Masonry Buildings Subjected to Landslide-Induced Settlements: From Load Path Method to Evolutionary Optimization Method

    NASA Astrophysics Data System (ADS)

    Palmisano, Fabrizio; Elia, Angelo

    2017-10-01

    One of the main difficulties, when dealing with landslide structural vulnerability, is the diagnosis of the causes of crack patterns. This is also due to the excessive complexity of models based on classical structural mechanics that makes them inappropriate especially when there is the necessity to perform a rapid vulnerability assessment at the territorial scale. This is why, a new approach, based on a ‘simple model’ (i.e. the Load Path Method, LPM), has been proposed by Palmisano and Elia for the interpretation of the behaviour of masonry buildings subjected to landslide-induced settlements. However, the LPM is very useful for rapidly finding the 'most plausible solution' instead of the exact solution. To find the solution, optimization algorithms are necessary. In this scenario, this article aims to show how the Bidirectional Evolutionary Structural Optimization method by Huang and Xie, can be very useful to optimize the strut-and-tie models obtained by using the Load Path Method.

  5. Inference of Evolutionary Forces Acting on Human Biological Pathways

    PubMed Central

    Daub, Josephine T.; Dupanloup, Isabelle; Robinson-Rechavi, Marc; Excoffier, Laurent

    2015-01-01

    Because natural selection is likely to act on multiple genes underlying a given phenotypic trait, we study here the potential effect of ongoing and past selection on the genetic diversity of human biological pathways. We first show that genes included in gene sets are generally under stronger selective constraints than other genes and that their evolutionary response is correlated. We then introduce a new procedure to detect selection at the pathway level based on a decomposition of the classical McDonald–Kreitman test extended to multiple genes. This new test, called 2DNS, detects outlier gene sets and takes into account past demographic effects and evolutionary constraints specific to gene sets. Selective forces acting on gene sets can be easily identified by a mere visual inspection of the position of the gene sets relative to their two-dimensional null distribution. We thus find several outlier gene sets that show signals of positive, balancing, or purifying selection but also others showing an ancient relaxation of selective constraints. The principle of the 2DNS test can also be applied to other genomic contrasts. For instance, the comparison of patterns of polymorphisms private to African and non-African populations reveals that most pathways show a higher proportion of nonsynonymous mutations in non-Africans than in Africans, potentially due to different demographic histories and selective pressures. PMID:25971280

  6. An integrative method for testing form–function linkages and reconstructed evolutionary pathways of masticatory specialization

    PubMed Central

    Tseng, Z. Jack; Flynn, John J.

    2015-01-01

    Morphology serves as a ubiquitous proxy in macroevolutionary studies to identify potential adaptive processes and patterns. Inferences of functional significance of phenotypes or their evolution are overwhelmingly based on data from living taxa. Yet, correspondence between form and function has been tested in only a few model species, and those linkages are highly complex. The lack of explicit methodologies to integrate form and function analyses within a deep-time and phylogenetic context weakens inferences of adaptive morphological evolution, by invoking but not testing form–function linkages. Here, we provide a novel approach to test mechanical properties at reconstructed ancestral nodes/taxa and the strength and direction of evolutionary pathways in feeding biomechanics, in a case study of carnivorous mammals. Using biomechanical profile comparisons that provide functional signals for the separation of feeding morphologies, we demonstrate, using experimental optimization criteria on estimation of strength and direction of functional changes on a phylogeny, that convergence in mechanical properties and degree of evolutionary optimization can be decoupled. This integrative approach is broadly applicable to other clades, by using quantitative data and model-based tests to evaluate interpretations of function from morphology and functional explanations for observed macroevolutionary pathways. PMID:25994295

  7. The genomic landscape of rapid repeated evolutionary ...

    EPA Pesticide Factsheets

    Atlantic killifish populations have rapidly adapted to normally lethal levels of pollution in four urban estuaries. Through analysis of 384 whole killifish genome sequences and comparative transcriptomics in four pairs of sensitive and tolerant populations, we identify the aryl hydrocarbon receptor–based signaling pathway as a shared target of selection. This suggests evolutionary constraint on adaptive solutions to complex toxicant mixtures at each site. However, distinct molecular variants apparently contribute to adaptive pathway modification among tolerant populations. Selection also targets other toxicity-mediatinggenes and genes of connected signaling pathways; this indicates complex tolerance phenotypes and potentially compensatory adaptations. Molecular changes are consistent with selection on standing genetic variation. In killifish, high nucleotide diversityhas likely been a crucial substrate for selective sweeps to propel rapid adaptation. This manuscript describes genomic evaluations that contribute to our understanding of the ecological and evolutionary risks associated with chronic contaminant exposures to wildlife populations. Here, we assessed genetic patterns associated with long-term response to an important class of highly toxic environmental pollutants. Specifically, chemical-specific tolerance has rapidly and repeatedly evolved in an estuarine fish species resident to estuaries of the Atlantic U.S. coast. We used laboratory studies to ch

  8. Enzyme sequence similarity improves the reaction alignment method for cross-species pathway comparison

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ovacik, Meric A.; Androulakis, Ioannis P., E-mail: yannis@rci.rutgers.edu; Biomedical Engineering Department, Rutgers University, Piscataway, NJ 08854

    2013-09-15

    Pathway-based information has become an important source of information for both establishing evolutionary relationships and understanding the mode of action of a chemical or pharmaceutical among species. Cross-species comparison of pathways can address two broad questions: comparison in order to inform evolutionary relationships and to extrapolate species differences used in a number of different applications including drug and toxicity testing. Cross-species comparison of metabolic pathways is complex as there are multiple features of a pathway that can be modeled and compared. Among the various methods that have been proposed, reaction alignment has emerged as the most successful at predicting phylogeneticmore » relationships based on NCBI taxonomy. We propose an improvement of the reaction alignment method by accounting for sequence similarity in addition to reaction alignment method. Using nine species, including human and some model organisms and test species, we evaluate the standard and improved comparison methods by analyzing glycolysis and citrate cycle pathways conservation. In addition, we demonstrate how organism comparison can be conducted by accounting for the cumulative information retrieved from nine pathways in central metabolism as well as a more complete study involving 36 pathways common in all nine species. Our results indicate that reaction alignment with enzyme sequence similarity results in a more accurate representation of pathway specific cross-species similarities and differences based on NCBI taxonomy.« less

  9. Thermal adaptation of decomposer communities in warming soils

    PubMed Central

    Bradford, Mark A.

    2013-01-01

    Temperature regulates the rate of biogeochemical cycles. One way it does so is through control of microbial metabolism. Warming effects on metabolism change with time as physiology adjusts to the new temperature. I here propose that such thermal adaptation is observed in soil microbial respiration and growth, as the result of universal evolutionary trade-offs between the structure and function of both enzymes and membranes. I review the basis for these trade-offs and show that they, like substrate depletion, are plausible mechanisms explaining soil respiration responses to warming. I argue that controversies over whether soil microbes adapt to warming stem from disregarding the evolutionary physiology of cellular metabolism, and confusion arising from the term thermal acclimation to represent phenomena at the organism- and ecosystem-levels with different underlying mechanisms. Measurable physiological adjustments of the soil microbial biomass reflect shifts from colder- to warmer-adapted taxa. Hypothesized declines in the growth efficiency of soil microbial biomass under warming are controversial given limited data and a weak theoretical basis. I suggest that energy spilling (aka waste metabolism) is a more plausible mechanism for efficiency declines than the commonly invoked increase in maintenance-energy demands. Energy spilling has many fitness benefits for microbes and its response to climate warming is uncertain. Modeled responses of soil carbon to warming are sensitive to microbial growth efficiency, but declines in efficiency mitigate warming-induced carbon losses in microbial models and exacerbate them in conventional models. Both modeling structures assume that microbes regulate soil carbon turnover, highlighting the need for a third structure where microbes are not regulators. I conclude that microbial physiology must be considered if we are to have confidence in projected feedbacks between soil carbon stocks, atmospheric CO2, and climate change. PMID:24339821

  10. Cause of Cambrian Explosion - Terrestrial or Cosmic?

    PubMed

    Steele, Edward J; Al-Mufti, Shirwan; Augustyn, Kenneth A; Chandrajith, Rohana; Coghlan, John P; Coulson, S G; Ghosh, Sudipto; Gillman, Mark; Gorczynski, Reginald M; Klyce, Brig; Louis, Godfrey; Mahanama, Kithsiri; Oliver, Keith R; Padron, Julio; Qu, Jiangwen; Schuster, John A; Smith, W E; Snyder, Duane P; Steele, Julian A; Stewart, Brent J; Temple, Robert; Tokoro, Gensuke; Tout, Christopher A; Unzicker, Alexander; Wainwright, Milton; Wallis, Jamie; Wallis, Daryl H; Wallis, Max K; Wetherall, John; Wickramasinghe, D T; Wickramasinghe, J T; Wickramasinghe, N Chandra; Liu, Yongsheng

    2018-08-01

    We review the salient evidence consistent with or predicted by the Hoyle-Wickramasinghe (H-W) thesis of Cometary (Cosmic) Biology. Much of this physical and biological evidence is multifactorial. One particular focus are the recent studies which date the emergence of the complex retroviruses of vertebrate lines at or just before the Cambrian Explosion of ∼500 Ma. Such viruses are known to be plausibly associated with major evolutionary genomic processes. We believe this coincidence is not fortuitous but is consistent with a key prediction of H-W theory whereby major extinction-diversification evolutionary boundaries coincide with virus-bearing cometary-bolide bombardment events. A second focus is the remarkable evolution of intelligent complexity (Cephalopods) culminating in the emergence of the Octopus. A third focus concerns the micro-organism fossil evidence contained within meteorites as well as the detection in the upper atmosphere of apparent incoming life-bearing particles from space. In our view the totality of the multifactorial data and critical analyses assembled by Fred Hoyle, Chandra Wickramasinghe and their many colleagues since the 1960s leads to a very plausible conclusion - life may have been seeded here on Earth by life-bearing comets as soon as conditions on Earth allowed it to flourish (about or just before 4.1 Billion years ago); and living organisms such as space-resistant and space-hardy bacteria, viruses, more complex eukaryotic cells, fertilised ova and seeds have been continuously delivered ever since to Earth so being one important driver of further terrestrial evolution which has resulted in considerable genetic diversity and which has led to the emergence of mankind. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Experimental evolution reveals hidden diversity in evolutionary pathways

    PubMed Central

    Lind, Peter A; Farr, Andrew D; Rainey, Paul B

    2015-01-01

    Replicate populations of natural and experimental organisms often show evidence of parallel genetic evolution, but the causes are unclear. The wrinkly spreader morph of Pseudomonas fluorescens arises repeatedly during experimental evolution. The mutational causes reside exclusively within three pathways. By eliminating these, 13 new mutational pathways were discovered with the newly arising WS types having fitnesses similar to those arising from the commonly passaged routes. Our findings show that parallel genetic evolution is strongly biased by constraints and we reveal the genetic bases. From such knowledge, and in instances where new phenotypes arise via gene activation, we suggest a set of principles: evolution proceeds firstly via pathways subject to negative regulation, then via promoter mutations and gene fusions, and finally via activation by intragenic gain-of-function mutations. These principles inform evolutionary forecasting and have relevance to interpreting the diverse array of mutations associated with clinically identical instances of disease in humans. DOI: http://dx.doi.org/10.7554/eLife.07074.001 PMID:25806684

  12. The predictability of evolution: glimpses into a post-Darwinian world.

    PubMed

    Conway Morris, Simon

    2009-11-01

    The very success of the Darwinian explanation, in not only demonstrating evolution from multiple lines of evidence but also in providing some plausible explanations, paradoxically seems to have served to have stifled explorations into other areas of investigation. The fact of evolution is now almost universally yoked to the assumption that its outcomes are random, trends are little more than drunkard's walks, and most evolutionary products are masterpieces of improvisation and far from perfect. But is this correct? Let us consider some alternatives. Is there evidence that evolution could in anyway be predictable? Can we identify alternative forms of biological organizations and if so how viable are they? Why are some molecules so extraordinarily versatile, while others can be spoken of as "molecules of choice"? How fortuitous are the major transitions in the history of life? What implications might this have for the Tree of Life? To what extent is evolutionary diversification constrained or facilitated by prior states? Are evolutionary outcomes merely sufficient or alternatively are they highly efficient, even superb? Here I argue that in sharp contradistinction to an orthodox Darwinian view, not only is evolution much more predictable than generally assumed but also investigation of its organizational substrates, including those of sensory systems, which indicates that it is possible to identify a predictability to the process and outcomes of evolution. If correct, the implications may be of some significance, not least in separating the unexceptional Darwinian mechanisms from underlying organizational principles, which may indicate evolutionary inevitabilities.

  13. GOSAP: Gene Ontology-Based Semantic Alignment of Biological Pathways.

    PubMed

    Gamalielsson, Jonas; Olsson, Bjorn

    2008-01-01

    We present a new method for semantic comparison of biological pathways, aiming to discover evolutionary conservation of pathways between species. Our method uses all three sub-ontologies of Gene Ontology (GO) and a measure of semantic similarity to calculate match scores between gene products. These scores are used for finding local pairwise pathway alignments. This approach has the advantage of being applicable to all types of pathways where nodes are gene products, e.g., regulatory pathways, signalling pathways and metabolic enzyme-to-enzyme pathways. We demonstrate the usefulness of the method using regulatory and metabolic pathways from E. coli and S. cerevisiae as examples.

  14. Rapid Evolution and the Importance of Recombination to the Gastroenteric Pathogen Campylobacter jejuni

    PubMed Central

    Gabriel, Edith; Leatherbarrow, Andrew J.H.; Cheesbrough, John; Gee, Steven; Bolton, Eric; Fox, Andrew; Hart, C. Anthony; Diggle, Peter J.; Fearnhead, Paul

    2009-01-01

    Responsible for the majority of bacterial gastroenteritis in the developed world, Campylobacter jejuni is a pervasive pathogen of humans and animals, but its evolution is obscure. In this paper, we exploit contemporary genetic diversity and empirical evidence to piece together the evolutionary history of C. jejuni and quantify its evolutionary potential. Our combined population genetics–phylogenetics approach reveals a surprising picture. Campylobacter jejuni is a rapidly evolving species, subject to intense purifying selection that purges 60% of novel variation, but possessing a massive evolutionary potential. The low mutation rate is offset by a large effective population size so that a mutation at any site can occur somewhere in the population within the space of a week. Recombination has a fundamental role, generating diversity at twice the rate of de novo mutation, and facilitating gene flow between C. jejuni and its sister species Campylobacter coli. We attempt to calibrate the rate of molecular evolution in C. jejuni based solely on within-species variation. The rates we obtain are up to 1,000 times faster than conventional estimates, placing the C. jejuni–C. coli split at the time of the Neolithic revolution. We weigh the plausibility of such recent bacterial evolution against alternative explanations and discuss the evidence required to settle the issue. PMID:19008526

  15. Childhood Behavior Problems and Health at Midlife: 35-Year Follow-Up of a Scottish Birth Cohort

    ERIC Educational Resources Information Center

    von Stumm, Sophie; Deary, Ian J.; Kivimaki, Mika; Jokela, Markus; Clark, Heather; Batty, G. David

    2011-01-01

    Background: Childhood behavior problems are associated with premature mortality. To identify plausible pathways that may account for this association, we explored the extent to which childhood behavior problems relate to health behaviors and health outcomes at midlife. Methods: The Aberdeen Children of the 1950s (ACONF) study comprises 12,500…

  16. How evolutionary principles improve the understanding of human health and disease.

    PubMed

    Gluckman, Peter D; Low, Felicia M; Buklijas, Tatjana; Hanson, Mark A; Beedle, Alan S

    2011-03-01

    An appreciation of the fundamental principles of evolutionary biology provides new insights into major diseases and enables an integrated understanding of human biology and medicine. However, there is a lack of awareness of their importance amongst physicians, medical researchers, and educators, all of whom tend to focus on the mechanistic (proximate) basis for disease, excluding consideration of evolutionary (ultimate) reasons. The key principles of evolutionary medicine are that selection acts on fitness, not health or longevity; that our evolutionary history does not cause disease, but rather impacts on our risk of disease in particular environments; and that we are now living in novel environments compared to those in which we evolved. We consider these evolutionary principles in conjunction with population genetics and describe several pathways by which evolutionary processes can affect disease risk. These perspectives provide a more cohesive framework for gaining insights into the determinants of health and disease. Coupled with complementary insights offered by advances in genomic, epigenetic, and developmental biology research, evolutionary perspectives offer an important addition to understanding disease. Further, there are a number of aspects of evolutionary medicine that can add considerably to studies in other domains of contemporary evolutionary studies.

  17. How evolutionary principles improve the understanding of human health and disease

    PubMed Central

    Gluckman, Peter D; Low, Felicia M; Buklijas, Tatjana; Hanson, Mark A; Beedle, Alan S

    2011-01-01

    An appreciation of the fundamental principles of evolutionary biology provides new insights into major diseases and enables an integrated understanding of human biology and medicine. However, there is a lack of awareness of their importance amongst physicians, medical researchers, and educators, all of whom tend to focus on the mechanistic (proximate) basis for disease, excluding consideration of evolutionary (ultimate) reasons. The key principles of evolutionary medicine are that selection acts on fitness, not health or longevity; that our evolutionary history does not cause disease, but rather impacts on our risk of disease in particular environments; and that we are now living in novel environments compared to those in which we evolved. We consider these evolutionary principles in conjunction with population genetics and describe several pathways by which evolutionary processes can affect disease risk. These perspectives provide a more cohesive framework for gaining insights into the determinants of health and disease. Coupled with complementary insights offered by advances in genomic, epigenetic, and developmental biology research, evolutionary perspectives offer an important addition to understanding disease. Further, there are a number of aspects of evolutionary medicine that can add considerably to studies in other domains of contemporary evolutionary studies. PMID:25567971

  18. Molecular evolution of multiple-level control of heme biosynthesis pathway in animal kingdom.

    PubMed

    Tzou, Wen-Shyong; Chu, Ying; Lin, Tzung-Yi; Hu, Chin-Hwa; Pai, Tun-Wen; Liu, Hsin-Fu; Lin, Han-Jia; Cases, Ildeofonso; Rojas, Ana; Sanchez, Mayka; You, Zong-Ye; Hsu, Ming-Wei

    2014-01-01

    Adaptation of enzymes in a metabolic pathway can occur not only through changes in amino acid sequences but also through variations in transcriptional activation, mRNA splicing and mRNA translation. The heme biosynthesis pathway, a linear pathway comprised of eight consecutive enzymes in animals, provides researchers with ample information for multiple types of evolutionary analyses performed with respect to the position of each enzyme in the pathway. Through bioinformatics analysis, we found that the protein-coding sequences of all enzymes in this pathway are under strong purifying selection, from cnidarians to mammals. However, loose evolutionary constraints are observed for enzymes in which self-catalysis occurs. Through comparative genomics, we found that in animals, the first intron of the enzyme-encoding genes has been co-opted for transcriptional activation of the genes in this pathway. Organisms sense the cellular content of iron, and through iron-responsive elements in the 5' untranslated regions of mRNAs and the intron-exon boundary regions of pathway genes, translational inhibition and exon choice in enzymes may be enabled, respectively. Pathway product (heme)-mediated negative feedback control can affect the transport of pathway enzymes into the mitochondria as well as the ubiquitin-mediated stability of enzymes. Remarkably, the positions of these controls on pathway activity are not ubiquitous but are biased towards the enzymes in the upstream portion of the pathway. We revealed that multiple-level controls on the activity of the heme biosynthesis pathway depend on the linear depth of the enzymes in the pathway, indicating a new strategy for discovering the molecular constraints that shape the evolution of a metabolic pathway.

  19. Pathways to cognitive design.

    PubMed

    Wertz, Annie E; Moya, Cristina

    2018-05-30

    Despite a shared recognition that the design of the human mind and the design of human culture are tightly linked, researchers in the evolutionary social sciences tend to specialize in understanding one at the expense of the other. The disciplinary boundaries roughly correspond to research traditions that focus more on natural selection and those that focus more on cultural evolution. In this paper, we articulate how two research traditions within the evolutionary social sciences-evolutionary psychology and cultural evolution-approach the study of design. We focus our analysis on the design of cognitive mechanisms that are the result of the interplay of genetic and cultural evolution. We aim to show how the approaches of these two research traditions can complement each other, and provide a framework for developing a wider range of testable hypotheses about cognitive design. To do so, we provide concrete illustrations of how this integrated approach can be used to interrogate cognitive design using examples from our own work on plant and symbolic group boundary cognition. We hope this recognition of different pathways to design will broaden the hypothesis space in the evolutionary social sciences and encourage methodological pluralism in the investigation of the mind. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. The hippocampo-prefrontal pathway: a possible therapeutic target for negative and cognitive symptoms of schizophrenia

    PubMed Central

    Ghoshal, Ayan; Conn, P Jeffrey

    2015-01-01

    The hippocampo-prefrontal (H-PFC) pathway has been linked to cognitive and emotional disturbances in several psychiatric disorders including schizophrenia. Preclinical evidence from the NMDA receptor antagonism rodent model of schizophrenia shows severe pathology selective to the H-PFC pathway. It is speculated that there is an increased excitatory drive from the hippocampus to the prefrontal cortex due to dysfunctions in the H-PFC plasticity, which may serve as the basis for the behavioral consequences observed in this rodent model. Thus, the H-PFC pathway is currently emerging as a promising therapeutic target for the negative and cognitive symptom clusters of schizophrenia. Here, we have reviewed the physiological, pharmacological and functional characteristics of the H-PFC pathway and we propose that allosteric activation of glutamatergic and cholinergic neurotransmission can serve as a plausible therapeutic approach. PMID:25825588

  1. An ecoimmunological approach to study evolutionary and ancient links between coagulation, complement and Innate immunity

    PubMed Central

    Kasetty, Gopinath; Alyafei, Saud; Smeds, Emanuel; Salo-Ahen, Outi M. H.; Hansson, Stefan R.; Egesten, Arne; Herwald, Heiko

    2018-01-01

    ABSTRACT Coagulation, complement, and innate immunity are tightly interwoven and form an alliance that can be traced back to early eukaryotic evolution. Here we employed an ecoimmunological approach using Tissue Factor Pathway Inhibitor (TFPI)-1-derived peptides from the different classes of vertebrates (i.e. fish, reptile, bird, and mammals) and tested whether they can boost killing of various human bacterial pathogens in plasma. We found signs of species-specific conservation and diversification during evolution in these peptides that significantly impact their antibacterial activity. Though all peptides tested executed bactericidal activity in mammalian plasma (with the exception of rodents), no killing was observed in plasma from birds, reptiles, and fish, pointing to a crucial role for the classical pathway of the complement system. We also observed an interference of these peptides with the human intrinsic pathway of coagulation though, unlike complement activation, this mechanism appears not to be evolutionary conserved. PMID:29473457

  2. Time to Evolve? Potential Evolutionary Responses of Fraser River Sockeye Salmon to Climate Change and Effects on Persistence

    PubMed Central

    Reed, Thomas E.; Schindler, Daniel E.; Hague, Merran J.; Patterson, David A.; Meir, Eli; Waples, Robin S.; Hinch, Scott G.

    2011-01-01

    Evolutionary adaptation affects demographic resilience to climate change but few studies have attempted to project changes in selective pressures or quantify impacts of trait responses on population dynamics and extinction risk. We used a novel individual-based model to explore potential evolutionary changes in migration timing and the consequences for population persistence in sockeye salmon Oncorhynchus nerka in the Fraser River, Canada, under scenarios of future climate warming. Adult sockeye salmon are highly sensitive to increases in water temperature during their arduous upriver migration, raising concerns about the fate of these ecologically, culturally, and commercially important fish in a warmer future. Our results suggest that evolution of upriver migration timing could allow these salmon to avoid increasingly frequent stressful temperatures, with the odds of population persistence increasing in proportion to the trait heritability and phenotypic variance. With a simulated 2°C increase in average summer river temperatures by 2100, adult migration timing from the ocean to the river advanced by ∼10 days when the heritability was 0.5, while the risk of quasi-extinction was only 17% of that faced by populations with zero evolutionary potential (i.e., heritability fixed at zero). The rates of evolution required to maintain persistence under simulated scenarios of moderate to rapid warming are plausible based on estimated heritabilities and rates of microevolution of timing traits in salmon and related species, although further empirical work is required to assess potential genetic and ecophysiological constraints on phenological adaptation. These results highlight the benefits to salmon management of maintaining evolutionary potential within populations, in addition to conserving key habitats and minimizing additional stressors where possible, as a means to build resilience to ongoing climate change. More generally, they demonstrate the importance and feasibility of considering evolutionary processes, in addition to ecology and demography, when projecting population responses to environmental change. PMID:21738573

  3. The role of inflammation in depression: from evolutionary imperative to modern treatment target.

    PubMed

    Miller, Andrew H; Raison, Charles L

    2016-01-01

    Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with pathogens and predators. However, in modern times, such interactions between inflammation and the brain appear to drive the development of depression and may contribute to non-responsiveness to current antidepressant therapies. Recent data have elucidated the mechanisms by which the innate and adaptive immune systems interact with neurotransmitters and neurocircuits to influence the risk for depression. Here, we detail our current understanding of these pathways and discuss the therapeutic potential of targeting the immune system to treat depression.

  4. Comparative genomics explains the evolutionary success of reef-forming corals

    PubMed Central

    Bhattacharya, Debashish; Agrawal, Shobhit; Aranda, Manuel; Baumgarten, Sebastian; Belcaid, Mahdi; Drake, Jeana L; Erwin, Douglas; Foret, Sylvian; Gates, Ruth D; Gruber, David F; Kamel, Bishoy; Lesser, Michael P; Levy, Oren; Liew, Yi Jin; MacManes, Matthew; Mass, Tali; Medina, Monica; Mehr, Shaadi; Meyer, Eli; Price, Dana C; Putnam, Hollie M; Qiu, Huan; Shinzato, Chuya; Shoguchi, Eiichi; Stokes, Alexander J; Tambutté, Sylvie; Tchernov, Dan; Voolstra, Christian R; Wagner, Nicole; Walker, Charles W; Weber, Andreas PM; Weis, Virginia; Zelzion, Ehud; Zoccola, Didier; Falkowski, Paul G

    2016-01-01

    Transcriptome and genome data from twenty stony coral species and a selection of reference bilaterians were studied to elucidate coral evolutionary history. We identified genes that encode the proteins responsible for the precipitation and aggregation of the aragonite skeleton on which the organisms live, and revealed a network of environmental sensors that coordinate responses of the host animals to temperature, light, and pH. Furthermore, we describe a variety of stress-related pathways, including apoptotic pathways that allow the host animals to detoxify reactive oxygen and nitrogen species that are generated by their intracellular photosynthetic symbionts, and determine the fate of corals under environmental stress. Some of these genes arose through horizontal gene transfer and comprise at least 0.2% of the animal gene inventory. Our analysis elucidates the evolutionary strategies that have allowed symbiotic corals to adapt and thrive for hundreds of millions of years. DOI: http://dx.doi.org/10.7554/eLife.13288.001 PMID:27218454

  5. Controls on the geochemical evolution of Prairie Pothole Region lakes and wetlands over decadal time scales

    USGS Publications Warehouse

    Goldhaber, Martin B.; Mills, Christopher T.; Mushet, David M.; McCleskey, R. Blaine; Rover, Jennifer

    2016-01-01

    One hundred sixty-seven Prairie Pothole lakes, ponds and wetlands (largely lakes) previously analyzed chemically during the late 1960’s and early to mid-1970’s were resampled and reanalyzed in 2011–2012. The two sampling periods differed climatically. The earlier sampling took place during normal to slightly dry conditions, whereas the latter occurred during and immediately following exceptionally wet conditions. As reported previously in Mushet et al. (2015), the dominant effect was expansion of the area of these lakes and dilution of their major ions. However, within that context, there were significant differences in the evolutionary pathways of major ions. To establish these pathways, we employed the inverse modeling computer code NetpathXL. This code takes the initial and final lake composition and, using mass balance constrained by the composition of diluting waters, and input and output of phases, calculates plausible geochemical evolution pathways. Despite the fact that in most cases major ions decreased, a subset of the lakes had an increase in SO42−. This distinction is significant because SO42− is the dominant anion in a majority of Prairie Pothole Region wetlands and lakes. For lakes with decreasing SO42−, the proportion of original lake water required for mass balance was subordinate to rainwater and/or overland flow. In contrast, lakes with increasing SO42− between the two sampling episodes tended to be dominated by original lake water. This suite of lakes tended to be smaller and have lower initial SO42−concentrations such that inputs of sulfur from dissolution of the minerals gypsum or pyrite had a significant impact on the final sulfur concentration given the lower dilution factors. Thus, our study provides context for how Prairie Pothole Region water bodies evolve geochemically as climate changes. Because wetland geochemistry in turn controls the ecology of these water bodies, this research contributes to the prediction of the impact of climate change on this important complex of ecosystems.

  6. Gene Transfers Shaped the Evolution of De Novo NAD+ Biosynthesis in Eukaryotes

    PubMed Central

    Ternes, Chad M.; Schönknecht, Gerald

    2014-01-01

    NAD+ is an essential molecule for life, present in each living cell. It can function as an electron carrier or cofactor in redox biochemistry and energetics, and serves as substrate to generate the secondary messenger cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate. Although de novo NAD+ biosynthesis is essential, different metabolic pathways exist in different eukaryotic clades. The kynurenine pathway starting with tryptophan was most likely present in the last common ancestor of all eukaryotes, and is active in fungi and animals. The aspartate pathway, detected in most photosynthetic eukaryotes, was probably acquired from the cyanobacterial endosymbiont that gave rise to chloroplasts. An evolutionary analysis of enzymes catalyzing de novo NAD+ biosynthesis resulted in evolutionary trees incongruent with established organismal phylogeny, indicating numerous gene transfers. Endosymbiotic gene transfers probably introduced the aspartate pathway into eukaryotes and may have distributed it among different photosynthetic clades. In addition, several horizontal gene transfers substituted eukaryotic genes with bacterial orthologs. Although horizontal gene transfer is accepted as a key mechanism in prokaryotic evolution, it is supposed to be rare in eukaryotic evolution. The essential metabolic pathway of de novo NAD+ biosynthesis in eukaryotes was shaped by numerous gene transfers. PMID:25169983

  7. Evo-devo: Hydra raises its Noggin.

    PubMed

    Chandramore, Kalpana; Ghaskadbi, Surendra

    2011-08-01

    Noggin, along with other secreted bone morphogenetic protein (BMP) inhibitors, plays a crucial role in neural induction and neural tube patterning as well as in somitogenesis, cardiac morphogenesis and formation of the skeleton in vertebrates. The BMP signalling pathway is one of the seven fundamental pathways that drive embryonic development and pattern formation in animals. Understanding its evolutionary origin and role in pattern formation is, therefore, important to evolutionary developmental biology (evo-devo). We have studied the evolutionary origin of BMP-Noggin antagonism in hydra, which is a powerful diploblastic model to study evolution of pattern-forming mechanisms because of the unusual cellular dynamics during its pattern formation and its remarkable ability to regenerate. We cloned and characterized the noggin gene from hydra and found it to exhibit considerable similarity with its orthologues at the amino acid level. Microinjection of hydra Noggin mRNA led to duplication of the dorsoventral axis in Xenopus embryos, demonstrating its functional conservation across the taxa. Our data, along with those of others, indicate that the evolutionarily conserved antagonism between BMP and its inhibitors predates bilateral divergence. This article reviews the various roles of Noggin in different organisms and some of our recent work on hydra Noggin in the context of evolution of developmental signalling pathways.

  8. Immune pathways and defence mechanisms in honey bees Apis mellifera

    PubMed Central

    Evans, J D; Aronstein, K; Chen, Y P; Hetru, C; Imler, J-L; Jiang, H; Kanost, M; Thompson, G J; Zou, Z; Hultmark, D

    2006-01-01

    Social insects are able to mount both group-level and individual defences against pathogens. Here we focus on individual defences, by presenting a genome-wide analysis of immunity in a social insect, the honey bee Apis mellifera. We present honey bee models for each of four signalling pathways associated with immunity, identifying plausible orthologues for nearly all predicted pathway members. When compared to the sequenced Drosophila and Anopheles genomes, honey bees possess roughly one-third as many genes in 17 gene families implicated in insect immunity. We suggest that an implied reduction in immune flexibility in bees reflects either the strength of social barriers to disease, or a tendency for bees to be attacked by a limited set of highly coevolved pathogens. PMID:17069638

  9. GNAq mutations are not identified in papillary thyroid carcinomas and hyperfunctioning thyroid nodules.

    PubMed

    Cassol, Clarissa A; Guo, Miao; Ezzat, Shereen; Asa, Sylvia L

    2010-12-01

    Activating mutations of GNAq protein in a hotspot at codon 209 have been recently described in uveal melanomas. Since these neoplasms share with thyroid carcinomas a high frequency of MAP kinase pathway-activating mutations, we hypothesized whether GNAq mutations could also play a role in the development of thyroid carcinomas. Additionally, activating mutations of another subtype of G protein (GNAS1) are frequently found in hyperfunctioning thyroid adenomas, making it plausible that GNAq-activating mutations could also be found in some of these nodules. To investigate thyroid papillary carcinomas and thyroid hyperfunctioning nodules for GNAq mutations in exon 5, codon 209, a total of 32 RET/PTC, BRAF, and RAS negative thyroid papillary carcinomas and 13 hyperfunctioning thyroid nodules were evaluated. No mutations were identified. Although plausible, GNAq mutations seem not to play an important role in the development of thyroid follicular neoplasms, either benign hyperfunctioning nodules or malignant papillary carcinomas. Our results are in accordance with the literature, in which no GNAq hotspot mutations were found in thyroid papillary carcinomas, as well as in an extensive panel of other tumors. The molecular basis for MAP-kinase pathway activation in RET-PTC/BRAF/RAS negative thyroid carcinomas remains to be determined.

  10. Wedelolactone mitigates UVB induced oxidative stress, inflammation and early tumor promotion events in murine skin: plausible role of NFkB pathway.

    PubMed

    Ali, Farrah; Khan, Bilal Azhar; Sultana, Sarwat

    2016-09-05

    UVB (Ultra-violet B) radiation is one of the major etiological factors in various dermal pathology viz. dermatitis, actinic folliculitis, solar urticaria, psoriasis and cancer among many others. UVB causes toxic manifestation in tissues by inciting inflammatory and tumor promoting events. We have designed this study to assess the anti-inflammatory and anti-tumor promotion effect of Wedelolactone (WDL) a specific IKK inhibitor. Results indicate significant restoration of anti-oxidative enzymes due to WDL treatments. We also found that WDL was effective in mitigating inflammatory markers consisting of MPO (myeloperoxidase), Mast cells trafficking, Langerhans cells suppression and COX 2 expression up regulation due to UVB exposure. We also deduce that WDL presented a promising intervention in attenuating early tumor promotion events caused by UVB exposure as indicated by the results of ODC (Ornithine Decarboxylase), Thymidine assay, Vimentin and VEGF (Vascular-endothelial growth factor) expression. This study was able to provide substantial cues for the therapeutic ability of Wedelolactone against inflammatory and tumor promoting events in murine skin depicting plausible role of NFkB pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Functional phylogenomics analysis of bacteria and archaea using consistent genome annotation with UniFam

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chai, Juanjuan; Kora, Guruprasad; Ahn, Tae-Hyuk

    2014-10-09

    To supply some background, phylogenetic studies have provided detailed knowledge on the evolutionary mechanisms of genes and species in Bacteria and Archaea. However, the evolution of cellular functions, represented by metabolic pathways and biological processes, has not been systematically characterized. Many clades in the prokaryotic tree of life have now been covered by sequenced genomes in GenBank. This enables a large-scale functional phylogenomics study of many computationally inferred cellular functions across all sequenced prokaryotes. Our results show a total of 14,727 GenBank prokaryotic genomes were re-annotated using a new protein family database, UniFam, to obtain consistent functional annotations for accuratemore » comparison. The functional profile of a genome was represented by the biological process Gene Ontology (GO) terms in its annotation. The GO term enrichment analysis differentiated the functional profiles between selected archaeal taxa. 706 prokaryotic metabolic pathways were inferred from these genomes using Pathway Tools and MetaCyc. The consistency between the distribution of metabolic pathways in the genomes and the phylogenetic tree of the genomes was measured using parsimony scores and retention indices. The ancestral functional profiles at the internal nodes of the phylogenetic tree were reconstructed to track the gains and losses of metabolic pathways in evolutionary history. In conclusion, our functional phylogenomics analysis shows divergent functional profiles of taxa and clades. Such function-phylogeny correlation stems from a set of clade-specific cellular functions with low parsimony scores. On the other hand, many cellular functions are sparsely dispersed across many clades with high parsimony scores. These different types of cellular functions have distinct evolutionary patterns reconstructed from the prokaryotic tree.« less

  12. Plausibility and the Theoreticians' Regress: Constructing the evolutionary fate of stars

    NASA Astrophysics Data System (ADS)

    Ipe, Alex Ike

    2002-10-01

    This project presents a case-study of a scientific controversy that occurred in theoretical astrophysics nearly seventy years ago following the conceptual discovery of a novel phenomenon relating to the evolution and structure of stellar matter, known as the limiting mass. The ensuing debate between the author of the finding, Subrahmanyan Chandrasekhar and his primary critic, Arthur Stanley Eddington, witnessed both scientists trying to convince one another, as well as the astrophysical community, that their respective positions on the issue was the correct one. Since there was no independent criterion—that is, no observational evidence—at the time of the dispute that could have been drawn upon to test the validity of the limiting mass concept, a logical, objective resolution to the controversy was not possible. In this respect, I argue that the dynamics of the Chandrasekhar-Eddington debate succinctly resonates with Kennefick's notion of the Theoreticians' Regress. However, whereas this model predicts that such a regress can be broken if both parties in a dispute come to agree on who was in error and collaborate on a calculation whose technical foundation can be agreed to, I argue that a more pragmatic path by which the Theoreticians' Regress is broken is when one side in a dispute is able to construct its argument as being more plausible than that of its opponent, and is so successful in doing so, that its opposition is subsequently forced to withdraw from the debate. In order to adequately deal with the construction of plausibility in the context of scientific controversies, I draw upon Harvey's Plausibility Model as well as Pickering's work on the role socio-cultural factors play in the resolution of intellectual disputes. It is believed that the ideas embedded in these social- relativist-constructivist perspectives provide the most parsimonious explanation as to the reasons for the genesis and ultimate closure of this particular scientific controversy.

  13. Revealing evolutionary pathways by fitness landscape reconstruction.

    PubMed

    Kogenaru, Manjunatha; de Vos, Marjon G J; Tans, Sander J

    2009-01-01

    The concept of epistasis has since long been used to denote non-additive fitness effects of genetic changes and has played a central role in understanding the evolution of biological systems. Owing to an array of novel experimental methodologies, it has become possible to experimentally determine epistatic interactions as well as more elaborate genotype-fitness maps. These data have opened up the investigation of a host of long-standing questions in evolutionary biology, such as the ruggedness of fitness landscapes and the accessibility of mutational trajectories, the evolution of sex, and the origin of robustness and modularity. Here we review this recent and timely marriage between systems biology and evolutionary biology, which holds the promise to understand evolutionary dynamics in a more mechanistic and predictive manner.

  14. How might contact with nature promote human health? Promising mechanisms and a possible central pathway.

    PubMed

    Kuo, Ming

    2015-01-01

    How might contact with nature promote human health? Myriad studies have linked the two; at this time the task of identifying the mechanisms underlying this link is paramount. This article offers: (1) a compilation of plausible pathways between nature and health; (2) criteria for identifying a possible central pathway; and (3) one promising candidate for a central pathway. The 21 pathways identified here include environmental factors, physiological and psychological states, and behaviors or conditions, each of which has been empirically tied to nature and has implications for specific physical and mental health outcomes. While each is likely to contribute to nature's impacts on health to some degree and under some circumstances, this paper explores the possibility of a central pathway by proposing criteria for identifying such a pathway and illustrating their use. A particular pathway is more likely to be central if it can account for the size of nature's impacts on health, account for nature's specific health outcomes, and subsume other pathways. By these criteria, enhanced immune functioning emerges as one promising candidate for a central pathway between nature and health. There may be others.

  15. Applying Evolutionary Anthropology

    PubMed Central

    Gibson, Mhairi A; Lawson, David W

    2015-01-01

    Evolutionary anthropology provides a powerful theoretical framework for understanding how both current environments and legacies of past selection shape human behavioral diversity. This integrative and pluralistic field, combining ethnographic, demographic, and sociological methods, has provided new insights into the ultimate forces and proximate pathways that guide human adaptation and variation. Here, we present the argument that evolutionary anthropological studies of human behavior also hold great, largely untapped, potential to guide the design, implementation, and evaluation of social and public health policy. Focusing on the key anthropological themes of reproduction, production, and distribution we highlight classic and recent research demonstrating the value of an evolutionary perspective to improving human well-being. The challenge now comes in transforming relevance into action and, for that, evolutionary behavioral anthropologists will need to forge deeper connections with other applied social scientists and policy-makers. We are hopeful that these developments are underway and that, with the current tide of enthusiasm for evidence-based approaches to policy, evolutionary anthropology is well positioned to make a strong contribution. PMID:25684561

  16. Applying evolutionary anthropology.

    PubMed

    Gibson, Mhairi A; Lawson, David W

    2015-01-01

    Evolutionary anthropology provides a powerful theoretical framework for understanding how both current environments and legacies of past selection shape human behavioral diversity. This integrative and pluralistic field, combining ethnographic, demographic, and sociological methods, has provided new insights into the ultimate forces and proximate pathways that guide human adaptation and variation. Here, we present the argument that evolutionary anthropological studies of human behavior also hold great, largely untapped, potential to guide the design, implementation, and evaluation of social and public health policy. Focusing on the key anthropological themes of reproduction, production, and distribution we highlight classic and recent research demonstrating the value of an evolutionary perspective to improving human well-being. The challenge now comes in transforming relevance into action and, for that, evolutionary behavioral anthropologists will need to forge deeper connections with other applied social scientists and policy-makers. We are hopeful that these developments are underway and that, with the current tide of enthusiasm for evidence-based approaches to policy, evolutionary anthropology is well positioned to make a strong contribution. © 2015 Wiley Periodicals, Inc.

  17. Chronic Diffuse Pain and Functional Gastrointestinal Disorders After Traumatic Stress: Pathophysiology Through a Polyvagal Perspective

    PubMed Central

    Kolacz, Jacek; Porges, Stephen W.

    2018-01-01

    Chronic diffuse pain disorders, such as fibromyalgia, and functional gastrointestinal disorders (FGIDs), such as irritable bowel syndrome, place substantial burden on those affected and on the medical system. Despite their sizable impact, their pathophysiology is poorly understood. In contrast to an approach that focuses on the correlation between heart rate variability (HRV) and a specific organ or symptom, we propose that a bio-evolutionary threat-related autonomic response—as outlined in the Polyvagal Theory—may serve as a plausible explanation of how HRV, particularly respiratory sinus arrhythmia (RSA), would index the pathophysiology of these disorders. Evidence comes from: (1) the well-documented atypical autonomic regulation of the heart common to fibromyalgia and irritable bowel syndrome reflected in dampened RSA, (2) the neural architecture that integrates the heart, pain pathways, and the gastrointestinal tract, (3) the common physical co-morbidities shared by chronic diffuse pain and FGIDs, many of which are functionally regulated by the autonomic nervous system, (4) the elevated risk of chronic diffuse pain and FGIDs following traumatic stress or abuse, (5) and the elevated risk of chronic diffuse pain and FGIDs in individuals with anxiety and panic disorders. This novel conceptualization points to a pathogenesis rooted in changes to brain-body autonomic feedback loops in response to evolutionarily-salient threat cues, providing an integrated biopsychosocial model of chronic diffuse pain and FGIDs and suggesting new, non-pharmacological treatment strategies. PMID:29904631

  18. Exploration of Venus' Deep Atmosphere and Surface Environment

    NASA Technical Reports Server (NTRS)

    Glaze, L. S.; Amato, M.; Garvin, J. B.; Johnson, N. M.

    2017-01-01

    Venus formed in the same part of our solar system as Earth, apparently from similar materials. Although both planets are about the same size, their differences are profound. Venus and Earth experienced vastly different evolutionary pathways resulting in unexplained differences in atmospheric composition and dynamics, as well as in geophysical processes of the planetary surfaces and interiors. Understanding when and why the evolutionary pathways of Venus and Earth diverged is key to understanding how terrestrial planets form and how their atmospheres and surfaces evolve. Measurements made in situ, within the near-surface or surface environment, are critical to addressing unanswered questions. We have made substantial progress modernizing and maturing pressure vessel technologies to enable science operations in the high temperature and pressure near-surface/surfaceenvironment of Venus.

  19. The role of inflammation in depression: from evolutionary imperative to modern treatment target

    PubMed Central

    Miller, Andrew H.; Raison, Charles L.

    2017-01-01

    Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with pathogens and predators. However, in modern times, such interactions between inflammation and the brain appear to drive the development of depression and may contribute to non-responsiveness to current antidepressant therapies. Recent data have elucidated the mechanisms by which the innate and adaptive immune systems interact with neurotransmitters and neurocircuits to influence the risk for depression. Here, we detail our current understanding of these pathways and discuss the therapeutic potential of targeting the immune system to treat depression. PMID:26711676

  20. Regulatory and evolutionary signatures of sex-biased genes on both the X chromosome and the autosomes.

    PubMed

    Shen, Jiangshan J; Wang, Ting-You; Yang, Wanling

    2017-11-02

    Sex is an important but understudied factor in the genetics of human diseases. Analyses using a combination of gene expression data, ENCODE data, and evolutionary data of sex-biased gene expression in human tissues can give insight into the regulatory and evolutionary forces acting on sex-biased genes. In this study, we analyzed the differentially expressed genes between males and females. On the X chromosome, we used a novel method and investigated the status of genes that escape X-chromosome inactivation (escape genes), taking into account the clonality of lymphoblastoid cell lines (LCLs). To investigate the regulation of sex-biased differentially expressed genes (sDEG), we conducted pathway and transcription factor enrichment analyses on the sDEGs, as well as analyses on the genomic distribution of sDEGs. Evolutionary analyses were also conducted on both sDEGs and escape genes. Genome-wide, we characterized differential gene expression between sexes in 462 RNA-seq samples and identified 587 sex-biased genes, or 3.2% of the genes surveyed. On the X chromosome, sDEGs were distributed in evolutionary strata in a similar pattern as escape genes. We found a trend of negative correlation between the gene expression breadth and nonsynonymous over synonymous mutation (dN/dS) ratios, showing a possible pleiotropic constraint on evolution of genes. Genome-wide, nine transcription factors were found enriched in binding to the regions surrounding the transcription start sites of female-biased genes. Many pathways and protein domains were enriched in sex-biased genes, some of which hint at sex-biased physiological processes. These findings lend insight into the regulatory and evolutionary forces shaping sex-biased gene expression and their involvement in the physiological and pathological processes in human health and diseases.

  1. A statistical test of unbiased evolution of body size in birds.

    PubMed

    Bokma, Folmer

    2002-12-01

    Of the approximately 9500 bird species, the vast majority is small-bodied. That is a general feature of evolutionary lineages, also observed for instance in mammals and plants. The avian interspecific body size distribution is right-skewed even on a logarithmic scale. That has previously been interpreted as evidence that body size evolution has been biased. However, a procedure to test for unbiased evolution from the shape of body size distributions was lacking. In the present paper unbiased body size evolution is defined precisely, and a statistical test is developed based on Monte Carlo simulation of unbiased evolution. Application of the test to birds suggests that it is highly unlikely that avian body size evolution has been unbiased as defined. Several possible explanations for this result are discussed. A plausible explanation is that the general model of unbiased evolution assumes that population size and generation time do not affect the evolutionary variability of body size; that is, that micro- and macroevolution are decoupled, which theory suggests is not likely to be the case.

  2. EVOLUTION OF TRANSIENT LOW-MASS X-RAY BINARIES TO REDBACK MILLISECOND PULSARS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jia, Kun; Li, Xiang-Dong, E-mail: lixd@nju.edu.cn

    2015-11-20

    Redback millisecond pulsars (MSPs; hereafter redbacks) are a subpopulation of eclipsing MSPs in close binaries. The formation processes of these systems are not clear. The three pulsars showing transitions between rotation- and accretion-powered states belong to both redbacks and transient low-mass X-ray binaries (LMXBs), suggesting a possible evolutionary link between them. Through binary evolution calculations, we show that the accretion disks in almost all LMXBs are subject to the thermal-viscous instability during certain evolutionary stages, and the parameter space for the disk instability covers the distribution of known redbacks in the orbital period—companion mass plane. We accordingly suggest that themore » abrupt reduction of the mass accretion rate during quiescence of transient LMXBs provides a plausible way to switch on the pulsar activity, leading to the formation of redbacks, if the neutron star has been spun up to be an energetic MSP. We investigate the evolution of redbacks, taking into account the evaporation feedback, and discuss its possible influence on the formation of black widow MSPs.« less

  3. Sex ratio meiotic drive as a plausible evolutionary mechanism for hybrid male sterility.

    PubMed

    Zhang, Linbin; Sun, Tianai; Woldesellassie, Fitsum; Xiao, Hailian; Tao, Yun

    2015-03-01

    Biological diversity on Earth depends on the multiplication of species or speciation, which is the evolution of reproductive isolation such as hybrid sterility between two new species. An unsolved puzzle is the exact mechanism(s) that causes two genomes to diverge from their common ancestor so that some divergent genes no longer function properly in the hybrids. Here we report genetic analyses of divergent genes controlling male fertility and sex ratio in two very young fruitfly species, Drosophila albomicans and D. nasuta. A majority of the genetic divergence for both traits is mapped to the same regions by quantitative trait loci mappings. With introgressions, six major loci are found to contribute to both traits. This genetic colocalization implicates that genes for hybrid male sterility have evolved primarily for controlling sex ratio. We propose that genetic conflicts over sex ratio may operate as a perpetual dynamo for genome divergence. This particular evolutionary mechanism may largely contribute to the rapid evolution of hybrid male sterility and the disproportionate enrichment of its underlying genes on the X chromosome--two patterns widely observed across animals.

  4. Sex Ratio Meiotic Drive as a Plausible Evolutionary Mechanism for Hybrid Male Sterility

    PubMed Central

    Zhang, Linbin; Xiao, Hailian; Tao, Yun

    2015-01-01

    Biological diversity on Earth depends on the multiplication of species or speciation, which is the evolution of reproductive isolation such as hybrid sterility between two new species. An unsolved puzzle is the exact mechanism(s) that causes two genomes to diverge from their common ancestor so that some divergent genes no longer function properly in the hybrids. Here we report genetic analyses of divergent genes controlling male fertility and sex ratio in two very young fruitfly species, Drosophila albomicans and D. nasuta. A majority of the genetic divergence for both traits is mapped to the same regions by quantitative trait loci mappings. With introgressions, six major loci are found to contribute to both traits. This genetic colocalization implicates that genes for hybrid male sterility have evolved primarily for controlling sex ratio. We propose that genetic conflicts over sex ratio may operate as a perpetual dynamo for genome divergence. This particular evolutionary mechanism may largely contribute to the rapid evolution of hybrid male sterility and the disproportionate enrichment of its underlying genes on the X chromosome – two patterns widely observed across animals. PMID:25822261

  5. Consistency of gene starts among Burkholderia genomes

    PubMed Central

    2011-01-01

    Background Evolutionary divergence in the position of the translational start site among orthologous genes can have significant functional impacts. Divergence can alter the translation rate, degradation rate, subcellular location, and function of the encoded proteins. Results Existing Genbank gene maps for Burkholderia genomes suggest that extensive divergence has occurred--53% of ortholog sets based on Genbank gene maps had inconsistent gene start sites. However, most of these inconsistencies appear to be gene-calling errors. Evolutionary divergence was the most plausible explanation for only 17% of the ortholog sets. Correcting probable errors in the Genbank gene maps decreased the percentage of ortholog sets with inconsistent starts by 68%, increased the percentage of ortholog sets with extractable upstream intergenic regions by 32%, increased the sequence similarity of intergenic regions and predicted proteins, and increased the number of proteins with identifiable signal peptides. Conclusions Our findings highlight an emerging problem in comparative genomics: single-digit percent errors in gene predictions can lead to double-digit percentages of inconsistent ortholog sets. The work demonstrates a simple approach to evaluate and improve the quality of gene maps. PMID:21342528

  6. Total Synthesis and Absolute Configuration of Laurenditerpenol: A Hypoxia Inducible Factor-1 Activation Inhibitor

    PubMed Central

    Chittiboyina, Amar G.; Kumar, Gundluru Mahesh; Carvalho, Paulo B.; Liu, Yang; Zhou, Yu-Dong; Nagle, Dale G.

    2010-01-01

    The absolute stereo structure of the natural product laurenditerpenol (1S, 6R, 7S, 10R, 11R, 14S, 15R) has been accomplished from eight plausible stereoisomers by its first asymmetric total synthesis in a highly convergent and flexible synthetic pathway. Six stereoisomers of laurenditerpenol were synthesized and evaluated for their biological activity. PMID:18004798

  7. Primate energy input and the evolutionary transition to energy-dense diets in humans.

    PubMed

    Simmen, Bruno; Pasquet, Patrick; Masi, Shelly; Koppert, Georgius J A; Wells, Jonathan C K; Hladik, Claude Marcel

    2017-06-14

    Humans and other large-brained hominins have been proposed to increase energy turnover during their evolutionary history. Such increased energy turnover is plausible, given the evolution of energy-rich diets, but requires empirical confirmation. Framing human energetics in a phylogenetic context, our meta-analysis of 17 wild non-human primate species shows that daily metabolizable energy input follows an allometric relationship with body mass where the allometric exponent for mass is 0.75 ± 0.04, close to that reported for daily energy expenditure measured with doubly labelled water in primates. Human populations at subsistence level ( n = 6) largely fall within the variation of primate species in the scaling of energy intake and therefore do not consume significantly more energy than predicted for a non-human primate of equivalent mass. By contrast, humans ingest a conspicuously lower mass of food (-64 ± 6%) compared with primates and maintain their energy intake relatively more constantly across the year. We conclude that our hominin hunter-gatherer ancestors did not increase their energy turnover beyond the allometric relationship characterizing all primate species. The reduction in digestive costs due to consumption of a lower mass of high-quality food, as well as stabilization of energy supply, may have been important evolutionary steps enabling encephalization in the absence of significantly raised energy intakes. © 2017 The Author(s).

  8. Y fuse? Sex chromosome fusions in fishes and reptiles.

    PubMed

    Pennell, Matthew W; Kirkpatrick, Mark; Otto, Sarah P; Vamosi, Jana C; Peichel, Catherine L; Valenzuela, Nicole; Kitano, Jun

    2015-05-01

    Chromosomal fusion plays a recurring role in the evolution of adaptations and reproductive isolation among species, yet little is known of the evolutionary drivers of chromosomal fusions. Because sex chromosomes (X and Y in male heterogametic systems, Z and W in female heterogametic systems) differ in their selective, mutational, and demographic environments, those differences provide a unique opportunity to dissect the evolutionary forces that drive chromosomal fusions. We estimate the rate at which fusions between sex chromosomes and autosomes become established across the phylogenies of both fishes and squamate reptiles. Both the incidence among extant species and the establishment rate of Y-autosome fusions is much higher than for X-autosome, Z-autosome, or W-autosome fusions. Using population genetic models, we show that this pattern cannot be reconciled with many standard explanations for the spread of fusions. In particular, direct selection acting on fusions or sexually antagonistic selection cannot, on their own, account for the predominance of Y-autosome fusions. The most plausible explanation for the observed data seems to be (a) that fusions are slightly deleterious, and (b) that the mutation rate is male-biased or the reproductive sex ratio is female-biased. We identify other combinations of evolutionary forces that might in principle account for the data although they appear less likely. Our results shed light on the processes that drive structural changes throughout the genome.

  9. Getting a better picture of microbial evolution en route to a network of genomes.

    PubMed

    Dagan, Tal; Martin, William

    2009-08-12

    Most current thinking about evolution is couched in the concept of trees. The notion of a tree with recursively bifurcating branches representing recurrent divergence events is a plausible metaphor to describe the evolution of multicellular organisms like vertebrates or land plants. But if we try to force the tree metaphor onto the whole of the evolutionary process, things go badly awry, because the more closely we inspect microbial genomes through the looking glass of gene and genome sequence comparisons, the smaller the amount of the data that fits the concept of a bifurcating tree becomes. That is mainly because among microbes, endosymbiosis and lateral gene transfer are important, two mechanisms of natural variation that differ from the kind of natural variation that Darwin had in mind. For such reasons, when it comes to discussing the relationships among all living things, that is, including the microbes and all of their genes rather than just one or a select few, many biologists are now beginning to talk about networks rather than trees in the context of evolutionary relationships among microbial chromosomes. But talk is not enough. If we were to actually construct networks instead of trees to describe the evolutionary process, what would they look like? Here we consider endosymbiosis and an example of a network of genomes involving 181 sequenced prokaryotes and how that squares off with some ideas about early cell evolution.

  10. Y Fuse? Sex Chromosome Fusions in Fishes and Reptiles

    PubMed Central

    Vamosi, Jana C.; Peichel, Catherine L.; Valenzuela, Nicole; Kitano, Jun

    2015-01-01

    Chromosomal fusion plays a recurring role in the evolution of adaptations and reproductive isolation among species, yet little is known of the evolutionary drivers of chromosomal fusions. Because sex chromosomes (X and Y in male heterogametic systems, Z and W in female heterogametic systems) differ in their selective, mutational, and demographic environments, those differences provide a unique opportunity to dissect the evolutionary forces that drive chromosomal fusions. We estimate the rate at which fusions between sex chromosomes and autosomes become established across the phylogenies of both fishes and squamate reptiles. Both the incidence among extant species and the establishment rate of Y-autosome fusions is much higher than for X-autosome, Z-autosome, or W-autosome fusions. Using population genetic models, we show that this pattern cannot be reconciled with many standard explanations for the spread of fusions. In particular, direct selection acting on fusions or sexually antagonistic selection cannot, on their own, account for the predominance of Y-autosome fusions. The most plausible explanation for the observed data seems to be (a) that fusions are slightly deleterious, and (b) that the mutation rate is male-biased or the reproductive sex ratio is female-biased. We identify other combinations of evolutionary forces that might in principle account for the data although they appear less likely. Our results shed light on the processes that drive structural changes throughout the genome. PMID:25993542

  11. Prebiotic synthesis of phosphoenol pyruvate by α-phosphorylation-controlled triose glycolysis

    NASA Astrophysics Data System (ADS)

    Coggins, Adam J.; Powner, Matthew W.

    2017-04-01

    Phosphoenol pyruvate is the highest-energy phosphate found in living organisms and is one of the most versatile molecules in metabolism. Consequently, it is an essential intermediate in a wide variety of biochemical pathways, including carbon fixation, the shikimate pathway, substrate-level phosphorylation, gluconeogenesis and glycolysis. Triose glycolysis (generation of ATP from glyceraldehyde 3-phosphate via phosphoenol pyruvate) is among the most central and highly conserved pathways in metabolism. Here, we demonstrate the efficient and robust synthesis of phosphoenol pyruvate from prebiotic nucleotide precursors, glycolaldehyde and glyceraldehyde. Furthermore, phosphoenol pyruvate is derived within an α-phosphorylation controlled reaction network that gives access to glyceric acid 2-phosphate, glyceric acid 3-phosphate, phosphoserine and pyruvate. Our results demonstrate that the key components of a core metabolic pathway central to energy transduction and amino acid, sugar, nucleotide and lipid biosyntheses can be reconstituted in high yield under mild, prebiotically plausible conditions.

  12. Assembling old tricks for new tasks: a neural model of instructional learning and control.

    PubMed

    Huang, Tsung-Ren; Hazy, Thomas E; Herd, Seth A; O'Reilly, Randall C

    2013-06-01

    We can learn from the wisdom of others to maximize success. However, it is unclear how humans take advice to flexibly adapt behavior. On the basis of data from neuroanatomy, neurophysiology, and neuroimaging, a biologically plausible model is developed to illustrate the neural mechanisms of learning from instructions. The model consists of two complementary learning pathways. The slow-learning parietal pathway carries out simple or habitual stimulus-response (S-R) mappings, whereas the fast-learning hippocampal pathway implements novel S-R rules. Specifically, the hippocampus can rapidly encode arbitrary S-R associations, and stimulus-cued responses are later recalled into the basal ganglia-gated pFC to bias response selection in the premotor and motor cortices. The interactions between the two model learning pathways explain how instructions can override habits and how automaticity can be achieved through motor consolidation.

  13. Living with death: The evolution of the mitochondrial pathway of apoptosis in animals

    PubMed Central

    Oberst, Andrew; Bender, Cheryl; Green, Douglas R.

    2008-01-01

    The mitochondrial pathway of cell death, in which apoptosis proceeds following mitochondrial outer membrane permeablization (MOMP), release of cytochrome c, and APAF-1 apoptosome-mediated caspase activation, represents the major pathway of physiological apoptosis in vertebrates. However, the well-characterized apoptotic pathways of the invertebrates C. elegans and D. melanogaster indicate that this apoptotic pathway is not universally conserved among animals. This review will compare the role of the mitochondria in the apoptotic programs of mammals, nematodes, and flies, and will survey our knowledge of the apoptotic pathways of other, less familiar model organisms in an effort to explore the evolutionary origins of the mitochondrial pathway of apoptosis. PMID:18451868

  14. Insights into the evolution of enzyme substrate promiscuity after the discovery of (βα)₈ isomerase evolutionary intermediates from a diverse metagenome.

    PubMed

    Noda-García, Lianet; Juárez-Vázquez, Ana L; Ávila-Arcos, María C; Verduzco-Castro, Ernesto A; Montero-Morán, Gabriela; Gaytán, Paul; Carrillo-Tripp, Mauricio; Barona-Gómez, Francisco

    2015-06-10

    Current sequence-based approaches to identify enzyme functional shifts, such as enzyme promiscuity, have proven to be highly dependent on a priori functional knowledge, hampering our ability to reconstruct evolutionary history behind these mechanisms. Hidden Markov Model (HMM) profiles, broadly used to classify enzyme families, can be useful to distinguish between closely related enzyme families with different specificities. The (βα)8-isomerase HisA/PriA enzyme family, involved in L-histidine (HisA, mono-substrate) biosynthesis in most bacteria and plants, but also in L-tryptophan (HisA/TrpF or PriA, dual-substrate) biosynthesis in most Actinobacteria, has been used as model system to explore evolutionary hypotheses and therefore has a considerable amount of evolutionary, functional and structural knowledge available. We searched for functional evolutionary intermediates between the HisA and PriA enzyme families in order to understand the functional divergence between these families. We constructed a HMM profile that correctly classifies sequences of unknown function into the HisA and PriA enzyme sub-families. Using this HMM profile, we mined a large metagenome to identify plausible evolutionary intermediate sequences between HisA and PriA. These sequences were used to perform phylogenetic reconstructions and to identify functionally conserved amino acids. Biochemical characterization of one selected enzyme (CAM1) with a mutation within the functionally essential N-terminus phosphate-binding site, namely, an alanine instead of a glycine in HisA or a serine in PriA, showed that this evolutionary intermediate has dual-substrate specificity. Moreover, site-directed mutagenesis of this alanine residue, either backwards into a glycine or forward into a serine, revealed the robustness of this enzyme. None of these mutations, presumably upon functionally essential amino acids, significantly abolished its enzyme activities. A truncated version of this enzyme (CAM2) predicted to adopt a (βα)6-fold, and thus entirely lacking a C-terminus phosphate-binding site, was identified and shown to have HisA activity. As expected, reconstruction of the evolution of PriA from HisA with HMM profiles suggest that functional shifts involve mutations in evolutionarily intermediate enzymes of otherwise functionally essential residues or motifs. These results are in agreement with a link between promiscuous enzymes and intragenic epistasis. HMM provides a convenient approach for gaining insights into these evolutionary processes.

  15. Rapid evolution and gene expression: a rapidly evolving Mendelian trait that silences field crickets has widespread effects on mRNA and protein expression.

    PubMed

    Pascoal, S; Liu, X; Ly, T; Fang, Y; Rockliffe, N; Paterson, S; Shirran, S L; Botting, C H; Bailey, N W

    2016-06-01

    A major advance in modern evolutionary biology is the ability to start linking phenotypic evolution in the wild with genomic changes that underlie that evolution. We capitalized on a rapidly evolving Hawaiian population of crickets (Teleogryllus oceanicus) to test hypotheses about the genomic consequences of a recent Mendelian mutation of large effect which disrupts the development of sound-producing structures on male forewings. The resulting silent phenotype, flatwing, persists because of natural selection imposed by an acoustically orienting parasitoid, but it interferes with mate attraction. We examined gene expression differences in developing wing buds of wild-type and flatwing male crickets using RNA-seq and quantitative proteomics. Most differentially expressed (DE) transcripts were down-regulated in flatwing males (625 up vs. 1716 down), whereas up- and down-regulated proteins were equally represented (30 up and 34 down). Differences between morphs were clearly not restricted to a single pathway, and we recovered annotations associated with a broad array of functions that would not be predicted a priori. Using a candidate gene detection test based on homology, we identified 30% of putative Drosophila wing development genes in the cricket transcriptome, but only 10% were DE. In addition to wing-related annotations, endocrine pathways and several biological processes such as reproduction, immunity and locomotion were DE in the mutant crickets at both biological levels. Our results illuminate the breadth of genetic pathways that are potentially affected in the early stages of adaptation. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  16. Gametophyte differentiation and imprinting control in plants: Crosstalk between RBR and chromatin.

    PubMed

    Johnston, Amal J; Gruissem, Wilhelm

    2009-01-01

    The Retinoblastoma (pRb) pathway has been implicated as a convergent regulatory unit in the control of cell cycle and disease. We have shown that a crosstalk between RETINOBLASTOMA RELATED (RBR), the Arabidopsis homologue of pRb, and the genes encoding proteins of the chromatin complexes involved in DNA or histone methylation, controls gametophytic and post-fertilization differentiation events and a subset of imprinting effects. We describe here a plausible model that incorporates several components of the plant Retinoblastoma pathway, thus offering a novel paradigm that merges the traditional cell cycle and the chromatin components in the control of cell differentiation and imprinting.

  17. Loss of the six3/6 controlling pathways might have resulted in pinhole-eye evolution in Nautilus.

    PubMed

    Ogura, Atsushi; Yoshida, Masa-aki; Moritaki, Takeya; Okuda, Yuki; Sese, Jun; Shimizu, Kentaro K; Sousounis, Konstantinos; Tsonis, Panagiotis A

    2013-01-01

    Coleoid cephalopods have an elaborate camera eye whereas nautiloids have primitive pinhole eye without lens and cornea. The Nautilus pinhole eye provides a unique example to explore the module of lens formation and its evolutionary mechanism. Here, we conducted an RNA-seq study of developing eyes of Nautilus and pygmy squid. First, we found that evolutionary distances from the common ancestor to Nautilus or squid are almost the same. Although most upstream eye development controlling genes were expressed in both species, six3/6 that are required for lens formation in vertebrates was not expressed in Nautilus. Furthermore, many downstream target genes of six3/6 including crystallin genes and other lens protein related genes were not expressed in Nautilus. As six3/6 and its controlling pathways are widely conserved among molluscs other than Nautilus, the present data suggest that deregulation of the six3/6 pathway led to the pinhole eye evolution in Nautilus.

  18. Loss of the six3/6 controlling pathways might have resulted in pinhole-eye evolution in Nautilus

    PubMed Central

    Ogura, Atsushi; Yoshida, Masa-aki; Moritaki, Takeya; Okuda, Yuki; Sese, Jun; Shimizu, Kentaro K.; Sousounis, Konstantinos; Tsonis, Panagiotis A.

    2013-01-01

    Coleoid cephalopods have an elaborate camera eye whereas nautiloids have primitive pinhole eye without lens and cornea. The Nautilus pinhole eye provides a unique example to explore the module of lens formation and its evolutionary mechanism. Here, we conducted an RNA-seq study of developing eyes of Nautilus and pygmy squid. First, we found that evolutionary distances from the common ancestor to Nautilus or squid are almost the same. Although most upstream eye development controlling genes were expressed in both species, six3/6 that are required for lens formation in vertebrates was not expressed in Nautilus. Furthermore, many downstream target genes of six3/6 including crystallin genes and other lens protein related genes were not expressed in Nautilus. As six3/6 and its controlling pathways are widely conserved among molluscs other than Nautilus, the present data suggest that deregulation of the six3/6 pathway led to the pinhole eye evolution in Nautilus. PMID:23478590

  19. The SOS response increases bacterial fitness, but not evolvability, under a sublethal dose of antibiotic.

    PubMed

    Torres-Barceló, Clara; Kojadinovic, Mila; Moxon, Richard; MacLean, R Craig

    2015-10-07

    Exposure to antibiotics induces the expression of mutagenic bacterial stress-response pathways, but the evolutionary benefits of these responses remain unclear. One possibility is that stress-response pathways provide a short-term advantage by protecting bacteria against the toxic effects of antibiotics. Second, it is possible that stress-induced mutagenesis provides a long-term advantage by accelerating the evolution of resistance. Here, we directly measure the contribution of the Pseudomonas aeruginosa SOS pathway to bacterial fitness and evolvability in the presence of sublethal doses of ciprofloxacin. Using short-term competition experiments, we demonstrate that the SOS pathway increases competitive fitness in the presence of ciprofloxacin. Continued exposure to ciprofloxacin results in the rapid evolution of increased fitness and antibiotic resistance, but we find no evidence that SOS-induced mutagenesis accelerates the rate of adaptation to ciprofloxacin during a 200 generation selection experiment. Intriguingly, we find that the expression of the SOS pathway decreases during adaptation to ciprofloxacin, and this helps to explain why this pathway does not increase long-term evolvability. Furthermore, we argue that the SOS pathway fails to accelerate adaptation to ciprofloxacin because the modest increase in the mutation rate associated with SOS mutagenesis is offset by a decrease in the effective strength of selection for increased resistance at a population level. Our findings suggest that the primary evolutionary benefit of the SOS response is to increase bacterial competitive ability, and that stress-induced mutagenesis is an unwanted side effect, and not a selected attribute, of this pathway. © 2015 The Authors.

  20. The SOS response increases bacterial fitness, but not evolvability, under a sublethal dose of antibiotic

    PubMed Central

    Torres-Barceló, Clara; Kojadinovic, Mila; Moxon, Richard; MacLean, R. Craig

    2015-01-01

    Exposure to antibiotics induces the expression of mutagenic bacterial stress–response pathways, but the evolutionary benefits of these responses remain unclear. One possibility is that stress–response pathways provide a short-term advantage by protecting bacteria against the toxic effects of antibiotics. Second, it is possible that stress-induced mutagenesis provides a long-term advantage by accelerating the evolution of resistance. Here, we directly measure the contribution of the Pseudomonas aeruginosa SOS pathway to bacterial fitness and evolvability in the presence of sublethal doses of ciprofloxacin. Using short-term competition experiments, we demonstrate that the SOS pathway increases competitive fitness in the presence of ciprofloxacin. Continued exposure to ciprofloxacin results in the rapid evolution of increased fitness and antibiotic resistance, but we find no evidence that SOS-induced mutagenesis accelerates the rate of adaptation to ciprofloxacin during a 200 generation selection experiment. Intriguingly, we find that the expression of the SOS pathway decreases during adaptation to ciprofloxacin, and this helps to explain why this pathway does not increase long-term evolvability. Furthermore, we argue that the SOS pathway fails to accelerate adaptation to ciprofloxacin because the modest increase in the mutation rate associated with SOS mutagenesis is offset by a decrease in the effective strength of selection for increased resistance at a population level. Our findings suggest that the primary evolutionary benefit of the SOS response is to increase bacterial competitive ability, and that stress-induced mutagenesis is an unwanted side effect, and not a selected attribute, of this pathway. PMID:26446807

  1. Comparative functional pan-genome analyses to build connections between genomic dynamics and phenotypic evolution in polycyclic aromatic hydrocarbon metabolism in the genus Mycobacterium.

    PubMed

    Kweon, Ohgew; Kim, Seong-Jae; Blom, Jochen; Kim, Sung-Kwan; Kim, Bong-Soo; Baek, Dong-Heon; Park, Su Inn; Sutherland, John B; Cerniglia, Carl E

    2015-02-14

    The bacterial genus Mycobacterium is of great interest in the medical and biotechnological fields. Despite a flood of genome sequencing and functional genomics data, significant gaps in knowledge between genome and phenome seriously hinder efforts toward the treatment of mycobacterial diseases and practical biotechnological applications. In this study, we propose the use of systematic, comparative functional pan-genomic analysis to build connections between genomic dynamics and phenotypic evolution in polycyclic aromatic hydrocarbon (PAH) metabolism in the genus Mycobacterium. Phylogenetic, phenotypic, and genomic information for 27 completely genome-sequenced mycobacteria was systematically integrated to reconstruct a mycobacterial phenotype network (MPN) with a pan-genomic concept at a network level. In the MPN, mycobacterial phenotypes show typical scale-free relationships. PAH degradation is an isolated phenotype with the lowest connection degree, consistent with phylogenetic and environmental isolation of PAH degraders. A series of functional pan-genomic analyses provide conserved and unique types of genomic evidence for strong epistatic and pleiotropic impacts on evolutionary trajectories of the PAH-degrading phenotype. Under strong natural selection, the detailed gene gain/loss patterns from horizontal gene transfer (HGT)/deletion events hypothesize a plausible evolutionary path, an epistasis-based birth and pleiotropy-dependent death, for PAH metabolism in the genus Mycobacterium. This study generated a practical mycobacterial compendium of phenotypic and genomic changes, focusing on the PAH-degrading phenotype, with a pan-genomic perspective of the evolutionary events and the environmental challenges. Our findings suggest that when selection acts on PAH metabolism, only a small fraction of possible trajectories is likely to be observed, owing mainly to a combination of the ambiguous phenotypic effects of PAHs and the corresponding pleiotropy- and epistasis-dependent evolutionary adaptation. Evolutionary constraints on the selection of trajectories, like those seen in PAH-degrading phenotypes, are likely to apply to the evolution of other phenotypes in the genus Mycobacterium.

  2. Functionally reciprocal mutations of the prolactin signalling pathway define hairy and slick cattle

    PubMed Central

    Littlejohn, Mathew D.; Henty, Kristen M.; Tiplady, Kathryn; Johnson, Thomas; Harland, Chad; Lopdell, Thomas; Sherlock, Richard G.; Li, Wanbo; Lukefahr, Steven D.; Shanks, Bruce C.; Garrick, Dorian J.; Snell, Russell G.; Spelman, Richard J.; Davis, Stephen R.

    2014-01-01

    Lactation, hair development and homeothermy are characteristic evolutionary features that define mammals from other vertebrate species. Here we describe the discovery of two autosomal dominant mutations with antagonistic, pleiotropic effects on all three of these biological processes, mediated through the prolactin signalling pathway. Most conspicuously, mutations in prolactin (PRL) and its receptor (PRLR) have an impact on thermoregulation and hair morphology phenotypes, giving prominence to this pathway outside of its classical roles in lactation. PMID:25519203

  3. The evolutionary origin and diversification of feathers.

    PubMed

    Prum, Richard O; Brush, Alan H

    2002-09-01

    Progress on the evolutionary origin and diversification of feathers has been hampered by conceptual problems and by the lack of plesiomorphic feather fossils. Recently, both of these limitations have been overcome by the proposal of the developmental theory of the origin of feathers, and the discovery of primitive feather fossils on nonavian theropod dinosaurs. The conceptual problems of previous theories of the origin of feathers are reviewed, and the alternative developmental theory is presented and discussed. The developmental theory proposes that feathers evolved through a series of evolutionary novelties in developmental mechanisms of the follicle and feather germ. The discovery of primitive and derived fossil feathers on a diversity of coelurosaurian theropod dinosaurs documents that feathers evolved and diversified in nonavian theropods before the origin of birds and before the origin of flight. The morphologies of these primitive feathers are congruent with the predictions of the developmental theory. Alternatives to the theropod origin of feathers are critique and rejected. Hypotheses for the initial function of feathers are reviewed. The aerodynamic theory of feather origins is falsified, but many other functions remain developmentally and phylogenetically plausible. Whatever their function, feathers evolved by selection for a follicle that would grow an emergent tubular appendage. Feathers are inherently tubular structures. The homology of feathers and scales is weakly supported. Feathers are composed of a suite of evolutionary novelties that evolved by the duplication, hierarchical organization, interaction, dissociation, and differentiation of morphological modules. The unique capacity for modular subdivision of the tubular feather follicle and germ has fostered the evolution of numerous innovations that characterize feathers. The evolution of feather keratin and the molecular basis of feather development are also discussed.

  4. Patterns of genetic variability and habitat occupancy in Crepis triasii (Asteraceae) at different spatial scales: insights on evolutionary processes leading to diversification in continental islands.

    PubMed

    Mayol, Maria; Palau, Carles; Rosselló, Josep A; González-Martínez, Santiago C; Molins, Arántzazu; Riba, Miquel

    2012-02-01

    Archipelagos are unique systems for studying evolutionary processes promoting diversification and speciation. The islands of the Mediterranean basin are major areas of plant richness, including a high proportion of narrow endemics. Many endemic plants are currently found in rocky habitats, showing varying patterns of habitat occupancy at different spatial scales throughout their range. The aim of the present study was to understand the impact of varying patterns of population distribution on genetic diversity and structure to shed light on demographic and evolutionary processes leading to population diversification in Crepis triasii, an endemic plant from the eastern Balearic Islands. Using allozyme and chloroplast markers, we related patterns of genetic structure and diversity to those of habitat occupancy at a regional (between islands and among populations within islands) and landscape (population size and connectivity) scale. Genetic diversity was highly structured both at the regional and at the landscape level, and was positively correlated with population connectivity in the landscape. Populations located in small isolated mountains and coastal areas, with restricted patterns of regional occupancy, were genetically less diverse and much more differentiated. In addition, more isolated populations had stronger fine-scale genetic structure than well-connected ones. Changes in habitat availability and quality arising from marine transgressions during the Quaternary, as well as progressive fragmentation associated with the aridification of the climate since the last glaciation, are the most plausible factors leading to the observed patterns of genetic diversity and structure. Our results emphasize the importance of gene flow in preventing genetic erosion and maintaining the evolutionary potential of populations. They also agree with recent studies highlighting the importance of restricted gene flow and genetic drift as drivers of plant evolution in Mediterranean continental islands.

  5. Stochastic noncooperative and cooperative evolutionary game strategies of a population of biological networks under natural selection.

    PubMed

    Chen, Bor-Sen; Yeh, Chin-Hsun

    2017-12-01

    We review current static and dynamic evolutionary game strategies of biological networks and discuss the lack of random genetic variations and stochastic environmental disturbances in these models. To include these factors, a population of evolving biological networks is modeled as a nonlinear stochastic biological system with Poisson-driven genetic variations and random environmental fluctuations (stimuli). To gain insight into the evolutionary game theory of stochastic biological networks under natural selection, the phenotypic robustness and network evolvability of noncooperative and cooperative evolutionary game strategies are discussed from a stochastic Nash game perspective. The noncooperative strategy can be transformed into an equivalent multi-objective optimization problem and is shown to display significantly improved network robustness to tolerate genetic variations and buffer environmental disturbances, maintaining phenotypic traits for longer than the cooperative strategy. However, the noncooperative case requires greater effort and more compromises between partly conflicting players. Global linearization is used to simplify the problem of solving nonlinear stochastic evolutionary games. Finally, a simple stochastic evolutionary model of a metabolic pathway is simulated to illustrate the procedure of solving for two evolutionary game strategies and to confirm and compare their respective characteristics in the evolutionary process. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Systems metabolic engineering strategies for the production of amino acids.

    PubMed

    Ma, Qian; Zhang, Quanwei; Xu, Qingyang; Zhang, Chenglin; Li, Yanjun; Fan, Xiaoguang; Xie, Xixian; Chen, Ning

    2017-06-01

    Systems metabolic engineering is a multidisciplinary area that integrates systems biology, synthetic biology and evolutionary engineering. It is an efficient approach for strain improvement and process optimization, and has been successfully applied in the microbial production of various chemicals including amino acids. In this review, systems metabolic engineering strategies including pathway-focused approaches, systems biology-based approaches, evolutionary approaches and their applications in two major amino acid producing microorganisms: Corynebacterium glutamicum and Escherichia coli, are summarized.

  7. PTH Reloaded: A New Evolutionary Perspective

    PubMed Central

    Suarez-Bregua, Paula; Cal, Laura; Cañestro, Cristian; Rotllant, Josep

    2017-01-01

    The parathyroid hormone (PTH) family is a group of structurally-related secreted peptides involved in bone mineral homeostasis and multitude of developmental processes in vertebrates. These peptides mediate actions through PTH receptors (PTHRs), which belong to the transmembrane G protein-coupled receptor group. To date, genes encoding for PTH and PTHR have only been identified in chordates, suggesting that this signaling pathway may be an evolutionary innovation of our phylum. In vertebrates, we found up to six PTH and three PTHR different paralogs, varying in number between mammals and teleost fishes due to the different rounds of whole-genome duplication and specific gene losses suffered between the two groups of animals. The diversification of the PTH gene family has been accompanied by both functional divergence and convergence, making sometimes difficult the comparison between PTH peptides of teleosts and mammals. Here, we review the roles of all Pth peptides in fishes, and based on the evolutionary history of PTH paralogs, we propose a new and simple nomenclature from PTH1 to PTH4. Moreover, the recent characterization of the Pth4 in zebrafish allows us to consider the prominent role of the brain-to-bone signaling pathway in the regulation of bone development and homeostasis. Finally, comparison between PTH peptides of fish and mammals allows us to discuss an evolutionary model for PTH functions related to bone mineral balance during the vertebrate transition from an aquatic to a terrestrial environment. PMID:29062283

  8. Evolutionary considerations on complex emotions and music-induced emotions. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

    NASA Astrophysics Data System (ADS)

    Gingras, Bruno; Marin, Manuela M.

    2015-06-01

    Recent efforts to uncover the neural underpinnings of emotional experiences have provided a foundation for novel neurophysiological theories of emotions, adding to the existing body of psychophysiological, motivational, and evolutionary theories. Besides explicitly modeling human-specific emotions and considering the interactions between emotions and language, Koelsch et al.'s original contribution to this challenging endeavor is to identify four brain areas as distinct "affect systems" which differ in terms of emotional qualia and evolutionary pathways [1]. Here, we comment on some features of this promising Quartet Theory of Emotions, focusing particularly on evolutionary and biological aspects related to the four affect systems and their relation to prevailing emotion theories, as well as on the role of music-induced emotions.

  9. Conversion of elderly to Alzheimer's dementia: role of confluence of hypothermia and senescent stigmata--the plausible pathway.

    PubMed

    Daulatzai, Mak Adam

    2010-01-01

    Aging is a consequence of progressive decline in special and somatosensory functions and specific brain stem nuclei. Many senescent stigmata, including hypoxia, hypoxemia, depressed cerebral blood flow and glucose metabolism, diseases of senescence, and their medications all enhance hypothermia as do alcohol, cold environment, and malnutrition. Hypothermia is a critical factor having deleterious impact on brain stem and neocortical functions. Additionally, anesthesia in elderly also promotes hypothermia; anesthetics not only cause consciousness (sensory and motor) changes, but memory impairment as well. Anesthesia inhibits cholinergic pathways, reticular and thalamocortical systems, cortico-cortical connectivity, and causes post-operative delirium and cognitive dysfunction. Increasing evidence indicates that anesthetic exposures may contribute to dementia onset and Alzheimer's disease (AD) in hypothermic elderly. Inhaled anesthetics potentiate caspases, BACE, tau hyperphosphorylation, and apoptosis. This paper addresses the important question: "Why do only some elderly fall victim to AD"? Based on information on the pathogenesis of early stages of cognitive dysfunction in elderly (i.e., due to senescent stigmata), and the effects of anesthesia superimposed, a detailed plausible neuropathological substrate (mechanism/pathway) is delineated here that reveals the possible cause(s) of AD. Basically, it encompasses several risk factors for cognitive dysfunction during senescence plus several hypothermia-enhancing routes; they all converge and tip the balance towards dementia onset. This knowledge of the confluence of heterogeneous risk factors in perpetuating dementia relentlessly is of importance in order to: (a) avoid their convergence; (b) take measures to stop/reverse cognitive dysfunction; and (c) to develop therapeutic strategies to enhance cognitive function and attenuate AD.

  10. Genomicus 2018: karyotype evolutionary trees and on-the-fly synteny computing

    PubMed Central

    Nguyen, Nga Thi Thuy; Vincens, Pierre

    2018-01-01

    Abstract Since 2010, the Genomicus web server is available online at http://genomicus.biologie.ens.fr/genomicus. This graphical browser provides access to comparative genomic analyses in four different phyla (Vertebrate, Plants, Fungi, and non vertebrate Metazoans). Users can analyse genomic information from extant species, as well as ancestral gene content and gene order for vertebrates and flowering plants, in an integrated evolutionary context. New analyses and visualization tools have recently been implemented in Genomicus Vertebrate. Karyotype structures from several genomes can now be compared along an evolutionary pathway (Multi-KaryotypeView), and synteny blocks can be computed and visualized between any two genomes (PhylDiagView). PMID:29087490

  11. Sulfidic Anion Concentrations on Early Earth for Surficial Origins-of-Life Chemistry.

    PubMed

    Ranjan, Sukrit; Todd, Zoe R; Sutherland, John D; Sasselov, Dimitar D

    2018-04-08

    A key challenge in origin-of-life studies is understanding the environmental conditions on early Earth under which abiogenesis occurred. While some constraints do exist (e.g., zircon evidence for surface liquid water), relatively few constraints exist on the abundances of trace chemical species, which are relevant to assessing the plausibility and guiding the development of postulated prebiotic chemical pathways which depend on these species. In this work, we combine literature photochemistry models with simple equilibrium chemistry calculations to place constraints on the plausible range of concentrations of sulfidic anions (HS - , HSO 3 - , SO 3 2- ) available in surficial aquatic reservoirs on early Earth due to outgassing of SO 2 and H 2 S and their dissolution into small shallow surface water reservoirs like lakes. We find that this mechanism could have supplied prebiotically relevant levels of SO 2 -derived anions, but not H 2 S-derived anions. Radiative transfer modeling suggests UV light would have remained abundant on the planet surface for all but the largest volcanic explosions. We apply our results to the case study of the proposed prebiotic reaction network of Patel et al. ( 2015 ) and discuss the implications for improving its prebiotic plausibility. In general, epochs of moderately high volcanism could have been especially conducive to cyanosulfidic prebiotic chemistry. Our work can be similarly applied to assess and improve the prebiotic plausibility of other postulated surficial prebiotic chemistries that are sensitive to sulfidic anions, and our methods adapted to study other atmospherically derived trace species. Key Words: Early Earth-Origin of life-Prebiotic chemistry-Volcanism-UV radiation-Planetary environments. Astrobiology 18, xxx-xxx.

  12. The Draft Genome Sequence of Actinokineospora bangkokensis 44EHWT Reveals the Biosynthetic Pathway of the Antifungal Thailandin Compounds with Unusual Butylmalonyl-CoA Extender Units.

    PubMed

    Greule, Anja; Intra, Bungonsiri; Flemming, Stephan; Rommel, Marcel G E; Panbangred, Watanalai; Bechthold, Andreas

    2016-11-23

    We report the draft genome sequence of Actinokineospora bangkokensis 44EHW T , the producer of the antifungal polyene compounds, thailandins A and B. The sequence contains 7.45 Mb, 74.1% GC content and 35 putative gene clusters for the biosynthesis of secondary metabolites. There are three gene clusters encoding large polyketide synthases of type I. Annotation of the ORF functions and targeted gene disruption enabled us to identify the cluster for thailandin biosynthesis. We propose a plausible biosynthetic pathway for thailandin, where the unusual butylmalonyl-CoA extender unit is incorporated and results in an untypical side chain.

  13. Targeting obesity-related adipose tissue dysfunction to prevent cancer development and progression

    PubMed Central

    Gucalp, Ayca; Iyengar, Neil M.; Hudis, Clifford A.; Dannenberg, Andrew J.

    2016-01-01

    The incidence of obesity, a leading modifiable risk factor for common solid tumors, is increasing. Effective interventions are needed to minimize the public health implications of obesity. Although the mechanisms linking increased adiposity to malignancy are incompletely understood, growing evidence points to complex interactions among multiple systemic and tissue-specific pathways including inflamed white adipose tissue. The metabolic and inflammatory consequences of white adipose tissue dysfunction collectively provide a plausible explanation for the link between overweight/obesity and carcinogenesis. Gaining a better understanding of these underlying molecular pathways and developing risk assessment tools that identify at-risk populations will be critical in implementing effective and novel cancer prevention and management strategies. PMID:26970134

  14. Tradeoff between robustness and elaboration in carotenoid networks produces cycles of avian color diversification.

    PubMed

    Badyaev, Alexander V; Morrison, Erin S; Belloni, Virginia; Sanderson, Michael J

    2015-08-20

    Resolution of the link between micro- and macroevolution calls for comparing both processes on the same deterministic landscape, such as genomic, metabolic or fitness networks. We apply this perspective to the evolution of carotenoid pigmentation that produces spectacular diversity in avian colors and show that basic structural properties of the underlying carotenoid metabolic network are reflected in global patterns of elaboration and diversification in color displays. Birds color themselves by consuming and metabolizing several dietary carotenoids from the environment. Such fundamental dependency on the most upstream external compounds should intrinsically constrain sustained evolutionary elongation of multi-step metabolic pathways needed for color elaboration unless the metabolic network gains robustness - the ability to synthesize the same carotenoid from an additional dietary starting point. We found that gains and losses of metabolic robustness were associated with evolutionary cycles of elaboration and stasis in expressed carotenoids in birds. Lack of metabolic robustness constrained lineage's metabolic explorations to the immediate biochemical vicinity of their ecologically distinct dietary carotenoids, whereas gains of robustness repeatedly resulted in sustained elongation of metabolic pathways on evolutionary time scales and corresponding color elaboration. The structural link between length and robustness in metabolic pathways may explain periodic convergence of phylogenetically distant and ecologically distinct species in expressed carotenoid pigmentation; account for stasis in carotenoid colors in some ecological lineages; and show how the connectivity of the underlying metabolic network provides a mechanistic link between microevolutionary elaboration and macroevolutionary diversification.

  15. Relevance theory: pragmatics and cognition.

    PubMed

    Wearing, Catherine J

    2015-01-01

    Relevance Theory is a cognitively oriented theory of pragmatics, i.e., a theory of language use. It builds on the seminal work of H.P. Grice(1) to develop a pragmatic theory which is at once philosophically sensitive and empirically plausible (in both psychological and evolutionary terms). This entry reviews the central commitments and chief contributions of Relevance Theory, including its Gricean commitment to the centrality of intention-reading and inference in communication; the cognitively grounded notion of relevance which provides the mechanism for explaining pragmatic interpretation as an intention-driven, inferential process; and several key applications of the theory (lexical pragmatics, metaphor and irony, procedural meaning). Relevance Theory is an important contribution to our understanding of the pragmatics of communication. © 2014 John Wiley & Sons, Ltd.

  16. Sex chromosomes and speciation in Drosophila

    PubMed Central

    Presgraves, Daven C.

    2010-01-01

    Two empirical rules suggest that sex chromosomes play a special role in speciation. The first is Haldane's rule— the preferential sterility and inviability of species hybrids of the heterogametic (XY) sex. The second is the disproportionately large effect of the X chromosome in genetic analyses of hybrid sterility. Whereas the causes of Haldane's rule are well established, the causes of the ‘large X-effect’ have remained controversial. New genetic analyses in Drosophila confirm that the X is a hotspot for hybrid male sterility factors, providing a proximate explanation for the large X-effect. Several other new findings— on faster X evolution, X chromosome meiotic drive, and the regulation of the X chromosome in the male-germline— provide plausible evolutionary explanations for the large X-effect. PMID:18514967

  17. Language evolution in the laboratory.

    PubMed

    Scott-Phillips, Thomas C; Kirby, Simon

    2010-09-01

    The historical origins of natural language cannot be observed directly. We can, however, study systems that support language and we can also develop models that explore the plausibility of different hypotheses about how language emerged. More recently, evolutionary linguists have begun to conduct language evolution experiments in the laboratory, where the emergence of new languages used by human participants can be observed directly. This enables researchers to study both the cognitive capacities necessary for language and the ways in which languages themselves emerge. One theme that runs through this work is how individual-level behaviours result in population-level linguistic phenomena. A central challenge for the future will be to explore how different forms of information transmission affect this process. 2010 Elsevier Ltd. All rights reserved.

  18. The puzzle of the Krebs citric acid cycle: assembling the pieces of chemically feasible reactions, and opportunism in the design of metabolic pathways during evolution.

    PubMed

    Meléndez-Hevia, E; Waddell, T G; Cascante, M

    1996-09-01

    The evolutionary origin of the Krebs citric acid cycle has been for a long time a model case in the understanding of the origin and evolution of metabolic pathways: How can the emergence of such a complex pathway be explained? A number of speculative studies have been carried out that have reached the conclusion that the Krebs cycle evolved from pathways for amino acid biosynthesis, but many important questions remain open: Why and how did the full pathway emerge from there? Are other alternative routes for the same purpose possible? Are they better or worse? Have they had any opportunity to be developed in cellular metabolism evolution? We have analyzed the Krebs cycle as a problem of chemical design to oxidize acetate yielding reduction equivalents to the respiratory chain to make ATP. Our analysis demonstrates that although there are several different chemical solutions to this problem, the design of this metabolic pathway as it occurs in living cells is the best chemical solution: It has the least possible number of steps and it also has the greatest ATP yielding. Study of the evolutionary possibilities of each one-taking the available material to build new pathways-demonstrates that the emergence of the Krebs cycle has been a typical case of opportunism in molecular evolution. Our analysis proves, therefore, that the role of opportunism in evolution has converted a problem of several possible chemical solutions into a single-solution problem, with the actual Krebs cycle demonstrated to be the best possible chemical design. Our results also allow us to derive the rules under which metabolic pathways emerged during the origin of life.

  19. Evidence of the evolved nature of the B[e] star MWC 137

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Muratore, M. F.; Arias, M. L.; Cidale, L.

    2015-01-01

    The evolutionary phase of B[e] stars is difficult to establish due to the uncertainties in their fundamental parameters. For instance, possible classifications for the Galactic B[e] star MWC 137 include pre-main-sequence and post-main-sequence phases, with a large range in luminosity. Our goal is to clarify the evolutionary stage of this peculiar object, and to study the CO molecular component of its circumstellar medium. To this purpose, we modeled the CO molecular bands using high-resolution K-band spectra. We find that MWC 137 is surrounded by a detached cool (T=1900±100 K) and dense (N=(3±1)×10{sup 21} cm{sup −2}) ring of CO gas orbitingmore » the star with a rotational velocity, projected to the line of sight, of 84 ± 2 km s{sup −1}. We also find that the molecular gas is enriched in the isotope {sup 13}C, excluding the classification of the star as a Herbig Be. The observed isotopic abundance ratio ({sup 12}C/{sup 13}C = 25 ± 2) derived from our modeling is compatible with a proto-planetary nebula, main-sequence, or supergiant evolutionary phase. However, based on some observable characteristics of MWC 137, we propose that the supergiant scenario seems to be the most plausible. Hence, we suggest that MWC 137 could be in an extremely short-lived phase, evolving from a B[e] supergiant to a blue supergiant with a bipolar ring nebula.« less

  20. Contrasting effects of intralocus sexual conflict on sexually antagonistic coevolution

    PubMed Central

    Pennell, Tanya M.; de Haas, Freek J. H.; Morrow, Edward H.; van Doorn, G. Sander

    2016-01-01

    Evolutionary conflict between the sexes can induce arms races in which males evolve traits that are detrimental to the fitness of their female partners, and vice versa. This interlocus sexual conflict (IRSC) has been proposed as a cause of perpetual intersexual antagonistic coevolution with wide-ranging evolutionary consequences. However, theory suggests that the scope for perpetual coevolution is limited, if traits involved in IRSC are subject to pleiotropic constraints. Here, we consider a biologically plausible form of pleiotropy that has hitherto been ignored in treatments of IRSC and arrive at drastically different conclusions. Our analysis is based on a quantitative genetic model of sexual conflict, in which genes controlling IRSC traits have side effects in the other sex, due to incompletely sex-limited gene expression. As a result, the genes are exposed to intralocus sexual conflict (IASC), a tug-of-war between opposing male- and female-specific selection pressures. We find that the interaction between the two forms of sexual conflict has contrasting effects on antagonistic coevolution: Pleiotropic constraints stabilize the dynamics of arms races if the mating traits are close to evolutionary equilibrium but can prevent populations from ever reaching such a state. Instead, the sexes are drawn into a continuous cycle of arms races, causing the buildup of IASC, alternated by phases of IASC resolution that trigger the next arms race. These results encourage an integrative perspective on the biology of sexual conflict and generally caution against relying exclusively on equilibrium stability analysis. PMID:26755609

  1. Infrared outbursts as potential tracers of common-envelope events in high-mass X-ray binary formation

    NASA Astrophysics Data System (ADS)

    Oskinova, Lidia M.; Bulik, Tomasz; Gómez-Morán, Ada Nebot

    2018-06-01

    Context. Classic massive binary evolutionary scenarios predict that a transitional common-envelope (CE) phase could be preceded as well as succeeded by the evolutionary stage when a binary consists of a compact object and a massive star, that is, a high-mass X-ray binary (HMXB). The observational manifestations of common envelope are poorly constrained. We speculate that its ejection might be observed in some cases as a transient event at mid-infrared (IR) wavelengths. Aims: We estimate the expected numbers of CE ejection events and HMXBs per star formation unit rate, and compare these theoretical estimates with observations. Methods: We compiled a list of 85 mid-IR transients of uncertain nature detected by the Spitzer Infrared Intensive Transients Survey and searched for their associations with X-ray, optical, and UV sources. Results: Confirming our theoretical estimates, we find that only one potential HMXB may be plausibly associated with an IR-transient and tentatively propose that X-ray source NGC 4490-X40 could be a precursor to the SPIRITS 16az event. Among other interesting sources, we suggest that the supernova remnant candidate [BWL2012] 063 might be associated with SPIRITS 16ajc. We also find that two SPIRITS events are likely associated with novae, and seven have potential optical counterparts. Conclusions: The massive binary evolutionary scenarios that involve CE events do not contradict currently available observations of IR transients and HMXBs in star-forming galaxies.

  2. Minimal metabolic pathway structure is consistent with associated biomolecular interactions

    PubMed Central

    Bordbar, Aarash; Nagarajan, Harish; Lewis, Nathan E; Latif, Haythem; Ebrahim, Ali; Federowicz, Stephen; Schellenberger, Jan; Palsson, Bernhard O

    2014-01-01

    Pathways are a universal paradigm for functionally describing cellular processes. Even though advances in high-throughput data generation have transformed biology, the core of our biological understanding, and hence data interpretation, is still predicated on human-defined pathways. Here, we introduce an unbiased, pathway structure for genome-scale metabolic networks defined based on principles of parsimony that do not mimic canonical human-defined textbook pathways. Instead, these minimal pathways better describe multiple independent pathway-associated biomolecular interaction datasets suggesting a functional organization for metabolism based on parsimonious use of cellular components. We use the inherent predictive capability of these pathways to experimentally discover novel transcriptional regulatory interactions in Escherichia coli metabolism for three transcription factors, effectively doubling the known regulatory roles for Nac and MntR. This study suggests an underlying and fundamental principle in the evolutionary selection of pathway structures; namely, that pathways may be minimal, independent, and segregated. PMID:24987116

  3. Commentary on "The Cerebellar System and What it Signifies from a Biological Perspective: A Communication by Christofredo Jakob (1866-1956) Before the Society of Neurology and Psychiatry of Buenos Aires, December 1938".

    PubMed

    Tzouma, Anny; Margulies, Daniel S; Triarhou, Lazaros C

    2016-08-01

    This commentary highlights a "cerebellar classic" by a pioneer of neurobiology, Christfried Jakob. Jakob discussed the connectivity between the cerebellum and mesencephalic, diencephalic, and telencephalic structures in an evolutionary, developmental, and histophysiological perspective. He proposed three evolutionary morphofunctional stages, the archicerebellar, paleocerebellar, and neocerebellar; he attributed the reduced cerebellospinal connections in humans, compared to other primates, to the perfection of the rubrolenticular and thalamocortical systems and the intense ascending pathways to the red nucleus in exchange for the more elementary descending efferent pathways. Jakob hypothesized the convergence of cerebellar pathways in associative cortical regions, insisting on the intimate collaboration of the cerebellum with the frontal lobe. The extensive lines of communication between regions throughout the association cortex substantiate Jakob's intuition and begin to outline the mechanisms for substantial cerebellar involvement in functions beyond the purely motor domain. Atop a foundation of anatomical and phylogenetic mastery, Jakob conceived ideas that were noteworthy, timely, and have much relevance to our current thinking on cerebellar structure and function.

  4. Functional characterization of p53 pathway components in the ancient metazoan Trichoplax adhaerens

    NASA Astrophysics Data System (ADS)

    Siau, Jia Wei; Coffill, Cynthia R.; Zhang, Weiyun Villien; Tan, Yaw Sing; Hundt, Juliane; Lane, David; Verma, Chandra; Ghadessy, Farid

    2016-09-01

    The identification of genes encoding a p53 family member and an Mdm2 ortholog in the ancient placozoan Trichoplax adhaerens advocates for the evolutionary conservation of a pivotal stress-response pathway observed in all higher eukaryotes. Here, we recapitulate several key functionalities ascribed to this known interacting protein pair by analysis of the placozoan proteins (Tap53 and TaMdm2) using both in vitro and cellular assays. In addition to interacting with each other, the Tap53 and TaMdm2 proteins are also able to respectively bind human Mdm2 and p53, providing strong evidence for functional conservation. The key p53-degrading function of Mdm2 is also conserved in TaMdm2. Tap53 retained DNA binding associated with p53 transcription activation function. However, it lacked transactivation function in reporter genes assays using a heterologous cell line, suggesting a cofactor incompatibility. Overall, the data supports functional roles for TaMdm2 and Tap53, and further defines the p53 pathway as an evolutionary conserved fulcrum mediating cellular response to stress.

  5. Use of game-theoretical methods in biochemistry and biophysics.

    PubMed

    Schuster, Stefan; Kreft, Jan-Ulrich; Schroeter, Anja; Pfeiffer, Thomas

    2008-04-01

    Evolutionary game theory can be considered as an extension of the theory of evolutionary optimisation in that two or more organisms (or more generally, units of replication) tend to optimise their properties in an interdependent way. Thus, the outcome of the strategy adopted by one species (e.g., as a result of mutation and selection) depends on the strategy adopted by the other species. In this review, the use of evolutionary game theory for analysing biochemical and biophysical systems is discussed. The presentation is illustrated by a number of instructive examples such as the competition between microorganisms using different metabolic pathways for adenosine triphosphate production, the secretion of extracellular enzymes, the growth of trees and photosynthesis. These examples show that, due to conflicts of interest, the global optimum (in the sense of being the best solution for the whole system) is not always obtained. For example, some yeast species use metabolic pathways that waste nutrients, and in a dense tree canopy, trees grow taller than would be optimal for biomass productivity. From the viewpoint of game theory, the examples considered can be described by the Prisoner's Dilemma, snowdrift game, Tragedy of the Commons and rock-scissors-paper game.

  6. Convergence, recurrence and diversification of complex sperm traits in diving beetles (Dytiscidae)

    PubMed Central

    Higginson, Dawn M.; Miller, Kelly B.; Segraves, Kari A.; Pitnick, Scott

    2013-01-01

    Sperm display remarkable morphological diversity among even closely related species, a pattern that is widely attributed to postcopulatory sexual selection. Surprisingly few studies have used phylogenetic analyses to discern the details of evolutionary diversification in ornaments and armaments subject to sexual selection, and the origins of novel sperm traits and their subsequent modification are particularly poorly understood. Here we investigate sperm evolution in diving beetles (Dytiscidae), revealing dramatic diversification in flagellum length, head shape, presence of sperm heteromorphism, and the presence/type of sperm conjugation, an unusual trait where two or more sperm unite for motility or transport. Sperm conjugation was found to be the ancestral condition in diving beetles, with subsequent diversification into three forms, each exhibiting varying degrees of evolutionary loss, convergence and recurrence. Sperm head shape, but not length or heteromorphism, was found to evolve in a significantly correlated manner with conjugation, consistent with the different mechanisms of head alignment and binding required for the different forms of conjugation. Our study reveals that sperm morphological evolution is channeled along particular evolutionary pathways (i.e., conjugate form), yet subject to considerable diversification within those pathways through modification in sperm length, head shape and heteromorphism. PMID:22519797

  7. On the Evolution of the Cardiac Pacemaker

    PubMed Central

    Burkhard, Silja; van Eif, Vincent; Garric, Laurence; Christoffels, Vincent M.; Bakkers, Jeroen

    2017-01-01

    The rhythmic contraction of the heart is initiated and controlled by an intrinsic pacemaker system. Cardiac contractions commence at very early embryonic stages and coordination remains crucial for survival. The underlying molecular mechanisms of pacemaker cell development and function are still not fully understood. Heart form and function show high evolutionary conservation. Even in simple contractile cardiac tubes in primitive invertebrates, cardiac function is controlled by intrinsic, autonomous pacemaker cells. Understanding the evolutionary origin and development of cardiac pacemaker cells will help us outline the important pathways and factors involved. Key patterning factors, such as the homeodomain transcription factors Nkx2.5 and Shox2, and the LIM-homeodomain transcription factor Islet-1, components of the T-box (Tbx), and bone morphogenic protein (Bmp) families are well conserved. Here we compare the dominant pacemaking systems in various organisms with respect to the underlying molecular regulation. Comparative analysis of the pathways involved in patterning the pacemaker domain in an evolutionary context might help us outline a common fundamental pacemaker cell gene programme. Special focus is given to pacemaker development in zebrafish, an extensively used model for vertebrate development. Finally, we conclude with a summary of highly conserved key factors in pacemaker cell development and function. PMID:29367536

  8. A Distance Measure for Genome Phylogenetic Analysis

    NASA Astrophysics Data System (ADS)

    Cao, Minh Duc; Allison, Lloyd; Dix, Trevor

    Phylogenetic analyses of species based on single genes or parts of the genomes are often inconsistent because of factors such as variable rates of evolution and horizontal gene transfer. The availability of more and more sequenced genomes allows phylogeny construction from complete genomes that is less sensitive to such inconsistency. For such long sequences, construction methods like maximum parsimony and maximum likelihood are often not possible due to their intensive computational requirement. Another class of tree construction methods, namely distance-based methods, require a measure of distances between any two genomes. Some measures such as evolutionary edit distance of gene order and gene content are computational expensive or do not perform well when the gene content of the organisms are similar. This study presents an information theoretic measure of genetic distances between genomes based on the biological compression algorithm expert model. We demonstrate that our distance measure can be applied to reconstruct the consensus phylogenetic tree of a number of Plasmodium parasites from their genomes, the statistical bias of which would mislead conventional analysis methods. Our approach is also used to successfully construct a plausible evolutionary tree for the γ-Proteobacteria group whose genomes are known to contain many horizontally transferred genes.

  9. Challenges of the information age: the impact of false discovery on pathway identification.

    PubMed

    Rog, Colin J; Chekuri, Srinivasa C; Edgerton, Mary E

    2012-11-21

    Pathways with members that have known relevance to a disease are used to support hypotheses generated from analyses of gene expression and proteomic studies. Using cancer as an example, the pitfalls of searching pathways databases as support for genes and proteins that could represent false discoveries are explored. The frequency with which networks could be generated from 100 instances each of randomly selected five and ten genes sets as input to MetaCore, a commercial pathways database, was measured. A PubMed search enumerated cancer-related literature published for any gene in the networks. Using three, two, and one maximum intervening step between input genes to populate the network, networks were generated with frequencies of 97%, 77%, and 7% using ten gene sets and 73%, 27%, and 1% using five gene sets. PubMed reported an average of 4225 cancer-related articles per network gene. This can be attributed to the richly populated pathways databases and the interest in the molecular basis of cancer. As information sources become enriched, they are more likely to generate plausible mechanisms for false discoveries.

  10. Endocrine regulation of predator-induced phenotypic plasticity.

    PubMed

    Dennis, Stuart R; LeBlanc, Gerald A; Beckerman, Andrew P

    2014-11-01

    Elucidating the developmental and genetic control of phenotypic plasticity remains a central agenda in evolutionary ecology. Here, we investigate the physiological regulation of phenotypic plasticity induced by another organism, specifically predator-induced phenotypic plasticity in the model ecological and evolutionary organism Daphnia pulex. Our research centres on using molecular tools to test among alternative mechanisms of developmental control tied to hormone titres, receptors and their timing in the life cycle. First, we synthesize detail about predator-induced defenses and the physiological regulation of arthropod somatic growth and morphology, leading to a clear prediction that morphological defences are regulated by juvenile hormone and life-history plasticity by ecdysone and juvenile hormone. We then show how a small network of genes can differentiate phenotype expression between the two primary developmental control pathways in arthropods: juvenoid and ecdysteroid hormone signalling. Then, by applying an experimental gradient of predation risk, we show dose-dependent gene expression linking predator-induced plasticity to the juvenoid hormone pathway. Our data support three conclusions: (1) the juvenoid signalling pathway regulates predator-induced phenotypic plasticity; (2) the hormone titre (ligand), rather than receptor, regulates predator-induced developmental plasticity; (3) evolution has favoured the harnessing of a major, highly conserved endocrine pathway in arthropod development to regulate the response to cues about changing environments (risk) from another organism (predator).

  11. The Molecular Ecophysiology of Programmed Cell Death in Marine Phytoplankton

    NASA Astrophysics Data System (ADS)

    Bidle, Kay D.

    2015-01-01

    Planktonic, prokaryotic, and eukaryotic photoautotrophs (phytoplankton) share a diverse and ancient evolutionary history, during which time they have played key roles in regulating marine food webs, biogeochemical cycles, and Earth's climate. Because phytoplankton represent the basis of marine ecosystems, the manner in which they die critically determines the flow and fate of photosynthetically fixed organic matter (and associated elements), ultimately constraining upper-ocean biogeochemistry. Programmed cell death (PCD) and associated pathway genes, which are triggered by a variety of nutrient stressors and are employed by parasitic viruses, play an integral role in determining the cell fate of diverse photoautotrophs in the modern ocean. Indeed, these multifaceted death pathways continue to shape the success and evolutionary trajectory of diverse phytoplankton lineages at sea. Research over the past two decades has employed physiological, biochemical, and genetic techniques to provide a novel, comprehensive, mechanistic understanding of the factors controlling this key process. Here, I discuss the current understanding of the genetics, activation, and regulation of PCD pathways in marine model systems; how PCD evolved in unicellular photoautotrophs; how it mechanistically interfaces with viral infection pathways; how stress signals are sensed and transduced into cellular responses; and how novel molecular and biochemical tools are revealing the impact of PCD genes on the fate of natural phytoplankton assemblages.

  12. Deep Evolutionary Comparison of Gene Expression Identifies Parallel Recruitment of Trans-Factors in Two Independent Origins of C4 Photosynthesis

    PubMed Central

    Kümpers, Britta M. C.; Smith-Unna, Richard D.; Hibberd, Julian M.

    2014-01-01

    With at least 60 independent origins spanning monocotyledons and dicotyledons, the C4 photosynthetic pathway represents one of the most remarkable examples of convergent evolution. The recurrent evolution of this highly complex trait involving alterations to leaf anatomy, cell biology and biochemistry allows an increase in productivity by ∼50% in tropical and subtropical areas. The extent to which separate lineages of C4 plants use the same genetic networks to maintain C4 photosynthesis is unknown. We developed a new informatics framework to enable deep evolutionary comparison of gene expression in species lacking reference genomes. We exploited this to compare gene expression in species representing two independent C4 lineages (Cleome gynandra and Zea mays) whose last common ancestor diverged ∼140 million years ago. We define a cohort of 3,335 genes that represent conserved components of leaf and photosynthetic development in these species. Furthermore, we show that genes encoding proteins of the C4 cycle are recruited into networks defined by photosynthesis-related genes. Despite the wide evolutionary separation and independent origins of the C4 phenotype, we report that these species use homologous transcription factors to both induce C4 photosynthesis and to maintain the cell specific gene expression required for the pathway to operate. We define a core molecular signature associated with leaf and photosynthetic maturation that is likely shared by angiosperm species derived from the last common ancestor of the monocotyledons and dicotyledons. We show that deep evolutionary comparisons of gene expression can reveal novel insight into the molecular convergence of highly complex phenotypes and that parallel evolution of trans-factors underpins the repeated appearance of C4 photosynthesis. Thus, exploitation of extant natural variation associated with complex traits can be used to identify regulators. Moreover, the transcription factors that are shared by independent C4 lineages are key targets for engineering the C4 pathway into C3 crops such as rice. PMID:24901697

  13. Genomicus 2018: karyotype evolutionary trees and on-the-fly synteny computing.

    PubMed

    Nguyen, Nga Thi Thuy; Vincens, Pierre; Roest Crollius, Hugues; Louis, Alexandra

    2018-01-04

    Since 2010, the Genomicus web server is available online at http://genomicus.biologie.ens.fr/genomicus. This graphical browser provides access to comparative genomic analyses in four different phyla (Vertebrate, Plants, Fungi, and non vertebrate Metazoans). Users can analyse genomic information from extant species, as well as ancestral gene content and gene order for vertebrates and flowering plants, in an integrated evolutionary context. New analyses and visualization tools have recently been implemented in Genomicus Vertebrate. Karyotype structures from several genomes can now be compared along an evolutionary pathway (Multi-KaryotypeView), and synteny blocks can be computed and visualized between any two genomes (PhylDiagView). © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. Crystal structure of the Alcanivorax borkumensis YdaH transporter reveals an unusual topology

    NASA Astrophysics Data System (ADS)

    Bolla, Jani Reddy; Su, Chih-Chia; Delmar, Jared A.; Radhakrishnan, Abhijith; Kumar, Nitin; Chou, Tsung-Han; Long, Feng; Rajashankar, Kanagalaghatta R.; Yu, Edward W.

    2015-04-01

    The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been clinically validated. However, many pathogens have developed resistance to these antibiotics, prompting a re-evaluation of potential drug targets within the pathway. The ydaH gene of Alcanivorax borkumensis encodes an integral membrane protein of the AbgT family of transporters for which no structural information was available. Here we report the crystal structure of A. borkumensis YdaH, revealing a dimeric molecule with an architecture distinct from other families of transporters. YdaH is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins that suggest a plausible pathway for substrate transport. Further analyses also suggest that YdaH could act as an antibiotic efflux pump and mediate bacterial resistance to sulfonamide antimetabolite drugs.

  15. Volvalerine A, an unprecedented N-containing sesquiterpenoid dimer derivative from Valeriana officinalis var. latifolia.

    PubMed

    Wang, Peng-Cheng; Ran, Xin-Hui; Luo, Huai-Rong; Ma, Qing-Yun; Zhou, Jun; Hu, Jiang-Miao; Zhao, You-Xing

    2016-03-01

    Volvalerine A (1), a novel N-containing bisesquiterpenoid derivative with a dihydroisoxazole ring, and its possible biosynthetic precursor, 1-hydroxy-1,11,11-trimethyldecahydrocyclopropane azulene-10-one (2), were isolated from the roots of Valeriana officinalis var. latifolia. Their structures and relative configurations were identified using spectroscopic data and X-ray crystallography. A plausible biosynthetic pathway for 1 is also presented. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. From ether to acid: A plausible degradation pathway of glycerol dialkyl glycerol tetraethers

    NASA Astrophysics Data System (ADS)

    Liu, Xiao-Lei; Birgel, Daniel; Elling, Felix J.; Sutton, Paul A.; Lipp, Julius S.; Zhu, Rong; Zhang, Chuanlun; Könneke, Martin; Peckmann, Jörn; Rowland, Steven J.; Summons, Roger E.; Hinrichs, Kai-Uwe

    2016-06-01

    Glycerol dialkyl glycerol tetraethers (GDGTs) are ubiquitous microbial lipids with extensive demonstrated and potential roles as paleoenvironmental proxies. Despite the great attention they receive, comparatively little is known regarding their diagenetic fate. Putative degradation products of GDGTs, identified as hydroxyl and carboxyl derivatives, were detected in lipid extracts of marine sediment, seep carbonate, hot spring sediment and cells of the marine thaumarchaeon Nitrosopumilus maritimus. The distribution of GDGT degradation products in environmental samples suggests that both biotic and abiotic processes act as sinks for GDGTs. More than a hundred newly recognized degradation products afford a view of the stepwise degradation of GDGT via (1) ether bond hydrolysis yielding hydroxyl isoprenoids, namely, GDGTol (glycerol dialkyl glycerol triether alcohol), GMGD (glycerol monobiphytanyl glycerol diether), GDD (glycerol dibiphytanol diether), GMM (glycerol monobiphytanol monoether) and bpdiol (biphytanic diol); (2) oxidation of isoprenoidal alcohols into corresponding carboxyl derivatives and (3) chain shortening to yield C39 and smaller isoprenoids. This plausible GDGT degradation pathway from glycerol ethers to isoprenoidal fatty acids provides the link to commonly detected head-to-head linked long chain isoprenoidal hydrocarbons in petroleum and sediment samples. The problematic C80 to C82 tetraacids that cause naphthenate deposits in some oil production facilities can be generated from H-shaped glycerol monoalkyl glycerol tetraethers (GMGTs) following the same process, as indicated by the distribution of related derivatives in hydrothermally influenced sediments.

  17. Crosstalk of Autophagy and the Secretory Pathway and Its Role in Diseases.

    PubMed

    Zahoor, Muhammad; Farhan, Hesso

    2018-01-01

    The secretory and autophagic pathways are two fundamental, evolutionary highly conserved endomembrane processes. Typically, secretion is associated with biosynthesis and delivery of proteins. In contrast, autophagy is usually considered as a degradative pathway. Thus, an analogy to metabolic pathways is evident. Anabolic (biosynthetic) and catabolic (degradative) pathways are usually intimately linked and intertwined, and likewise, the secretory and autophagy pathways are intertwined. Investigation of this link is an emerging area of research, and we will provide an overview of some of the major advances that have been made to contribute to understanding of how secretion regulates autophagy and vice versa. Finally, we will highlight evidence that supports a potential involvement of the autophagy-secretion crosstalk in human diseases. © 2018 Elsevier Inc. All rights reserved.

  18. Characterization of the Gaseous Companion k Andromedae B* New Keck and LBTI High-contrast Observations

    NASA Technical Reports Server (NTRS)

    Bonnefoy, M.; Currie, T.; Marleau, G.-D.; Schlieder, J. E.; Wisniewski, J.; Carson, J.; Covey, K. R.; Henning, T.; Biller, B.; Hinz, P.; hide

    2013-01-01

    Context. We previously reported the direct detection of a low mass companion at a projected separation of 55+/-2 astronomical units around the B9 type star kappa Andromedae. The properties of the system (mass ratio, separation) make it a benchmark for the understanding of the formation and evolution of gas giant planets and brown dwarfs on wide-orbits. Aims. We present new angular differential imaging (ADI) images of the system at 2.146 (K(sub s)), 3.776 (L'), 4.052 (NB 4.05) and 4.78 micrometers (M') obtained with Keck/NIRC2 and LBTI/LMIRCam, as well as more accurate near-infrared photometry of the star with the MIMIR instrument. We aim to determine the near-infrared spectral energy distribution (SED) of the companion and use it to characterize the object. Methods. We used analysis methods adapted to ADI to extract the companion flux. We compared the photometry of the object to reference young/old objects and to a set of seven PHOENIX-based atmospheric models of cool objects accounting for the formation of dust. We used evolutionary models to derive mass estimates considering a wide range of plausible initial conditions. Finally, we used dedicated formation models to discuss the possible origin of the companion. Results. We derive a more accurate J = 15.86 +/- 0.21, H = 14.95 +/- 0.13, K(sub s) = 14.32 +/- 0.09 mag for kappa And b. We redetect the companion in all our high contrast observations. We confirm previous contrasts obtained at K(sub s) and L' band. We derive NB 4.05 = 13.0 +/- 0.2 and M' = 13.3 +/- 0.3 mag and estimate Log(base 10)(L/solar luminosity) = -3.76 +/- 0.06. Atmospheric models yield T(sub eff) = 1900(+100/-200) K. They do not set constrains on the surface gravity. "Hot-start" evolutionary models predict masses of 14(+25/-2) Jupiter mass based on the luminosity and temperature estimates, and considering a conservative age range for the system (30(+120/-10) million years). "warm-start" evolutionary tracks constrain the mass to M greater than or equal to 11 Jupiter mass. Conclusions. The mass of kappa Andromedae b mostly falls in the brown-dwarf regime, due to remaining uncertainties in age and mass-luminosity models. According to the formation models, disk instability in a primordial disk could account for the position and a wide range of plausible masses of kappa and b.

  19. A conceptual framework for the evolutionary origins of multicellularity

    NASA Astrophysics Data System (ADS)

    Libby, Eric; Rainey, Paul B.

    2013-06-01

    The evolution of multicellular organisms from unicellular counterparts involved a transition in Darwinian individuality from single cells to groups. A particular challenge is to understand the nature of the earliest groups, the causes of their evolution, and the opportunities for emergence of Darwinian properties. Here we outline a conceptual framework based on a logical set of possible pathways for evolution of the simplest self-replicating groups. Central to these pathways is the recognition of a finite number of routes by which genetic information can be transmitted between individual cells and groups. We describe the form and organization of each primordial group state and consider factors affecting persistence and evolution of the nascent multicellular forms. Implications arising from our conceptual framework become apparent when attempting to partition fitness effects at individual and group levels. These are discussed with reference to the evolutionary emergence of individuality and its manifestation in extant multicellular life—including those of marginal Darwinian status.

  20. Understanding plant reproductive diversity.

    PubMed

    Barrett, Spencer C H

    2010-01-12

    Flowering plants display spectacular floral diversity and a bewildering array of reproductive adaptations that promote mating, particularly outbreeding. A striking feature of this diversity is that related species often differ in pollination and mating systems, and intraspecific variation in sexual traits is not unusual, especially among herbaceous plants. This variation provides opportunities for evolutionary biologists to link micro-evolutionary processes to the macro-evolutionary patterns that are evident within lineages. Here, I provide some personal reflections on recent progress in our understanding of the ecology and evolution of plant reproductive diversity. I begin with a brief historical sketch of the major developments in this field and then focus on three of the most significant evolutionary transitions in the reproductive biology of flowering plants: the pathway from outcrossing to predominant self-fertilization, the origin of separate sexes (females and males) from hermaphroditism and the shift from animal pollination to wind pollination. For each evolutionary transition, I consider what we have discovered and some of the problems that still remain unsolved. I conclude by discussing how new approaches might influence future research in plant reproductive biology.

  1. Methylome evolution in plants.

    PubMed

    Vidalis, Amaryllis; Živković, Daniel; Wardenaar, René; Roquis, David; Tellier, Aurélien; Johannes, Frank

    2016-12-20

    Despite major progress in dissecting the molecular pathways that control DNA methylation patterns in plants, little is known about the mechanisms that shape plant methylomes over evolutionary time. Drawing on recent intra- and interspecific epigenomic studies, we show that methylome evolution over long timescales is largely a byproduct of genomic changes. By contrast, methylome evolution over short timescales appears to be driven mainly by spontaneous epimutational events. We argue that novel methods based on analyses of the methylation site frequency spectrum (mSFS) of natural populations can provide deeper insights into the evolutionary forces that act at each timescale.

  2. Chitin in the Silk Gland Ducts of the Spider Nephila edulis and the Silkworm Bombyx mori

    PubMed Central

    Davies, Gwilym J. G.; Knight, David P.; Vollrath, Fritz

    2013-01-01

    Here we report the detection and localisation of chitin in the cuticle of the spinning ducts of both the spider Nephila edulis and the silkworm Bombyx mori. Our observations demonstrate that the duct walls of both animals contain chitin notwithstanding totally independent evolutionary pathways of the systems. We conclude that chitin may well be an essential component for the construction of spinning ducts; we further conclude that in both species chitin may indicate the evolutionary origin of the spinning ducts. PMID:24015298

  3. Phylum-wide comparative genomics unravel the diversity of secondary metabolism in Cyanobacteria

    DOE PAGES

    Calteau, Alexandra; Fewer, David P.; Latifi, Amel; ...

    2014-11-18

    Cyanobacteria are an ancient lineage of photosynthetic bacteria from which hundreds of natural products have been described, including many notorious toxins but also potent natural products of interest to the pharmaceutical and biotechnological industries. Many of these compounds are the products of non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) pathways. However, current understanding of the diversification of these pathways is largely based on the chemical structure of the bioactive compounds, while the evolutionary forces driving their remarkable chemical diversity are poorly understood. We carried out a phylum-wide investigation of genetic diversification of the cyanobacterial NRPS and PKS pathways formore » the production of bioactive compounds. 452 NRPS and PKS gene clusters were identified from 89 cyanobacterial genomes, revealing a clear burst in late-branching lineages. Our genomic analysis further grouped the clusters into 286 highly diversified cluster families (CF) of pathways. Some CFs appeared vertically inherited, while others presented a more complex evolutionary history. Only a few horizontal gene transfers were evidenced amongst strongly conserved CFs in the phylum, while several others have undergone drastic gene shuffling events, which could result in the observed diversification of the pathways. In addition to toxin production, several NRPS and PKS gene clusters are devoted to important cellular processes of these bacteria such as nitrogen fixation and iron uptake. The majority of the biosynthetic clusters identified here have unknown end products, highlighting the power of genome mining for the discovery of new natural products.« less

  4. Phylum-wide comparative genomics unravel the diversity of secondary metabolism in Cyanobacteria

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Calteau, Alexandra; Fewer, David P.; Latifi, Amel

    Cyanobacteria are an ancient lineage of photosynthetic bacteria from which hundreds of natural products have been described, including many notorious toxins but also potent natural products of interest to the pharmaceutical and biotechnological industries. Many of these compounds are the products of non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) pathways. However, current understanding of the diversification of these pathways is largely based on the chemical structure of the bioactive compounds, while the evolutionary forces driving their remarkable chemical diversity are poorly understood. We carried out a phylum-wide investigation of genetic diversification of the cyanobacterial NRPS and PKS pathways formore » the production of bioactive compounds. 452 NRPS and PKS gene clusters were identified from 89 cyanobacterial genomes, revealing a clear burst in late-branching lineages. Our genomic analysis further grouped the clusters into 286 highly diversified cluster families (CF) of pathways. Some CFs appeared vertically inherited, while others presented a more complex evolutionary history. Only a few horizontal gene transfers were evidenced amongst strongly conserved CFs in the phylum, while several others have undergone drastic gene shuffling events, which could result in the observed diversification of the pathways. In addition to toxin production, several NRPS and PKS gene clusters are devoted to important cellular processes of these bacteria such as nitrogen fixation and iron uptake. The majority of the biosynthetic clusters identified here have unknown end products, highlighting the power of genome mining for the discovery of new natural products.« less

  5. Reprogrammed Glucose Metabolic Pathways of Inhibitor-Tolerant Yeast

    USDA-ARS?s Scientific Manuscript database

    Representative inhibitory compounds such as furfural and 5-hydroxymethylfurfural generated from lignocellulosic biomass pretreatment inhibit yeast growth and interfere with the subsequent ethanol fermentation. Evolutionary engineering under laboratory settings is a powerful tool that can be used to ...

  6. Reprogrammed glucose metabolic pathways of inhibitor-tolerant yeast

    USDA-ARS?s Scientific Manuscript database

    Representative inhibitory compounds such as furfural and 5-hydroxymethylfurfural generated from lignocellulosic biomass pretreatment inhibit yeast growth and interfere with the subsequent ethanol fermentation. Evolutionary engineering under laboratory settings is a powerful tool that can be used to...

  7. Gramene database: navigating plant comparative genomics resources

    USDA-ARS?s Scientific Manuscript database

    Gramene (http://www.gramene.org) is an online, open source, curated resource for plant comparative genomics and pathway analysis designed to support researchers working in plant genomics, breeding, evolutionary biology, system biology, and metabolic engineering. It exploits phylogenetic relationship...

  8. Spatial competition and price formation

    NASA Astrophysics Data System (ADS)

    Nagel, Kai; Shubik, Martin; Paczuski, Maya; Bak, Per

    2000-12-01

    We look at price formation in a retail setting, that is, companies set prices, and consumers either accept prices or go someplace else. In contrast to most other models in this context, we use a two-dimensional spatial structure for information transmission, that is, consumers can only learn from nearest neighbors. Many aspects of this can be understood in terms of generalized evolutionary dynamics. In consequence, we first look at spatial competition and cluster formation without price. This leads to establishement size distributions, which we compare to reality. After some theoretical considerations, which at least heuristically explain our simulation results, we finally return to price formation, where we demonstrate that our simple model with nearly no organized planning or rationality on the part of any of the agents indeed leads to an economically plausible price.

  9. Synthesis of cytidine ribonucleotides by stepwise assembly of the heterocycle on a sugar phosphate.

    PubMed

    Ingar, Abdul-Aziz; Luke, Richard W A; Hayter, Barry R; Sutherland, John D

    2003-06-06

    Although various syntheses of the nucleic acid bases exist and ribose is a product of the formose reaction, no prebiotically plausible methods for attaching pyrimidine bases to ribose to give nucleosides have been described. Kinetic and thermodynamic factors are thought to mitigate against such condensation reactions in aqueous solution. This inability to produce pyrimidine nucleosides and hence nucleotides is a major stumbling block of the "RNA World" hypothesis and has led to suggestions of alternative nucleic acids as evolutionary precursors to RNA. Here, we show that a process in which the base is assembled in stages on a sugar phosphate can produce cytidine nucleotides. The sequential action of cyanamide and cyanoacetylene on arabinose-3-phosphate produces cytidine-2',3'-cyclophosphate and arabinocytidine-3'-phosphate.

  10. European freshwater vulnerability under high rates of global warming and plausible socio-economic narratives.

    NASA Astrophysics Data System (ADS)

    Koutroulis, Aristeidis; Papadimitriou, Lamprini; Grillakis, Manolis; Tsanis, Ioannis

    2017-04-01

    Recent developments could postpone climate actions in the frame of the global climate deal of the Paris Agreement, making higher-end global warming increasingly plausible. Although not clear in the COP21 water security is fundamental to achieving low-carbon ambitions, thus climate and water policies are closely related. The projection of the relationship between global warming, water availability and water stress through their complex interactions among different sectors, along with the synergies and trade-offs between adaptation and mitigation actions, is a rather challenging task under the prism of climate change. Here we try to develop and apply a simple, transparent conceptual framework describing European vulnerability to hydrological drought of current hydro-climatic and socioeconomic status as well as projected vulnerability at specific levels of global warming (1.5oC, 2oC and 4oC) following highly rates of climatic change (RCP8.5) and considering different levels of adaptation associated to specific socioeconomic pathways (SSP2, SSP3 and SSP5).

  11. A novel withanolide with an unprecedented carbon skeleton from Physalis angulata.

    PubMed

    Sun, Cheng-Peng; Kutateladze, Andrei G; Zhao, Feng; Chen, Li-Xia; Qiu, Feng

    2017-02-01

    A novel withanolide, aromaphysalin A (1), possessing an exceptional C(11)-C(15) bond and an unprecedented 4,9-cyclized aromatic ring (ring A), is isolated from stems and leaves of Physalis angulata L. Its structure was determined by a combination of HRESIMS, 2D NMR spectra, and theoretical calculations. Compound 1 exhibited inhibitory activity on NO production with an IC 50 value of 51.64 μM. A plausible biosynthetic pathway for 1 is also discussed.

  12. Penibruguieramine A, a novel pyrrolizidine alkaloid from the endophytic fungus Penicillium sp. GD6 associated with Chinese mangrove Bruguiera gymnorrhiza.

    PubMed

    Zhou, Zhen-Fang; Kurtán, Tibor; Yang, Xiao-Hong; Mándi, Attila; Geng, Mei-Yu; Ye, Bo-Ping; Taglialatela-Scafati, Orazio; Guo, Yue-Wei

    2014-03-07

    A novel pyrrolizidine alkaloid, penibruguieramine A (1), characterized by an unprecedented 1-alkenyl-2-methyl-8-hydroxymethylpyrrolizidin-3-one skeleton, was isolated from the endophytic fungus Penicillium sp. GD6, associated with the Chinese mangrove Bruguiera gymnorrhiza. The absolute configuration of penibruguieramine A (1) was established by TDDFT ECD calculations of the vacuum and solution conformers, exploiting the transitions of the lactam chromophore. A plausible pathway for its biosynthesis has been proposed.

  13. Non-24-hour sleep-wake syndrome following a car accident.

    PubMed

    Boivin, D B; James, F O; Santo, J B; Caliyurt, O; Chalk, C

    2003-06-10

    The authors report the case of a 39-year-old sighted woman who displayed non-24-hour sleep-wake cycles following a car accident. The phase relationship between endogenous circadian markers such as plasma melatonin and 6-sulfatoxymelatonin rhythms and self-selected sleep times was abnormal. A laboratory investigation indicated that she was sensitive to bright light as a circadian synchronizer. MRI and brain CT scans were normal, but microscopic brain damage in the vicinity of the suprachiasmatic nucleus or its output pathways is plausible.

  14. The Role of ERK1/2 in the Progression of Anti-Androgen Resistance of MtDNA Deficient Prostate Cancer

    DTIC Science & Technology

    2012-03-01

    proto-oncogenic pathway, it is plausible that the mitoGPS is a ubiquitous (patho) physiological response to the etiology and/or progression of a broad...the mitochondrion as a direct physiological source of hypoxia in an in vitro system. Our results demonstrate that the reduction of the mitochondrial...ubiquitous (patho) physiological response to the etiology and/or progression of a broad spectrum of human diseases that are attributed to respiratory

  15. Formation of nucleoside 5'-polyphosphates under potentially prebiological conditions

    NASA Technical Reports Server (NTRS)

    Lohrmann, R.

    1976-01-01

    The characteristics and efficiencies of biochemical reactions involving nucleoside 5'-diphosphates and -triphosphates (important substrates of RNA and DNA synthesis) under conditions corresponding to the primitive prebiotic earth are investigated. Urea catalysis of the formation of linear inorganic polyphosphates and metal ions promoting the reactions are discussed. Linear polyphosphate was incubated with Mg(++) in the presence of a nucleoside 5'-phosphate, to yield nucleoside 5'-polyphosphates when products are dried, while Mg(++) prompts depolymerization to trimetaphosphate in aqueous solutions. Plausible biogenetic pathways are examined.

  16. (+)- and (-)-Cajanusine, a pair of new enantiomeric stilbene dimers with a new skeleton from the leaves of Cajanus cajan.

    PubMed

    Li, Xiao-Long; Zhao, Bing-Xin; Huang, Xiao-Jun; Zhang, Dong-Mei; Jiang, Ren-Wang; Li, Ying-Jie; Jian, Yu-Qing; Wang, Ying; Li, Yao-Lan; Ye, Wen-Cai

    2014-01-03

    A pair of new enantiomeric stilbene dimers, (+)- and (-)-cajanusine [(+)-1 and (-)-1], with a unique coupling pattern were isolated from the leaves of Cajanus cajan . Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic and single-crystal X-ray diffraction analyses, as well as CD calculations. The plausible biogenetic pathway of 1 was also proposed. Additionally, (±)-1, (+)-1, and (-)-1 exhibited inhibitory activities on the growth of human hepatocellular carcinoma cells.

  17. Advanced Extravehicular Activity Breakout Group Summary

    NASA Technical Reports Server (NTRS)

    Kosmo, Joseph J.; Perka, Alan; Walz, Carl; Cobb, Sharon; Hanford, Anthony; Eppler, Dean

    2005-01-01

    This viewgraph document summarizes the workings of the Advanced Extravehicular Activity (AEVA) Breakout group in a Martian environment. The group was tasked with: identifying potential contaminants and pathways for AEVA systems with respect to forward and backward contamination; identifying plausible mitigation alternatives and obstacles for pertinent missions; identifying topics that require further research and technology development and discuss development strategies with uncertain Planetary Protection (PP) requirements; Identifying PP requirements that impose the greatest mission/development costs; Identifying PP requirements/topics that require further definition;

  18. Duplicated Female Receptacle Organs for Traumatic Insemination in the Tropical Bed Bug Cimex hemipterus: Adaptive Variation or Malformation?

    PubMed Central

    Kamimura, Yoshitaka; Mitsumoto, Hiroyuki; Lee, Chow-Yang

    2014-01-01

    During mating, male bed bugs (Cimicidae) pierce the female abdomen to inject sperm using their needle-like genitalia. Females evolved specialized paragenital organs (the spermalege and associated structures) to receive traumatically injected ejaculates. In Leptocimex duplicatus, the spermalege is duplicated, but the evolutionary significance of this is unclear. In Cimex hemipterus and C. lectularius, in which females normally develop a single spermalege on the right side of the abdomen, similar duplication sometimes occurs. Using these aberrant morphs (D-females) of C. hemipterus, we tested the hypothesis that both of the duplicated spermaleges are functionally competent. Scars on female abdominal exoskeletons indicated frequent misdirected piercing by male genitalia. However, the piercing sites showed a highly biased distribution towards the right side of the female body. A mating experiment showed that when the normal insemination site (the right-side spermalege) was artificially covered, females remained unfertilized. This was true even when females also had a spermalege on the left side (D-females). This result was attributed to handedness in male mating behavior. Irrespective of the observed disuse of the left-side spermalege by males for insemination, histological examination failed to detect any differences between the right-side and left-side spermaleges. Moreover, an artificial insemination experiment confirmed that spermatozoa injected into the left-side spermalege show apparently normal migration behavior to the female reproductive organs, indicating an evolutionary potential for functionally-competent duplicated spermaleges. We discuss possible mechanisms for the evolutionary maintenance of D-females and propose a plausible route to the functionally-competent duplicated spermaleges observed in L. duplicatus. PMID:24586643

  19. Pan-Genome Analysis Links the Hereditary Variation of Leptospirillum ferriphilum With Its Evolutionary Adaptation

    PubMed Central

    Zhang, Xian; Liu, Xueduan; Yang, Fei; Chen, Lv

    2018-01-01

    Niche adaptation has long been recognized to drive intra-species differentiation and speciation, yet knowledge about its relatedness with hereditary variation of microbial genomes is relatively limited. Using Leptospirillum ferriphilum species as a case study, we present a detailed analysis of genomic features of five recognized strains. Genome-to-genome distance calculation preliminarily determined the roles of spatial distance and environmental heterogeneity that potentially contribute to intra-species variation within L. ferriphilum species at the genome level. Mathematical models were further constructed to extrapolate the expansion of L. ferriphilum genomes (an ‘open’ pan-genome), indicating the emergence of novel genes with new sequenced genomes. The identification of diverse mobile genetic elements (MGEs) (such as transposases, integrases, and phage-associated genes) revealed the prevalence of horizontal gene transfer events, which is an important evolutionary mechanism that provides avenues for the recruitment of novel functionalities and further for the genetic divergence of microbial genomes. Comprehensive analysis also demonstrated that the genome reduction by gene loss in a broad sense might contribute to the observed diversification. We thus inferred a plausible explanation to address this observation: the community-dependent adaptation that potentially economizes the limiting resources of the entire community. Now that the introduction of new genes is accompanied by a parallel abandonment of some other ones, our results provide snapshots on the biological fitness cost of environmental adaptation within the L. ferriphilum genomes. In short, our genome-wide analyses bridge the relation between genetic variation of L. ferriphilum with its evolutionary adaptation. PMID:29636744

  20. The β-cyanoalanine synthase pathway: beyond cyanide detoxification.

    PubMed

    Machingura, Marylou; Salomon, Eitan; Jez, Joseph M; Ebbs, Stephen D

    2016-10-01

    Production of cyanide through biological and environmental processes requires the detoxification of this metabolic poison. In the 1960s, discovery of the β-cyanoalanine synthase (β-CAS) pathway in cyanogenic plants provided the first insight on cyanide detoxification in nature. Fifty years of investigations firmly established the protective role of the β-CAS pathway in cyanogenic plants and its role in the removal of cyanide produced from ethylene synthesis in plants, but also revealed the importance of this pathway for plant growth and development and the integration of nitrogen and sulfur metabolism. This review describes the β-CAS pathway, its distribution across and within higher plants, and the diverse biological functions of the pathway in cyanide assimilation, plant growth and development, stress tolerance, regulation of cyanide and sulfide signalling, and nitrogen and sulfur metabolism. The collective roles of the β-CAS pathway highlight its potential evolutionary and ecological importance in plants. © 2016 John Wiley & Sons Ltd.

  1. The origins of music in auditory scene analysis and the roles of evolution and culture in musical creation

    PubMed Central

    Trainor, Laurel J.

    2015-01-01

    Whether music was an evolutionary adaptation that conferred survival advantages or a cultural creation has generated much debate. Consistent with an evolutionary hypothesis, music is unique to humans, emerges early in development and is universal across societies. However, the adaptive benefit of music is far from obvious. Music is highly flexible, generative and changes rapidly over time, consistent with a cultural creation hypothesis. In this paper, it is proposed that much of musical pitch and timing structure adapted to preexisting features of auditory processing that evolved for auditory scene analysis (ASA). Thus, music may have emerged initially as a cultural creation made possible by preexisting adaptations for ASA. However, some aspects of music, such as its emotional and social power, may have subsequently proved beneficial for survival and led to adaptations that enhanced musical behaviour. Ontogenetic and phylogenetic evidence is considered in this regard. In particular, enhanced auditory–motor pathways in humans that enable movement entrainment to music and consequent increases in social cohesion, and pathways enabling music to affect reward centres in the brain should be investigated as possible musical adaptations. It is concluded that the origins of music are complex and probably involved exaptation, cultural creation and evolutionary adaptation. PMID:25646512

  2. The origins of music in auditory scene analysis and the roles of evolution and culture in musical creation.

    PubMed

    Trainor, Laurel J

    2015-03-19

    Whether music was an evolutionary adaptation that conferred survival advantages or a cultural creation has generated much debate. Consistent with an evolutionary hypothesis, music is unique to humans, emerges early in development and is universal across societies. However, the adaptive benefit of music is far from obvious. Music is highly flexible, generative and changes rapidly over time, consistent with a cultural creation hypothesis. In this paper, it is proposed that much of musical pitch and timing structure adapted to preexisting features of auditory processing that evolved for auditory scene analysis (ASA). Thus, music may have emerged initially as a cultural creation made possible by preexisting adaptations for ASA. However, some aspects of music, such as its emotional and social power, may have subsequently proved beneficial for survival and led to adaptations that enhanced musical behaviour. Ontogenetic and phylogenetic evidence is considered in this regard. In particular, enhanced auditory-motor pathways in humans that enable movement entrainment to music and consequent increases in social cohesion, and pathways enabling music to affect reward centres in the brain should be investigated as possible musical adaptations. It is concluded that the origins of music are complex and probably involved exaptation, cultural creation and evolutionary adaptation.

  3. Cancer Biomarkers from Genome-Scale DNA Methylation: Comparison of Evolutionary and Semantic Analysis Methods

    PubMed Central

    Valavanis, Ioannis; Pilalis, Eleftherios; Georgiadis, Panagiotis; Kyrtopoulos, Soterios; Chatziioannou, Aristotelis

    2015-01-01

    DNA methylation profiling exploits microarray technologies, thus yielding a wealth of high-volume data. Here, an intelligent framework is applied, encompassing epidemiological genome-scale DNA methylation data produced from the Illumina’s Infinium Human Methylation 450K Bead Chip platform, in an effort to correlate interesting methylation patterns with cancer predisposition and, in particular, breast cancer and B-cell lymphoma. Feature selection and classification are employed in order to select, from an initial set of ~480,000 methylation measurements at CpG sites, predictive cancer epigenetic biomarkers and assess their classification power for discriminating healthy versus cancer related classes. Feature selection exploits evolutionary algorithms or a graph-theoretic methodology which makes use of the semantics information included in the Gene Ontology (GO) tree. The selected features, corresponding to methylation of CpG sites, attained moderate-to-high classification accuracies when imported to a series of classifiers evaluated by resampling or blindfold validation. The semantics-driven selection revealed sets of CpG sites performing similarly with evolutionary selection in the classification tasks. However, gene enrichment and pathway analysis showed that it additionally provides more descriptive sets of GO terms and KEGG pathways regarding the cancer phenotypes studied here. Results support the expediency of this methodology regarding its application in epidemiological studies. PMID:27600245

  4. Assembly constraints drive co-evolution among ribosomal constituents.

    PubMed

    Mallik, Saurav; Akashi, Hiroshi; Kundu, Sudip

    2015-06-23

    Ribosome biogenesis, a central and essential cellular process, occurs through sequential association and mutual co-folding of protein-RNA constituents in a well-defined assembly pathway. Here, we construct a network of co-evolving nucleotide/amino acid residues within the ribosome and demonstrate that assembly constraints are strong predictors of co-evolutionary patterns. Predictors of co-evolution include a wide spectrum of structural reconstitution events, such as cooperativity phenomenon, protein-induced rRNA reconstitutions, molecular packing of different rRNA domains, protein-rRNA recognition, etc. A correlation between folding rate of small globular proteins and their topological features is known. We have introduced an analogous topological characteristic for co-evolutionary network of ribosome, which allows us to differentiate between rRNA regions subjected to rapid reconstitutions from those hindered by kinetic traps. Furthermore, co-evolutionary patterns provide a biological basis for deleterious mutation sites and further allow prediction of potential antibiotic targeting sites. Understanding assembly pathways of multicomponent macromolecules remains a key challenge in biophysics. Our study provides a 'proof of concept' that directly relates co-evolution to biophysical interactions during multicomponent assembly and suggests predictive power to identify candidates for critical functional interactions as well as for assembly-blocking antibiotic target sites. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Update of the human and mouse Fanconi anemia genes.

    PubMed

    Dong, Hongbin; Nebert, Daniel W; Bruford, Elspeth A; Thompson, David C; Joenje, Hans; Vasiliou, Vasilis

    2015-11-24

    Fanconi anemia (FA) is a recessively inherited disease manifesting developmental abnormalities, bone marrow failure, and increased risk of malignancies. Whereas FA has been studied for nearly 90 years, only in the last 20 years have increasing numbers of genes been implicated in the pathogenesis associated with this genetic disease. To date, 19 genes have been identified that encode Fanconi anemia complementation group proteins, all of which are named or aliased, using the root symbol "FANC." Fanconi anemia subtype (FANC) proteins function in a common DNA repair pathway called "the FA pathway," which is essential for maintaining genomic integrity. The various FANC mutant proteins contribute to distinct steps associated with FA pathogenesis. Herein, we provide a review update of the 19 human FANC and their mouse orthologs, an evolutionary perspective on the FANC genes, and the functional significance of the FA DNA repair pathway in association with clinical disorders. This is an example of a set of genes--known to exist in vertebrates, invertebrates, plants, and yeast--that are grouped together on the basis of shared biochemical and physiological functions, rather than evolutionary phylogeny, and have been named on this basis by the HUGO Gene Nomenclature Committee (HGNC).

  6. Terminal addition in a cellular world.

    PubMed

    Torday, J S; Miller, William B

    2018-07-01

    Recent advances in our understanding of evolutionary development permit a reframed appraisal of Terminal Addition as a continuous historical process of cellular-environmental complementarity. Within this frame of reference, evolutionary terminal additions can be identified as environmental induction of episodic adjustments to cell-cell signaling patterns that yield the cellular-molecular pathways that lead to differing developmental forms. Phenotypes derive, thereby, through cellular mutualistic/competitive niche constructions in reciprocating responsiveness to environmental stresses and epigenetic impacts. In such terms, Terminal Addition flows according to a logic of cellular needs confronting environmental challenges over space-time. A reconciliation of evolutionary development and Terminal Addition can be achieved through a combined focus on cell-cell signaling, molecular phylogenies and a broader understanding of epigenetic phenomena among eukaryotic organisms. When understood in this manner, Terminal Addition has an important role in evolutionary development, and chronic disease might be considered as a form of 'reverse evolution' of the self-same processes. Copyright © 2017. Published by Elsevier Ltd.

  7. Evolutionary game theory: cells as players.

    PubMed

    Hummert, Sabine; Bohl, Katrin; Basanta, David; Deutsch, Andreas; Werner, Sarah; Theissen, Günter; Schroeter, Anja; Schuster, Stefan

    2014-12-01

    In two papers we review game theory applications in biology below the level of cognitive living beings. It can be seen that evolution and natural selection replace the rationality of the actors appropriately. Even in these micro worlds, competing situations and cooperative relationships can be found and modeled by evolutionary game theory. Also those units of the lowest levels of life show different strategies for different environmental situations or different partners. We give a wide overview of evolutionary game theory applications to microscopic units. In this first review situations on the cellular level are tackled. In particular metabolic problems are discussed, such as ATP-producing pathways, secretion of public goods and cross-feeding. Further topics are cyclic competition among more than two partners, intra- and inter-cellular signalling, the struggle between pathogens and the immune system, and the interactions of cancer cells. Moreover, we introduce the theoretical basics to encourage scientists to investigate problems in cell biology and molecular biology by evolutionary game theory.

  8. Ecological divergence and evolutionary transition of resprouting types in Banksia attenuata.

    PubMed

    He, Tianhua

    2014-08-01

    Resprouting is a key functional trait that allows plants to survive diverse disturbances. The fitness benefits associated with resprouting include a rapid return to adult growth, early flowering, and setting seed. The resprouting responses observed following fire are varied, as are the ecological outcomes. Understanding the ecological divergence and evolutionary pathways of different resprouting types and how the environment and genetics interact to drive such morphological evolution represents an important, but under-studied, topic. In the present study, microsatellite markers and microevolutionary approaches were used to better understand: (1) whether genetic differentiation is related to morphological divergence among resprouting types and if so, whether there are any specific genetic variations associated with morphological divergence and (2) the evolutionary pathway of the transitions between two resprouting types in Banksia attenuata (epicormic resprouting from aerial stems or branch; resprouting from a underground lignotuber). The results revealed an association between population genetic differentiation and the morphological divergence of postfire resprouting types in B. attenuata. A microsatellite allele has been shown to be associated with epicormic populations. Approximate Bayesian Computation analysis revealed a likely evolutionary transition from epicormic to lignotuberous resprouting in B. attenuata. It is concluded that the postfire resprouting type in B. attenuata is likely determined by the fire's characteristics. The differentiated expression of postfire resprouting types in different environments is likely a consequence of local genetic adaptation. The capacity to shift the postfire resprouting type to adapt to diverse fire regimes is most likely the key factor explaining why B. attenuata is the most widespread member of the Banksia genus.

  9. Computational genomic identification and functional reconstitution of plant natural product biosynthetic pathways

    PubMed Central

    2016-01-01

    Covering: 2003 to 2016 The last decade has seen the first major discoveries regarding the genomic basis of plant natural product biosynthetic pathways. Four key computationally driven strategies have been developed to identify such pathways, which make use of physical clustering, co-expression, evolutionary co-occurrence and epigenomic co-regulation of the genes involved in producing a plant natural product. Here, we discuss how these approaches can be used for the discovery of plant biosynthetic pathways encoded by both chromosomally clustered and non-clustered genes. Additionally, we will discuss opportunities to prioritize plant gene clusters for experimental characterization, and end with a forward-looking perspective on how synthetic biology technologies will allow effective functional reconstitution of candidate pathways using a variety of genetic systems. PMID:27321668

  10. Patterns of genetic variability and habitat occupancy in Crepis triasii (Asteraceae) at different spatial scales: insights on evolutionary processes leading to diversification in continental islands

    PubMed Central

    Mayol, Maria; Palau, Carles; Rosselló, Josep A.; González-Martínez, Santiago C.; Molins, Arántzazu; Riba, Miquel

    2012-01-01

    Background and Aims Archipelagos are unique systems for studying evolutionary processes promoting diversification and speciation. The islands of the Mediterranean basin are major areas of plant richness, including a high proportion of narrow endemics. Many endemic plants are currently found in rocky habitats, showing varying patterns of habitat occupancy at different spatial scales throughout their range. The aim of the present study was to understand the impact of varying patterns of population distribution on genetic diversity and structure to shed light on demographic and evolutionary processes leading to population diversification in Crepis triasii, an endemic plant from the eastern Balearic Islands. Methods Using allozyme and chloroplast markers, we related patterns of genetic structure and diversity to those of habitat occupancy at a regional (between islands and among populations within islands) and landscape (population size and connectivity) scale. Key Results Genetic diversity was highly structured both at the regional and at the landscape level, and was positively correlated with population connectivity in the landscape. Populations located in small isolated mountains and coastal areas, with restricted patterns of regional occupancy, were genetically less diverse and much more differentiated. In addition, more isolated populations had stronger fine-scale genetic structure than well-connected ones. Changes in habitat availability and quality arising from marine transgressions during the Quaternary, as well as progressive fragmentation associated with the aridification of the climate since the last glaciation, are the most plausible factors leading to the observed patterns of genetic diversity and structure. Conclusions Our results emphasize the importance of gene flow in preventing genetic erosion and maintaining the evolutionary potential of populations. They also agree with recent studies highlighting the importance of restricted gene flow and genetic drift as drivers of plant evolution in Mediterranean continental islands. PMID:22167790

  11. Why are women so intelligent? The effect of maternal IQ on childhood mortality may be a relevant evolutionary factor.

    PubMed

    Charlton, Bruce G

    2010-03-01

    Humans are an unusual species because they exhibit an economic division of labour. Most theories concerning the evolution of specifically human intelligence have focused either on economic problems or sexual selection mechanisms, both of which apply more to men than women. Yet while there is evidence for men having a slightly higher average IQ, the sexual dimorphism of intelligence is not obvious (except at unusually high and low levels). However, a more female-specific selection mechanism concerns the distinctive maternal role in child care during the offspring's early years. It has been reported that increasing maternal intelligence is associated with reducing child mortality. This would lead to a greater level of reproductive success for intelligent women, and since intelligence is substantially heritable, this is a plausible mechanism by which natural selection might tend to increase female intelligence in humans. Any effect of maternal intelligence on improving child survival would likely be amplified by assortative mating for IQ by which people tend to marry others of similar intelligence - combining female maternal and male economic or sexual selection factors. Furthermore, since general intelligence seems to have the functional attribute of general purpose problem-solving and more rapid learning, the advantages of maternal IQ are likely to be greater as the environment for child-rearing is more different from the African hunter-gatherer society and savannah environment in which ancestral humans probably evolved. However, the effect of maternal IQ on child mortality would probably only be of major evolutionary significance in environments where childhood mortality rates were high. The modern situation is that population growth is determined mostly by birth rates; so in modern conditions, maternal intelligence may no longer have a significant effect on reproductive success; the effect of female IQ on reproductive success is often negative. Nonetheless, in the past it is plausible that the link between maternal IQ and child survival constituted a strong selection pressure acting specifically on women. Copyright (c) 2009. Published by Elsevier Ltd.

  12. Model framework for integrating multiple exposure pathways to chemicals in household cleaning products.

    PubMed

    Shin, H-M; McKone, T E; Bennett, D H

    2017-07-01

    We present a screening-level exposure-assessment method which integrates exposure from all plausible exposure pathways as a result of indoor residential use of cleaning products. The exposure pathways we considered are (i) exposure to a user during product use via inhalation and dermal, (ii) exposure to chemical residues left on clothing, (iii) exposure to all occupants from the portion released indoors during use via inhalation and dermal, and (iv) exposure to the general population due to down-the-drain disposal via inhalation and ingestion. We use consumer product volatilization models to account for the chemical fractions volatilized to air (f volatilized ) and disposed down the drain (f down-the-drain ) during product use. For each exposure pathway, we use a fate and exposure model to estimate intake rates (iR) in mg/kg/d. Overall, the contribution of the four exposure pathways to the total exposure varies by the type of cleaning activities and with chemical properties. By providing a more comprehensive exposure model and by capturing additional exposures from often-overlooked exposure pathways, our method allows us to compare the relative contribution of various exposure routes and could improve high-throughput exposure assessment for chemicals in cleaning products. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. JCoDA: a tool for detecting evolutionary selection.

    PubMed

    Steinway, Steven N; Dannenfelser, Ruth; Laucius, Christopher D; Hayes, James E; Nayak, Sudhir

    2010-05-27

    The incorporation of annotated sequence information from multiple related species in commonly used databases (Ensembl, Flybase, Saccharomyces Genome Database, Wormbase, etc.) has increased dramatically over the last few years. This influx of information has provided a considerable amount of raw material for evaluation of evolutionary relationships. To aid in the process, we have developed JCoDA (Java Codon Delimited Alignment) as a simple-to-use visualization tool for the detection of site specific and regional positive/negative evolutionary selection amongst homologous coding sequences. JCoDA accepts user-inputted unaligned or pre-aligned coding sequences, performs a codon-delimited alignment using ClustalW, and determines the dN/dS calculations using PAML (Phylogenetic Analysis Using Maximum Likelihood, yn00 and codeml) in order to identify regions and sites under evolutionary selection. The JCoDA package includes a graphical interface for Phylip (Phylogeny Inference Package) to generate phylogenetic trees, manages formatting of all required file types, and streamlines passage of information between underlying programs. The raw data are output to user configurable graphs with sliding window options for straightforward visualization of pairwise or gene family comparisons. Additionally, codon-delimited alignments are output in a variety of common formats and all dN/dS calculations can be output in comma-separated value (CSV) format for downstream analysis. To illustrate the types of analyses that are facilitated by JCoDA, we have taken advantage of the well studied sex determination pathway in nematodes as well as the extensive sequence information available to identify genes under positive selection, examples of regional positive selection, and differences in selection based on the role of genes in the sex determination pathway. JCoDA is a configurable, open source, user-friendly visualization tool for performing evolutionary analysis on homologous coding sequences. JCoDA can be used to rapidly screen for genes and regions of genes under selection using PAML. It can be freely downloaded at http://www.tcnj.edu/~nayaklab/jcoda.

  14. JCoDA: a tool for detecting evolutionary selection

    PubMed Central

    2010-01-01

    Background The incorporation of annotated sequence information from multiple related species in commonly used databases (Ensembl, Flybase, Saccharomyces Genome Database, Wormbase, etc.) has increased dramatically over the last few years. This influx of information has provided a considerable amount of raw material for evaluation of evolutionary relationships. To aid in the process, we have developed JCoDA (Java Codon Delimited Alignment) as a simple-to-use visualization tool for the detection of site specific and regional positive/negative evolutionary selection amongst homologous coding sequences. Results JCoDA accepts user-inputted unaligned or pre-aligned coding sequences, performs a codon-delimited alignment using ClustalW, and determines the dN/dS calculations using PAML (Phylogenetic Analysis Using Maximum Likelihood, yn00 and codeml) in order to identify regions and sites under evolutionary selection. The JCoDA package includes a graphical interface for Phylip (Phylogeny Inference Package) to generate phylogenetic trees, manages formatting of all required file types, and streamlines passage of information between underlying programs. The raw data are output to user configurable graphs with sliding window options for straightforward visualization of pairwise or gene family comparisons. Additionally, codon-delimited alignments are output in a variety of common formats and all dN/dS calculations can be output in comma-separated value (CSV) format for downstream analysis. To illustrate the types of analyses that are facilitated by JCoDA, we have taken advantage of the well studied sex determination pathway in nematodes as well as the extensive sequence information available to identify genes under positive selection, examples of regional positive selection, and differences in selection based on the role of genes in the sex determination pathway. Conclusions JCoDA is a configurable, open source, user-friendly visualization tool for performing evolutionary analysis on homologous coding sequences. JCoDA can be used to rapidly screen for genes and regions of genes under selection using PAML. It can be freely downloaded at http://www.tcnj.edu/~nayaklab/jcoda. PMID:20507581

  15. Investigation of Mechanistic Pathway for Trimethyl Borate Mediated Amidation of (R)-Mandelic Acid for the Synthesis of Mirabegron, an Antimuscarinic Agent.

    PubMed

    Deshmukh, Dattatray G; Bangal, Mukund N; Patekar, Mukunda R; Medhane, Vijay J; Mathad, Vijayavitthal Thippannachar

    2018-03-01

    The present work describes investigation of mechanistic pathway for trimethyl borate mediated amidation of (R)-mandelic acid (3) with 4-nitophenylethylamine (2) to provide (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide (4) during mirabegron synthesis. Plausible reaction mechanism is proposed by isolating and elucidating the active α-hydroxy ester intermediate 16 from the reaction mass. Trimethyl borate mediated approach proved to be selective in providing 4 without disturbing α-hydroxyl group and stereochemistry of the chiral center, and is also a greener, more economic and production friendly over the reported methods. The developed approach is rapid and efficient for the preparation of 4 with an overall yield of 85-87% and around 99.0% purity by HPLC at scale.

  16. Use of the University of Minnesota Biocatalysis/Biodegradation Database for study of microbial degradation

    PubMed Central

    2012-01-01

    Microorganisms are ubiquitous on earth and have diverse metabolic transformative capabilities important for environmental biodegradation of chemicals that helps maintain ecosystem and human health. Microbial biodegradative metabolism is the main focus of the University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD). UM-BBD data has also been used to develop a computational metabolic pathway prediction system that can be applied to chemicals for which biodegradation data is currently lacking. The UM-Pathway Prediction System (UM-PPS) relies on metabolic rules that are based on organic functional groups and predicts plausible biodegradative metabolism. The predictions are useful to environmental chemists that look for metabolic intermediates, for regulators looking for potential toxic products, for microbiologists seeking to understand microbial biodegradation, and others with a wide-range of interests. PMID:22587916

  17. DNA methylation as a potential mediator of environmental risks in the development of childhood acute lymphoblastic leukemia.

    PubMed

    Timms, Jessica A; Relton, Caroline L; Rankin, Judith; Strathdee, Gordon; McKay, Jill A

    2016-04-01

    5-year survival rate for childhood acute lymphoblastic leukemia (ALL) has risen to approximately 90%, yet the causal disease pathway is still poorly understood. Evidence suggests multiple 'hits' are required for disease progression; an initial genetic abnormality followed by additional secondary 'hits'. It is plausible that environmental influences may trigger these secondary hits, and with the peak incidence of diagnosis between 2 and 5 years of age, early life exposures are likely to be key. DNA methylation can be modified by many environmental exposures and is dramatically altered in cancers, including childhood ALL. Here we explore the potential that DNA methylation may be involved in the causal pathway toward disease by acting as a mediator between established environmental factors and childhood ALL development.

  18. Homeopathic drug discovery: theory update and methodological aspect.

    PubMed

    Khuda-Bukhsh, Anisur Rahman; Pathak, Surajit

    2008-08-01

    Homeopathy treats patient on the basis of totality of symptoms and is based on the principle of 'like cures like'. It uses ultra-low doses of highly diluted natural substances as remedies that originate from plants, minerals or animals. The objectives of this review are to discuss concepts, controversies and research related to understanding homeopathy in the light of modern science. Attempts have been made to focus on current views of homeopathy and to delineate its most plausible mechanism(s) of action. Although some areas of concern remain, research carried out so far both in vitro and in vivo validates the effects of highly diluted homeopathic medicines in a wide variety of organisms. The precise mechanism(s) and pathway(s) of action of highly diluted homeopathic drugs are still unknown.

  19. Evidence Theory Based Uncertainty Quantification in Radiological Risk due to Accidental Release of Radioactivity from a Nuclear Power Plant

    NASA Astrophysics Data System (ADS)

    Ingale, S. V.; Datta, D.

    2010-10-01

    Consequence of the accidental release of radioactivity from a nuclear power plant is assessed in terms of exposure or dose to the members of the public. Assessment of risk is routed through this dose computation. Dose computation basically depends on the basic dose assessment model and exposure pathways. One of the exposure pathways is the ingestion of contaminated food. The aim of the present paper is to compute the uncertainty associated with the risk to the members of the public due to the ingestion of contaminated food. The governing parameters of the ingestion dose assessment model being imprecise, we have approached evidence theory to compute the bound of the risk. The uncertainty is addressed by the belief and plausibility fuzzy measures.

  20. Heat in evolution's kitchen: evolutionary perspectives on the functions and origin of the facial pit of pitvipers (Viperidae: Crotalinae).

    PubMed

    Krochmal, Aaron R; Bakken, George S; LaDuc, Travis J

    2004-11-01

    Pitvipers (Viperidae: Crotalinae) possess thermal radiation receptors, the facial pits, which allow them to detect modest temperature fluctuations within their environments. It was previously thought that these organs were used solely to aid in prey acquisition, but recent findings demonstrated that western diamondback rattlesnakes (Crotalus atrox) use them to direct behavioral thermoregulation, suggesting that facial pits might be general purpose organs used to drive a suite of behaviors. To investigate this further, we conducted a phylogenetic survey of viperine thermoregulatory behavior cued by thermal radiation. We assessed this behavior in 12 pitviper species, representing key nodes in the evolution of pitvipers and a broad range of thermal environments, and a single species of true viper (Viperidae: Viperinae), a closely related subfamily of snakes that lack facial pits but possess a putative thermal radiation receptor. All pitviper species were able to rely on their facial pits to direct thermoregulatory movements, while the true viper was unable to do so. Our results suggest that thermoregulatory behavior cued by thermal radiation is a universal role of facial pits and probably represents an ancestral trait among pitvipers. Further, they establish behavioral thermoregulation as a plausible hypothesis explaining the evolutionary origin of the facial pit.

  1. Older fathers' children have lower evolutionary fitness across four centuries and in four populations

    PubMed Central

    Willführ, Kai P.; Frans, Emma M.; Verweij, Karin J. H.; Bürkner, Paul-Christian; Myrskylä, Mikko; Voland, Eckart; Zietsch, Brendan P.; Penke, Lars

    2017-01-01

    Higher paternal age at offspring conception increases de novo genetic mutations. Based on evolutionary genetic theory we predicted older fathers' children, all else equal, would be less likely to survive and reproduce, i.e. have lower fitness. In sibling control studies, we find support for negative paternal age effects on offspring survival and reproductive success across four large populations with an aggregate N > 1.4 million. Three populations were pre-industrial (1670–1850) Western populations and showed negative paternal age effects on infant survival and offspring reproductive success. In twentieth-century Sweden, we found minuscule paternal age effects on survival, but found negative effects on reproductive success. Effects survived tests for key competing explanations, including maternal age and parental loss, but effects varied widely over different plausible model specifications and some competing explanations such as diminishing paternal investment and epigenetic mutations could not be tested. We can use our findings to aid in predicting the effect increasingly older parents in today's society will have on their children's survival and reproductive success. To the extent that we succeeded in isolating a mutation-driven effect of paternal age, our results can be understood to show that de novo mutations reduce offspring fitness across populations and time periods. PMID:28904145

  2. Common liability to addiction and “gateway hypothesis”: Theoretical, empirical and evolutionary perspective

    PubMed Central

    Vanyukov, Michael M.; Tarter, Ralph E.; Kirillova, Galina P.; Kirisci, Levent; Reynolds, Maureen D.; Kreek, Mary Jeanne; Conway, Kevin P.; Maher, Brion S.; Iacono, William G.; Bierut, Laura; Neale, Michael C.; Clark, Duncan B.; Ridenour, Ty A.

    2013-01-01

    Background Two competing concepts address the development of involvement with psychoactive substances: the “gateway hypothesis” (GH) and common liability to addiction (CLA). Method The literature on theoretical foundations and empirical findings related to both concepts is reviewed. Results The data suggest that drug use initiation sequencing, the core GH element, is variable and opportunistic rather than uniform and developmentally deterministic. The association between risks for use of different substances, if any, can be more readily explained by common underpinnings than by specific staging. In contrast, the CLA concept is grounded in genetic theory and supported by data identifying common sources of variation in the risk for specific addictions. This commonality has identifiable neurobiological substrate and plausible evolutionary explanations. Conclusions Whereas the “gateway” hypothesis does not specify mechanistic connections between “stages”, and does not extend to the risks for addictions, the concept of common liability to addictions incorporates sequencing of drug use initiation as well as extends to related addictions and their severity, provides a parsimonious explanation of substance use and addiction co-occurrence, and establishes a theoretical and empirical foundation to research in etiology, quantitative risk and severity measurement, as well as targeted non-drug-specific prevention and early intervention. PMID:22261179

  3. The RNA world hypothesis: the worst theory of the early evolution of life (except for all the others)a

    PubMed Central

    2012-01-01

    The problems associated with the RNA world hypothesis are well known. In the following I discuss some of these difficulties, some of the alternative hypotheses that have been proposed, and some of the problems with these alternative models. From a biosynthetic – as well as, arguably, evolutionary – perspective, DNA is a modified RNA, and so the chicken-and-egg dilemma of “which came first?” boils down to a choice between RNA and protein. This is not just a question of cause and effect, but also one of statistical likelihood, as the chance of two such different types of macromolecule arising simultaneously would appear unlikely. The RNA world hypothesis is an example of a ‘top down’ (or should it be ‘present back’?) approach to early evolution: how can we simplify modern biological systems to give a plausible evolutionary pathway that preserves continuity of function? The discovery that RNA possesses catalytic ability provides a potential solution: a single macromolecule could have originally carried out both replication and catalysis. RNA – which constitutes the genome of RNA viruses, and catalyzes peptide synthesis on the ribosome – could have been both the chicken and the egg! However, the following objections have been raised to the RNA world hypothesis: (i) RNA is too complex a molecule to have arisen prebiotically; (ii) RNA is inherently unstable; (iii) catalysis is a relatively rare property of long RNA sequences only; and (iv) the catalytic repertoire of RNA is too limited. I will offer some possible responses to these objections in the light of work by our and other labs. Finally, I will critically discuss an alternative theory to the RNA world hypothesis known as ‘proteins first’, which holds that proteins either preceded RNA in evolution, or – at the very least – that proteins and RNA coevolved. I will argue that, while theoretically possible, such a hypothesis is probably unprovable, and that the RNA world hypothesis, although far from perfect or complete, is the best we currently have to help understand the backstory to contemporary biology. Reviewers This article was reviewed by Eugene Koonin, Anthony Poole and Michael Yarus (nominated by Laura Landweber). PMID:22793875

  4. Urotensin-II System in Genetic Control of Blood Pressure and Renal Function

    PubMed Central

    Debiec, Radoslaw; Christofidou, Paraskevi; Denniff, Matthew; Bloomer, Lisa D.; Bogdanski, Pawel; Wojnar, Lukasz; Musialik, Katarzyna; Charchar, Fadi J.; Thompson, John R.; Waterworth, Dawn; Song, Kijoung; Vollenweider, Peter; Waeber, Gerard; Zukowska-Szczechowska, Ewa; Samani, Nilesh J.; Lambert, David; Tomaszewski, Maciej

    2013-01-01

    Urotensin-II controls ion/water homeostasis in fish and vascular tone in rodents. We hypothesised that common genetic variants in urotensin-II pathway genes are associated with human blood pressure or renal function. We performed family-based analysis of association between blood pressure, glomerular filtration and genes of the urotensin-II pathway (urotensin-II, urotensin-II related peptide, urotensin-II receptor) saturated with 28 tagging single nucleotide polymorphisms in 2024 individuals from 520 families; followed by an independent replication in 420 families and 7545 unrelated subjects. The expression studies of the urotensin-II pathway were carried out in 97 human kidneys. Phylogenetic evolutionary analysis was conducted in 17 vertebrate species. One single nucleotide polymorphism (rs531485 in urotensin-II gene) was associated with adjusted estimated glomerular filtration rate in the discovery cohort (p = 0.0005). It showed no association with estimated glomerular filtration rate in the combined replication resource of 8724 subjects from 6 populations. Expression of urotensin-II and its receptor showed strong linear correlation (r = 0.86, p<0.0001). There was no difference in renal expression of urotensin-II system between hypertensive and normotensive subjects. Evolutionary analysis revealed accumulation of mutations in urotensin-II since the divergence of primates and weaker conservation of urotensin-II receptor in primates than in lower vertebrates. Our data suggest that urotensin-II system genes are unlikely to play a major role in genetic control of human blood pressure or renal function. The signatures of evolutionary forces acting on urotensin-II system indicate that it may have evolved towards loss of function since the divergence of primates. PMID:24391740

  5. Rainfall and temperatures changes have confounding impacts on Phytophthora cinnamomi occurrence risk in the southwestern USA under climate change scenarios.

    PubMed

    Thompson, Sally E; Levin, Simon; Rodriguez-Iturbe, Ignacio

    2014-04-01

    Global change will simultaneously impact many aspects of climate, with the potential to exacerbate the risks posed by plant pathogens to agriculture and the natural environment; yet, most studies that explore climate impacts on plant pathogen ranges consider individual climatic factors separately. In this study, we adopt a stochastic modeling approach to address multiple pathways by which climate can constrain the range of the generalist plant pathogen Phytophthora cinnamomi (Pc): through changing winter soil temperatures affecting pathogen survival; spring soil temperatures and thus pathogen metabolic rates; and changing spring soil moisture conditions and thus pathogen growth rates through host root systems. We apply this model to the southwestern USA for contemporary and plausible future climate scenarios and evaluate the changes in the potential range of Pc. The results indicate that the plausible range of this pathogen in the southwestern USA extends over approximately 200,000 km(2) under contemporary conditions. While warming temperatures as projected by the IPCC A2 and B1 emissions scenarios greatly expand the range over which the pathogen can survive winter, projected reductions in spring rainfall reduce its feasible habitat, leading to spatially complex patterns of changing risk. The study demonstrates that temperature and rainfall changes associated with possible climate futures in the southwestern USA have confounding impacts on the range of Pc, suggesting that projections of future pathogen dynamics and ranges should account for multiple pathways of climate-pathogen interaction. © 2014 John Wiley & Sons Ltd.

  6. Using ancient protein kinases to unravel a modern cancer drug's mechanism

    DOE PAGES

    Wilson, C.; Agafonov, R. V.; Hoemberger, M.; ...

    2015-02-19

    Macromolecular function is rooted in energy landscapes, where sequence determines not a single structure but an ensemble of conformations. Hence, evolution modifies a protein’s function by altering its energy landscape. Consequently, we recreate the evolutionary pathway between two modern human oncogenes, Src and Abl, by reconstructing their common ancestors. Our evolutionary reconstruction combined with x-ray structures of the common ancestor and pre–steady-state kinetics reveals a detailed atomistic mechanism for selectivity of the successful cancer drug Gleevec. Gleevec affinity is gained during the evolutionary trajectory toward Abl and lost toward Src, primarily by shifting an induced-fit equilibrium that is also disruptedmore » in the clinical T315I resistance mutation. Lastly, this work reveals the mechanism of Gleevec specificity while offering insights into how energy landscapes evolve.« less

  7. Wybutosine biosynthesis: Structural and mechanistic overview

    PubMed Central

    Perche-Letuvée, Phanélie; Molle, Thibaut; Forouhar, Farhad; Mulliez, Etienne; Atta, Mohamed

    2014-01-01

    Over the last 10 years, significant progress has been made in understanding the genetics, enzymology and structural components of the wybutosine (yW) biosynthetic pathway. These studies have played a key role in expanding our understanding of yW biosynthesis and have revealed unexpected evolutionary ties, which are presently being unraveled. The enzymes catalyzing the 5 steps of this pathway, from genetically encoded guanosine to wybutosine base, provide an ensemble of amazing reaction mechanisms that are to be discussed in this review article. PMID:25629788

  8. A hidden oncogenic positive feedback loop caused by crosstalk between Wnt and ERK pathways.

    PubMed

    Kim, D; Rath, O; Kolch, W; Cho, K-H

    2007-07-05

    The Wnt and the extracellular signal regulated-kinase (ERK) pathways are both involved in the pathogenesis of various kinds of cancers. Recently, the existence of crosstalk between Wnt and ERK pathways was reported. Gathering all reported results, we have discovered a positive feedback loop embedded in the crosstalk between the Wnt and ERK pathways. We have developed a plausible model that represents the role of this hidden positive feedback loop in the Wnt/ERK pathway crosstalk based on the integration of experimental reports and employing established basic mathematical models of each pathway. Our analysis shows that the positive feedback loop can generate bistability in both the Wnt and ERK signaling pathways, and this prediction was further validated by experiments. In particular, using the commonly accepted assumption that mutations in signaling proteins contribute to cancerogenesis, we have found two conditions through which mutations could evoke an irreversible response leading to a sustained activation of both pathways. One condition is enhanced production of beta-catenin, the other is a reduction of the velocity of MAP kinase phosphatase(s). This enables that high activities of Wnt and ERK pathways are maintained even without a persistent extracellular signal. Thus, our study adds a novel aspect to the molecular mechanisms of carcinogenesis by showing that mutational changes in individual proteins can cause fundamental functional changes well beyond the pathway they function in by a positive feedback loop embedded in crosstalk. Thus, crosstalk between signaling pathways provides a vehicle through which mutations of individual components can affect properties of the system at a larger scale.

  9. Programmed cell death as a defence against infection

    PubMed Central

    Jorgensen, Ine; Rayamajhi, Manira; Miao, Edward A.

    2017-01-01

    Eukaryotic cells can die from physical trauma, resulting in necrosis. Alternately, they can die via programmed cell death upon stimulation of specific signalling pathways. Here we discuss the utility of four cell death pathways in innate immune defence against bacterial and viral infection: apoptosis, necroptosis, pyroptosis and NETosis. We describe the interactions that interweave different programmed cell death pathways, which create complex signalling networks that cross-guard each other in the evolutionary arms race with pathogens. Finally, we describe how the resulting cell corpses — apoptotic bodies, pore-induced intracellular traps (PITs) and neutrophil extracellular traps (NETs) — promote clearance of infection. PMID:28138137

  10. A Genome Sequence-directed Investigation of D-Tagatose Utilization by Kosmotoga Olearia

    NASA Astrophysics Data System (ADS)

    Butzin, N. C.; Bradnan, D. M.; Noll, K. M.

    2010-04-01

    The research goals are to determine the pathway that Kosmotoga olearia uses tagatose, the roles of Kole_0686, Kole_0737 and Kole_1652 in this process, and the evolutionary history of the genes that encode the proteins involved in tagatose catabolism.

  11. Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat.

    PubMed

    Atanur, Santosh S; Diaz, Ana Garcia; Maratou, Klio; Sarkis, Allison; Rotival, Maxime; Game, Laurence; Tschannen, Michael R; Kaisaki, Pamela J; Otto, Georg W; Ma, Man Chun John; Keane, Thomas M; Hummel, Oliver; Saar, Kathrin; Chen, Wei; Guryev, Victor; Gopalakrishnan, Kathirvel; Garrett, Michael R; Joe, Bina; Citterio, Lorena; Bianchi, Giuseppe; McBride, Martin; Dominiczak, Anna; Adams, David J; Serikawa, Tadao; Flicek, Paul; Cuppen, Edwin; Hubner, Norbert; Petretto, Enrico; Gauguier, Dominique; Kwitek, Anne; Jacob, Howard; Aitman, Timothy J

    2013-08-01

    Large numbers of inbred laboratory rat strains have been developed for a range of complex disease phenotypes. To gain insights into the evolutionary pressures underlying selection for these phenotypes, we sequenced the genomes of 27 rat strains, including 11 models of hypertension, diabetes, and insulin resistance, along with their respective control strains. Altogether, we identified more than 13 million single-nucleotide variants, indels, and structural variants across these rat strains. Analysis of strain-specific selective sweeps and gene clusters implicated genes and pathways involved in cation transport, angiotensin production, and regulators of oxidative stress in the development of cardiovascular disease phenotypes in rats. Many of the rat loci that we identified overlap with previously mapped loci for related traits in humans, indicating the presence of shared pathways underlying these phenotypes in rats and humans. These data represent a step change in resources available for evolutionary analysis of complex traits in disease models. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Sex pheromone biosynthetic pathways are conserved between moths and the butterfly Bicyclus anynana

    PubMed Central

    Liénard, Marjorie A; Wang, Hong-Lei; Lassance, Jean-Marc; Löfstedt, Christer

    2014-01-01

    Although phylogenetically nested within the moths, butterflies have diverged extensively in a number of life history traits. Whereas moths rely greatly on chemical signals, visual advertisement is the hallmark of mate finding in butterflies. In the context of courtship, however, male chemical signals are widespread in both groups although they likely have multiple evolutionary origins. Here, we report that in males of the butterfly Bicyclus anynana, courtship scents are produced de novo via biosynthetic pathways shared with females of many moth species. We show that two of the pheromone components that play a major role in mate choice, namely the (Z)-9-tetradecenol and hexadecanal, are produced through the activity of a fatty acyl Δ11-desaturase and two specialized alcohol-forming fatty acyl reductases. Our study provides the first evidence of conservation and sharing of ancestral genetic modules for the production of FA-derived pheromones over a long evolutionary timeframe thereby reconciling mate communication in moths and butterflies. PMID:24862548

  13. Genome Sequencing Reveals Loci under Artificial Selection that Underlie Disease Phenotypes in the Laboratory Rat

    PubMed Central

    Atanur, Santosh S.; Diaz, Ana Garcia; Maratou, Klio; Sarkis, Allison; Rotival, Maxime; Game, Laurence; Tschannen, Michael R.; Kaisaki, Pamela J.; Otto, Georg W.; Ma, Man Chun John; Keane, Thomas M.; Hummel, Oliver; Saar, Kathrin; Chen, Wei; Guryev, Victor; Gopalakrishnan, Kathirvel; Garrett, Michael R.; Joe, Bina; Citterio, Lorena; Bianchi, Giuseppe; McBride, Martin; Dominiczak, Anna; Adams, David J.; Serikawa, Tadao; Flicek, Paul; Cuppen, Edwin; Hubner, Norbert; Petretto, Enrico; Gauguier, Dominique; Kwitek, Anne; Jacob, Howard; Aitman, Timothy J.

    2013-01-01

    Summary Large numbers of inbred laboratory rat strains have been developed for a range of complex disease phenotypes. To gain insights into the evolutionary pressures underlying selection for these phenotypes, we sequenced the genomes of 27 rat strains, including 11 models of hypertension, diabetes, and insulin resistance, along with their respective control strains. Altogether, we identified more than 13 million single-nucleotide variants, indels, and structural variants across these rat strains. Analysis of strain-specific selective sweeps and gene clusters implicated genes and pathways involved in cation transport, angiotensin production, and regulators of oxidative stress in the development of cardiovascular disease phenotypes in rats. Many of the rat loci that we identified overlap with previously mapped loci for related traits in humans, indicating the presence of shared pathways underlying these phenotypes in rats and humans. These data represent a step change in resources available for evolutionary analysis of complex traits in disease models. PaperClip PMID:23890820

  14. Impairment of learning and memory performances induced by BPA: Evidences from the literature of a MoA mediated through an ED.

    PubMed

    Mhaouty-Kodja, Sakina; Belzunces, Luc P; Canivenc, Marie-Chantal; Schroeder, Henri; Chevrier, Cécile; Pasquier, Elodie

    2018-03-29

    Many rodent studies and a few non-human primate data report impairments of spatial and non-spatial memory induced by exposure to bisphenol A (BPA), which are associated with neural modifications, particularly in processes involved in synaptic plasticity. BPA-induced alterations involve disruption of the estrogenic pathway as established by reversal of BPA-induced effects with estrogenic receptor antagonist or by interference of BPA with administered estradiol in ovariectomized animals. Sex differences in hormonal impregnation during critical periods of development and their influence on maturation of learning and memory processes may explain the sexual dimorphism observed in BPA-induced effects in some studies. Altogether, these data highly support the plausibility that alteration of learning and memory and synaptic plasticity by BPA is essentially mediated by disturbance of the estrogenic pathways. As memory function in humans involves similar signaling pathways, this mode of action of BPA has the potential to alter human cognitive abilities. Copyright © 2018. Published by Elsevier B.V.

  15. Crystal structure of the Alcanivorax borkumensis YdaH transporter reveals an unusual topology

    DOE PAGES

    Bolla, Jani Reddy; Su, Chih-Chia; Delmar, Jared A.; ...

    2015-04-20

    The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been clinically validated. However, many pathogens have developed resistance to these antibiotics, prompting a re-evaluation of potential drug targets within the pathway. The ydaH gene of Alcanivorax borkumensis encodes an integral membrane protein of the AbgT family of transporters for which no structural information was available. Here we report the crystal structure of A. borkumensis YdaH, revealing a dimeric molecule with an architecture distinct from other families of transporters. YdaH is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm tomore » halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins that suggest a plausible pathway for substrate transport. Further analyses also suggest that YdaH could act as an antibiotic efflux pump and mediate bacterial resistance to sulfonamide antimetabolite drugs.« less

  16. Changing shapes of glycogen-autophagy nexus in neurons: perspective from a rare epilepsy.

    PubMed

    Singh, Pankaj Kumar; Singh, Sweta

    2015-01-01

    In brain, glycogen metabolism is predominantly restricted to astrocytes but it also indirectly supports neuronal functions. Increased accumulation of glycogen in neurons is mysteriously pathogenic triggering neurodegeneration as seen in "Lafora disease" (LD) and in other transgenic animal models of neuronal glycogen accumulation. LD is a fatal neurodegenerative disorder with excessive glycogen inclusions in neurons. Autophagy, a pathway for bulk degradation of obsolete cellular constituents also degrades metabolites like lipid and glycogen. Recently, defects in this pathway emerged as a plausible reason for glycogen accumulation in neurons in LD, although some contradictions prevail. Albeit surprising, a reciprocal regulation of autophagy by glycogen in neurons has also just been proposed. Notably, increasing evidences of interaction between proteins of autophagy and glycogen metabolism from diverse model systems indicate a conserved, dynamic, and regulatory cross-talk between these two pathways. Concerning these findings, we herein provide certain models for the molecular basis of this cross-talk and discuss its potential implication in the pathophysiology of LD.

  17. Completion of biosynthetic pathways for bacteriochlorophyll g in Heliobacterium modesticaldum: The C8-ethylidene group formation.

    PubMed

    Tsukatani, Yusuke; Yamamoto, Haruki; Mizoguchi, Tadashi; Fujita, Yuichi; Tamiaki, Hitoshi

    2013-10-01

    Heliobacteria have the simplest photosynthetic apparatus, i.e., a type-I reaction center lacking a peripheral light-harvesting complex. Bacteriochlorophyll (BChl) g molecules are bound to the reaction center complex and work both as special-pair and antenna pigments. The C8-ethylidene group formation for BChl g is the last missing link in biosynthetic pathways for bacterial special-pair pigments, which include BChls a and b as well. Here, we report that chlorophyllide a oxidoreductase (COR) of Heliobacterium modesticaldum catalyzes the C8-ethylidene formation from 8-vinyl-chlorophyllide a, producing bacteriochlorophyllide g, the direct precursor for BChl g without the farnesyl tail. The finding led to plausible biosynthetic pathways for 8(1)-hydroxy-chlorophyll a, a primary electron acceptor from the special pair in heliobacterial reaction centers. Proposed catalytic mechanisms on hydrogenation reaction of the ethylidene synthase-type CORs are also discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Origin and thermal evolution of Mars

    NASA Technical Reports Server (NTRS)

    Schubert, Gerald; Soloman, S. C.; Turcotte, D. L.; Drake, M. J.; Sleep, N. H.

    1990-01-01

    The thermal evolution of Mars is governed by subsolidus mantle convection beneath a thick lithosphere. Models of the interior evolution are developed by parameterizing mantle convective heat transport in terms of mantle viscosity, the superadiabatic temperature rise across the mantle, and mantle heat production. Geological, geophysical, and geochemical observations of the compositon and structure of the interior and of the timing of major events in Martian evolution are used to constrain the model computations. Such evolutionary events include global differentiation, atmospheric outgassing, and the formation of the hemispherical dichotomy and Tharsis. Numerical calculations of fully three-dimensional, spherical convection in a shell the size of the Martian mantle are performed to explore plausible patterns of Martian mantel convection and to relate convective features, such as plumes, to surface features, such as Tharsis. The results from the model calculations are presented.

  19. On the Plausibility of Pseudosugar Formation in Cometary Ices and Oxygen-rich Tholins

    NASA Astrophysics Data System (ADS)

    Lavado, Nieves; Ávalos, Martín; Babiano, Reyes; Cintas, Pedro; Light, Mark E.; Jiménez, José Luis; Palacios, Juan C.

    2016-03-01

    We revisit herein the formation and structure of dihydroxy dioxanes, which can be obtained from prebiotically available precursors and can be regarded as primeval sugar surrogates. Previous studies dealing with the heterogeneous composition of interstellar bodies point to the existence of significant amounts of small polyalcohols along with oxygen-containing oligomers. Even though such derivatives did not give rise to nucleosides and oligonucleotides, nor they were incorporated into subsequent metabolic routes, molecular chimeras based on sugar-like species could be opportunistic scaffolds in pre-evolutionary scenarios. We could figure out that pseudosugars, assembled by hemiacetalic bonds from available precursors in both interstellar and terrestrial scenarios, were presumably more abundant than thought. Moreover, these species share some key features with naturally-occurring sugar rings, such as anomeric preferences, coordinating ability, and the prevalent occurrence of racemic compounds.

  20. Strangers With Benefits: Attraction to Outgroup Men Increases as Fertility Increases Across the Menstrual Cycle.

    PubMed

    Salvatore, Joseph F; Meltzer, Andrea L; March, David S; Gaertner, Lowell

    2017-02-01

    Research typically reveals that outgroups are regarded with disinterest at best and hatred and enmity at worst. Working from an evolutionary framework, we identify a unique pattern of outgroup attraction. The small-group lifestyle of pre-human ancestors plausibly limited access to genetically diverse mates. Ancestral females may have solved the inbreeding dilemma while balancing parental investment pressures by mating with outgroup males either via converting to an outgroup or cuckolding the ingroup. A vestige of those mating strategies might manifest in human women as a cyclic pattern of attraction across the menstrual cycle, such that attraction to outgroup men increases as fertility increases across the cycle. Two studies, one using a longitudinal method and the other an experimental method, evidenced the hypothesized linear relationship between attraction to outgroup men and fertility in naturally cycling women.

  1. Tubaramure, a Food-Assisted Integrated Health and Nutrition Program in Burundi, Increases Maternal and Child Hemoglobin Concentrations and Reduces Anemia: A Theory-Based Cluster-Randomized Controlled Intervention Trial.

    PubMed

    Leroy, Jef L; Olney, Deanna; Ruel, Marie

    2016-08-01

    Despite their popularity, food-assisted maternal and child health and nutrition (MCHN) programs have not been evaluated rigorously, and evidence of their impacts on maternal and child outcomes is scant. This study estimated the impact of Tubaramure, a food-assisted MCHN program implemented by Catholic Relief Services and partners in eastern Burundi, on hemoglobin and anemia (primary outcome) in children aged 0-23.9 mo and their mothers and explored the impact pathways. The program targeted women and their children during their first 1000 d of life and included 1) food rations, 2) strengthening and promotion of the use of health services, and 3) behavior change communication. This was a cluster-randomized controlled study to assess program impact by using cluster fixed-effects double-difference models with repeated cross-sectional data (baseline and follow-up 2 y later). We explored impact pathways by estimating impact on intermediary factors addressed by Tubaramure that are known determinants of hemoglobin and anemia and by regressing hemoglobin and anemia on each determinant to assess the plausibility that the effect operated through each determinant. Hemoglobin decreased and anemia increased markedly from baseline to follow-up, but Tubaramure had a significant (P < 0.05) beneficial effect on both children [6.1 percentage points (pps)] and mothers who had given birth in the previous 3 mo (34.9 pps). The program also had significant (P < 0.05) impacts on factors along the hypothesized impact pathways: dietary diversity, consumption of iron-rich foods, morbidity, and fever for child hemoglobin and dietary diversity, consumption of iron-rich foods, and current bed-net use for maternal anemia. We showed, for the first time to our knowledge, that a food-assisted MCHN program had a positive impact on anemia and hemoglobin in both mothers and children. The plausible pathways identified highlight the importance of addressing multiple determinants of anemia. This trial was registered at clinicaltrials.gov as NCT01072279. © 2016 American Society for Nutrition.

  2. A global evolutionary and metabolic analysis of human obesity gene risk variants.

    PubMed

    Castillo, Joseph J; Hazlett, Zachary S; Orlando, Robert A; Garver, William S

    2017-09-05

    It is generally accepted that the selection of gene variants during human evolution optimized energy metabolism that now interacts with our obesogenic environment to increase the prevalence of obesity. The purpose of this study was to perform a global evolutionary and metabolic analysis of human obesity gene risk variants (110 human obesity genes with 127 nearest gene risk variants) identified using genome-wide association studies (GWAS) to enhance our knowledge of early and late genotypes. As a result of determining the mean frequency of these obesity gene risk variants in 13 available populations from around the world our results provide evidence for the early selection of ancestral risk variants (defined as selection before migration from Africa) and late selection of derived risk variants (defined as selection after migration from Africa). Our results also provide novel information for association of these obesity genes or encoded proteins with diverse metabolic pathways and other human diseases. The overall results indicate a significant differential evolutionary pattern for the selection of obesity gene ancestral and derived risk variants proposed to optimize energy metabolism in varying global environments and complex association with metabolic pathways and other human diseases. These results are consistent with obesity genes that encode proteins possessing a fundamental role in maintaining energy metabolism and survival during the course of human evolution. Copyright © 2017. Published by Elsevier B.V.

  3. A System-Level Pathway-Phenotype Association Analysis Using Synthetic Feature Random Forest

    PubMed Central

    Pan, Qinxin; Hu, Ting; Malley, James D.; Andrew, Angeline S.; Karagas, Margaret R.; Moore, Jason H.

    2015-01-01

    As the cost of genome-wide genotyping decreases, the number of genome-wide association studies (GWAS) has increased considerably. However, the transition from GWAS findings to the underlying biology of various phenotypes remains challenging. As a result, due to its system-level interpretability, pathway analysis has become a popular tool for gaining insights on the underlying biology from high-throughput genetic association data. In pathway analyses, gene sets representing particular biological processes are tested for significant associations with a given phenotype. Most existing pathway analysis approaches rely on single-marker statistics and assume that pathways are independent of each other. As biological systems are driven by complex biomolecular interactions, embracing the complex relationships between single-nucleotide polymorphisms (SNPs) and pathways needs to be addressed. To incorporate the complexity of gene-gene interactions and pathway-pathway relationships, we propose a system-level pathway analysis approach, synthetic feature random forest (SF-RF), which is designed to detect pathway-phenotype associations without making assumptions about the relationships among SNPs or pathways. In our approach, the genotypes of SNPs in a particular pathway are aggregated into a synthetic feature representing that pathway via Random Forest (RF). Multiple synthetic features are analyzed using RF simultaneously and the significance of a synthetic feature indicates the significance of the corresponding pathway. We further complement SF-RF with pathway-based Statistical Epistasis Network (SEN) analysis that evaluates interactions among pathways. By investigating the pathway SEN, we hope to gain additional insights into the genetic mechanisms contributing to the pathway-phenotype association. We apply SF-RF to a population-based genetic study of bladder cancer and further investigate the mechanisms that help explain the pathway-phenotype associations using SEN. The bladder cancer associated pathways we found are both consistent with existing biological knowledge and reveal novel and plausible hypotheses for future biological validations. PMID:24535726

  4. Biofuels Fuels Technology Pathway Options for Advanced Drop-in Biofuels Production

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kevin L Kenney

    2011-09-01

    Advanced drop-in hydrocarbon biofuels require biofuel alternatives for refinery products other than gasoline. Candidate biofuels must have performance characteristics equivalent to conventional petroleum-based fuels. The technology pathways for biofuel alternatives also must be plausible, sustainable (e.g., positive energy balance, environmentally benign, etc.), and demonstrate a reasonable pathway to economic viability and end-user affordability. Viable biofuels technology pathways must address feedstock production and environmental issues through to the fuel or chemical end products. Potential end products include compatible replacement fuel products (e.g., gasoline, diesel, and JP8 and JP5 jet fuel) and other petroleum products or chemicals typically produced from a barrelmore » of crude. Considering the complexity and technology diversity of a complete biofuels supply chain, no single entity or technology provider is capable of addressing in depth all aspects of any given pathway; however, all the necessary expert entities exist. As such, we propose the assembly of a team capable of conducting an in-depth technology pathway options analysis (including sustainability indicators and complete LCA) to identify and define the domestic biofuel pathways for a Green Fleet. This team is not only capable of conducting in-depth analyses on technology pathways, but collectively they are able to trouble shoot and/or engineer solutions that would give industrial technology providers the highest potential for success. Such a team would provide the greatest possible down-side protection for high-risk advanced drop-in biofuels procurement(s).« less

  5. Physanolide A, a novel skeleton steroid, and other cytotoxic principles from Physalis angulata.

    PubMed

    Kuo, Ping-Chung; Kuo, Tsung-Hsiao; Damu, Amooru G; Su, Chung-Ren; Lee, E-Jian; Wu, Tian-Shung; Shu, Rexen; Chen, Chou-Ming; Bastow, Kenneth F; Chen, Tzu-Hsuan; Lee, Kuo-Hsiung

    2006-07-06

    [reaction: see text] A novel withasteroid, physanolide A (1), with an unprecedented skeleton containing a seven-membered ring, and two new physalins, physalins U (2) and V (3), were isolated from Physalis angulata. The structures were elucidated from spectroscopic analysis, and plausible biosynthetic pathways were postulated. Physalins B (4), D (5), and F (6) showed strong cytotoxicity against multiple tumor cell lines, including KB, A431, HCT-8, PC-3, and ZR751, with EC(50) values less than 4 microg/mL.

  6. Unprecedented 22,26-seco physalins from Physalis angulata and their anti-inflammatory potential.

    PubMed

    Sun, Cheng-Peng; Oppong, Mahmood Brobbey; Zhao, Feng; Chen, Li-Xia; Qiu, Feng

    2017-10-25

    Two novel physalins, including a 22,26-seco physalin, physalin X (1), and a 11,15-cyclo-9(10),14(17),22(26)-triseco physalin with an unprecedented aromatic ring, aromaphysalin B (2), were isolated from Physalis angulata L. Their structures were determined by IR, UV, HRESIMS, and 2D NMR spectra as well as theoretical calculations. Compounds 1 and 2 exhibited inhibitory activities on NO production with IC 50 values of 68.50 and 29.69 μM, respectively. A plausible biosynthetic pathway for 2 is also discussed.

  7. Guapsidial A and Guadials B and C: Three New Meroterpenoids with Unusual Skeletons from the Leaves of Psidium guajava.

    PubMed

    Jian, Yu-Qing; Huang, Xiao-Jun; Zhang, Dong-Mei; Jiang, Ren-Wang; Chen, Min-Feng; Zhao, Bing-Xin; Wang, Ying; Ye, Wen-Cai

    2015-06-15

    A novel sesquiterpene-based Psidium meroterpenoid, possessing an unusual coupling pattern, and two new monoterpene-based meroterpenoids with unprecedented skeletons were isolated from the leaves of Psidium guajava. Their structures and absolute configurations were elucidated by spectroscopic, X-ray diffraction, and computational methods. The plausible biosynthetic pathway of these meroterpenoids as well as their cytotoxicities toward HepG2 and HepG2/ADM cells were also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Sophopterocarpan A, a novel pterocarpine derivative with a benzotetrahydrofuran-fused bicyclo [3.3.1] nonane from Sophora flavescens.

    PubMed

    Zhu, Hui; Yang, Ya-Nan; Xu, Kuo; Xie, Jing; Feng, Zi-Ming; Jiang, Jian-Shuang; Zhang, Pei-Cheng

    2017-07-05

    Sophopterocarpan A (1), with a novel benzotetrahydrofuran-fused bicyclo [3.3.1] nonane ring, was isolated from the roots of Sophora flavescens Ait. Its unusual structure, including its stereochemistry, was determined on the basis of a comprehensive spectroscopic data analysis. A plausible biogenetic pathway for 1 is presented. Sophopterocarpan A was identified as a potential autophagy activator. Additionally, it was found that 1 exhibited cytotoxic activity in MCF-7 cells with an IC 50 of 29.36 μM.

  9. Origin of eukaryotes from within archaea, archaeal eukaryome and bursts of gene gain: eukaryogenesis just made easier?

    PubMed Central

    Koonin, Eugene V.

    2015-01-01

    The origin of eukaryotes is a fundamental, forbidding evolutionary puzzle. Comparative genomic analysis clearly shows that the last eukaryotic common ancestor (LECA) possessed most of the signature complex features of modern eukaryotic cells, in particular the mitochondria, the endomembrane system including the nucleus, an advanced cytoskeleton and the ubiquitin network. Numerous duplications of ancestral genes, e.g. DNA polymerases, RNA polymerases and proteasome subunits, also can be traced back to the LECA. Thus, the LECA was not a primitive organism and its emergence must have resulted from extensive evolution towards cellular complexity. However, the scenario of eukaryogenesis, and in particular the relationship between endosymbiosis and the origin of eukaryotes, is far from being clear. Four recent developments provide new clues to the likely routes of eukaryogenesis. First, evolutionary reconstructions suggest complex ancestors for most of the major groups of archaea, with the subsequent evolution dominated by gene loss. Second, homologues of signature eukaryotic proteins, such as actin and tubulin that form the core of the cytoskeleton or the ubiquitin system, have been detected in diverse archaea. The discovery of this ‘dispersed eukaryome’ implies that the archaeal ancestor of eukaryotes was a complex cell that might have been capable of a primitive form of phagocytosis and thus conducive to endosymbiont capture. Third, phylogenomic analyses converge on the origin of most eukaryotic genes of archaeal descent from within the archaeal evolutionary tree, specifically, the TACK superphylum. Fourth, evidence has been presented that the origin of the major archaeal phyla involved massive acquisition of bacterial genes. Taken together, these findings make the symbiogenetic scenario for the origin of eukaryotes considerably more plausible and the origin of the organizational complexity of eukaryotic cells more readily explainable than they appeared until recently. PMID:26323764

  10. God, the Devil, and Darwin - A Critique of Intelligent Design Theory

    NASA Astrophysics Data System (ADS)

    Shanks, Niall

    2007-03-01

    In the last fifteen years a controversial new theory of the origins of biological complexity and the nature of the universe has been fomenting bitter debates in education and science policy across North America, Europe, and Australia. Backed by intellectuals at respectable universities, Intelligent Design theory (ID) proposes an alternative to accepted accounts of evolutionary theory: that life is so complex, and that the universe is so fine-tuned for the appearance of life, that the only plausible explanation is the existence of an intelligent designer. For many ID theorists, the designer is taken to be the god of Christianity. Niall Shanks has written the first accessible introduction to, and critique of, this controversial new intellectual movement. Shanks locates the growth of ID in the last two decades of the twentieth century in the growing influence of the American religious right. But as he shows, its roots go back beyond Aquinas to Ancient Greece. After looking at the historical roots of ID, Shanks takes a hard look at its intellectual underpinnings, discussing modern understandings of thermodynamics, and how self-organizing processes lead to complex physical, chemical, and biological systems. He considers cosmological arguments for ID rooted in so-called "anthropic coincidences" and also tackles new biochemical arguments for ID based on "irreducible biological complexity." Throughout he shows how arguments for ID lack cohesion, rest on errors and unfounded suppositions, and generally are grossly inferior to evolutionary explanations. While ID has been proposed as a scientific alternative to evolutionary biology, Shanks argues that ID is in fact "old creationist wine in new designer label bottles" and moreover is a serious threat to the scientific and democratic values that are our cultural and intellectual inheritance from the Enlightenment.

  11. Exploring the Phenotypic Space and the Evolutionary History of a Natural Mutation in Drosophila melanogaster.

    PubMed

    Ullastres, Anna; Petit, Natalia; González, Josefa

    2015-07-01

    A major challenge of modern Biology is elucidating the functional consequences of natural mutations. Although we have a good understanding of the effects of laboratory-induced mutations on the molecular- and organismal-level phenotypes, the study of natural mutations has lagged behind. In this work, we explore the phenotypic space and the evolutionary history of a previously identified adaptive transposable element insertion. We first combined several tests that capture different signatures of selection to show that there is evidence of positive selection in the regions flanking FBti0019386 insertion. We then explored several phenotypes related to known phenotypic effects of nearby genes, and having plausible connections to fitness variation in nature. We found that flies with FBti0019386 insertion had a shorter developmental time and were more sensitive to stress, which are likely to be the adaptive effect and the cost of selection of this mutation, respectively. Interestingly, these phenotypic effects are not consistent with a role of FBti0019386 in temperate adaptation as has been previously suggested. Indeed, a global analysis of the population frequency of FBti0019386 showed that climatic variables explain well the FBti0019386 frequency patterns only in Australia. Finally, although FBti0019386 insertion could be inducing the formation of heterochromatin by recruiting HP1a (Heterochromatin Protein 1a) protein, the insertion is associated with upregulation of sra in adult females. Overall, our integrative approach allowed us to shed light on the evolutionary history, the relevant fitness effects, and the likely molecular mechanisms of an adaptive mutation and highlights the complexity of natural genetic variants. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  12. A "footprint" of plant carbon fixation cycle functions during the development of a heterotrophic fungus.

    PubMed

    Lyu, Xueliang; Shen, Cuicui; Xie, Jiatao; Fu, Yanping; Jiang, Daohong; Hu, Zijin; Tang, Lihua; Tang, Liguang; Ding, Feng; Li, Kunfei; Wu, Song; Hu, Yanping; Luo, Lilian; Li, Yuanhao; Wang, Qihua; Li, Guoqing; Cheng, Jiasen

    2015-08-11

    Carbon fixation pathway of plants (CFPP) in photosynthesis converts solar energy to biomass, bio-products and biofuel. Intriguingly, a large number of heterotrophic fungi also possess enzymes functionally associated with CFPP, raising the questions about their roles in fungal development and in evolution. Here, we report on the presence of 17 CFPP associated enzymes (ten in Calvin-Benson-Basham reductive pentose phosphate pathway and seven in C4-dicarboxylic acid cycle) in the genome of Sclerotinia sclerotiorum, a heterotrophic phytopathogenic fungus, and only two unique enzymes: ribulose-1, 5-bisphosphate carboxylase-oxygenase (Rubisco) and phosphoribulokinase (PRK) were absent. This data suggested an incomplete CFPP-like pathway (CLP) in fungi. Functional profile analysis demonstrated that the activity of the incomplete CLP was dramatically regulated during different developmental stages of S. sclerotiorum. Subsequent experiments confirmed that many of them were essential to the virulence and/or sclerotial formation. Most of the CLP associated genes are conserved in fungi. Phylogenetic analysis showed that many of them have undergone gene duplication, gene acquisition or loss and functional diversification in evolutionary history. These findings showed an evolutionary links in the carbon fixation processes of autotrophs and heterotrophs and implicated the functions of related genes were in course of continuous change in different organisms in evolution.

  13. Manipulation of Fgf and Bmp signaling in teleost fishes suggests potential pathways for the evolutionary origin of multicuspid teeth

    PubMed Central

    Jackman, William R; Davies, Shelby H; Lyons, David B; Stauder, Caitlin K; Denton-Schneider, Benjamin R; Jowdry, Andrea; Aigler, Sharon R; Vogel, Scott A; Stock, David W

    2014-01-01

    Teeth with two or more cusps have arisen independently from an ancestral unicuspid condition in a variety of vertebrate lineages, including sharks, teleost fishes, amphibians, lizards, and mammals. One potential explanation for the repeated origins of multicuspid teeth is the existence of multiple adaptive pathways leading to them, as suggested by their different uses in these lineages. Another is that the addition of cusps required only minor changes in genetic pathways regulating tooth development. Here we provide support for the latter hypothesis by demonstrating that manipulation of the levels of Fibroblast growth factor (Fgf) or Bone morphogenetic protein (Bmp) signaling produces bicuspid teeth in the zebrafish (Danio rerio), a species lacking multicuspid teeth in its ancestry. The generality of these results for teleosts is suggested by the conversion of unicuspid pharyngeal teeth into bicuspid teeth by similar manipulations of the Mexican Tetra (Astyanax mexicanus). That these manipulations also produced supernumerary teeth in both species supports previous suggestions of similarities in the molecular control of tooth and cusp number. We conclude that despite their apparent complexity, the evolutionary origin of multicuspid teeth is positively constrained, likely requiring only slight modifications of a pre-existing mechanism for patterning the number and spacing of individual teeth. PMID:25098636

  14. Manipulation of Fgf and Bmp signaling in teleost fishes suggests potential pathways for the evolutionary origin of multicuspid teeth.

    PubMed

    Jackman, William R; Davies, Shelby H; Lyons, David B; Stauder, Caitlin K; Denton-Schneider, Benjamin R; Jowdry, Andrea; Aigler, Sharon R; Vogel, Scott A; Stock, David W

    2013-01-01

    Teeth with two or more cusps have arisen independently from an ancestral unicuspid condition in a variety of vertebrate lineages, including sharks, teleost fishes, amphibians, lizards, and mammals. One potential explanation for the repeated origins of multicuspid teeth is the existence of multiple adaptive pathways leading to them, as suggested by their different uses in these lineages. Another is that the addition of cusps required only minor changes in genetic pathways regulating tooth development. Here we provide support for the latter hypothesis by demonstrating that manipulation of the levels of Fibroblast growth factor (Fgf) or Bone morphogenetic protein (Bmp) signaling produces bicuspid teeth in the zebrafish (Danio rerio), a species lacking multicuspid teeth in its ancestry. The generality of these results for teleosts is suggested by the conversion of unicuspid pharyngeal teeth into bicuspid teeth by similar manipulations of the Mexican Tetra (Astyanax mexicanus). That these manipulations also produced supernumerary teeth in both species supports previous suggestions of similarities in the molecular control of tooth and cusp number. We conclude that despite their apparent complexity, the evolutionary origin of multicuspid teeth is positively constrained, likely requiring only slight modifications of a pre-existing mechanism for patterning the number and spacing of individual teeth. © 2013 Wiley Periodicals, Inc.

  15. Understanding the function of bacterial and eukaryotic thiolases II by integrating evolutionary and functional approaches.

    PubMed

    Fox, Ana Romina; Soto, Gabriela; Mozzicafreddo, Matteo; Garcia, Araceli Nora; Cuccioloni, Massimiliano; Angeletti, Mauro; Salerno, Juan Carlos; Ayub, Nicolás Daniel

    2014-01-01

    Acetoacetyl-CoA thiolase (EC 2.3.1.9), commonly named thiolase II, condenses two molecules of acetyl-CoA to give acetoacetyl-CoA and CoA. This enzyme acts in anabolic processes as the first step in the biosynthesis of isoprenoids and polyhydroxybutyrate in eukaryotes and bacteria, respectively. We have recently reported the evolutionary and functional equivalence of these enzymes, suggesting that thiolase II could be the rate limiting enzyme in these pathways and presented evidence indicating that this enzyme modulates the availability of reducing equivalents during abiotic stress adaptation in bacteria and plants. However, these results are not sufficient to clarify why thiolase II was evolutionary selected as a critical enzyme in the production of antioxidant compounds. Regarding this intriguing topic, we propose that thiolase II could sense changes in the acetyl-CoA/CoA ratio induced by the inhibition of the tricarboxylic acid cycle under abiotic stress. Thus, the high level of evolutionary and functional constraint of thiolase II may be due to the connection of this enzyme with an ancient and conserved metabolic route. © 2013.

  16. Comparative Analysis of Evolutionary Mechanisms of the Hemagglutinin and Three Internal Protein Genes of Influenza B Virus: Multiple Cocirculating Lineages and Frequent Reassortment of the NP, M, and NS Genes

    PubMed Central

    Lindstrom, Stephen E.; Hiromoto, Yasuaki; Nishimura, Hidekazu; Saito, Takehiko; Nerome, Reiko; Nerome, Kuniaki

    1999-01-01

    Phylogenetic profiles of the genes coding for the hemagglutinin (HA) protein, nucleoprotein (NP), matrix (M) protein, and nonstructural (NS) proteins of influenza B viruses isolated from 1940 to 1998 were analyzed in a parallel manner in order to understand the evolutionary mechanisms of these viruses. Unlike human influenza A (H3N2) viruses, the evolutionary pathways of all four genes of recent influenza B viruses revealed similar patterns of genetic divergence into two major lineages. Although evolutionary rates of the HA, NP, M, and NS genes of influenza B viruses were estimated to be generally lower than those of human influenza A viruses, genes of influenza B viruses demonstrated complex phylogenetic patterns, indicating alternative mechanisms for generation of virus variability. Topologies of the evolutionary trees of each gene were determined to be quite distinct from one another, showing that these genes were evolving in an independent manner. Furthermore, variable topologies were apparently the result of frequent genetic exchange among cocirculating epidemic viruses. Evolutionary analysis done in the present study provided further evidence for cocirculation of multiple lineages as well as sequestering and reemergence of phylogenetic lineages of the internal genes. In addition, comparison of deduced amino acid sequences revealed a novel amino acid deletion in the HA1 domain of the HA protein of recent isolates from 1998 belonging to the B/Yamagata/16/88-like lineage. It thus became apparent that, despite lower evolutionary rates, influenza B viruses were able to generate genetic diversity among circulating viruses through a combination of evolutionary mechanisms involving cocirculating lineages and genetic reassortment by which new variants with distinct gene constellations emerged. PMID:10196339

  17. Modular electron transfer circuits for synthetic biology

    PubMed Central

    Agapakis, Christina M

    2010-01-01

    Electron transfer is central to a wide range of essential metabolic pathways, from photosynthesis to fermentation. The evolutionary diversity and conservation of proteins that transfer electrons makes these pathways a valuable platform for engineered metabolic circuits in synthetic biology. Rational engineering of electron transfer pathways containing hydrogenases has the potential to lead to industrial scale production of hydrogen as an alternative source of clean fuel and experimental assays for understanding the complex interactions of multiple electron transfer proteins in vivo. We designed and implemented a synthetic hydrogen metabolism circuit in Escherichia coli that creates an electron transfer pathway both orthogonal to and integrated within existing metabolism. The design of such modular electron transfer circuits allows for facile characterization of in vivo system parameters with applications toward further engineering for alternative energy production. PMID:21468209

  18. DNA methylation as a potential mediator of environmental risks in the development of childhood acute lymphoblastic leukemia

    PubMed Central

    Timms, Jessica A; Relton, Caroline L; Rankin, Judith; Strathdee, Gordon; McKay, Jill A

    2016-01-01

    5-year survival rate for childhood acute lymphoblastic leukemia (ALL) has risen to approximately 90%, yet the causal disease pathway is still poorly understood. Evidence suggests multiple ‘hits’ are required for disease progression; an initial genetic abnormality followed by additional secondary ‘hits’. It is plausible that environmental influences may trigger these secondary hits, and with the peak incidence of diagnosis between 2 and 5 years of age, early life exposures are likely to be key. DNA methylation can be modified by many environmental exposures and is dramatically altered in cancers, including childhood ALL. Here we explore the potential that DNA methylation may be involved in the causal pathway toward disease by acting as a mediator between established environmental factors and childhood ALL development. PMID:27035209

  19. Facial Affect Processing and Depression Susceptibility: Cognitive Biases and Cognitive Neuroscience

    ERIC Educational Resources Information Center

    Bistricky, Steven L.; Ingram, Rick E.; Atchley, Ruth Ann

    2011-01-01

    Facial affect processing is essential to social development and functioning and is particularly relevant to models of depression. Although cognitive and interpersonal theories have long described different pathways to depression, cognitive-interpersonal and evolutionary social risk models of depression focus on the interrelation of interpersonal…

  20. Untemplated nonenzymatic polymerization of 3',5'cGMP: a plausible route to 3',5'-linked oligonucleotides in primordia.

    PubMed

    Šponer, Judit E; Šponer, Jiří; Giorgi, Alessandra; Di Mauro, Ernesto; Pino, Samanta; Costanzo, Giovanna

    2015-02-19

    The high-energy 3',5' phosphodiester linkages conserved in 3',5' cyclic GMPs offer a genuine solution for monomer activation required by the transphosphorylation reactions that could lead to the emergence of the first simple oligonucleotide sequences on the early Earth. In this work we provide an in-depth characterization of the effect of the reaction conditions on the yield of the polymerization reaction of 3',5' cyclic GMPs both in aqueous environment as well as under dehydrating conditions. We show that the threshold temperature of the polymerization is about 30 °C lower under dehydrating conditions than in solution. In addition, we present a plausible exergonic reaction pathway for the polymerization reaction, which involves transient formation of anionic centers at the O3' positions of the participating riboses. We suggest that excess Na(+) cations inhibit the polymerization reaction because they block the anionic mechanism via neutralizing the negatively charged O3'. Our experimental findings are compatible with a prebiotic scenario, where gradual desiccation of the environment could induce polymerization of 3',5' cyclic GMPs synthesized in liquid.

  1. Mosaic Convergence of Rodent Dentitions

    PubMed Central

    Lazzari, Vincent; Charles, Cyril; Tafforeau, Paul; Vianey-Liaud, Monique; Aguilar, Jean-Pierre; Jaeger, Jean-Jacques; Michaux, Jacques; Viriot, Laurent

    2008-01-01

    Background Understanding mechanisms responsible for changes in tooth morphology in the course of evolution is an area of investigation common to both paleontology and developmental biology. Detailed analyses of molar tooth crown shape have shown frequent homoplasia in mammalian evolution, which requires accurate investigation of the evolutionary pathways provided by the fossil record. The necessity of preservation of an effective occlusion has been hypothesized to functionally constrain crown morphological changes and to also facilitate convergent evolution. The Muroidea superfamily constitutes a relevant model for the study of molar crown diversification because it encompasses one third of the extant mammalian biodiversity. Methodology/Principal Findings Combined microwear and 3D-topographic analyses performed on fossil and extant muroid molars allow for a first quantification of the relationships between changes in crown morphology and functionality of occlusion. Based on an abundant fossil record and on a well resolved phylogeny, our results show that the most derived functional condition associates longitudinal chewing and non interlocking of cusps. This condition has been reached at least 7 times within muroids via two main types of evolutionary pathways each respecting functional continuity. In the first type, the flattening of tooth crown which induces the removal of cusp interlocking occurs before the rotation of the chewing movement. In the second type however, flattening is subsequent to rotation of the chewing movement which can be associated with certain changes in cusp morphology. Conclusion/Significance The reverse orders of the changes involved in these different pathways reveal a mosaic evolution of mammalian dentition in which direction of chewing and crown shape seem to be partly decoupled. Either can change in respect to strong functional constraints affecting occlusion which thereby limit the number of the possible pathways. Because convergent pathways imply distinct ontogenetic trajectories, new Evo/Devo comparative studies on cusp morphogenesis are necessary. PMID:18974837

  2. Relative size of auditory pathways in symmetrically and asymmetrically eared owls.

    PubMed

    Gutiérrez-Ibáñez, Cristián; Iwaniuk, Andrew N; Wylie, Douglas R

    2011-01-01

    Owls are highly efficient predators with a specialized auditory system designed to aid in the localization of prey. One of the most unique anatomical features of the owl auditory system is the evolution of vertically asymmetrical ears in some species, which improves their ability to localize the elevational component of a sound stimulus. In the asymmetrically eared barn owl, interaural time differences (ITD) are used to localize sounds in azimuth, whereas interaural level differences (ILD) are used to localize sounds in elevation. These two features are processed independently in two separate neural pathways that converge in the external nucleus of the inferior colliculus to form an auditory map of space. Here, we present a comparison of the relative volume of 11 auditory nuclei in both the ITD and the ILD pathways of 8 species of symmetrically and asymmetrically eared owls in order to investigate evolutionary changes in the auditory pathways in relation to ear asymmetry. Overall, our results indicate that asymmetrically eared owls have much larger auditory nuclei than owls with symmetrical ears. In asymmetrically eared owls we found that both the ITD and ILD pathways are equally enlarged, and other auditory nuclei, not directly involved in binaural comparisons, are also enlarged. We suggest that the hypertrophy of auditory nuclei in asymmetrically eared owls likely reflects both an improved ability to precisely locate sounds in space and an expansion of the hearing range. Additionally, our results suggest that the hypertrophy of nuclei that compute space may have preceded that of the expansion of the hearing range and evolutionary changes in the size of the auditory system occurred independently of phylogeny. Copyright © 2011 S. Karger AG, Basel.

  3. Large-Scale Evolutionary Analysis of Genes and Supergene Clusters from Terpenoid Modular Pathways Provides Insights into Metabolic Diversification in Flowering Plants

    PubMed Central

    Hofberger, Johannes A.; Ramirez, Aldana M.; van den Bergh, Erik; Zhu, Xinguang; Bouwmeester, Harro J.; Schuurink, Robert C.; Schranz, M. Eric

    2015-01-01

    An important component of plant evolution is the plethora of pathways producing more than 200,000 biochemically diverse specialized metabolites with pharmacological, nutritional and ecological significance. To unravel dynamics underlying metabolic diversification, it is critical to determine lineage-specific gene family expansion in a phylogenomics framework. However, robust functional annotation is often only available for core enzymes catalyzing committed reaction steps within few model systems. In a genome informatics approach, we extracted information from early-draft gene-space assemblies and non-redundant transcriptomes to identify protein families involved in isoprenoid biosynthesis. Isoprenoids comprise terpenoids with various roles in plant-environment interaction, such as pollinator attraction or pathogen defense. Combining lines of evidence provided by synteny, sequence homology and Hidden-Markov-Modelling, we screened 17 genomes including 12 major crops and found evidence for 1,904 proteins associated with terpenoid biosynthesis. Our terpenoid genes set contains evidence for 840 core terpene-synthases and 338 triterpene-specific synthases. We further identified 190 prenyltransferases, 39 isopentenyl-diphosphate isomerases as well as 278 and 219 proteins involved in mevalonate and methylerithrol pathways, respectively. Assessing the impact of gene and genome duplication to lineage-specific terpenoid pathway expansion, we illustrated key events underlying terpenoid metabolic diversification within 250 million years of flowering plant radiation. By quantifying Angiosperm-wide versatility and phylogenetic relationships of pleiotropic gene families in terpenoid modular pathways, our analysis offers significant insight into evolutionary dynamics underlying diversification of plant secondary metabolism. Furthermore, our data provide a blueprint for future efforts to identify and more rapidly clone terpenoid biosynthetic genes from any plant species. PMID:26046541

  4. Comprehensive analysis of the flowering genes in Chinese cabbage and examination of evolutionary pattern of CO-like genes in plant kingdom

    NASA Astrophysics Data System (ADS)

    Song, Xiaoming; Duan, Weike; Huang, Zhinan; Liu, Gaofeng; Wu, Peng; Liu, Tongkun; Li, Ying; Hou, Xilin

    2015-09-01

    In plants, flowering is the most important transition from vegetative to reproductive growth. The flowering patterns of monocots and eudicots are distinctly different, but few studies have described the evolutionary patterns of the flowering genes in them. In this study, we analysed the evolutionary pattern, duplication and expression level of these genes. The main results were as follows: (i) characterization of flowering genes in monocots and eudicots, including the identification of family-specific, orthologous and collinear genes; (ii) full characterization of CONSTANS-like genes in Brassica rapa (BraCOL genes), the key flowering genes; (iii) exploration of the evolution of COL genes in plant kingdom and construction of the evolutionary pattern of COL genes; (iv) comparative analysis of CO and FT genes between Brassicaceae and Grass, which identified several family-specific amino acids, and revealed that CO and FT protein structures were similar in B. rapa and Arabidopsis but different in rice; and (v) expression analysis of photoperiod pathway-related genes in B. rapa under different photoperiod treatments by RT-qPCR. This analysis will provide resources for understanding the flowering mechanisms and evolutionary pattern of COL genes. In addition, this genome-wide comparative study of COL genes may also provide clues for evolution of other flowering genes.

  5. A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure

    NASA Astrophysics Data System (ADS)

    Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

    2016-05-01

    Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

  6. A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure.

    PubMed

    Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

    2016-05-17

    Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

  7. Phylogeography and population structure of the Reevese's Butterfly Lizard (Leiolepis reevesii) inferred from mitochondrial DNA sequences.

    PubMed

    Lin, Long-Hui; Ji, Xiang; Diong, Cheong-Hoong; Du, Yu; Lin, Chi-Xian

    2010-08-01

    Butterfly lizards of the genus Leiolepis (Agamidae) are widely distributed in coastal regions of Southeast Asia and South China, with the Reevese's Butterfly Lizard Leiolepis reevesii having a most northerly distribution that ranges from Vietnam to South China. To assess the genetic diversity within L. reevesii, and its population structure and evolutionary history, we sequenced 1004 bp of cytochrome b for 448 individuals collected from 28 localities covering almost the whole range of the lizard. One hundred and forty variable sites were observed, and 93 haplotypes were defined. We identified three genetically distinct clades, of which Clade A includes haplotypes mainly from southeastern Hainan, Clade B from Guangdong and northern Hainan, and Clade C from Vietnam and the other localities of China. Clade A was well distinguished and divergent from the other two. The Wuzhishan and Yinggeling mountain ranges were important barriers limiting gene exchange between populations on the both sides of the mountain series, whereas the Gulf of Tonkin and the Qiongzhou Strait were not. One plausible scenario to explain our genetic data is a historical dispersion of L. reevesii as proceeding from Vietnam to Hainan, followed by a second wave of dispersal from Hainan to Guangdong and Guangxi. Another equally plausible scenario is a historically widespread population that has been structured by vicariant factors such as the mountains in Hainan and sea level fluctuations. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Effect of curcumin on aged Drosophila melanogaster: a pathway prediction analysis.

    PubMed

    Zhang, Zhi-guo; Niu, Xu-yan; Lu, Ai-ping; Xiao, Gary Guishan

    2015-02-01

    To re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin. Microarray data generated from other study aiming to investigate effect of curcumin on extending lifespan of Drosophila melanogaster were further used for pathway prediction analysis. The differentially expressed genes were identified by using GeneSpring GX with a criterion of 3.0-fold change. Two Cytoscape plugins including BisoGenet and molecular complex detection (MCODE) were used to establish the protein-protein interaction (PPI) network based upon differential genes in order to detect highly connected regions. The function annotation clustering tool of Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for pathway analysis. A total of 87 genes expressed differentially in D. melanogaster melanogaster treated with curcumin were identified, among which 50 were up-regulated significantly and 37 were remarkably down-regulated in D. melanogaster melanogaster treated with curcumin. Based upon these differential genes, PPI network was constructed with 1,082 nodes and 2,412 edges. Five highly connected regions in PPI networks were detected by MCODE algorithm, suggesting anti-aging effect of curcumin may be underlined through five different pathways including Notch signaling pathway, basal transcription factors, cell cycle regulation, ribosome, Wnt signaling pathway, and p53 pathway. Genes and their associated pathways in D. melanogaster melanogaster treated with anti-aging agent curcumin were identified using PPI network and MCODE algorithm, suggesting that curcumin may be developed as an alternative therapeutic medicine for treating aging-associated diseases.

  9. The origins of religious disbelief.

    PubMed

    Norenzayan, Ara; Gervais, Will M

    2013-01-01

    Although most people are religious, there are hundreds of millions of religious disbelievers in the world. What is religious disbelief and how does it arise? Recent developments in the scientific study of religious beliefs and behaviors point to the conclusion that religious disbelief arises from multiple interacting pathways, traceable to cognitive, motivational, and cultural learning mechanisms. We identify four such pathways, leading to four distinct forms of atheism, which we term mindblind atheism, apatheism, inCREDulous atheism, and analytic atheism. Religious belief and disbelief share the same underlying pathways and can be explained within a single evolutionary framework that is grounded in both genetic and cultural evolution. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Effects of a Protic Ionic Liquid on the Reaction Pathway during Non-Aqueous Sol–Gel Synthesis of Silica: A Raman Spectroscopic Investigation

    PubMed Central

    Martinelli, Anna

    2014-01-01

    The reaction pathway during the formation of silica via a two-component “non-aqueou” sol-gel synthesis is studied by in situ time-resolved Raman spectroscopy. This synthetic route is followed with and without the addition of the protic ionic liquid 1-ethylimidazolium bis(trifluoromethanesulfonyl)imide (C2HImTFSI) in order to investigate its effect on the reaction pathway. We demonstrate that Raman spectroscopy is suitable to discriminate between different silica intermediates, which are produced and consumed at different rates with respect to the point of gelation. We find that half-way to gelation monomers and shorter chains are the most abundant silica species, while the formation of silica rings strongly correlates to the sol-to-gel transition. Thus, curling up of linear chains is here proposed as a plausible mechanism for the formation of small rings. These in turn act as nucleation sites for the condensation of larger rings and thus the formation of the open and polymeric silica network. We find that the protic ionic liquid does not change the reaction pathway per se, but accelerates the cyclization process, intermediated by the faster inclusion of monomeric species. PMID:24743891

  11. Development of an algorithm to provide awareness in choosing study designs for inclusion in systematic reviews of healthcare interventions: a method study

    PubMed Central

    Peinemann, Frank; Kleijnen, Jos

    2015-01-01

    Objectives To develop an algorithm that aims to provide guidance and awareness for choosing multiple study designs in systematic reviews of healthcare interventions. Design Method study: (1) To summarise the literature base on the topic. (2) To apply the integration of various study types in systematic reviews. (3) To devise decision points and outline a pragmatic decision tree. (4) To check the plausibility of the algorithm by backtracking its pathways in four systematic reviews. Results (1) The results of our systematic review of the published literature have already been published. (2) We recaptured the experience from our four previously conducted systematic reviews that required the integration of various study types. (3) We chose length of follow-up (long, short), frequency of events (rare, frequent) and types of outcome as decision points (death, disease, discomfort, disability, dissatisfaction) and aligned the study design labels according to the Cochrane Handbook. We also considered practical or ethical concerns, and the problem of unavailable high-quality evidence. While applying the algorithm, disease-specific circumstances and aims of interventions should be considered. (4) We confirmed the plausibility of the pathways of the algorithm. Conclusions We propose that the algorithm can assist to bring seminal features of a systematic review with multiple study designs to the attention of anyone who is planning to conduct a systematic review. It aims to increase awareness and we think that it may reduce the time burden on review authors and may contribute to the production of a higher quality review. PMID:26289450

  12. Bacterially-Associated Transcriptional Remodelling in a Distinct Genomic Subtype of Colorectal Cancer Provides a Plausible Molecular Basis for Disease Development

    PubMed Central

    Goosen, Ryan W.

    2016-01-01

    The relevance of specific microbial colonisation to colorectal cancer (CRC) disease pathogenesis is increasingly recognised, but our understanding of possible underlying molecular mechanisms that may link colonisation to disease in vivo remains limited. Here, we investigate the relationships between the most commonly studied CRC-associated bacteria (Enterotoxigenic Bacteroides fragilis, pks+ Escherichia coli, Fusobacterium spp., afaC+ E. coli, Enterococcus faecalis & Enteropathogenic E. coli) and altered transcriptomic and methylation profiles of CRC patients, in order to gain insight into the potential contribution of these bacteria in the aetiopathogenesis of CRC. We show that colonisation by E. faecalis and high levels of Fusobacterium is associated with a specific transcriptomic subtype of CRC that is characterised by CpG island methylation, microsatellite instability and a significant increase in inflammatory and DNA damage pathways. Analysis of the significant, bacterially-associated changes in host gene expression, both at the level of individual genes as well as pathways, revealed a transcriptional remodeling that provides a plausible mechanistic link between specific bacterial colonisation and colorectal cancer disease development and progression in this subtype; these included upregulation of REG3A, REG1A and REG1P in the case of high-level colonization by Fusobacterium, and CXCL10 and BMI1 in the case of colonisation by E. faecalis. The enrichment of both E. faecalis and Fusobacterium in this CRC subtype suggests that polymicrobial colonisation of the colonic epithelium may well be an important aspect of colonic tumourigenesis. PMID:27846243

  13. The impact of age, biogenesis, and genomic clustering on Drosophila microRNA evolution

    PubMed Central

    Mohammed, Jaaved; Flynt, Alex S.; Siepel, Adam; Lai, Eric C.

    2013-01-01

    The molecular evolutionary signatures of miRNAs inform our understanding of their emergence, biogenesis, and function. The known signatures of miRNA evolution have derived mostly from the analysis of deeply conserved, canonical loci. In this study, we examine the impact of age, biogenesis pathway, and genomic arrangement on the evolutionary properties of Drosophila miRNAs. Crucial to the accuracy of our results was our curation of high-quality miRNA alignments, which included nearly 150 corrections to ortholog calls and nucleotide sequences of the global 12-way Drosophilid alignments currently available. Using these data, we studied primary sequence conservation, normalized free-energy values, and types of structure-preserving substitutions. We expand upon common miRNA evolutionary patterns that reflect fundamental features of miRNAs that are under functional selection. We observe that melanogaster-subgroup-specific miRNAs, although recently emerged and rapidly evolving, nonetheless exhibit evolutionary signatures that are similar to well-conserved miRNAs and distinct from other structured noncoding RNAs and bulk conserved non-miRNA hairpins. This provides evidence that even young miRNAs may be selected for regulatory activities. More strikingly, we observe that mirtrons and clustered miRNAs both exhibit distinct evolutionary properties relative to solo, well-conserved miRNAs, even after controlling for sequence depth. These studies highlight the previously unappreciated impact of biogenesis strategy and genomic location on the evolutionary dynamics of miRNAs, and affirm that miRNAs do not evolve as a unitary class. PMID:23882112

  14. Differences in evolutionary pressure acting within highly conserved ortholog groups.

    PubMed

    Przytycka, Teresa M; Jothi, Raja; Aravind, L; Lipman, David J

    2008-07-17

    In highly conserved widely distributed ortholog groups, the main evolutionary force is assumed to be purifying selection that enforces sequence conservation, with most divergence occurring by accumulation of neutral substitutions. Using a set of ortholog groups from prokaryotes, with a single representative in each studied organism, we asked the question if this evolutionary pressure is acting similarly on different subgroups of orthologs defined as major lineages (e.g. Proteobacteria or Firmicutes). Using correlations in entropy measures as a proxy for evolutionary pressure, we observed two distinct behaviors within our ortholog collection. The first subset of ortholog groups, called here informational, consisted mostly of proteins associated with information processing (i.e. translation, transcription, DNA replication) and the second, the non-informational ortholog groups, mostly comprised of proteins involved in metabolic pathways. The evolutionary pressure acting on non-informational proteins is more uniform relative to their informational counterparts. The non-informational proteins show higher level of correlation between entropy profiles and more uniformity across subgroups. The low correlation of entropy profiles in the informational ortholog groups suggest that the evolutionary pressure acting on the informational ortholog groups is not uniform across different clades considered this study. This might suggest "fine-tuning" of informational proteins in each lineage leading to lineage-specific differences in selection. This, in turn, could make these proteins less exchangeable between lineages. In contrast, the uniformity of the selective pressure acting on the non-informational groups might allow the exchange of the genetic material via lateral gene transfer.

  15. A RuBisCO-mediated carbon metabolic pathway in methanogenic archaea

    PubMed Central

    Kono, Takunari; Mehrotra, Sandhya; Endo, Chikako; Kizu, Natsuko; Matusda, Mami; Kimura, Hiroyuki; Mizohata, Eiichi; Inoue, Tsuyoshi; Hasunuma, Tomohisa; Yokota, Akiho; Matsumura, Hiroyoshi; Ashida, Hiroki

    2017-01-01

    Two enzymes are considered to be unique to the photosynthetic Calvin–Benson cycle: ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), responsible for CO2 fixation, and phosphoribulokinase (PRK). Some archaea possess bona fide RuBisCOs, despite not being photosynthetic organisms, but are thought to lack PRK. Here we demonstrate the existence in methanogenic archaea of a carbon metabolic pathway involving RuBisCO and PRK, which we term ‘reductive hexulose-phosphate' (RHP) pathway. These archaea possess both RuBisCO and a catalytically active PRK whose crystal structure resembles that of photosynthetic bacterial PRK. Capillary electrophoresis-mass spectrometric analysis of metabolites reveals that the RHP pathway, which differs from the Calvin–Benson cycle only in a few steps, is active in vivo. Our work highlights evolutionary and functional links between RuBisCO-mediated carbon metabolic pathways in methanogenic archaea and photosynthetic organisms. Whether the RHP pathway allows for autotrophy (that is, growth exclusively with CO2 as carbon source) remains unknown. PMID:28082747

  16. Wolf-Rayet stars, black holes and the first detected gravitational wave source

    NASA Astrophysics Data System (ADS)

    Bogomazov, A. I.; Cherepashchuk, A. M.; Lipunov, V. M.; Tutukov, A. V.

    2018-01-01

    The recently discovered burst of gravitational waves GW150914 provides a good new chance to verify the current view on the evolution of close binary stars. Modern population synthesis codes help to study this evolution from two main sequence stars up to the formation of two final remnant degenerate dwarfs, neutron stars or black holes (Masevich and Tutukov, 1988). To study the evolution of the GW150914 predecessor we use the ;Scenario Machine; code presented by Lipunov et al. (1996). The scenario modeling conducted in this study allowed to describe the evolution of systems for which the final stage is a massive BH+BH merger. We find that the initial mass of the primary component can be 100÷140M⊙ and the initial separation of the components can be 50÷350R⊙. Our calculations show the plausibility of modern evolutionary scenarios for binary stars and the population synthesis modeling based on it.

  17. Sex ratio dynamics and fluctuating selection on personality.

    PubMed

    Del Giudice, Marco

    2012-03-21

    Fluctuating selection has often been proposed as an explanation for the maintenance of genetic variation in personality. Here I argue that the temporal dynamics of the sex ratio can be a powerful source of fluctuating selection on personality traits, and develop this hypothesis with respect to humans. First, I review evidence that sex ratios modulate a wide range of social processes related to mating and parenting. Since most personality traits affect mating and parenting behavior, changes in the sex ratio can be expected to result in variable selection on personality. I then show that the temporal dynamics of the sex ratio are intrinsically characterized by fluctuations at various timescales. Finally, I address a number of evolutionary genetic challenges to the hypothesis. I conclude that the sex ratio hypothesis is a plausible explanation of genetic variation in human personality, and may be fruitfully applied to other species as well. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Is supernova 1987A a stripped asymptotic-branch giant in a binary system?

    NASA Technical Reports Server (NTRS)

    Joss, P. C.; Podsiadlowski, PH.; Hsu, J. J. L.; Rappaport, S.

    1988-01-01

    It is proposed that the progenitor of supernova 1987A was a previously undetected red star in orbit about a blue supergiant. The progenitor was the remnant of an asymptotic-branch giant that had lost most of its hydrogen-rich envelope to its blue companion by type C mass transfer. A detailed evolutionary model strongly supports the feasibility of this proposition. It is found that the original mass of the supernova precursor was 10-15 solar (unless a large fraction of the mass was ejected from the binary sytem), and its final mass, just before the supernova event, was 3-6 solar. The system remained bound, with a new orbital period of 3-10 yr and an eccentricity of 0.1-0.4. This picture can provide plausible qualitative explanations for several anomalies in the observational properties of this supernova.

  19. Override the controversy: Analytic thinking predicts endorsement of evolution.

    PubMed

    Gervais, Will M

    2015-09-01

    Despite overwhelming scientific consensus, popular opinions regarding evolution are starkly divided. In the USA, for example, nearly one in three adults espouse a literal and recent divine creation account of human origins. Plausibly, resistance to scientific conclusions regarding the origins of species-like much resistance to other scientific conclusions (Bloom & Weisberg, 2007)-gains support from reliably developing intuitions. Intuitions about essentialism, teleology, agency, and order may combine to make creationism potentially more cognitively attractive than evolutionary concepts. However, dual process approaches to cognition recognize that people can often analytically override their intuitions. Two large studies (total N=1324) found consistent evidence that a tendency to engage analytic thinking predicted endorsement of evolution, even controlling for relevant demographic, attitudinal, and religious variables. Meanwhile, exposure to religion predicted reduced endorsement of evolution. Cognitive style is one factor among many affecting opinions on the origin of species. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Therapeutic Assessment in Personality Disorders: Toward the Restoration of Epistemic Trust.

    PubMed

    Kamphuis, Jan H; Finn, Stephen E

    2018-06-06

    Research evidence suggests Therapeutic Assessment positively affects clients with problems in living, including clients with personality disorders, who are typically quite resistant to change. Importantly, this change takes place quickly, in relatively few sessions. This article draws on a relatively new evolutionary-based theory of epistemic trust (ET) and epistemic hypervigilance (EH) as a lens to plausibly explain the efficacy of TA, and especially its influence on PD clients' alliance and motivation for subsequent psychotherapy (Fonagy, Luyten, & Alison, 2015 ). ET is the willingness to take in relevant interpersonally transmited information and it is essential to the immediate success of psychotherapy and its long-term impact. The collaborative, intersubjective framework of TA and many of its specific techniques might be understood as highly relevant to restoring ET in clients, especially those with PD. We close by discussing implications for psychological assessment, psychotherapy, and research.

  1. The evolution of magnetic hot massive stars: Implementation of the quantitative influence of surface magnetic fields in modern models of stellar evolution

    NASA Astrophysics Data System (ADS)

    Keszthelyi, Zsolt; Wade, Gregg A.; Petit, Veronique

    2017-11-01

    Large-scale dipolar surface magnetic fields have been detected in a fraction of OB stars, however only few stellar evolution models of massive stars have considered the impact of these fossil fields. We are performing 1D hydrodynamical model calculations taking into account evolutionary consequences of the magnetospheric-wind interactions in a simplified parametric way. Two effects are considered: i) the global mass-loss rates are reduced due to mass-loss quenching, and ii) the surface angular momentum loss is enhanced due to magnetic braking. As a result of the magnetic mass-loss quenching, the mass of magnetic massive stars remains close to their initial masses. Thus magnetic massive stars - even at Galactic metallicity - have the potential to be progenitors of "heavy" stellar mass black holes. Similarly, at Galactic metallicity, the formation of pair instability supernovae is plausible with a magnetic progenitor.

  2. Bioprecipitation: a feedback cycle linking earth history, ecosystem dynamics and land use through biological ice nucleators in the atmosphere.

    PubMed

    Morris, Cindy E; Conen, Franz; Alex Huffman, J; Phillips, Vaughan; Pöschl, Ulrich; Sands, David C

    2014-02-01

    Landscapes influence precipitation via the water vapor and energy fluxes they generate. Biologically active landscapes also generate aerosols containing microorganisms, some being capable of catalyzing ice formation and crystal growth in clouds at temperatures near 0 °C. The resulting precipitation is beneficial for the growth of plants and microorganisms. Mounting evidence from observations and numerical simulations support the plausibility of a bioprecipitation feedback cycle involving vegetated landscapes and the microorganisms they host. Furthermore, the evolutionary history of ice nucleation-active bacteria such as Pseudomonas syringae supports that they have been part of this process on geological time scales since the emergence of land plants. Elucidation of bioprecipitation feedbacks involving landscapes and their microflora could contribute to appraising the impact that modified landscapes have on regional weather and biodiversity, and to avoiding inadvertent, negative consequences of landscape management. © 2013 John Wiley & Sons Ltd.

  3. The evolution of contralateral control of the body by the brain: is it a protective mechanism?

    PubMed

    Whitehead, Lorne; Banihani, Saleh

    2014-01-01

    Contralateral control, the arrangement whereby most of the human motor and sensory fibres cross the midline in order to provide control for contralateral portions of the body, presents a puzzle from an evolutionary perspective. What caused such a counterintuitive and complex arrangement to become dominant? In this paper we offer a new perspective on this question by showing that in a complex interactive control system there could be a significant net survival advantage with contralateral control, associated with the effect of injuries of intermediate severity. In such cases an advantage could arise from a combination of non-linear system response combined with correlations between injuries on the same side of the head and body. We show that a simple mathematical model of these ideas emulates such an advantage. Based on this model, we conclude that effects of this kind are a plausible driving force for the evolution of contralateral control.

  4. Application of Adverse Outcome Pathways to U.S. EPA’s Endocrine Disruptor Screening Program

    PubMed Central

    Noyes, Pamela D.; Casey, Warren M.; Dix, David J.

    2017-01-01

    Background: The U.S. EPA’s Endocrine Disruptor Screening Program (EDSP) screens and tests environmental chemicals for potential effects in estrogen, androgen, and thyroid hormone pathways, and it is one of the only regulatory programs designed around chemical mode of action. Objectives: This review describes the EDSP’s use of adverse outcome pathway (AOP) and toxicity pathway frameworks to organize and integrate diverse biological data for evaluating the endocrine activity of chemicals. Using these frameworks helps to establish biologically plausible links between endocrine mechanisms and apical responses when those end points are not measured in the same assay. Results: Pathway frameworks can facilitate a weight of evidence determination of a chemical’s potential endocrine activity, identify data gaps, aid study design, direct assay development, and guide testing strategies. Pathway frameworks also can be used to evaluate the performance of computational approaches as alternatives for low-throughput and animal-based assays and predict downstream key events. In cases where computational methods can be validated based on performance, they may be considered as alternatives to specific assays or end points. Conclusions: A variety of biological systems affect apical end points used in regulatory risk assessments, and without mechanistic data, an endocrine mode of action cannot be determined. Because the EDSP was designed to consider mode of action, toxicity pathway and AOP concepts are a natural fit. Pathway frameworks have diverse applications to endocrine screening and testing. An estrogen pathway example is presented, and similar approaches are being used to evaluate alternative methods and develop predictive models for androgen and thyroid pathways. https://doi.org/10.1289/EHP1304 PMID:28934726

  5. The Search for New Luminous Blue Variable Stars: Near-Infrared Spectroscopy of Stars With 24 micron Shells

    NASA Astrophysics Data System (ADS)

    Stringfellow, Guy; Gvaramadze, Vasilii

    2010-02-01

    Luminous Blue Variable (LBV) stars represent an extremely rare class of very luminous and massive stars. Only about a dozen confirmed Galactic LBV stars are known to date, which precludes us from determining a solid evolutionary connection between LBV and other intermediate (e.g. Ofpe/WN9, WNL) phases in the life of very massive stars. The known LBV stars each have their own unique properties, so new discoveries add insight into the properties and evolutionary status of LBVs and massive stars; even one new discovery of objects of this type could provide break-through results in the understanding of the intermediate stages of massive star evolution. We have culled a prime sample of possible LBV candidates from the Spitzer 24 (micron) archival data. All have circumstellar nebulae, rings, and shells (typical of LBVs and related stars) surrounding reddened central stars. Spectroscopic followup of about two dozen optically visible central stars associated with the shells from this sample showed that they are either candidate LBVs, late WN-type Wolf-Rayet stars or blue supergiants. We propose infrared spectroscopic observations of the central stars for a large fraction (23 stars) of our northern sample to determine their nature and discover additional LBV candidates. These stars have no plausible optical counterparts, so infrared spectra are needed. This program requires two nights of Hale time using TripleSpec.

  6. Carbon Metabolic Pathways in Phototrophic Bacteria and Their Broader Evolutionary Implications

    PubMed Central

    Tang, Kuo-Hsiang; Tang, Yinjie J.; Blankenship, Robert Eugene

    2011-01-01

    Photosynthesis is the biological process that converts solar energy to biomass, bio-products, and biofuel. It is the only major natural solar energy storage mechanism on Earth. To satisfy the increased demand for sustainable energy sources and identify the mechanism of photosynthetic carbon assimilation, which is one of the bottlenecks in photosynthesis, it is essential to understand the process of solar energy storage and associated carbon metabolism in photosynthetic organisms. Researchers have employed physiological studies, microbiological chemistry, enzyme assays, genome sequencing, transcriptomics, and 13C-based metabolomics/fluxomics to investigate central carbon metabolism and enzymes that operate in phototrophs. In this report, we review diverse CO2 assimilation pathways, acetate assimilation, carbohydrate catabolism, the tricarboxylic acid cycle and some key, and/or unconventional enzymes in central carbon metabolism of phototrophic microorganisms. We also discuss the reducing equivalent flow during photoautotrophic and photoheterotrophic growth, evolutionary links in the central carbon metabolic network, and correlations between photosynthetic and non-photosynthetic organisms. Considering the metabolic versatility in these fascinating and diverse photosynthetic bacteria, many essential questions in their central carbon metabolism still remain to be addressed. PMID:21866228

  7. Multi-target drugs to address multiple checkpoints in complex inflammatory pathologies: evolutionary cues for novel "first-in-class" anti-inflammatory drug candidates: a reviewer's perspective.

    PubMed

    Mathew, Geetha; Unnikrishnan, M K

    2015-10-01

    Inflammation is a complex, metabolically expensive process involving multiple signaling pathways and regulatory mechanisms which have evolved over evolutionary timescale. Addressing multiple targets of inflammation holistically, in moderation, is probably a more evolutionarily viable strategy, as compared to current therapy which addresses drug targets in isolation. Polypharmacology, addressing multiple targets, is commonly used in complex ailments, suggesting the superior safety and efficacy profile of multi-target (MT) drugs. Phenotypic drug discovery, which generated successful MT and first-in-class drugs in the past, is now re-emerging. A multi-pronged approach, which modulates the evolutionarily conserved, robust and pervasive cellular mechanisms of tissue repair, with AMPK at the helm, regulating the complex metabolic/immune/redox pathways underlying inflammation, is perhaps a more viable strategy than addressing single targets in isolation. Molecules that modulate multiple molecular mechanisms of inflammation in moderation (modulating TH cells toward the anti-inflammatory phenotype, activating AMPK, stimulating Nrf2 and inhibiting NFκB) might serve as a model for a novel Darwinian "first-in-class" therapeutic category that holistically addresses immune, redox and metabolic processes associated with inflammatory repair. Such a multimodal biological activity is supported by the fact that several non-calorific pleiotropic natural products with anti-inflammatory action have been incorporated into diet (chiefly guided by the adaptive development of olfacto-gustatory preferences over evolutionary timescales) rendering such molecules, endowed with evolutionarily privileged molecular scaffolds, naturally oriented toward multiple targets.

  8. A Potential Benefit of Albinism in Astyanax Cavefish: Downregulation of the oca2 Gene Increases Tyrosine and Catecholamine Levels as an Alternative to Melanin Synthesis

    PubMed Central

    Parkhurst, Amy; Jeffery, William R.

    2013-01-01

    Albinism, the loss of melanin pigmentation, has evolved in a diverse variety of cave animals but the responsible evolutionary mechanisms are unknown. In Astyanax mexicanus, which has a pigmented surface dwelling form (surface fish) and several albino cave-dwelling forms (cavefish), albinism is caused by loss of function mutations in the oca2 gene, which operates during the first step of the melanin synthesis pathway. In addition to albinism, cavefish have evolved differences in behavior, including feeding and sleep, which are under the control of the catecholamine system. The catecholamine and melanin synthesis pathways diverge after beginning with the same substrate, L-tyrosine. Here we describe a novel relationship between the catecholamine and melanin synthesis pathways in Astyanax. Our results show significant increases in L-tyrosine, dopamine, and norepinephrine in pre-feeding larvae and adult brains of Pachón cavefish relative to surface fish. In addition, norepinephrine is elevated in cavefish adult kidneys, which contain the teleost homologs of catecholamine synthesizing adrenal cells. We further show that the oca2 gene is expressed during surface fish development but is downregulated in cavefish embryos. A key finding is that knockdown of oca2 expression in surface fish embryos delays the development of pigmented melanophores and simultaneously increases L-tyrosine and dopamine. We conclude that a potential evolutionary benefit of albinism in Astyanax cavefish may be to provide surplus L-tyrosine as a precursor for the elevated catecholamine synthesis pathway, which could be important for adaptation to the challenging cave environment. PMID:24282555

  9. Evolution of Chemical Diversity in Echinocandin Lipopeptide Antifungal Metabolites

    PubMed Central

    Yue, Qun; Chen, Li; Zhang, Xiaoling; Li, Kuan; Sun, Jingzu; Liu, Xingzhong

    2015-01-01

    The echinocandins are a class of antifungal drugs that includes caspofungin, micafungin, and anidulafungin. Gene clusters encoding most of the structural complexity of the echinocandins provided a framework for hypotheses about the evolutionary history and chemical logic of echinocandin biosynthesis. Gene orthologs among echinocandin-producing fungi were identified. Pathway genes, including the nonribosomal peptide synthetases (NRPSs), were analyzed phylogenetically to address the hypothesis that these pathways represent descent from a common ancestor. The clusters share cooperative gene contents and linkages among the different strains. Individual pathway genes analyzed in the context of similar genes formed unique echinocandin-exclusive phylogenetic lineages. The echinocandin NRPSs, along with the NRPS from the inp gene cluster in Aspergillus nidulans and its orthologs, comprise a novel lineage among fungal NRPSs. NRPS adenylation domains from different species exhibited a one-to-one correspondence between modules and amino acid specificity that is consistent with models of tandem duplication and subfunctionalization. Pathway gene trees and Ascomycota phylogenies are congruent and consistent with the hypothesis that the echinocandin gene clusters have a common origin. The disjunct Eurotiomycete-Leotiomycete distribution appears to be consistent with a scenario of vertical descent accompanied by incomplete lineage sorting and loss of the clusters from most lineages of the Ascomycota. We present evidence for a single evolutionary origin of the echinocandin family of gene clusters and a progression of structural diversification in two fungal classes that diverged approximately 290 to 390 million years ago. Lineage-specific gene cluster evolution driven by selection of new chemotypes contributed to diversification of the molecular functionalities. PMID:26024901

  10. Drosophila sex combs as a model of evolutionary innovations.

    PubMed

    Kopp, Artyom

    2011-01-01

    The diversity of animal and plant forms is shaped by nested evolutionary innovations. Understanding the genetic and molecular changes responsible for these innovations is therefore one of the key goals of evolutionary biology. From the genetic point of view, the origin of novel traits implies the origin of new regulatory pathways to control their development. To understand how these new pathways are assembled in the course of evolution, we need model systems that combine relatively recent innovations with a powerful set of genetic and molecular tools. One such model is provided by the Drosophila sex comb-a male-specific morphological structure that evolved in a relatively small lineage related to the model species D. melanogaster. Our extensive knowledge of sex comb development in D. melanogaster provides the basis for investigating the genetic changes responsible for sex comb origin and diversification. At the same time, sex combs can change on microevolutionary timescales and differ spectacularly among closely related species, providing opportunities for direct genetic analysis and for integrating developmental and population-genetic approaches. Sex comb evolution is associated with the origin of novel interactions between Hox and sex determination genes. Activity of the sex determination pathway was brought under the control of the Hox code to become segment-specific, while Hox gene expression became sexually dimorphic. At the same time, both Hox and sex determination genes were integrated into the intrasegmental spatial patterning network, and acquired new joint downstream targets. Phylogenetic analysis shows that similar sex comb morphologies evolved independently in different lineages. Convergent evolution at the phenotypic level reflects convergent changes in the expression of Hox and sex determination genes, involving both independent gains and losses of regulatory interactions. However, the downstream cell-differentiation programs have diverged between species, and in some lineages, similar adult morphologies are produced by different morphogenetic mechanisms. These features make the sex comb an excellent model for examining not only the genetic changes responsible for its evolution, but also the cellular processes that translate DNA sequence changes into morphological diversity. The origin and diversification of sex combs provides insights into the roles of modularity, cooption, and regulatory changes in evolutionary innovations, and can serve as a model for understanding the origin of the more drastic novelties that define higher order taxa. © 2011 Wiley Periodicals, Inc.

  11. Drosophila Sex Combs as a Model of Evolutionary Innovations

    PubMed Central

    Kopp, Artyom

    2011-01-01

    The diversity of animal and plant forms is shaped by nested evolutionary innovations. Understanding the genetic and molecular changes responsible for these innovations is therefore one of the key goals of evolutionary biology. From the genetic point of view, the origin of novel traits implies the origin of new regulatory pathways to control their development. To understand how these new pathways are assembled in the course of evolution, we need model systems that combine relatively recent innovations with a powerful set of genetic and molecular tools. One such model is provided by the Drosophila sex comb – a male-specific morphological structure that evolved in a relatively small lineage related to the model species D. melanogaster. Our extensive knowledge of sex comb development in D. melanogaster provides the basis for investigating the genetic changes responsible for sex comb origin and diversification. At the same time, sex combs can change on microevolutionary timescales and differ spectacularly among closely related species, providing opportunities for direct genetic analysis and for integrating developmental and population-genetic approaches. Sex comb evolution is associated with the origin of novel interactions between HOX and sex determination genes. Activity of the sex determination pathway was brought under the control of the HOX code to become segment-specific, while HOX gene expression became sexually dimorphic. At the same time, both HOX and sex determination genes were integrated into the intrasegmental spatial patterning network, and acquired new joint downstream targets. Phylogenetic analysis shows that similar sex comb morphologies evolved independently in different lineages. Convergent evolution at the phenotypic level reflects convergent changes in the expression of HOX and sex determination genes, involving both independent gains and losses of regulatory interactions. However, the downstream cell differentiation programs have diverged between species, and in some lineages similar adult morphologies are produced by different morphogenetic mechanisms. These features make the sex comb an excellent model for examining not only the genetic changes responsible for its evolution, but also the cellular processes that translate DNA sequence changes into morphological diversity. The origin and diversification of sex combs provides insights into the roles of modularity, cooption, and regulatory changes in evolutionary innovations, and can serve as a model for understanding the origin of the more drastic novelties that define higher-order taxa. PMID:23016935

  12. Diversity of bile salts in fish and amphibians: evolution of a complex biochemical pathway.

    PubMed

    Hagey, Lee R; Møller, Peter R; Hofmann, Alan F; Krasowski, Matthew D

    2010-01-01

    Bile salts are the major end metabolites of cholesterol and are also important in lipid and protein digestion, as well as shaping of the gut microflora. Previous studies had demonstrated variation of bile salt structures across vertebrate species. We greatly extend prior surveys of bile salt variation in fish and amphibians, particularly in analysis of the biliary bile salts of Agnatha and Chondrichthyes. While there is significant structural variation of bile salts across all fish orders, bile salt profiles are generally stable within orders of fish and do not correlate with differences in diet. This large data set allowed us to infer evolutionary changes in the bile salt synthetic pathway. The hypothesized ancestral bile salt synthetic pathway, likely exemplified in extant hagfish, is simpler and much shorter than the pathway of most teleost fish and terrestrial vertebrates. Thus, the bile salt synthetic pathway has become longer and more complex throughout vertebrate evolution. Analysis of the evolution of bile salt synthetic pathways provides a rich model system for the molecular evolution of a complex biochemical pathway in vertebrates.

  13. Minireview: The Roles of Small RNA Pathways in Reproductive Medicine

    PubMed Central

    Buchold, Gregory M.

    2011-01-01

    The discovery of small noncoding RNA, including P-element-induced wimpy testis-interacting RNA, small interfering RNA, and microRNA, has energized research in reproductive medicine. In the two decades since the identification of small RNA, first in Caenorhabditis elegans and then in other animals, scientists in many disciplines have made significant progress in elucidating their biology. A powerful battery of tools, including knockout mice and small RNA mimics and antagonists, has facilitated investigation into the functional roles and therapeutic potential of these small RNA pathways. Current data indicate that small RNA play significant roles in normal development and physiology and pathological conditions of the reproductive tracts of females and males. Biologically plausible mRNA targets for these microRNA are aggressively being discovered. The next phase of research will focus on elucidating the clinical utility of small RNA-selective agonists and antagonists. PMID:21546411

  14. Shift work and cardiovascular disease - pathways from circadian stress to morbidity.

    PubMed

    Puttonen, Sampsa; Härmä, Mikko; Hublin, Christer

    2010-03-01

    In order to establish a causal relation between shift work and cardiovascular disease (CVD), we need to verify the pathways from the former to the latter. This paper aims to review the current knowledge of the mechanisms between shift work and CVD. Shift work can increase the risk of CVD by several interrelated psychosocial, behavioral, and physiological mechanisms. The psychosocial mechanisms relate to difficulties in controlling working hours, decreased work-life balance, and poor recovery following work. The most probable behavioral changes are weight gain and smoking. The plausible physiological and biological mechanisms are related to the activation of the autonomic nervous system, inflammation, changed lipid and glucose metabolism, and related changes in the risk for atherosclerosis, metabolic syndrome, and type II diabetes. The data provide evidence for possible disease mechanisms between shift work and CVD, but compelling evidence on any specific mechanism is missing.

  15. Niche construction through phenological plasticity: life history dynamics and ecological consequences.

    PubMed

    Donohue, Kathleen

    2005-04-01

    The ability of an organism to alter the environment that it experiences has been termed 'niche construction'. Plants have several ways whereby they can determine the environment to which they are exposed at different life stages. This paper discusses three of these: plasticity in dispersal, flowering timing and germination timing. It reviews pathways through which niche construction alters evolutionary and ecological trajectories by altering the selective environment to which organisms are exposed, the phenotypic expression of plastic characters, and the expression of genetic variation. It provides examples whereby niche construction creates positive or negative feedbacks between phenotypes and environments, which in turn cause novel evolutionary constraints and novel life-history expression. Copyright New Phytologist (2005).

  16. Neural-network-enhanced evolutionary algorithm applied to supported metal nanoparticles

    NASA Astrophysics Data System (ADS)

    Kolsbjerg, E. L.; Peterson, A. A.; Hammer, B.

    2018-05-01

    We show that approximate structural relaxation with a neural network enables orders of magnitude faster global optimization with an evolutionary algorithm in a density functional theory framework. The increased speed facilitates reliable identification of global minimum energy structures, as exemplified by our finding of a hollow Pt13 nanoparticle on an MgO support. We highlight the importance of knowing the correct structure when studying the catalytic reactivity of the different particle shapes. The computational speedup further enables screening of hundreds of different pathways in the search for optimum kinetic transitions between low-energy conformers and hence pushes the limits of the insight into thermal ensembles that can be obtained from theory.

  17. Exact dynamic properties of molecular motors

    NASA Astrophysics Data System (ADS)

    Boon, N. J.; Hoyle, R. B.

    2012-08-01

    Molecular motors play important roles within a biological cell, performing functions such as intracellular transport and gene transcription. Recent experimental work suggests that there are many plausible biochemical mechanisms that molecules such as myosin-V could use to achieve motion. To account for the abundance of possible discrete-stochastic frameworks that can arise when modeling molecular motor walks, a generalized and straightforward graphical method for calculating their dynamic properties is presented. It allows the calculation of the velocity, dispersion, and randomness ratio for any proposed system through analysis of its structure. This article extends work of King and Altman ["A schematic method of deriving the rate laws of enzyme-catalyzed reactions," J. Phys. Chem. 60, 1375-1378 (1956)], 10.1021/j150544a010 on networks of enzymatic reactions by calculating additional dynamic properties for spatially hopping systems. Results for n-state systems are presented: single chain, parallel pathway, divided pathway, and divided pathway with a chain. A novel technique for combining multiple system architectures coupled at a reference state is also demonstrated. Four-state examples illustrate the effectiveness and simplicity of these methods.

  18. Activation and Resolution of Periodontal Inflammation and Its Systemic Impact

    PubMed Central

    Hasturk, Hatice; Kantarci, Alpdogan

    2015-01-01

    Inflammation is a highly organized event impacting upon organs, tissues and biological systems. Periodontal diseases are characterized by dysregulation or dysfunction of resolution pathways of inflammation resulting in a failure of healing and a dominant chronic, progressive, destructive and predominantly unresolved inflammation. The biological consequences of inflammatory processes may be independent of the etiological agents such as trauma, microbial organisms and stress. The impact of the inflammatory pathological process depends upon the affected tissues or organ system. Whilst mediators are similar, there is a tissue specificity for the inflammatory events. It is plausible that inflammatory processes in one organ could directly lead to pathologies in another organ or tissue. Communication between distant parts of the body and their inflammatory status is also mediated by common signaling mechanisms mediated via cells and soluble mediators. This review focuses on periodontal inflammation, its systemic associations and advances in therapeutic approaches based on mediators acting through orchestration of natural pathway to resolution of inflammation. We also discuss a new treatment concept where natural pathways of resolution of periodontal inflammation can be used to limit systemic inflammation and promote healing and regeneration. PMID:26252412

  19. Why We Should Create Artificial Offspring: Meaning and the Collective Afterlife.

    PubMed

    Danaher, John

    2017-07-03

    This article argues that the creation of artificial offspring could make our lives more meaningful (i.e. satisfy more meaning-relevant conditions of value). By 'artificial offspring' I mean beings that we construct, with a mix of human and non-human-like qualities. Robotic artificial intelligences are paradigmatic examples of the form. There are two reasons for thinking that the creation of such beings could make our lives more meaningful and valuable. The first is that the existence of a collective afterlife-i.e. a set of human-like lives that continue after we die-is likely to be an important source and sustainer of meaning in our present lives (Scheffler in Death and the afterlife, OUP, Oxford, 2013). The second is that the creation of artificial offspring provides a plausible and potentially better pathway to a collective afterlife than the traditional biological pathway (i.e. there are reasons to favour this pathway and there are no good defeaters to trying it out). Both of these arguments are defended from a variety of objections and misunderstandings.

  20. Protein Interactome of Muscle Invasive Bladder Cancer

    PubMed Central

    Bhat, Akshay; Heinzel, Andreas; Mayer, Bernd; Perco, Paul; Mühlberger, Irmgard; Husi, Holger; Merseburger, Axel S.; Zoidakis, Jerome; Vlahou, Antonia; Schanstra, Joost P.; Mischak, Harald; Jankowski, Vera

    2015-01-01

    Muscle invasive bladder carcinoma is a complex, multifactorial disease caused by disruptions and alterations of several molecular pathways that result in heterogeneous phenotypes and variable disease outcome. Combining this disparate knowledge may offer insights for deciphering relevant molecular processes regarding targeted therapeutic approaches guided by molecular signatures allowing improved phenotype profiling. The aim of the study is to characterize muscle invasive bladder carcinoma on a molecular level by incorporating scientific literature screening and signatures from omics profiling. Public domain omics signatures together with molecular features associated with muscle invasive bladder cancer were derived from literature mining to provide 286 unique protein-coding genes. These were integrated in a protein-interaction network to obtain a molecular functional map of the phenotype. This feature map educated on three novel disease-associated pathways with plausible involvement in bladder cancer, namely Regulation of actin cytoskeleton, Neurotrophin signalling pathway and Endocytosis. Systematic integration approaches allow to study the molecular context of individual features reported as associated with a clinical phenotype and could potentially help to improve the molecular mechanistic description of the disorder. PMID:25569276

  1. Coutilization of D-Glucose, D-Xylose, and L-Arabinose in Saccharomyces cerevisiae by Coexpressing the Metabolic Pathways and Evolutionary Engineering

    PubMed Central

    Zhao, Jianzhi; Qiu, Chenxi; Wang, Shihao; Du, Binghai

    2017-01-01

    Efficient and cost-effective fuel ethanol production from lignocellulosic materials requires simultaneous cofermentation of all hydrolyzed sugars, mainly including D-glucose, D-xylose, and L-arabinose. Saccharomyces cerevisiae is a traditional D-glucose fermenting strain and could utilize D-xylose and L-arabinose after introducing the initial metabolic pathways. The efficiency and simultaneous coutilization of the two pentoses and D-glucose for ethanol production in S. cerevisiae still need to be optimized. Previously, we constructed an L-arabinose-utilizing S. cerevisiae BSW3AP. In this study, we further introduced the XI and XR-XDH metabolic pathways of D-xylose into BSW3AP to obtain D-glucose, D-xylose, and L-arabinose cofermenting strain. Benefits of evolutionary engineering: the resulting strain BSW4XA3 displayed a simultaneous coutilization of D-xylose and L-arabinose with similar consumption rates, and the D-glucose metabolic capacity was not decreased. After 120 h of fermentation on mixed D-glucose, D-xylose, and L-arabinose, BSW4XA3 consumed 24% more amounts of pentoses and the ethanol yield of mixed sugars was increased by 30% than that of BSW3AP. The resulting strain BSW4XA3 was a useful chassis for further enhancing the coutilization efficiency of mixed sugars for bioethanol production. PMID:28459063

  2. Molecular and cellular bases of adaptation to a changing environment in microorganisms.

    PubMed

    Bleuven, Clara; Landry, Christian R

    2016-10-26

    Environmental heterogeneity constitutes an evolutionary challenge for organisms. While evolutionary dynamics under variable conditions has been explored for decades, we still know relatively little about the cellular and molecular mechanisms involved. It is of paramount importance to examine these molecular bases because they may play an important role in shaping the course of evolution. In this review, we examine the diversity of adaptive mechanisms in the face of environmental changes. We exploit the recent literature on microbial systems because those have benefited the most from the recent emergence of genetic engineering and experimental evolution followed by genome sequencing. We identify four emerging trends: (i) an adaptive molecular change in a pathway often results in fitness trade-off in alternative environments but the effects are dependent on a mutation's genetic background; (ii) adaptive changes often modify transcriptional and signalling pathways; (iii) several adaptive changes may occur within the same molecular pathway but be associated with pleiotropy of different signs across environments; (iv) because of their large associated costs, macromolecular changes such as gene amplification and aneuploidy may be a rapid mechanism of adaptation in the short-term only. The course of adaptation in a variable environment, therefore, depends on the complexity of the environment but also on the molecular relationships among the genes involved and between the genes and the phenotypes under selection. © 2016 The Author(s).

  3. A framework for the establishment of a cnidarian gene regulatory network for "endomesoderm" specification: the inputs of ß-catenin/TCF signaling.

    PubMed

    Röttinger, Eric; Dahlin, Paul; Martindale, Mark Q

    2012-01-01

    Understanding the functional relationship between intracellular factors and extracellular signals is required for reconstructing gene regulatory networks (GRN) involved in complex biological processes. One of the best-studied bilaterian GRNs describes endomesoderm specification and predicts that both mesoderm and endoderm arose from a common GRN early in animal evolution. Compelling molecular, genomic, developmental, and evolutionary evidence supports the hypothesis that the bifunctional gastrodermis of the cnidarian-bilaterian ancestor is derived from the same evolutionary precursor of both endodermal and mesodermal germ layers in all other triploblastic bilaterian animals. We have begun to establish the framework of a provisional cnidarian "endomesodermal" gene regulatory network in the sea anemone, Nematostella vectensis, by using a genome-wide microarray analysis on embryos in which the canonical Wnt/ß-catenin pathway was ectopically targeted for activation by two distinct pharmaceutical agents (lithium chloride and 1-azakenpaullone) to identify potential targets of endomesoderm specification. We characterized 51 endomesodermally expressed transcription factors and signaling molecule genes (including 18 newly identified) with fine-scale temporal (qPCR) and spatial (in situ) analysis to define distinct co-expression domains within the animal plate of the embryo and clustered genes based on their earliest zygotic expression. Finally, we determined the input of the canonical Wnt/ß-catenin pathway into the cnidarian endomesodermal GRN using morpholino and mRNA overexpression experiments to show that NvTcf/canonical Wnt signaling is required to pattern both the future endomesodermal and ectodermal domains prior to gastrulation, and that both BMP and FGF (but not Notch) pathways play important roles in germ layer specification in this animal. We show both evolutionary conserved as well as profound differences in endomesodermal GRN structure compared to bilaterians that may provide fundamental insight into how GRN subcircuits have been adopted, rewired, or co-opted in various animal lineages that give rise to specialized endomesodermal cell types.

  4. Appearance of metastable B2 phase during solidification of Ni 50 Zr 50 alloy: electrostatic levitation and molecular dynamics simulation studies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Quirinale, D. G.; Rustan, G. E.; Wilson, S. R.

    2015-02-04

    High-energy x-ray diffraction measurements of undercooled, electrostatically levitated Ni 50Zr 50 liquid droplets were performed. The observed solidification pathway proceeded through the nucleation and growth of the metastable B2 phase, which persisted for several seconds before the rapid appearance of the stable B33 phase. This sequence is shown to be consistent with predictions from classical nucleation theory using data obtained from molecular dynamics (MD) simulations. A plausible mechanism for the B2–B33 transformation is proposed and investigated through further MD simulations.

  5. HCN - A plausible source of purines, pyrimidines and amino acids on the primitive earth

    NASA Technical Reports Server (NTRS)

    Ferris, J.-P.; Joshi, P. C.; Edelson, E. H.; Lawless, J. G.

    1978-01-01

    Dilute (0.1 M) solutions of HCN condense to oligomers at pH 9.2, and hydrolysis of these oligomers yields 4,5-dihydroxypyrimidine, orotic acid, 5-hydroxyuracil, adenine, 4-aminoimidazole-5-carboxamide, and amino acids. It is suggested that the three main classes of nitrogen-containing biomolecules - purines, pyrimidines, and amino acids may have originated from HCN on the primitive earth. It is also suggested that the presence of orotic acid and 4-aminoimidazole-5-carboxamide might indicate that contemporary biosynthetic pathways for nucleotides evolved from the compounds released on hydrolysis of HCN oligomers.

  6. Grignard reagent/CuI/LiCl-mediated stereoselective cascade addition/cyclization of diynes: a novel pathway for the construction of 1-methyleneindene derivatives.

    PubMed

    Li, De-Yao; Wei, Yin; Shi, Min

    2013-11-11

    Diynes containing a cyclopropane group smoothly undergo a novel intramolecular and stereoselective cascade addition/cyclization reaction to produce the corresponding 1-methyleneindene derivatives in moderate to good yields. This interesting transformation is mediated by Grignard reagent/CuI with LiCl as an additive under mild conditions. The obtained product can easily be further functionalized through cyclopropyl ring opening. A plausible reaction mechanism has also been presented on the basis of deuterium labeling and control experiments. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Hypophyllins A-D, Labdane-Type Diterpenoids with Vasorelaxant Activity from Hypoestes phyllostachya "Rosea".

    PubMed

    Wu, Xing-De; Luo, Dan; Tu, Wen-Chao; Deng, Zhen-Tao; Chen, Xue-Jiao; Su, Jia; Ji, Xu; Zhao, Qin-Shi

    2016-12-16

    Three rearranged labdane-type diterpenoids, hypophyllins A-C (1-3), and a caged labdane diterpenoid possessing a 8,9-dioxatricyclic[4.2.1.1 3,7 ]decane moiety, hypophyllin D (4), as well as two new biogenetically related diterpernoids, hypophyllins E (5) and F (6), were isolated from the aerial parts of Hypoestes phyllostachya "Rosea". The absolute configurations of 1-4 were determined by X-ray diffraction analysis. The plausible biogenetic pathway for 1-4 was also proposed. Compounds 4 and 5 showed potent vasorelaxant activity on endothelium-intact thoracic aorta rings precontracted with KCl.

  8. Racemic alkaloids from the fungus Ganoderma cochlear.

    PubMed

    Wang, Xin-Long; Dou, Man; Luo, Qi; Cheng, Li-Zhi; Yan, Yong-Ming; Li, Rong-Tao; Cheng, Yong-Xian

    2017-01-01

    Seven pairs of new alkaloid enantiomers, ganocochlearines C-I (1, 3-8), and three pairs of known alkaloids were isolated from the fruiting bodies of Ganoderma cochlear. The chemical structures of new compounds were elucidated on the basis of 1D and 2D NMR data. The absolute configurations of compounds 1, 3-10 were assigned by ECD calculations. Biological activities of these isolates against renal fibrosis were accessed in rat normal or diseased renal interstitial fibroblast cells. Importantly, the plausible biosynthetic pathway for this class of alkaloids was originally proposed. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. TAS3 miR390-dependent loci in non-vascular land plants: towards a comprehensive reconstruction of the gene evolutionary history.

    PubMed

    Morozov, Sergey Y; Milyutina, Irina A; Erokhina, Tatiana N; Ozerova, Liudmila V; Troitsky, Alexey V; Solovyev, Andrey G

    2018-01-01

    Trans-acting small interfering RNAs (ta-siRNAs) are transcribed from protein non-coding genomic TAS loci and belong to a plant-specific class of endogenous small RNAs. These siRNAs have been found to regulate gene expression in most taxa including seed plants, gymnosperms, ferns and mosses. In this study, bioinformatic and experimental PCR-based approaches were used as tools to analyze TAS3 and TAS6 loci in transcriptomes and genomic DNAs from representatives of evolutionary distant non-vascular plant taxa such as Bryophyta, Marchantiophyta and Anthocerotophyta. We revealed previously undiscovered TAS3 loci in plant classes Sphagnopsida and Anthocerotopsida, as well as TAS6 loci in Bryophyta classes Tetraphidiopsida, Polytrichopsida, Andreaeopsida and Takakiopsida. These data further unveil the evolutionary pathway of the miR390-dependent TAS3 loci in land plants. We also identified charophyte alga sequences coding for SUPPRESSOR OF GENE SILENCING 3 (SGS3), which is required for generation of ta-siRNAs in plants, and hypothesized that the appearance of TAS3-related sequences could take place at a very early step in evolutionary transition from charophyte algae to an earliest common ancestor of land plants.

  10. Evolutionary History of the Enzymes Involved in the Calvin-Benson Cycle in Euglenids.

    PubMed

    Markunas, Chelsea M; Triemer, Richard E

    2016-05-01

    Euglenids are an ancient lineage that may have existed as early as 2 billion years ago. A mere 65 years ago, Melvin Calvin and Andrew A. Benson performed experiments on Euglena gracilis and elucidated the series of reactions by which carbon was fixed and reduced during photosynthesis. However, the evolutionary history of this pathway (Calvin-Benson cycle) in euglenids was more complex than Calvin and Benson could have imagined. The chloroplast present today in euglenophytes arose from a secondary endosymbiosis between a phagotrophic euglenid and a prasinophyte green alga. A long period of evolutionary time existed before this secondary endosymbiotic event took place, which allowed for other endosymbiotic events or gene transfers to occur prior to the establishment of the green chloroplast. This research revealed the evolutionary history of the major enzymes of the Calvin-Benson cycle throughout the euglenid lineage and showed that the majority of genes for Calvin-Benson cycle enzymes shared an ancestry with red algae and/or chromophytes suggesting they may have been transferred to the nucleus prior to the acquisition of the green chloroplast. © 2015 The Author(s) Journal of Eukaryotic Microbiology © 2015 International Society of Protistologists.

  11. Evolutionary medicine.

    PubMed

    Swynghedauw, B

    2004-04-01

    Nothing in biology makes sense except in the light of evolution. Evolutionary, or darwinian, medicine takes the view that contemporary diseases result from incompatibility between the conditions under which the evolutionary pressure had modified our genetic endowment and the lifestyle and dietary habits in which we are currently living, including the enhanced lifespan, the changes in dietary habits and the lack of physical activity. An evolutionary trait express a genetic polymorphism which finally improve fitness, it needs million years to become functional. A limited genetic diversity is a necessary prerequisite for evolutionary medicine. Nevertheless, search for a genetic endowment would become nearly impossible if the human races were genetically different. From a genetic point of view, homo sapiens, is homogeneous, and the so-called human races have only a socio-economic definition. Historically, Heart Failure, HF, had an infectious origin and resulted from mechanical overload which triggered mechanoconversion by using phylogenically ancient pleiotropic pathways. Adaptation was mainly caused by negative inotropism. Recently, HF was caused by a complex remodelling caused by the trophic effects of mechanics, ischemia, senescence, diabetes and, neurohormones. The generally admitted hypothesis is that cancers were largely caused by a combination of modern reproductive and dietary lifestyles mismatched with genotypic traits, plus the longer time available for a confrontation. Such a concept is illustrated for skin and breast cancers, and also for the link between cancer risk and dietary habits.

  12. Dependence of prevalence of contiguous pathways in proteins on structural complexity.

    PubMed

    Thayer, Kelly M; Galganov, Jesse C; Stein, Avram J

    2017-01-01

    Allostery is a regulatory mechanism in proteins where an effector molecule binds distal from an active site to modulate its activity. Allosteric signaling may occur via a continuous path of residues linking the active and allosteric sites, which has been suggested by large conformational changes evident in crystal structures. An alternate possibility is that the signal occurs in the realm of ensemble dynamics via an energy landscape change. While the latter was first proposed on theoretical grounds, increasing evidence suggests that such a control mechanism is plausible. A major difficulty for testing the two methods is the ability to definitively determine that a residue is directly involved in allosteric signal transduction. Statistical Coupling Analysis (SCA) is a method that has been successful at predicting pathways, and experimental tests involving mutagenesis or domain substitution provide the best available evidence of signaling pathways. However, ascertaining energetic pathways which need not be contiguous is far more difficult. To date, simple estimates of the statistical significance of a pathway in a protein remain to be established. The focus of this work is to estimate such benchmarks for the statistical significance of contiguous pathways for the null model of selecting residues at random. We found that when 20% of residues in proteins are randomly selected, contiguous pathways at the 6 Å cutoff level were found with success rates of 51% in PDZ, 30% in p53, and 3% in MutS. The results suggest that the significance of pathways may have system specific factors involved. Furthermore, the possible existence of false positives for contiguous pathways implies that signaling could be occurring via alternate routes including those consistent with the energetic landscape model.

  13. The MST/Hippo Pathway and Cell Death: A Non-Canonical Affair

    PubMed Central

    Fallahi, Emma; O’Driscoll, Niamh A.; Matallanas, David

    2016-01-01

    The MST/Hippo signalling pathway was first described over a decade ago in Drosophila melanogaster and the core of the pathway is evolutionary conserved in mammals. The mammalian MST/Hippo pathway regulates organ size, cell proliferation and cell death. In addition, it has been shown to play a central role in the regulation of cellular homeostasis and it is commonly deregulated in human tumours. The delineation of the canonical pathway resembles the behaviour of the Hippo pathway in the fly where the activation of the core kinases of the pathway prevents the proliferative signal mediated by the key effector of the pathway YAP. Nevertheless, several lines of evidence support the idea that the mammalian MST/Hippo pathway has acquired new features during evolution, including different regulators and effectors, crosstalk with other essential signalling pathways involved in cellular homeostasis and the ability to actively trigger cell death. Here we describe the current knowledge of the mechanisms that mediate MST/Hippo dependent cell death, especially apoptosis. We include evidence for the existence of complex signalling networks where the core proteins of the pathway play a central role in controlling the balance between survival and cell death. Finally, we discuss the possible involvement of these signalling networks in several human diseases such as cancer, diabetes and neurodegenerative disorders. PMID:27322327

  14. The Universal Plausibility Metric (UPM) & Principle (UPP).

    PubMed

    Abel, David L

    2009-12-03

    Mere possibility is not an adequate basis for asserting scientific plausibility. A precisely defined universal bound is needed beyond which the assertion of plausibility, particularly in life-origin models, can be considered operationally falsified. But can something so seemingly relative and subjective as plausibility ever be quantified? Amazingly, the answer is, "Yes." A method of objectively measuring the plausibility of any chance hypothesis (The Universal Plausibility Metric [UPM]) is presented. A numerical inequality is also provided whereby any chance hypothesis can be definitively falsified when its UPM metric of xi is < 1 (The Universal Plausibility Principle [UPP]). Both UPM and UPP pre-exist and are independent of any experimental design and data set. No low-probability hypothetical plausibility assertion should survive peer-review without subjection to the UPP inequality standard of formal falsification (xi < 1).

  15. Tum1 is involved in the metabolism of sterol esters in Saccharomyces cerevisiae.

    PubMed

    Uršič, Katja; Ogrizović, Mojca; Kordiš, Dušan; Natter, Klaus; Petrovič, Uroš

    2017-08-22

    The only hitherto known biological role of yeast Saccharomyces cerevisiae Tum1 protein is in the tRNA thiolation pathway. The mammalian homologue of the yeast TUM1 gene, the thiosulfate sulfurtransferase (a.k.a. rhodanese) Tst, has been proposed as an obesity-resistance and antidiabetic gene. To assess the role of Tum1 in cell metabolism and the putative functional connection between lipid metabolism and tRNA modification, we analysed evolutionary conservation of the rhodanese protein superfamily, investigated the role of Tum1 in lipid metabolism, and examined the phenotype of yeast strains expressing the mouse homologue of Tum1, TST. We analysed evolutionary relationships in the rhodanese superfamily and established that its members are widespread in bacteria, archaea and in all major eukaryotic groups. We found that the amount of sterol esters was significantly higher in the deletion strain tum1Δ than in the wild-type strain. Expression of the mouse TST protein in the deletion strain did not rescue this phenotype. Moreover, although Tum1 deficiency in the thiolation pathway was complemented by re-introducing TUM1, it was not complemented by the introduction of the mouse homologue Tst. We further showed that the tRNA thiolation pathway is not involved in the regulation of sterol ester content in S. cerevisiae, as overexpression of the tE UUC , tK UUU and tQ UUG tRNAs did not rescue the lipid phenotype in the tum1Δ deletion strain, and, additionally, deletion of the key gene for the tRNA thiolation pathway, UBA4, did not affect sterol ester content. The rhodanese superfamily of proteins is widespread in all organisms, and yeast TUM1 is a bona fide orthologue of mammalian Tst thiosulfate sulfurtransferase gene. However, the mouse TST protein cannot functionally replace yeast Tum1 protein, neither in its lipid metabolism-related function, nor in the tRNA thiolation pathway. We show here that Tum1 protein is involved in lipid metabolism by decreasing the sterol ester content in yeast cells, and that this function of Tum1 is not exerted through the tRNA thiolation pathway, but through another, currently unknown pathway.

  16. The Use of Signal-Transduction and Metabolic Pathways to Predict Human Disease Targets from Electric and Magnetic Fields Using in vitro Data in Human Cell Lines

    PubMed Central

    Parham, Fred; Portier, Christopher J.; Chang, Xiaoqing; Mevissen, Meike

    2016-01-01

    Using in vitro data in human cell lines, several research groups have investigated changes in gene expression in cellular systems following exposure to extremely low frequency (ELF) and radiofrequency (RF) electromagnetic fields (EMF). For ELF EMF, we obtained five studies with complete microarray data and three studies with only lists of significantly altered genes. Likewise, for RF EMF, we obtained 13 complete microarray datasets and 5 limited datasets. Plausible linkages between exposure to ELF and RF EMF and human diseases were identified using a three-step process: (a) linking genes associated with classes of human diseases to molecular pathways, (b) linking pathways to ELF and RF EMF microarray data, and (c) identifying associations between human disease and EMF exposures where the pathways are significantly similar. A total of 60 pathways were associated with human diseases, mostly focused on basic cellular functions like JAK–STAT signaling or metabolic functions like xenobiotic metabolism by cytochrome P450 enzymes. ELF EMF datasets were sporadically linked to human diseases, but no clear pattern emerged. Individual datasets showed some linkage to cancer, chemical dependency, metabolic disorders, and neurological disorders. RF EMF datasets were not strongly linked to any disorders but strongly linked to changes in several pathways. Based on these analyses, the most promising area for further research would be to focus on EMF and neurological function and disorders. PMID:27656641

  17. A Systems Biology Analysis Unfolds the Molecular Pathways and Networks of Two Proteobacteria in Spaceflight and Simulated Microgravity Conditions

    NASA Astrophysics Data System (ADS)

    Roy, Raktim; Phani Shilpa, P.; Bagh, Sangram

    2016-09-01

    Bacteria are important organisms for space missions due to their increased pathogenesis in microgravity that poses risks to the health of astronauts and for projected synthetic biology applications at the space station. We understand little about the effect, at the molecular systems level, of microgravity on bacteria, despite their significant incidence. In this study, we proposed a systems biology pipeline and performed an analysis on published gene expression data sets from multiple seminal studies on Pseudomonas aeruginosa and Salmonella enterica serovar Typhimurium under spaceflight and simulated microgravity conditions. By applying gene set enrichment analysis on the global gene expression data, we directly identified a large number of new, statistically significant cellular and metabolic pathways involved in response to microgravity. Alteration of metabolic pathways in microgravity has rarely been reported before, whereas in this analysis metabolic pathways are prevalent. Several of those pathways were found to be common across studies and species, indicating a common cellular response in microgravity. We clustered genes based on their expression patterns using consensus non-negative matrix factorization. The genes from different mathematically stable clusters showed protein-protein association networks with distinct biological functions, suggesting the plausible functional or regulatory network motifs in response to microgravity. The newly identified pathways and networks showed connection with increased survival of pathogens within macrophages, virulence, and antibiotic resistance in microgravity. Our work establishes a systems biology pipeline and provides an integrated insight into the effect of microgravity at the molecular systems level.

  18. The evolutionary capacitor HSP90 buffers the regulatory effects of mammalian endogenous retroviruses.

    PubMed

    Hummel, Barbara; Hansen, Erik C; Yoveva, Aneliya; Aprile-Garcia, Fernando; Hussong, Rebecca; Sawarkar, Ritwick

    2017-03-01

    Understanding how genotypes are linked to phenotypes is important in biomedical and evolutionary studies. The chaperone heat-shock protein 90 (HSP90) buffers genetic variation by stabilizing proteins with variant sequences, thereby uncoupling phenotypes from genotypes. Here we report an unexpected role of HSP90 in buffering cis-regulatory variation affecting gene expression. By using the tripartite-motif-containing 28 (TRIM28; also known as KAP1)-mediated epigenetic pathway, HSP90 represses the regulatory influence of endogenous retroviruses (ERVs) on neighboring genes that are critical for mouse development. Our data based on natural variations in the mouse genome show that genes respond to HSP90 inhibition in a manner dependent on their genomic location with regard to strain-specific ERV-insertion sites. The evolutionary-capacitor function of HSP90 may thus have facilitated the exaptation of ERVs as key modifiers of gene expression and morphological diversification. Our findings add a new regulatory layer through which HSP90 uncouples phenotypic outcomes from individual genotypes.

  19. Light-harvesting antenna complexes in the moss Physcomitrella patens: implications for the evolutionary transition from green algae to land plants.

    PubMed

    Iwai, Masakazu; Yokono, Makio

    2017-06-01

    Plants have successfully adapted to a vast range of terrestrial environments during their evolution. To elucidate the evolutionary transition of light-harvesting antenna proteins from green algae to land plants, the moss Physcomitrella patens is ideally placed basally among land plants. Compared to the genomes of green algae and land plants, the P. patens genome codes for more diverse and redundant light-harvesting antenna proteins. It also encodes Lhcb9, which has characteristics not found in other light-harvesting antenna proteins. The unique complement of light-harvesting antenna proteins in P. patens appears to facilitate protein interactions that include those lost in both green algae and land plants with regard to stromal electron transport pathways and photoprotection mechanisms. This review will highlight unique characteristics of the P. patens light-harvesting antenna system and the resulting implications about the evolutionary transition during plant terrestrialization. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Science, precaution, and the politics of technological risk: converging implications in evolutionary and social scientific perspectives.

    PubMed

    Stirling, Andy

    2008-04-01

    This paper examines apparent tensions between "science-based," "precautionary," and "participatory" approaches to decision making on risk. Partly by reference to insights currently emerging in evolutionary studies, the present paper looks for ways to reconcile some of the contradictions. First, I argue that technological evolution is a much more plural and open-ended process than is conventionally supposed. Risk politics is thus implicitly as much about social choice of technological pathways as narrow issues of safety. Second, it is shown how conventional "science-based" risk assessment techniques address only limited aspects of incomplete knowledge in complex, dynamic, evolutionary processes. Together, these understandings open the door to more sophisticated, comprehensive, rational, and robust decision-making processes. Despite their own limitations, it is found that precautionary and participatory approaches help to address these needs. A concrete framework is outlined through which the synergies can be more effectively harnessed. By this means, we can hope simultaneously to improve scientific rigor and democratic legitimacy in risk governance.

  1. Combining chemoinformatics with bioinformatics: in silico prediction of bacterial flavor-forming pathways by a chemical systems biology approach "reverse pathway engineering".

    PubMed

    Liu, Mengjin; Bienfait, Bruno; Sacher, Oliver; Gasteiger, Johann; Siezen, Roland J; Nauta, Arjen; Geurts, Jan M W

    2014-01-01

    The incompleteness of genome-scale metabolic models is a major bottleneck for systems biology approaches, which are based on large numbers of metabolites as identified and quantified by metabolomics. Many of the revealed secondary metabolites and/or their derivatives, such as flavor compounds, are non-essential in metabolism, and many of their synthesis pathways are unknown. In this study, we describe a novel approach, Reverse Pathway Engineering (RPE), which combines chemoinformatics and bioinformatics analyses, to predict the "missing links" between compounds of interest and their possible metabolic precursors by providing plausible chemical and/or enzymatic reactions. We demonstrate the added-value of the approach by using flavor-forming pathways in lactic acid bacteria (LAB) as an example. Established metabolic routes leading to the formation of flavor compounds from leucine were successfully replicated. Novel reactions involved in flavor formation, i.e. the conversion of alpha-hydroxy-isocaproate to 3-methylbutanoic acid and the synthesis of dimethyl sulfide, as well as the involved enzymes were successfully predicted. These new insights into the flavor-formation mechanisms in LAB can have a significant impact on improving the control of aroma formation in fermented food products. Since the input reaction databases and compounds are highly flexible, the RPE approach can be easily extended to a broad spectrum of applications, amongst others health/disease biomarker discovery as well as synthetic biology.

  2. The Role of Influenza in the Delay between Low Temperature and Ischemic Heart Disease: Evidence from Simulation and Mortality Data from Japan

    PubMed Central

    Imai, Chisato; Barnett, Adrian G.; Hashizume, Masahiro; Honda, Yasushi

    2016-01-01

    Many studies have found that cardiovascular deaths mostly occur within a few days of exposure to heat, whereas cold-related deaths can occur up to 30 days after exposure. We investigated whether influenza infection could explain the delayed cold effects on ischemic heart diseases (IHD) as they can trigger IHD. We hypothesized two pathways between cold exposure and IHD: a direct pathway and an indirect pathway through influenza infection. We created a multi-state model of the pathways and simulated incidence data to examine the observed delayed patterns in cases. We conducted cross-correlation and time series analysis with Japanese daily pneumonia and influenza (P&I) mortality data to help validate our model. Simulations showed the IHD incidence through the direct pathway occurred mostly within 10 days, while IHD through influenza infection peaked at 4–6 days, followed by delayed incidences of up to 20–30 days. In the mortality data from Japan, P&I lagged IHD in cross-correlations. Time series analysis showed strong delayed cold effects in the older population. There was also a strong delay on intense days of influenza which was more noticeable in the older population. Influenza can therefore be a plausible explanation for the delayed association between cold exposure and cardiovascular mortality. PMID:27136571

  3. Resveratrol Interferes with an Early Step in the Fibrillization Pathway of Human Lysozyme and Modulates it towards Less-Toxic, Off-Pathway Aggregates.

    PubMed

    Kamal Zaidi, Fatima; Bhat, Rajiv

    2018-01-18

    The effect of resveratrol, a polyphenol in red wine, on the amyloid fibril formation of human lysozyme (HuL) was investigated, towards elucidating the mechanism of resveratrol action and probing its role as a possible modulator of lysozyme aggregation and toxicity. By using a number of biophysical tools, resveratrol was observed to alter the fibrillization kinetics of HuL and inhibit its fibrillization by binding with weak to moderate affinity to the conformations populated at the early stages of the pathway with concomitant stabilization of these initial conformations. The marginal decrease in the lifetime of HuL in the presence of resveratrol by time-resolved fluorescence measurements indicated the involvement of a static quenching mechanism in the interaction between HuL and resveratrol. Docking studies predicted the binding of resveratrol to aggregation-prone regions in HuL, and structure and activity analyses demonstrated the retention of much of the α-helical structure and activity of HuL in the presence of resveratrol. Resveratrol modulated the fibrillization pathway towards less-hydrophobic, less-toxic, off-pathway aggregates. These results demonstrate that binding of resveratrol to HuL could protect against the formation of pathogenic, cytotoxic aggregates formed in amyloidogenic disorders, such as systemic amyloidosis; thus suggesting its potential as a plausible therapeutic agent against lysozyme amyloidosis. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. ABERRANT SPLICING OF A BRAIN-ENRICHED ALTERNATIVE EXON ELIMINATES TUMOR SUPPRESSOR FUNCTION AND PROMOTES ONCOGENE FUNCTION DURING BRAIN TUMORIGENESIS

    PubMed Central

    Bredel, Markus; Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; Elverfeldt, Dominik v.; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.

    2014-01-01

    BACKGROUND: Tissue-specific alternative splicing is known to be critical to emergence of tissue identity during development, yet its role in malignant transformation is undefined. Tissue-specific splicing involves evolutionary-conserved, alternative exons, which represent only a minority of total alternative exons. Many, however, have functional features that influence activity in signaling pathways to profound biological effect. Given that tissue-specific splicing has a determinative role in brain development and the enrichment of genes containing tissue-specific exons for proteins with roles in signaling and development, it is thus plausible that changes in such exons could rewire normal neurogenesis towards malignant transformation. METHODS: We used integrated molecular genetic and cell biology analyses, computational biology, animal modeling, and clinical patient profiles to characterize the effect of aberrant splicing of a brain-enriched alternative exon in the membrane-binding tumor suppressor Annexin A7 (ANXA7) on oncogene regulation and brain tumorigenesis. RESULTS: We show that aberrant splicing of a tissue-specific cassette exon in ANXA7 diminishes endosomal targeting and consequent termination of the signal of the EGFR oncoprotein during brain tumorigenesis. Splicing of this exon is mediated by the ribonucleoprotein Polypyrimidine Tract-Binding Protein 1 (PTBP1), which is normally repressed during brain development but, we find, is excessively expressed in glioblastomas through either gene amplification or loss of a neuron-specific microRNA, miR-124. Silencing of PTBP1 attenuates both malignancy and angiogenesis in a stem cell-derived glioblastoma animal model characterized by a high native propensity to generate tumor endothelium or vascular pericytes to support tumor growth. We show that EGFR amplification and PTBP1 overexpression portend a similarly poor clinical outcome, further highlighting the importance of PTBP1-mediated activation of EGFR. CONCLUSIONS: Our data illustrate how anomalous splicing of a tissue-regulated exon in a constituent of an oncogenic signaling pathway eliminates its tumor suppressor function and promotes tumorigenesis. This paradigm of malignant glial transformation as a consequence of tissue-specific alternative exon splicing in a tumor suppressor, may have widespread applicability in explaining how changes in critical tissue-specific regulatory mechanisms reprogram normal development to oncogenesis. SECONDARY CATEGORY: n/a.

  5. The Universal Plausibility Metric (UPM) & Principle (UPP)

    PubMed Central

    2009-01-01

    Background Mere possibility is not an adequate basis for asserting scientific plausibility. A precisely defined universal bound is needed beyond which the assertion of plausibility, particularly in life-origin models, can be considered operationally falsified. But can something so seemingly relative and subjective as plausibility ever be quantified? Amazingly, the answer is, "Yes." A method of objectively measuring the plausibility of any chance hypothesis (The Universal Plausibility Metric [UPM]) is presented. A numerical inequality is also provided whereby any chance hypothesis can be definitively falsified when its UPM metric of ξ is < 1 (The Universal Plausibility Principle [UPP]). Both UPM and UPP pre-exist and are independent of any experimental design and data set. Conclusion No low-probability hypothetical plausibility assertion should survive peer-review without subjection to the UPP inequality standard of formal falsification (ξ < 1). PMID:19958539

  6. Population structure and phylogeography reveal pathways of colonization by a migratory marine reptile (Chelonia mydas) in the central and eastern Pacific.

    PubMed

    Dutton, Peter H; Jensen, Michael P; Frey, Amy; LaCasella, Erin; Balazs, George H; Zárate, Patricia; Chassin-Noria, Omar; Sarti-Martinez, Adriana Laura; Velez, Elizabeth

    2014-11-01

    Climate, behavior, ecology, and oceanography shape patterns of biodiversity in marine faunas in the absence of obvious geographic barriers. Marine turtles are an example of highly migratory creatures with deep evolutionary lineages and complex life histories that span both terrestrial and marine environments. Previous studies have focused on the deep isolation of evolutionary lineages (>3 mya) through vicariance; however, little attention has been given to the pathways of colonization of the eastern Pacific and the processes that have shaped diversity within the most recent evolutionary time. We sequenced 770 bp of the mtDNA control region to examine the stock structure and phylogeography of 545 green turtles from eight different rookeries in the central and eastern Pacific. We found significant differentiation between the geographically separated nesting populations and identified five distinct stocks (F ST = 0.08-0.44, P < 0.005). Central and eastern Pacific Chelonia mydas form a monophyletic group containing 3 subclades, with Hawaii more closely related to the eastern Pacific than western Pacific populations. The split between sampled central/eastern and western Pacific haplotypes was estimated at around 0.34 mya, suggesting that the Pacific region west of Hawaii has been a more formidable barrier to gene flow in C. mydas than the East Pacific Barrier. Our results suggest that the eastern Pacific was colonized from the western Pacific via the Central North Pacific and that the Revillagigedos Islands provided a stepping-stone for radiation of green turtles from the Hawaiian Archipelago to the eastern Pacific. Our results fit with a broader paradigm that has been described for marine biodiversity, where oceanic islands, such as Hawaii and Revillagigedo, rather than being peripheral evolutionary "graveyards", serve as sources and recipients of diversity and provide a mechanism for further radiation.

  7. Population structure and phylogeography reveal pathways of colonization by a migratory marine reptile (Chelonia mydas) in the central and eastern Pacific

    PubMed Central

    Dutton, Peter H; Jensen, Michael P; Frey, Amy; LaCasella, Erin; Balazs, George H; Zárate, Patricia; Chassin-Noria, Omar; Sarti-Martinez, Adriana Laura; Velez, Elizabeth

    2014-01-01

    Climate, behavior, ecology, and oceanography shape patterns of biodiversity in marine faunas in the absence of obvious geographic barriers. Marine turtles are an example of highly migratory creatures with deep evolutionary lineages and complex life histories that span both terrestrial and marine environments. Previous studies have focused on the deep isolation of evolutionary lineages (>3 mya) through vicariance; however, little attention has been given to the pathways of colonization of the eastern Pacific and the processes that have shaped diversity within the most recent evolutionary time. We sequenced 770 bp of the mtDNA control region to examine the stock structure and phylogeography of 545 green turtles from eight different rookeries in the central and eastern Pacific. We found significant differentiation between the geographically separated nesting populations and identified five distinct stocks (FST = 0.08–0.44, P < 0.005). Central and eastern Pacific Chelonia mydas form a monophyletic group containing 3 subclades, with Hawaii more closely related to the eastern Pacific than western Pacific populations. The split between sampled central/eastern and western Pacific haplotypes was estimated at around 0.34 mya, suggesting that the Pacific region west of Hawaii has been a more formidable barrier to gene flow in C. mydas than the East Pacific Barrier. Our results suggest that the eastern Pacific was colonized from the western Pacific via the Central North Pacific and that the Revillagigedos Islands provided a stepping-stone for radiation of green turtles from the Hawaiian Archipelago to the eastern Pacific. Our results fit with a broader paradigm that has been described for marine biodiversity, where oceanic islands, such as Hawaii and Revillagigedo, rather than being peripheral evolutionary “graveyards”, serve as sources and recipients of diversity and provide a mechanism for further radiation. PMID:25540693

  8. A Cross-Grade Study Validating the Evolutionary Pathway of Student Mental Models in Electric Circuits

    ERIC Educational Resources Information Center

    Lin, Jing-Wen

    2017-01-01

    Cross-grade studies are valuable for the development of sequential curriculum. However such studies are time and resource intensive and fail to provide a clear representation to integrate different levels of representational complexity. Lin (Lin, 2006; Lin & Chiu, 2006; Lin, Chiu, & Hsu, 2006) proposed a cladistics approach in conceptual…

  9. The Evolution of the Krebs Cycle: A Promising Subject for Meaningful Learning of Biochemistry

    ERIC Educational Resources Information Center

    da Costa, Caetano; Galembeck, Eduardo

    2016-01-01

    Evolution has been recognized as a key concept for biologists. To enhance comprehension and motivate biology undergraduates for the contents of central energetic metabolism, we addressed the Krebs cycle structure and functions in an evolutionary view. To this end, we created a study guide that contextualizes the emergence of the cyclic pathway, in…

  10. Change Ahead: Transient Scenarios for Long-term Water Management

    NASA Astrophysics Data System (ADS)

    Haasnoot, Marjolijn; Beersma, Jules; Schellekens, Jaap

    2013-04-01

    While the use of an ensemble of transient scenarios is common in climate change studies, they are rarely used in water management studies. Present planning studies on long-term water management often use a few plausible futures for one or two projection years, ignoring the dynamic aspect of adaptation through the interaction between the water system and society. Over the course of time society experiences, learns and adapts to changes and events, making policy responses part of a plausible future, and thus the success of a water management strategy. Exploring transient scenarios and policy options over time can support decision making on water management strategies in an uncertain and changing environment. We have developed and applied such a method, called exploring adaptation pathways (Haasnoot et al., 2012; Haasnoot et al., 2011). This method uses multiple realisations of transient scenarios to assess the efficacy of policy actions over time. In case specified objectives are not achieved anymore, an adaptation tipping point (Kwadijk et al., 2010) is reached. After reaching a tipping point, additional actions are needed to reach the objectives. As a result, a pathway emerges. In this presentation we describe the development of transient scenarios for long term water management, and how these scenarios can be used for long term water management under uncertainty. We illustrate this with thought experiments, and results from computational modeling experiment for exploring adaptation pathways in the lower Rhine delta. The results and the thought experiments show, among others, that climate variability is at least just as important as climate change for taking decisions in water management. References Haasnoot, M., Middelkoop, H., Offermans, A., Beek, E., Deursen, W.A.v. (2012) Exploring pathways for sustainable water management in river deltas in a changing environment. Climatic Change 115, 795-819. Haasnoot, M., Middelkoop, H., van Beek, E., van Deursen, W.P.A. (2011) A Method to Develop Sustainable Water Management Strategies for an Uncertain Future. Sustainable Development 19, 369-381. Kwadijk, J.C.J., Haasnoot, M., Mulder, J.P.M., Hoogvliet, M.M.C., Jeuken, A.B.M., van der Krogt, R.A.A., van Oostrom, N.G.C., Schelfhout, H.A., van Velzen, E.H., van Waveren, H., de Wit, M.J.M. (2010) Using adaptation tipping points to prepare for climate change and sea level rise: a case study in the Netherlands. Wiley Interdisciplinary Reviews: Climate Change 1, 729-740.

  11. The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals.

    PubMed

    Wu, Nan; Nguyen, Quy; Wan, Ying; Zhou, Tiaohao; Venter, Julie; Frampton, Gabriel A; DeMorrow, Sharon; Pan, Duojia; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco; Bai, Haibo

    2017-07-01

    The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development.

  12. The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals

    PubMed Central

    Wu, Nan; Nguyen, Quy; Wan, Ying; Zhou, Tiaohao; Venter, Julie; Frampton, Gabriel A; DeMorrow, Sharon; Pan, Duojia; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco; Bai, Haibo

    2018-01-01

    The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development. PMID:28581486

  13. Programmed cell death in trypanosomatids and other unicellular organisms.

    PubMed

    Debrabant, Alain; Lee, Nancy; Bertholet, Sylvie; Duncan, Robert; Nakhasi, Hira L

    2003-03-01

    In multicellular organisms, cellular growth and development can be controlled by programmed cell death (PCD), which is defined by a sequence of regulated events. However, PCD is thought to have evolved not only to regulate growth and development in multicellular organisms but also to have a functional role in the biology of unicellular organisms. In protozoan parasites and in other unicellular organisms, features of PCD similar to those in multicellular organisms have been reported, suggesting some commonality in the PCD pathway between unicellular and multicellular organisms. However, more extensive studies are needed to fully characterise the PCD pathway and to define the factors that control PCD in the unicellular organisms. The understanding of the PCD pathway in unicellular organisms could delineate the evolutionary origin of this pathway. Further characterisation of the PCD pathway in the unicellular parasites could provide information regarding their pathogenesis, which could be exploited to target new drugs to limit their growth and treat the disease they cause.

  14. Optimal regulatory strategies for metabolic pathways in Escherichia coli depending on protein costs

    PubMed Central

    Wessely, Frank; Bartl, Martin; Guthke, Reinhard; Li, Pu; Schuster, Stefan; Kaleta, Christoph

    2011-01-01

    While previous studies have shed light on the link between the structure of metabolism and its transcriptional regulation, the extent to which transcriptional regulation controls metabolism has not yet been fully explored. In this work, we address this problem by integrating a large number of experimental data sets with a model of the metabolism of Escherichia coli. Using a combination of computational tools including the concept of elementary flux patterns, methods from network inference and dynamic optimization, we find that transcriptional regulation of pathways reflects the protein investment into these pathways. While pathways that are associated to a high protein cost are controlled by fine-tuned transcriptional programs, pathways that only require a small protein cost are transcriptionally controlled in a few key reactions. As a reason for the occurrence of these different regulatory strategies, we identify an evolutionary trade-off between the conflicting requirements to reduce protein investment and the requirement to be able to respond rapidly to changes in environmental conditions. PMID:21772263

  15. The cold response of CBF genes in barley is regulated by distinct signaling mechanisms.

    PubMed

    Marozsán-Tóth, Zsuzsa; Vashegyi, Ildikó; Galiba, Gábor; Tóth, Balázs

    2015-06-01

    Cold acclimation ability is crucial in the winter survival of cereals. In this process CBF transcription factors play key role, therefore understanding the regulation of these genes might provide useful knowledge for molecular breeding. In the present study the signal transduction pathways leading to the cold induction of different CBF genes were investigated in barley cv. Nure using pharmacological approach. Our results showed that the cold induced expression of CBF9 and CBF14 transcription factors is regulated by phospholipase C, phospholipase D pathways and calcium. On the contrary, these pathways have negative effect on the cold induction of CBF12 that is regulated by a different, as yet unidentified pathway. The diversity in the regulation of these transcription factors corresponds to their sequence based phylogenetic relationships suggesting that their evolutionary separation happened on structural, functional and regulational levels as well. On the CBF effector gene level, the signaling regulation is more complex, resultant effect of multiple pathways. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. Aldolase positively regulates of the canonical Wnt signaling pathway

    PubMed Central

    2014-01-01

    The Wnt signaling pathway is an evolutionary conserved system, having pivotal roles during animal development. When over-activated, this signaling pathway is involved in cancer initiation and progression. The canonical Wnt pathway regulates the stability of β-catenin primarily by a destruction complex containing a number of different proteins, including Glycogen synthase kinase 3β (GSK-3β) and Axin, that promote proteasomal degradation of β-catenin. As this signaling cascade is modified by various proteins, novel screens aimed at identifying new Wnt signaling regulators were conducted in our laboratory. One of the different genes that were identified as Wnt signaling activators was Aldolase C (ALDOC). Here we report that ALDOC, Aldolase A (ALDOA) and Aldolase B (ALDOB) activate Wnt signaling in a GSK-3β-dependent mechanism, by disrupting the GSK-3β-Axin interaction and targeting Axin to the dishevelled (Dvl)-induced signalosomes that positively regulate the Wnt pathway thus placing the Aldolase proteins as novel Wnt signaling regulators. PMID:24993527

  17. A Systems Biology Analysis Unfolds the Molecular Pathways and Networks of Two Proteobacteria in Spaceflight and Simulated Microgravity Conditions.

    PubMed

    Roy, Raktim; Shilpa, P Phani; Bagh, Sangram

    2016-09-01

    Bacteria are important organisms for space missions due to their increased pathogenesis in microgravity that poses risks to the health of astronauts and for projected synthetic biology applications at the space station. We understand little about the effect, at the molecular systems level, of microgravity on bacteria, despite their significant incidence. In this study, we proposed a systems biology pipeline and performed an analysis on published gene expression data sets from multiple seminal studies on Pseudomonas aeruginosa and Salmonella enterica serovar Typhimurium under spaceflight and simulated microgravity conditions. By applying gene set enrichment analysis on the global gene expression data, we directly identified a large number of new, statistically significant cellular and metabolic pathways involved in response to microgravity. Alteration of metabolic pathways in microgravity has rarely been reported before, whereas in this analysis metabolic pathways are prevalent. Several of those pathways were found to be common across studies and species, indicating a common cellular response in microgravity. We clustered genes based on their expression patterns using consensus non-negative matrix factorization. The genes from different mathematically stable clusters showed protein-protein association networks with distinct biological functions, suggesting the plausible functional or regulatory network motifs in response to microgravity. The newly identified pathways and networks showed connection with increased survival of pathogens within macrophages, virulence, and antibiotic resistance in microgravity. Our work establishes a systems biology pipeline and provides an integrated insight into the effect of microgravity at the molecular systems level. Systems biology-Microgravity-Pathways and networks-Bacteria. Astrobiology 16, 677-689.

  18. Impact of constitutional copy number variants on biological pathway evolution.

    PubMed

    Poptsova, Maria; Banerjee, Samprit; Gokcumen, Omer; Rubin, Mark A; Demichelis, Francesca

    2013-01-23

    Inherited Copy Number Variants (CNVs) can modulate the expression levels of individual genes. However, little is known about how CNVs alter biological pathways and how this varies across different populations. To trace potential evolutionary changes of well-described biological pathways, we jointly queried the genomes and the transcriptomes of a collection of individuals with Caucasian, Asian or Yoruban descent combining high-resolution array and sequencing data. We implemented an enrichment analysis of pathways accounting for CNVs and genes sizes and detected significant enrichment not only in signal transduction and extracellular biological processes, but also in metabolism pathways. Upon the estimation of CNV population differentiation (CNVs with different polymorphism frequencies across populations), we evaluated that 22% of the pathways contain at least one gene that is proximal to a CNV (CNV-gene pair) that shows significant population differentiation. The majority of these CNV-gene pairs belong to signal transduction pathways and 6% of the CNV-gene pairs show statistical association between the copy number states and the transcript levels. The analysis suggested possible examples of positive selection within individual populations including NF-kB, MAPK signaling pathways, and Alu/L1 retrotransposition factors. Altogether, our results suggest that constitutional CNVs may modulate subtle pathway changes through specific pathway enzymes, which may become fixed in some populations.

  19. Impact of constitutional copy number variants on biological pathway evolution

    PubMed Central

    2013-01-01

    Background Inherited Copy Number Variants (CNVs) can modulate the expression levels of individual genes. However, little is known about how CNVs alter biological pathways and how this varies across different populations. To trace potential evolutionary changes of well-described biological pathways, we jointly queried the genomes and the transcriptomes of a collection of individuals with Caucasian, Asian or Yoruban descent combining high-resolution array and sequencing data. Results We implemented an enrichment analysis of pathways accounting for CNVs and genes sizes and detected significant enrichment not only in signal transduction and extracellular biological processes, but also in metabolism pathways. Upon the estimation of CNV population differentiation (CNVs with different polymorphism frequencies across populations), we evaluated that 22% of the pathways contain at least one gene that is proximal to a CNV (CNV-gene pair) that shows significant population differentiation. The majority of these CNV-gene pairs belong to signal transduction pathways and 6% of the CNV-gene pairs show statistical association between the copy number states and the transcript levels. Conclusions The analysis suggested possible examples of positive selection within individual populations including NF-kB, MAPK signaling pathways, and Alu/L1 retrotransposition factors. Altogether, our results suggest that constitutional CNVs may modulate subtle pathway changes through specific pathway enzymes, which may become fixed in some populations. PMID:23342974

  20. Characterization of the gaseous companion κ Andromedae b. New Keck and LBTI high-contrast observations

    NASA Astrophysics Data System (ADS)

    Bonnefoy, M.; Currie, T.; Marleau, G.-D.; Schlieder, J. E.; Wisniewski, J.; Carson, J.; Covey, K. R.; Henning, T.; Biller, B.; Hinz, P.; Klahr, H.; Marsh Boyer, A. N.; Zimmerman, N.; Janson, M.; McElwain, M.; Mordasini, C.; Skemer, A.; Bailey, V.; Defrère, D.; Thalmann, C.; Skrutskie, M.; Allard, F.; Homeier, D.; Tamura, M.; Feldt, M.; Cumming, A.; Grady, C.; Brandner, W.; Helling, C.; Witte, S.; Hauschildt, P.; Kandori, R.; Kuzuhara, M.; Fukagawa, M.; Kwon, J.; Kudo, T.; Hashimoto, J.; Kusakabe, N.; Abe, L.; Brandt, T.; Egner, S.; Guyon, O.; Hayano, Y.; Hayashi, M.; Hayashi, S.; Hodapp, K.; Ishii, M.; Iye, M.; Knapp, G.; Matsuo, T.; Mede, K.; Miyama, M.; Morino, J.-I.; Moro-Martin, A.; Nishimura, T.; Pyo, T.; Serabyn, E.; Suenaga, T.; Suto, H.; Suzuki, R.; Takahashi; Takami, M.; Takato, N.; Terada, H.; Tomono, D.; Turner, E.; Watanabe, M.; Yamada, T.; Takami, H.; Usuda, T.

    2014-02-01

    Context. We previously reported the direct detection of a low-mass companion at a projected separation of 55 ± 2 AU around the B9-type star κ Andromedae. The properties of the system (mass ratio, separation) make it a benchmark for understanding the formation and evolution of gas giant planets and brown dwarfs on wide orbits. Aims: We present new angular differential imaging (ADI) images of the system at 2.146 (Ks), 3.776 (L'), 4.052 (NB_4.05), and 4.78 μm (M') obtained with Keck/NIRC2 and LBTI/LMIRCam, as well as more accurate near-infrared photometry of the star with the MIMIR instrument. We aim to determine the near-infrared spectral energy distribution of the companion and use it to characterize the object. Methods: We used analysis methods adapted to ADI to extract the companion flux. We compared the photometry of the object to reference young, and old objects and to a set of seven PHOENIX-based atmospheric models of cool objects accounting for the formation of dust. We used evolutionary models to derive mass estimates considering a wide range of plausible initial conditions. Finally, we used dedicated formation models to discuss the possible origin of the companion. Results: We derive a more accurate J = 15.86 ± 0.21, H = 14.95 ± 0.13, Ks = 14.32 ± 0.09 mag for κ And b. We detect the companion in all our high-contrast observations. We confirm previous contrasts obtained at Ks and L' band. We derive NB_4.05 = 13.0 ± 0.2, and M' = 13.3 ± 0.3 mag and estimate log 10(L/L⊙) = -3.76 ± 0.06. Atmospheric models yield Teff = 1900+100-200 K. They do not set any constraint on the surface gravity. "Hot-start" evolutionary models predict masses of 14+25-2 MJup based on the luminosity and temperature estimates, and when considering a conservative age range for the system (30+120-10 Myr), "warm-start" evolutionary tracks constrain the mass to M ≥ 10MJup. Conclusions: The mass of κ Andromedae b mostly falls in the brown-dwarf regime, owing to remaining uncertainties in age and in mass-luminosity models. According to the formation models, disk instability in a primordial disk may account for the position and a wide range of plausible masses of κ And b. The LBT is an international collaboration among institutions in the United States, Italy, and Germany. LBT Corporation partners are: The University of Arizona on behalf of the Arizona university system; Instituto Nazionale di Astrofisica, Italy; LBT Beteiligungsgesellschaft, Germany, representing the Max-Planck Society, the Astrophysical Institute Potsdam, and Heidelberg University; The Ohio State University, and The Research Corporation, on behalf of the University of Notre Dame, University of Minnesota, and University of Virginia.Appendices are available in electronic form at http://www.aanda.org

  1. Cultural group selection plays an essential role in explaining human cooperation: A sketch of the evidence.

    PubMed

    Richerson, Peter; Baldini, Ryan; Bell, Adrian V; Demps, Kathryn; Frost, Karl; Hillis, Vicken; Mathew, Sarah; Newton, Emily K; Naar, Nicole; Newson, Lesley; Ross, Cody; Smaldino, Paul E; Waring, Timothy M; Zefferman, Matthew

    2016-01-01

    Human cooperation is highly unusual. We live in large groups composed mostly of non-relatives. Evolutionists have proposed a number of explanations for this pattern, including cultural group selection and extensions of more general processes such as reciprocity, kin selection, and multi-level selection acting on genes. Evolutionary processes are consilient; they affect several different empirical domains, such as patterns of behavior and the proximal drivers of that behavior. In this target article, we sketch the evidence from five domains that bear on the explanatory adequacy of cultural group selection and competing hypotheses to explain human cooperation. Does cultural transmission constitute an inheritance system that can evolve in a Darwinian fashion? Are the norms that underpin institutions among the cultural traits so transmitted? Do we observe sufficient variation at the level of groups of considerable size for group selection to be a plausible process? Do human groups compete, and do success and failure in competition depend upon cultural variation? Do we observe adaptations for cooperation in humans that most plausibly arose by cultural group selection? If the answer to one of these questions is "no," then we must look to other hypotheses. We present evidence, including quantitative evidence, that the answer to all of the questions is "yes" and argue that we must take the cultural group selection hypothesis seriously. If culturally transmitted systems of rules (institutions) that limit individual deviance organize cooperation in human societies, then it is not clear that any extant alternative to cultural group selection can be a complete explanation.

  2. Annals of morphology. Atavisms: phylogenetic Lazarus?

    PubMed

    Zanni, Ginevra; Opitz, John M

    2013-11-01

    Dedication: with highest respect and affection to Prof. Giovanni Neri on the eve of his official administrative retirement as Chair of the Institute of Medical Genetics of the Università Cattolica of Rome for leadership in medical genetics and medical science and friendship for decades. The concept "atavism," reversion, throwback, Rückschlag remains an epistemological challenge in biology; unwise or implausible over-interpretation of a given structure as such has led some to almost total skepticism as to its existence. Originating in botany in the 18th century it became applied to zoology (and humans) with increasing frequency over the last two centuries such that the very concept became widely discredited. Presently, atavisms have acquired a new life and reconsideration given certain reasonable criteria, including: Homology of structure of the postulated atavism to that of ancestral fossils or collateral species with plausible soft tissue reconstructions taking into account relationships of parts, obvious sites of origin and insertion of muscles, vascular channels, etc. Most parsimonious, plausible phylogenetic assumptions. Evident rudimentary or vestigial anatomical state in prior generations or in morphogenesis of a given organism. Developmental instability in prior generations, that is, some closely related species facultatively with or without the trait. Genetic identity or phylogenomic similarity inferred in ancestors and corroborated in more or less closely related species. Fluctuating asymmetry may be the basis for the striking evolutionary diversification and common atavisms in limbs; however, strong selection and developmental constraints would make atavisms in, for example, cardiac or CNS development less likely. Thus, purported atavisms must be examined critically in light of the above criteria. © 2013 Wiley Periodicals, Inc.

  3. Spatiotemporal analysis of projected impacts of climate change on the major C3 and C4 crop yield under representative concentration pathway 4.5: Insight from the coasts of Tamil Nadu, South India

    PubMed Central

    A, Ramachandran; Praveen, Dhanya; R, Jaganathan; D, RajaLakshmi; K, Palanivelu

    2017-01-01

    India's dependence on a climate sensitive sector like agriculture makes it highly vulnerable to its impacts. However, agriculture is highly heterogeneous across the country owing to regional disparities in exposure, sensitivity, and adaptive capacity. It is essential to know and quantify the possible impacts of changes in climate on crop yield for successful agricultural management and planning at a local scale. The Hadley Centre Global Environment Model version 2-Earth System (HadGEM-ES) was employed to generate regional climate projections for the study area using the Regional Climate Model (RCM) RegCM4.4. The dynamics in potential impacts at the sub-district level were evaluated using the Representative Concentration Pathway 4.5 (RCPs). The aim of this study was to simulate the crop yield under a plausible change in climate for the coastal areas of South India through the end of this century. The crop simulation model, the Decision Support System for Agrotechnology Transfer (DSSAT) 4.5, was used to understand the plausible impacts on the major crop yields of rice, groundnuts, and sugarcane under the RCP 4.5 trajectory. The findings reveal that under the RCP 4.5 scenario there will be decreases in the major C3 and C4 crop yields in the study area. This would affect not only the local food security, but the livelihood security as well. This necessitates timely planning to achieve sustainable crop productivity and livelihood security. On the other hand, this situation warrants appropriate adaptations and policy intervention at the sub-district level for achieving sustainable crop productivity in the future. PMID:28753605

  4. Spatiotemporal analysis of projected impacts of climate change on the major C3 and C4 crop yield under representative concentration pathway 4.5: Insight from the coasts of Tamil Nadu, South India.

    PubMed

    A, Ramachandran; Praveen, Dhanya; R, Jaganathan; D, RajaLakshmi; K, Palanivelu

    2017-01-01

    India's dependence on a climate sensitive sector like agriculture makes it highly vulnerable to its impacts. However, agriculture is highly heterogeneous across the country owing to regional disparities in exposure, sensitivity, and adaptive capacity. It is essential to know and quantify the possible impacts of changes in climate on crop yield for successful agricultural management and planning at a local scale. The Hadley Centre Global Environment Model version 2-Earth System (HadGEM-ES) was employed to generate regional climate projections for the study area using the Regional Climate Model (RCM) RegCM4.4. The dynamics in potential impacts at the sub-district level were evaluated using the Representative Concentration Pathway 4.5 (RCPs). The aim of this study was to simulate the crop yield under a plausible change in climate for the coastal areas of South India through the end of this century. The crop simulation model, the Decision Support System for Agrotechnology Transfer (DSSAT) 4.5, was used to understand the plausible impacts on the major crop yields of rice, groundnuts, and sugarcane under the RCP 4.5 trajectory. The findings reveal that under the RCP 4.5 scenario there will be decreases in the major C3 and C4 crop yields in the study area. This would affect not only the local food security, but the livelihood security as well. This necessitates timely planning to achieve sustainable crop productivity and livelihood security. On the other hand, this situation warrants appropriate adaptations and policy intervention at the sub-district level for achieving sustainable crop productivity in the future.

  5. Ambient air pollution and thrombosis.

    PubMed

    Robertson, Sarah; Miller, Mark R

    2018-01-03

    Air pollution is a growing public health concern of global significance. Acute and chronic exposure is known to impair cardiovascular function, exacerbate disease and increase cardiovascular mortality. Several plausible biological mechanisms have been proposed for these associations, however, at present, the pathways are incomplete. A seminal review by the American Heart Association (2010) concluded that the thrombotic effects of particulate air pollution likely contributed to their effects on cardiovascular mortality and morbidity. The aim of the current review is to appraise the newly accumulated scientific evidence (2009-2016) on contribution of haemostasis and thrombosis towards cardiovascular disease induced by exposure to both particulate and gaseous pollutants.Seventy four publications were reviewed in-depth. The weight of evidence suggests that acute exposure to fine particulate matter (PM 2.5 ) induces a shift in the haemostatic balance towards a pro-thrombotic/pro-coagulative state. Insufficient data was available to ascertain if a similar relationship exists for gaseous pollutants, and very few studies have addressed long-term exposure to ambient air pollution. Platelet activation, oxidative stress, interplay between interleukin-6 and tissue factor, all appear to be potentially important mechanisms in pollution-mediated thrombosis, together with an emerging role for circulating microvesicles and epigenetic changes.Overall, the recent literature supports, and arguably strengthens, the contention that air pollution contributes to cardiovascular morbidity by promoting haemostasis. The volume and diversity of the evidence highlights the complexity of the pathophysiologic mechanisms by which air pollution promotes thrombosis; multiple pathways are plausible and it is most likely they act in concert. Future research should address the role gaseous pollutants play in the cardiovascular effects of air pollution mixture and direct comparison of potentially susceptible groups to healthy individuals.

  6. Compact continuum brain model for human electroencephalogram

    NASA Astrophysics Data System (ADS)

    Kim, J. W.; Shin, H.-B.; Robinson, P. A.

    2007-12-01

    A low-dimensional, compact brain model has recently been developed based on physiologically based mean-field continuum formulation of electric activity of the brain. The essential feature of the new compact model is a second order time-delayed differential equation that has physiologically plausible terms, such as rapid corticocortical feedback and delayed feedback via extracortical pathways. Due to its compact form, the model facilitates insight into complex brain dynamics via standard linear and nonlinear techniques. The model successfully reproduces many features of previous models and experiments. For example, experimentally observed typical rhythms of electroencephalogram (EEG) signals are reproduced in a physiologically plausible parameter region. In the nonlinear regime, onsets of seizures, which often develop into limit cycles, are illustrated by modulating model parameters. It is also shown that a hysteresis can occur when the system has multiple attractors. As a further illustration of this approach, power spectra of the model are fitted to those of sleep EEGs of two subjects (one with apnea, the other with narcolepsy). The model parameters obtained from the fittings show good matches with previous literature. Our results suggest that the compact model can provide a theoretical basis for analyzing complex EEG signals.

  7. Protoenzymes: the case of hyperbranched polyesters

    NASA Astrophysics Data System (ADS)

    Mamajanov, Irena; Cody, George D.

    2017-11-01

    Enzymes are biopolymeric complexes that catalyse biochemical reactions and shape metabolic pathways. Enzymes usually work with small molecule cofactors that actively participate in reaction mechanisms and complex, usually globular, polymeric structures capable of specific substrate binding, encapsulation and orientation. Moreover, the globular structures of enzymes possess cavities with modulated microenvironments, facilitating the progression of reaction(s). The globular structure is ensured by long folded protein or RNA strands. Synthesis of such elaborate complexes has proven difficult under prebiotically plausible conditions. We explore here that catalysis may have been performed by alternative polymeric structures, namely hyperbranched polymers. Hyperbranched polymers are relatively complex structures that can be synthesized under prebiotically plausible conditions; their globular structure is ensured by virtue of their architecture rather than folding. In this study, we probe the ability of tertiary amine-bearing hyperbranched polyesters to form hydrophobic pockets as a reaction-promoting medium for the Kemp elimination reaction. Our results show that polyesters formed upon reaction between glycerol, triethanolamine and organic acid containing hydrophobic groups, i.e. adipic and methylsuccinic acid, are capable of increasing the rate of Kemp elimination by a factor of up to 3 over monomeric triethanolamine. This article is part of the themed issue 'Reconceptualizing the origins of life'.

  8. Application of Adverse Outcome Pathways (AOPs) in Human ...

    EPA Pesticide Factsheets

    The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making. Because many fundamental molecular and cellular pathways are conserved across taxa, data from assays that screen chemicals for their ability to interact with specific biomolecular targets can often be credibly applied to a broad range of species, even if the apical outcomes of those perturbations may differ. Information concerning the different trajectories of adversity that molecular initiating events may take in different taxa, life stages, and sexes of organisms can be captured in the form of an AOP network. As an example, AOPs documenting divergent consequences of thyroid peroxidase (TPO) and deiodinase (DIO) inhibition in mammals, amphibians, and fish have been developed. These AOPs provide the foundation for using data from common in vitro assays for TPO or DIO activity to inform both human health and ecological risk assessments. They also provide the foundation for an integrated approach to testing and assessment, where available information and biological understanding can be integrated in order to formulate plausible and testable hypotheses which can be used to target in vivo testing on the endpoints of greatest concern. Application of this AOP knowledge in several different r

  9. Comparative Study on Interaction of Form and Motion Processing Streams by Applying Two Different Classifiers in Mechanism for Recognition of Biological Movement

    PubMed Central

    2014-01-01

    Research on psychophysics, neurophysiology, and functional imaging shows particular representation of biological movements which contains two pathways. The visual perception of biological movements formed through the visual system called dorsal and ventral processing streams. Ventral processing stream is associated with the form information extraction; on the other hand, dorsal processing stream provides motion information. Active basic model (ABM) as hierarchical representation of the human object had revealed novelty in form pathway due to applying Gabor based supervised object recognition method. It creates more biological plausibility along with similarity with original model. Fuzzy inference system is used for motion pattern information in motion pathway creating more robustness in recognition process. Besides, interaction of these paths is intriguing and many studies in various fields considered it. Here, the interaction of the pathways to get more appropriated results has been investigated. Extreme learning machine (ELM) has been implied for classification unit of this model, due to having the main properties of artificial neural networks, but crosses from the difficulty of training time substantially diminished in it. Here, there will be a comparison between two different configurations, interactions using synergetic neural network and ELM, in terms of accuracy and compatibility. PMID:25276860

  10. Application of adverse outcome pathways (AOPs) in human ...

    EPA Pesticide Factsheets

    The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making. Because many fundamental molecular and cellular pathways are conserved across taxa, data from assays that screen chemicals for their ability to interact with specific biomolecular targets can often be credibly applied to a broad range of species, even if the apical outcomes of those perturbations may differ. Information concerning the different trajectories of adversity that molecular initiating events may take in different taxa, life stages, and sexes of organisms can be captured in the form of an AOP network. As an example, AOPs documenting divergent consequences of thyroid peroxidase (TPO) and deiodinase (DIO) inhibition in mammals, amphibians, and fish have been developed. These AOPs provide the foundation for using data from common in vitro assays for TPO or DIO activity to inform both human health and ecological risk assessments. They also provide the foundation for an integrated approach to testing and assessment, where available information and biological understanding can be integrated in order to formulate plausible and testable hypotheses which can be used to target in vivo testing on the endpoints of greatest concern. Application of this AOP knowledge in several different r

  11. The Evolutionary Fate of the Genes Encoding the Purine Catabolic Enzymes in Hominoids, Birds, and Reptiles

    PubMed Central

    Keebaugh, Alaine C.; Thomas, James W.

    2010-01-01

    Gene loss has been proposed to play a major role in adaptive evolution, and recent studies are beginning to reveal its importance in human evolution. However, the potential consequence of a single gene-loss event upon the fates of functionally interrelated genes is poorly understood. Here, we use the purine metabolic pathway as a model system in which to explore this important question. The loss of urate oxidase (UOX) activity, a necessary step in this pathway, has occurred independently in the hominoid and bird/reptile lineages. Because the loss of UOX would have removed the functional constraint upon downstream genes in this pathway, these downstream genes are generally assumed to have subsequently deteriorated. In this study, we used a comparative genomics approach to empirically determine the fate of UOX itself and the downstream genes in five hominoids, two birds, and a reptile. Although we found that the loss of UOX likely triggered the genetic deterioration of the immediate downstream genes in the hominoids, surprisingly in the birds and reptiles, the UOX locus itself and some of the downstream genes were present in the genome and predicted to encode proteins. To account for the variable pattern of gene retention and loss after the inactivation of UOX, we hypothesize that although gene loss is a common fate for genes that have been rendered obsolete due to the upstream loss of an enzyme a metabolic pathway, it is also possible that same lack of constraint will foster the evolution of new functions or allow the optimization of preexisting alternative functions in the downstream genes, thereby resulting in gene retention. Thus, adaptive single-gene losses have the potential to influence the long-term evolutionary fate of functionally interrelated genes. PMID:20106906

  12. The evolutionary fate of the genes encoding the purine catabolic enzymes in hominoids, birds, and reptiles.

    PubMed

    Keebaugh, Alaine C; Thomas, James W

    2010-06-01

    Gene loss has been proposed to play a major role in adaptive evolution, and recent studies are beginning to reveal its importance in human evolution. However, the potential consequence of a single gene-loss event upon the fates of functionally interrelated genes is poorly understood. Here, we use the purine metabolic pathway as a model system in which to explore this important question. The loss of urate oxidase (UOX) activity, a necessary step in this pathway, has occurred independently in the hominoid and bird/reptile lineages. Because the loss of UOX would have removed the functional constraint upon downstream genes in this pathway, these downstream genes are generally assumed to have subsequently deteriorated. In this study, we used a comparative genomics approach to empirically determine the fate of UOX itself and the downstream genes in five hominoids, two birds, and a reptile. Although we found that the loss of UOX likely triggered the genetic deterioration of the immediate downstream genes in the hominoids, surprisingly in the birds and reptiles, the UOX locus itself and some of the downstream genes were present in the genome and predicted to encode proteins. To account for the variable pattern of gene retention and loss after the inactivation of UOX, we hypothesize that although gene loss is a common fate for genes that have been rendered obsolete due to the upstream loss of an enzyme a metabolic pathway, it is also possible that same lack of constraint will foster the evolution of new functions or allow the optimization of preexisting alternative functions in the downstream genes, thereby resulting in gene retention. Thus, adaptive single-gene losses have the potential to influence the long-term evolutionary fate of functionally interrelated genes.

  13. Stability-activity tradeoffs constrain the adaptive evolution of RubisCO.

    PubMed

    Studer, Romain A; Christin, Pascal-Antoine; Williams, Mark A; Orengo, Christine A

    2014-02-11

    A well-known case of evolutionary adaptation is that of ribulose-1,5-bisphosphate carboxylase (RubisCO), the enzyme responsible for fixation of CO2 during photosynthesis. Although the majority of plants use the ancestral C3 photosynthetic pathway, many flowering plants have evolved a derived pathway named C4 photosynthesis. The latter concentrates CO2, and C4 RubisCOs consequently have lower specificity for, and faster turnover of, CO2. The C4 forms result from convergent evolution in multiple clades, with substitutions at a small number of sites under positive selection. To understand the physical constraints on these evolutionary changes, we reconstructed in silico ancestral sequences and 3D structures of RubisCO from a large group of related C3 and C4 species. We were able to precisely track their past evolutionary trajectories, identify mutations on each branch of the phylogeny, and evaluate their stability effect. We show that RubisCO evolution has been constrained by stability-activity tradeoffs similar in character to those previously identified in laboratory-based experiments. The C4 properties require a subset of several ancestral destabilizing mutations, which from their location in the structure are inferred to mainly be involved in enhancing conformational flexibility of the open-closed transition in the catalytic cycle. These mutations are near, but not in, the active site or at intersubunit interfaces. The C3 to C4 transition is preceded by a sustained period in which stability of the enzyme is increased, creating the capacity to accept the functionally necessary destabilizing mutations, and is immediately followed by compensatory mutations that restore global stability.

  14. Analysis of the nicotinamide phosphoribosyltransferase family provides insight into vertebrate adaptation to different oxygen levels during the water-to-land transition.

    PubMed

    Fang, Chengchi; Guan, Lihong; Zhong, Zaixuan; Gan, Xiaoni; He, Shunping

    2015-08-01

    One of the most important events in vertebrate evolutionary history is the water-to-land transition, during which some morphological and physiological changes occurred in concert with the loss of specific genes in tetrapods. However, the molecular mechanisms underlying this transition have not been well explored. To explore vertebrate adaptation to different oxygen levels during the water-to-land transition, we performed comprehensive bioinformatics and experimental analysis aiming to investigate the NAMPT family in vertebrates. NAMPT, a rate-limiting enzyme in the salvage pathway of NAD+ biosynthesis, is critical for cell survival in a hypoxic environment, and a high level of NAMPT significantly augments oxidative stress in normoxic environments. Phylogenetic analysis showed that NAMPT duplicates arose from a second round whole-genome duplication event. NAMPTA existed in all classes of vertebrates, whereas NAMPTB was only found in fishes and not tetrapods. Asymmetric evolutionary rates and purifying selection were the main evolutionary forces involved. Although functional analysis identified several functionally divergent sites during NAMPT family evolution, in vitro experimental data demonstrated that NAMPTA and NAMPTB were functionally conserved for NAMPT enzymatic function in the NAD+ salvage pathway. In situ hybridization revealed broad NAMPTA and NAMPTB expression patterns, implying regulatory functions over a wide range of developmental processes. The morpholino-mediated knockdown data demonstrated that NAMPTA was more essential than NAMPTB for vertebrate embryo development. We propose that the retention of NAMPTB in water-breathing fishes and its loss in air-breathing tetrapods resulted from vertebrate adaptation to different oxygen levels during the water-to-land transition. © 2015 FEBS.

  15. Marine toxins and nonmarine toxins: convergence or symbiotic organisms?

    PubMed

    Daly, John W

    2004-08-01

    Bioactive marine natural products occur only rarely in nonmarine sources. The converse also is true. Divergent evolutionary pathways for the biosynthesis of bioactive secondary metabolites seem to be the rule. Marine biosynthetic pathways lead to a wide variety of different structural classes, among which polyethers, macrolides, terpenes, unusual amino acids/peptides, and alkaloids are notable. Nonmarine biosynthetic pathways also lead to a similar wide variety of structural classes. However, the structures are usually quite different from the marine analogues. The alkaloids of plants are notable, but again there appears little convergence between the marine and nonmarine alkaloids. However, tetrodotoxin, a remarkable, highly polar, marine alkaloid, does occur in various amphibians. The occurrence and possible origin of tetrodotoxin and congeners, including chiriquitoxin, and of the saxitoxin analogue zetekitoxin in amphibians are reviewed.

  16. Producing the Ethylene Signal: Regulation and Diversification of Ethylene Biosynthetic Enzymes1

    PubMed Central

    Booker, Matthew A.; DeLong, Alison

    2015-01-01

    Strictly controlled production of ethylene gas lies upstream of the signaling activities of this crucial regulator throughout the plant life cycle. Although the biosynthetic pathway is enzymatically simple, the regulatory circuits that modulate signal production are fine tuned to allow integration of responses to environmental and intrinsic cues. Recently identified posttranslational mechanisms that control ethylene production converge on one family of biosynthetic enzymes and overlay several independent reversible phosphorylation events and distinct mediators of ubiquitin-dependent protein degradation. Although the core pathway is conserved throughout seed plants, these posttranslational regulatory mechanisms may represent evolutionarily recent innovations. The evolutionary origins of the pathway and its regulators are not yet clear; outside the seed plants, numerous biochemical and phylogenetic questions remain to be addressed. PMID:26134162

  17. Epimerization of Alanyl-Alanine Induced by γ-Rays Irradiation in Aqueous Solutions.

    PubMed

    Munegumi, Toratane

    2017-03-01

    Living organisms have homochiral L-amino acids in proteins and homochiral D-mononucleotides in nucleic acids. The chemical evolutionary process to protein homochirality has been discussed for many years. Although many scenarios have been proposed for homochirality in the monomeric compounds, homochirality in amino acids and mononucleotides does not always guarantee homochirality in polypeptides and polynucleotides. Integrated scenarios containing the pathways from monomer to polymer should be proposed because in the pathways oligomers and polymers as well as monomers racemize (or epimerize), degrade, and condense. This research addresses epimerization and degradation of dipeptides under γ-rays irradiation by a cobalt-60 ( 60 Co) radiation source. The different rate constants of epimerization between diastereomeric dipeptides in the research suggest that the potential pathway toward homochirality could be much more complex.

  18. Evolutionary Analyses of Entire Genomes Do Not Support the Association of mtDNA Mutations with Ras/MAPK Pathway Syndromes

    PubMed Central

    Cerezo, María; Balboa, Emilia; Heredia, Claudia; Castro-Feijóo, Lidia; Rica, Itxaso; Barreiro, Jesús; Eirís, Jesús; Cabanas, Paloma; Martínez-Soto, Isabel; Fernández-Toral, Joaquín; Castro-Gago, Manuel; Pombo, Manuel; Carracedo, Ángel; Barros, Francisco

    2011-01-01

    Background There are several known autosomal genes responsible for Ras/MAPK pathway syndromes, including Noonan syndrome (NS) and related disorders (such as LEOPARD, neurofibromatosis type 1), although mutations of these genes do not explain all cases. Due to the important role played by the mitochondrion in the energetic metabolism of cardiac muscle, it was recently proposed that variation in the mitochondrial DNA (mtDNA) genome could be a risk factor in the Noonan phenotype and in hypertrophic cardiomyopathy (HCM), which is a common clinical feature in Ras/MAPK pathway syndromes. In order to test these hypotheses, we sequenced entire mtDNA genomes in the largest series of patients suffering from Ras/MAPK pathway syndromes analyzed to date (n = 45), most of them classified as NS patients (n = 42). Methods/Principal Findings The results indicate that the observed mtDNA lineages were mostly of European ancestry, reproducing in a nutshell the expected haplogroup (hg) patterns of a typical Iberian dataset (including hgs H, T, J, and U). Three new branches of the mtDNA phylogeny (H1j1, U5b1e, and L2a5) are described for the first time, but none of these are likely to be related to NS or Ras/MAPK pathway syndromes when observed under an evolutionary perspective. Patterns of variation in tRNA and protein genes, as well as redundant, private and heteroplasmic variants, in the mtDNA genomes of patients were as expected when compared with the patterns inferred from a worldwide mtDNA phylogeny based on more than 8700 entire genomes. Moreover, most of the mtDNA variants found in patients had already been reported in healthy individuals and constitute common polymorphisms in human population groups. Conclusions/Significance As a whole, the observed mtDNA genome variation in the NS patients was difficult to reconcile with previous findings that indicated a pathogenic role of mtDNA variants in NS. PMID:21526175

  19. Modeling of the Dorsal Gradient across Species Reveals Interaction between Embryo Morphology and Toll Signaling Pathway during Evolution

    PubMed Central

    Koslen, Hannah R.; Chiel, Hillel J.; Mizutani, Claudia Mieko

    2014-01-01

    Morphogenetic gradients are essential to allocate cell fates in embryos of varying sizes within and across closely related species. We previously showed that the maternal NF-κB/Dorsal (Dl) gradient has acquired different shapes in Drosophila species, which result in unequally scaled germ layers along the dorso-ventral axis and the repositioning of the neuroectodermal borders. Here we combined experimentation and mathematical modeling to investigate which factors might have contributed to the fast evolutionary changes of this gradient. To this end, we modified a previously developed model that employs differential equations of the main biochemical interactions of the Toll (Tl) signaling pathway, which regulates Dl nuclear transport. The original model simulations fit well the D. melanogaster wild type, but not mutant conditions. To broaden the applicability of this model and probe evolutionary changes in gradient distributions, we adjusted a set of 19 independent parameters to reproduce three quantified experimental conditions (i.e. Dl levels lowered, nuclear size and density increased or decreased). We next searched for the most relevant parameters that reproduce the species-specific Dl gradients. We show that adjusting parameters relative to morphological traits (i.e. embryo diameter, nuclear size and density) alone is not sufficient to reproduce the species Dl gradients. Since components of the Tl pathway simulated by the model are fast-evolving, we next asked which parameters related to Tl would most effectively reproduce these gradients and identified a particular subset. A sensitivity analysis reveals the existence of nonlinear interactions between the two fast-evolving traits tested above, namely the embryonic morphological changes and Tl pathway components. Our modeling further suggests that distinct Dl gradient shapes observed in closely related melanogaster sub-group lineages may be caused by similar sequence modifications in Tl pathway components, which are in agreement with their phylogenetic relationships. PMID:25165818

  20. Evolutionary origins and functions of the carotenoid biosynthetic pathway in marine diatoms.

    PubMed

    Coesel, Sacha; Oborník, Miroslav; Varela, Joao; Falciatore, Angela; Bowler, Chris

    2008-08-06

    Carotenoids are produced by all photosynthetic organisms, where they play essential roles in light harvesting and photoprotection. The carotenoid biosynthetic pathway of diatoms is largely unstudied, but is of particular interest because these organisms have a very different evolutionary history with respect to the Plantae and are thought to be derived from an ancient secondary endosymbiosis between heterotrophic and autotrophic eukaryotes. Furthermore, diatoms have an additional xanthophyll-based cycle for dissipating excess light energy with respect to green algae and higher plants. To explore the origins and functions of the carotenoid pathway in diatoms we searched for genes encoding pathway components in the recently completed genome sequences of two marine diatoms. Consistent with the supplemental xanthophyll cycle in diatoms, we found more copies of the genes encoding violaxanthin de-epoxidase (VDE) and zeaxanthin epoxidase (ZEP) enzymes compared with other photosynthetic eukaryotes. However, the similarity of these enzymes with those of higher plants indicates that they had very probably diversified before the secondary endosymbiosis had occurred, implying that VDE and ZEP represent early eukaryotic innovations in the Plantae. Consequently, the diatom chromist lineage likely obtained all paralogues of ZEP and VDE genes during the process of secondary endosymbiosis by gene transfer from the nucleus of the algal endosymbiont to the host nucleus. Furthermore, the presence of a ZEP gene in Tetrahymena thermophila provides the first evidence for a secondary plastid gene encoded in a heterotrophic ciliate, providing support for the chromalveolate hypothesis. Protein domain structures and expression analyses in the pennate diatom Phaeodactylum tricornutum indicate diverse roles for the different ZEP and VDE isoforms and demonstrate that they are differentially regulated by light. These studies therefore reveal the ancient origins of several components of the carotenoid biosynthesis pathway in photosynthetic eukaryotes and provide information about how they have diversified and acquired new functions in the diatoms.

  1. Bioprospecting and evolving alternative xylose and arabinose pathway enzymes for use in Saccharomyces cerevisiae.

    PubMed

    Lee, Sun-Mi; Jellison, Taylor; Alper, Hal S

    2016-03-01

    Bioprospecting is an effective way to find novel enzymes from strains with desirable phenotypes. Such bioprospecting has enabled organisms such as Saccharomyces cerevisiae to utilize nonnative pentose sugars. Yet, the efficiency of this pentose catabolism (especially for the case of arabinose) remains suboptimal. Thus, further pathway optimization or identification of novel, optimal pathways is needed. Previously, we identified a novel set of xylan catabolic pathway enzymes from a superior pentose-utilizing strain of Ustilago bevomyces. These enzymes were used to successfully engineer a xylan-utilizing S. cerevisiae through a blended approach of bioprospecting and evolutionary engineering. Here, we expanded this approach to xylose and arabinose catabolic pathway engineering and demonstrated that bioprospected xylose and arabinose catabolic pathways from U. bevomyces offer alternative choices for enabling efficient pentose catabolism in S. cerevisiae. By introducing a novel set of xylose catabolic genes from U. bevomyces, growth rates were improved up to 85 % over a set of traditional Scheffersomyces stipitis pathway genes. In addition, we suggested an alternative arabinose catabolic pathway which, after directed evolution and pathway engineering, enabled S. cerevisiae to grow on arabinose as a sole carbon source in minimal medium with growth rates upwards of 0.05 h(-1). This pathway represents the most efficient growth of yeast on pure arabinose minimal medium. These pathways provide great starting points for further strain development and demonstrate the utility of bioprospecting from U. bevomyces.

  2. Rapid Evolution of piRNA Pathway in the Teleost Fish: Implication for an Adaptation to Transposon Diversity

    PubMed Central

    Yi, Minhan; Chen, Feng; Luo, Majing; Cheng, Yibin; Zhao, Huabin; Cheng, Hanhua; Zhou, Rongjia

    2014-01-01

    The Piwi-interacting RNA (piRNA) pathway is responsible for germline specification, gametogenesis, transposon silencing, and genome integrity. Transposable elements can disrupt genome and its functions. However, piRNA pathway evolution and its adaptation to transposon diversity in the teleost fish remain unknown. This article unveils evolutionary scene of piRNA pathway and its association with diverse transposons by systematically comparative analysis on diverse teleost fish genomes. Selective pressure analysis on piRNA pathway and miRNA/siRNA (microRNA/small interfering RNA) pathway genes between teleosts and mammals showed an accelerated evolution of piRNA pathway genes in the teleost lineages, and positive selection on functional PAZ (Piwi/Ago/Zwille) and Tudor domains involved in the Piwi–piRNA/Tudor interaction, suggesting that the amino acid substitutions are adaptive to their functions in piRNA pathway in the teleost fish species. Notably five piRNA pathway genes evolved faster in the swamp eel, a kind of protogynous hermaphrodite fish, than the other teleosts, indicating a differential evolution of piRNA pathway between the swamp eel and other gonochoristic fishes. In addition, genome-wide analysis showed higher diversity of transposons in the teleost fish species compared with mammals. Our results suggest that rapidly evolved piRNA pathway in the teleost fish is likely to be involved in the adaption to transposon diversity. PMID:24846630

  3. Lens fibre cell differentiation and organelle loss: many paths lead to clarity

    PubMed Central

    Wride, Michael A.

    2011-01-01

    The programmed removal of organelles from differentiating lens fibre cells contributes towards lens transparency through formation of an organelle-free zone (OFZ). Disruptions in OFZ formation are accompanied by the persistence of organelles in lens fibre cells and can contribute towards cataract. A great deal of work has gone into elucidating the nature of the mechanisms and signalling pathways involved. It is apparent that multiple, parallel and redundant pathways are involved in this process and that these pathways form interacting networks. Furthermore, it is possible that the pathways can functionally compensate for each other, for example in mouse knockout studies. This makes sense given the importance of lens clarity in an evolutionary context. Apoptosis signalling and proteolytic pathways have been implicated in both lens fibre cell differentiation and organelle loss, including the Bcl-2 and inhibitor of apoptosis families, tumour necrosis factors, p53 and its regulators (such as Mdm2) and proteolytic enzymes, including caspases, cathepsins, calpains and the ubiquitin–proteasome pathway. Ongoing approaches being used to dissect the molecular pathways involved, such as transgenics, lens-specific gene deletion and zebrafish mutants, are discussed here. Finally, some of the remaining unresolved issues and potential areas for future studies are highlighted. PMID:21402582

  4. Euryhalinity in an evolutionary context

    USGS Publications Warehouse

    Schultz, Eric T.; McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.

    2013-01-01

    This chapter focuses on the evolutionary importance and taxonomic distribution of euryhalinity. Euryhalinity refers to broad halotolerance and broad halohabitat distribution. Salinity exposure experiments have demonstrated that species vary tenfold in their range of tolerable salinity levels, primarily because of differences in upper limits. Halotolerance breadth varies with the species’ evolutionary history, as represented by its ordinal classification, and with the species’ halohabitat. Freshwater and seawater species tolerate brackish water; their empirically-determined fundamental haloniche is broader than their realized haloniche, as revealed by the halohabitats they occupy. With respect to halohabitat distribution, a minority of species (<10%) are euryhaline. Habitat-euryhalinity is prevalent among basal actinopterygian fishes, is largely absent from orders arising from intermediate nodes, and reappears in the most derived taxa. There is pronounced family-level variability in the tendency to be halohabitat-euryhaline, which may have arisen during a burst of diversification following the Cretaceous-Palaeogene extinction. Low prevalence notwithstanding, euryhaline species are potent sources of evolutionary diversity. Euryhalinity is regarded as a key innovation trait whose evolution enables exploitation of new adaptive zone, triggering cladogenesis. We review phylogenetically-informed studies that demonstrate freshwater species diversifying from euryhaline ancestors through processes such as landlocking. These studies indicate that some euryhaline taxa are particularly susceptible to changes in halohabitat and subsequent diversification, and some geographic regions have been hotspots for transitions to freshwater. Comparative studies on mechanisms among multiple taxa and at multiple levels of biological integration are needed to clarify evolutionary pathways to, and from, euryhalinity.

  5. Salt tolerance evolves more frequently in C4 grass lineages.

    PubMed

    Bromham, L; Bennett, T H

    2014-03-01

    Salt tolerance has evolved many times in the grass family, and yet few cereal crops are salt tolerant. Why has it been so difficult to develop crops tolerant of saline soils when salt tolerance has evolved so frequently in nature? One possible explanation is that some grass lineages have traits that predispose them to developing salt tolerance and that without these background traits, salt tolerance is harder to achieve. One candidate background trait is photosynthetic pathway, which has also been remarkably labile in grasses. At least 22 independent origins of the C4 photosynthetic pathway have been suggested to occur within the grass family. It is possible that the evolution of C4 photosynthesis aids exploitation of saline environments, because it reduces transpiration, increases water-use efficiency and limits the uptake of toxic ions. But the observed link between the evolution of C4 photosynthesis and salt tolerance could simply be due to biases in phylogenetic distribution of halophytes or C4 species. Here, we use a phylogenetic analysis to investigate the association between photosynthetic pathway and salt tolerance in the grass family Poaceae. We find that salt tolerance is significantly more likely to occur in lineages with C4 photosynthesis than in C3 lineages. We discuss the possible links between C4 photosynthesis and salt tolerance and consider the limitations of inferring the direction of causality of this relationship. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  6. Effects of Hybridization and Evolutionary Constraints on Secondary Metabolites: The Genetic Architecture of Phenylpropanoids in European Populus Species

    PubMed Central

    Caseys, Celine; Stritt, Christoph; Glauser, Gaetan; Blanchard, Thierry; Lexer, Christian

    2015-01-01

    The mechanisms responsible for the origin, maintenance and evolution of plant secondary metabolite diversity remain largely unknown. Decades of phenotypic studies suggest hybridization as a key player in generating chemical diversity in plants. Knowledge of the genetic architecture and selective constraints of phytochemical traits is key to understanding the effects of hybridization on plant chemical diversity and ecological interactions. Using the European Populus species P. alba (White poplar) and P. tremula (European aspen) and their hybrids as a model, we examined levels of inter- and intraspecific variation, heritabilities, phenotypic correlations, and the genetic architecture of 38 compounds of the phenylpropanoid pathway measured by liquid chromatography and mass spectrometry (UHPLC-MS). We detected 41 quantitative trait loci (QTL) for chlorogenic acids, salicinoids and flavonoids by genetic mapping in natural hybrid crosses. We show that these three branches of the phenylpropanoid pathway exhibit different geographic patterns of variation, heritabilities, and genetic architectures, and that they are affected differently by hybridization and evolutionary constraints. Flavonoid abundances present high species specificity, clear geographic structure, and strong genetic determination, contrary to salicinoids and chlorogenic acids. Salicinoids, which represent important defence compounds in Salicaceae, exhibited pronounced genetic correlations on the QTL map. Our results suggest that interspecific phytochemical differentiation is concentrated in downstream sections of the phenylpropanoid pathway. In particular, our data point to glycosyltransferase enzymes as likely targets of rapid evolution and interspecific differentiation in the ‘model forest tree’ Populus. PMID:26010156

  7. Effects of hybridization and evolutionary constraints on secondary metabolites: the genetic architecture of phenylpropanoids in European populus species.

    PubMed

    Caseys, Celine; Stritt, Christoph; Glauser, Gaetan; Blanchard, Thierry; Lexer, Christian

    2015-01-01

    The mechanisms responsible for the origin, maintenance and evolution of plant secondary metabolite diversity remain largely unknown. Decades of phenotypic studies suggest hybridization as a key player in generating chemical diversity in plants. Knowledge of the genetic architecture and selective constraints of phytochemical traits is key to understanding the effects of hybridization on plant chemical diversity and ecological interactions. Using the European Populus species P. alba (White poplar) and P. tremula (European aspen) and their hybrids as a model, we examined levels of inter- and intraspecific variation, heritabilities, phenotypic correlations, and the genetic architecture of 38 compounds of the phenylpropanoid pathway measured by liquid chromatography and mass spectrometry (UHPLC-MS). We detected 41 quantitative trait loci (QTL) for chlorogenic acids, salicinoids and flavonoids by genetic mapping in natural hybrid crosses. We show that these three branches of the phenylpropanoid pathway exhibit different geographic patterns of variation, heritabilities, and genetic architectures, and that they are affected differently by hybridization and evolutionary constraints. Flavonoid abundances present high species specificity, clear geographic structure, and strong genetic determination, contrary to salicinoids and chlorogenic acids. Salicinoids, which represent important defence compounds in Salicaceae, exhibited pronounced genetic correlations on the QTL map. Our results suggest that interspecific phytochemical differentiation is concentrated in downstream sections of the phenylpropanoid pathway. In particular, our data point to glycosyltransferase enzymes as likely targets of rapid evolution and interspecific differentiation in the 'model forest tree' Populus.

  8. Nature's inordinate fondness for metabolic enzymes: why metabolic enzyme loci are so frequently targets of selection.

    PubMed

    Marden, James H

    2013-12-01

    Metabolic enzyme loci were some of the first genes accessible for molecular evolution and ecology research. New technologies now make the whole genome, transcriptome or proteome readily accessible, allowing unbiased scans for loci exhibiting significant differences in allele frequency or expression level and associated with phenotypes and/or responses to natural selection. With surprising frequency and in many cases in proportions greater than chance relative to other genes, glycolysis and TCA cycle enzyme loci appear among the genes with significant associations in these studies. Hence, there is an ongoing need to understand the basis for fitness effects of metabolic enzyme polymorphisms. Allele-specific effects on the binding affinity and catalytic rate of individual enzymes are well known, but often of uncertain significance because metabolic control theory and in vivo studies indicate that many individual metabolic enzymes do not affect pathway flux rate. I review research, so far little used in evolutionary biology, showing that metabolic enzyme substrates affect signalling pathways that regulate cell and organismal biology, and that these enzymes have moonlighting functions. To date there is little knowledge of how alleles in natural populations affect these phenotypes. I discuss an example in which alleles of a TCA enzyme locus associate with differences in a signalling pathway and development, organismal performance, and ecological dynamics. Ultimately, understanding how metabolic enzyme polymorphisms map to phenotypes and fitness remains a compelling and ongoing need for gaining robust knowledge of ecological and evolutionary processes. © 2013 John Wiley & Sons Ltd.

  9. In Silico/In Vivo Insights into the Functional and Evolutionary Pathway of Pseudomonas aeruginosa Oleate-Diol Synthase. Discovery of a New Bacterial Di-Heme Cytochrome C Peroxidase Subfamily

    PubMed Central

    Estupiñán, Mónica; Álvarez-García, Daniel; Barril, Xavier; Diaz, Pilar; Manresa, Angeles

    2015-01-01

    As previously reported, P. aeruginosa genes PA2077 and PA2078 code for 10S-DOX (10S-Dioxygenase) and 7,10-DS (7,10-Diol Synthase) enzymes involved in long-chain fatty acid oxygenation through the recently described oleate-diol synthase pathway. Analysis of the amino acid sequence of both enzymes revealed the presence of two heme-binding motifs (CXXCH) on each protein. Phylogenetic analysis showed the relation of both proteins to bacterial di-heme cytochrome c peroxidases (Ccps), similar to Xanthomonas sp. 35Y rubber oxidase RoxA. Structural homology modelling of PA2077 and PA2078 was achieved using RoxA (pdb 4b2n) as a template. From the 3D model obtained, presence of significant amino acid variations in the predicted heme-environment was found. Moreover, the presence of palindromic repeats located in enzyme-coding regions, acting as protein evolution elements, is reported here for the first time in P. aeruginosa genome. These observations and the constructed phylogenetic tree of the two proteins, allow the proposal of an evolutionary pathway for P. aeruginosa oleate-diol synthase operon. Taking together the in silico and in vivo results obtained we conclude that enzymes PA2077 and PA2078 are the first described members of a new subfamily of bacterial peroxidases, designated as Fatty acid-di-heme Cytochrome c peroxidases (FadCcp). PMID:26154497

  10. Evolution of animal and plant dicers: early parallel duplications and recurrent adaptation of antiviral RNA binding in plants.

    PubMed

    Mukherjee, Krishanu; Campos, Henry; Kolaczkowski, Bryan

    2013-03-01

    RNA interference (RNAi) is a eukaryotic molecular system that serves two primary functions: 1) gene regulation and 2) protection against selfish elements such as viruses and transposable DNA. Although the biochemistry of RNAi has been detailed in model organisms, very little is known about the broad-scale patterns and forces that have shaped RNAi evolution. Here, we provide a comprehensive evolutionary analysis of the Dicer protein family, which carries out the initial RNA recognition and processing steps in the RNAi pathway. We show that Dicer genes duplicated and diversified independently in early animal and plant evolution, coincident with the origins of multicellularity. We identify a strong signature of long-term protein-coding adaptation that has continually reshaped the RNA-binding pocket of the plant Dicer responsible for antiviral immunity, suggesting an evolutionary arms race with viral factors. We also identify key changes in Dicer domain architecture and sequence leading to specialization in either gene-regulatory or protective functions in animal and plant paralogs. As a whole, these results reveal a dynamic picture in which the evolution of Dicer function has driven elaboration of parallel RNAi functional pathways in animals and plants.

  11. Hybridization and differential introgression associated with environmental shifts in a mistletoe species complex.

    PubMed

    Baena-Díaz, Fernanda; Ramírez-Barahona, Santiago; Ornelas, Juan Francisco

    2018-04-03

    Host specialization after host shifting is traditionally viewed as the pathway to speciation in parasitic plants. However, geographical and environmental changes can also influence parasite speciation, through hybridization processes. Here we investigated the impact of past climatic fluctuations, environment, and host shifts on the genetic structure and patterns of hybridization and gene flow between Psittacanthus calyculatus and P. schiedeanus, a Mesoamerican species complex. Using microsatellites (408 individuals), we document moderate genetic diversity but high genetic differentiation between widespread parental clusters, calyculatus in dry pine-oak forests and schiedeanus in cloud forests. Bayesian analyses identified a third cluster, with admixture between parental clusters in areas of xeric and tropical dry forests and high levels of migration rates following secondary contact. Coincidently host associations in these areas differ from those in areas of parental species, suggesting that past hybridization played a role in environmental and host shifts. Overall, the observed genetic and geographic patterns suggest that these Psittacanthus populations could have entered a distinct evolutionary pathway. The results provide evidence for highlights on the importance of the Pleistocene climate changes, habitat differences, and potential host shifts in the evolutionary history of Neotropical mistletoes.

  12. Prebiotic replicase evolution in a surface-bound metabolic system: parasites as a source of adaptive evolution

    PubMed Central

    2008-01-01

    Background The remarkable potential of recent forms of life for reliably passing on genetic information through many generations now depends on the coordinated action of thousands of specialized biochemical "machines" (enzymes) that were obviously absent in prebiotic times. Thus the question how a complicated system like the living cell could have assembled on Earth seems puzzling. In seeking for a scientific explanation one has to search for step-by-step evolutionary changes from prebiotic chemistry to the emergence of the first proto-cell. Results We try to sketch a plausible scenario for the first steps of prebiotic evolution by exploring the ecological feasibility of a mineral surface-bound replicator system that facilitates a primitive metabolism. Metabolism is a hypothetical network of simple chemical reactions producing monomers for the template-copying of RNA-like replicators, which in turn catalyse metabolic reactions. Using stochastic cellular automata (SCA) simulations we show that the surface-bound metabolic replicator system is viable despite internal competition among the genes and that it also maintains a set of mild "parasitic" sequences which occasionally evolve functions such as that of a replicase. Conclusion Replicase activity is shown to increase even at the expense of slowing down the replication of the evolving ribozyme itself, due to indirect mutualistic benefits in a diffuse form of group selection among neighbouring replicators. We suggest possible paths for further evolutionary changes in the metabolic replicator system leading to increased metabolic efficiency, improved replicase functionality, and membrane production. PMID:18826645

  13. Coordinated Rates of Evolution between Interacting Plastid and Nuclear Genes in Geraniaceae

    PubMed Central

    Zhang, Jin; Ruhlman, Tracey A.; Sabir, Jamal; Blazier, J. Chris; Jansen, Robert K.

    2015-01-01

    Although gene coevolution has been widely observed within individuals and between different organisms, rarely has this phenomenon been investigated within a phylogenetic framework. The Geraniaceae is an attractive system in which to study plastid-nuclear genome coevolution due to the highly elevated evolutionary rates in plastid genomes. In plants, the plastid-encoded RNA polymerase (PEP) is a protein complex composed of subunits encoded by both plastid (rpoA, rpoB, rpoC1, and rpoC2) and nuclear genes (sig1-6). We used transcriptome and genomic data for 27 species of Geraniales in a systematic evaluation of coevolution between genes encoding subunits of the PEP holoenzyme. We detected strong correlations of dN (nonsynonymous substitutions) but not dS (synonymous substitutions) within rpoB/sig1 and rpoC2/sig2, but not for other plastid/nuclear gene pairs, and identified the correlation of dN/dS ratio between rpoB/C1/C2 and sig1/5/6, rpoC1/C2 and sig2, and rpoB/C2 and sig3 genes. Correlated rates between interacting plastid and nuclear sequences across the Geraniales could result from plastid-nuclear genome coevolution. Analyses of coevolved amino acid positions suggest that structurally mediated coevolution is not the major driver of plastid-nuclear coevolution. The detection of strong correlation of evolutionary rates between SIG and RNAP genes suggests a plausible explanation for plastome-genome incompatibility in Geraniaceae. PMID:25724640

  14. Network-level architecture and the evolutionary potential of underground metabolism.

    PubMed

    Notebaart, Richard A; Szappanos, Balázs; Kintses, Bálint; Pál, Ferenc; Györkei, Ádám; Bogos, Balázs; Lázár, Viktória; Spohn, Réka; Csörgő, Bálint; Wagner, Allon; Ruppin, Eytan; Pál, Csaba; Papp, Balázs

    2014-08-12

    A central unresolved issue in evolutionary biology is how metabolic innovations emerge. Low-level enzymatic side activities are frequent and can potentially be recruited for new biochemical functions. However, the role of such underground reactions in adaptation toward novel environments has remained largely unknown and out of reach of computational predictions, not least because these issues demand analyses at the level of the entire metabolic network. Here, we provide a comprehensive computational model of the underground metabolism in Escherichia coli. Most underground reactions are not isolated and 45% of them can be fully wired into the existing network and form novel pathways that produce key precursors for cell growth. This observation allowed us to conduct an integrated genome-wide in silico and experimental survey to characterize the evolutionary potential of E. coli to adapt to hundreds of nutrient conditions. We revealed that underground reactions allow growth in new environments when their activity is increased. We estimate that at least ∼20% of the underground reactions that can be connected to the existing network confer a fitness advantage under specific environments. Moreover, our results demonstrate that the genetic basis of evolutionary adaptations via underground metabolism is computationally predictable. The approach used here has potential for various application areas from bioengineering to medical genetics.

  15. Network Analysis of Plasmidomes: The Azospirillum brasilense Sp245 Case

    PubMed Central

    Fondi, Marco

    2014-01-01

    Azospirillum brasilense is a nitrogen-fixing bacterium living in association with plant roots. The genome of the strain Sp245, isolated in Brazil from wheat roots, consists of one chromosome and six plasmids. In this work, the A. brasilense Sp245 plasmids were analyzed in order to shed some light on the evolutionary pathways they followed over time. To this purpose, a similarity network approach was applied in order to identify the evolutionary relationships among all the A. brasilense plasmids encoded proteins; in this context a computational pipeline specifically devoted to the analysis and the visualization of the network-like evolutionary relationships among different plasmids molecules was developed. This information was supplemented with a detailed (in silico) functional characterization of both the connected (i.e., sharing homology with other sequences in the dataset) and the unconnected (i.e., not sharing homology) components of the network. Furthermore, the most likely source organism for each of the genes encoded by A. brasilense plasmids was checked, allowing the identification of possible trends of gene loss/gain in this microorganism. Data obtained provided a detailed description of the evolutionary landscape of the plasmids of A. brasilense Sp245, suggesting some of the molecular mechanisms responsible for the present-day structure of these molecules. PMID:25610702

  16. The Evolutionary Basis of Naturally Diverse Rice Leaves Anatomy

    PubMed Central

    Chatterjee, Jolly; Dionora, Jacqueline; Elmido-Mabilangan, Abigail; Wanchana, Samart; Thakur, Vivek; Bandyopadhyay, Anindya; Brar, Darshan S.; Quick, William Paul

    2016-01-01

    Rice contains genetically and ecologically diverse wild and cultivated species that show a wide variation in plant and leaf architecture. A systematic characterization of leaf anatomy is essential in understanding the dynamics behind such diversity. Therefore, leaf anatomies of 24 Oryza species spanning 11 genetically diverse rice genomes were studied in both lateral and longitudinal directions and possible evolutionary trends were examined. A significant inter-species variation in mesophyll cells, bundle sheath cells, and vein structure was observed, suggesting precise genetic control over these major rice leaf anatomical traits. Cellular dimensions, measured along three growth axes, were further combined proportionately to construct three-dimensional (3D) leaf anatomy models to compare the relative size and orientation of the major cell types present in a fully expanded leaf. A reconstruction of the ancestral leaf state revealed that the following are the major characteristics of recently evolved rice species: fewer veins, larger and laterally elongated mesophyll cells, with an increase in total mesophyll area and in bundle sheath cell number. A huge diversity in leaf anatomy within wild and domesticated rice species has been portrayed in this study, on an evolutionary context, predicting a two-pronged evolutionary pathway leading to the ‘sativa leaf type’ that we see today in domesticated species. PMID:27792743

  17. TAS3 miR390-dependent loci in non-vascular land plants: towards a comprehensive reconstruction of the gene evolutionary history

    PubMed Central

    Milyutina, Irina A.; Erokhina, Tatiana N.; Ozerova, Liudmila V.; Troitsky, Alexey V.; Solovyev, Andrey G.

    2018-01-01

    Trans-acting small interfering RNAs (ta-siRNAs) are transcribed from protein non-coding genomic TAS loci and belong to a plant-specific class of endogenous small RNAs. These siRNAs have been found to regulate gene expression in most taxa including seed plants, gymnosperms, ferns and mosses. In this study, bioinformatic and experimental PCR-based approaches were used as tools to analyze TAS3 and TAS6 loci in transcriptomes and genomic DNAs from representatives of evolutionary distant non-vascular plant taxa such as Bryophyta, Marchantiophyta and Anthocerotophyta. We revealed previously undiscovered TAS3 loci in plant classes Sphagnopsida and Anthocerotopsida, as well as TAS6 loci in Bryophyta classes Tetraphidiopsida, Polytrichopsida, Andreaeopsida and Takakiopsida. These data further unveil the evolutionary pathway of the miR390-dependent TAS3 loci in land plants. We also identified charophyte alga sequences coding for SUPPRESSOR OF GENE SILENCING 3 (SGS3), which is required for generation of ta-siRNAs in plants, and hypothesized that the appearance of TAS3-related sequences could take place at a very early step in evolutionary transition from charophyte algae to an earliest common ancestor of land plants. PMID:29682420

  18. Emergence and dynamics of self-producing information niches as a step towards pre-evolutionary organization

    PubMed Central

    Carter, Richard J.; Wiesner, Karoline

    2018-01-01

    As a step towards understanding pre-evolutionary organization in non-genetic systems, we develop a model to investigate the emergence and dynamics of proto-autopoietic networks in an interacting population of simple information processing entities (automata). Our simulations indicate that dynamically stable strongly connected networks of mutually producing communication channels emerge under specific environmental conditions. We refer to these distinct organizational steady states as information niches. In each case, we measure the information content by the Shannon entropy, and determine the fitness landscape, robustness and transition pathways for information niches subjected to intermittent environmental perturbations under non-evolutionary conditions. By determining the information required to generate each niche, we show that niche transitions are only allowed if accompanied by an equal or increased level of information production that arises internally or via environmental perturbations that serve as an exogenous source of population diversification. Overall, our simulations show how proto-autopoietic networks of basic information processors form and compete, and under what conditions they persist over time or go extinct. These findings may be relevant to understanding how inanimate systems such as chemically communicating protocells can initiate the transition to living matter prior to the onset of contemporary evolutionary and genetic mechanisms. PMID:29343630

  19. Conciliation biology: the eco-evolutionary management of permanently invaded biotic systems

    PubMed Central

    Carroll, Scott P

    2011-01-01

    Biotic invaders and similar anthropogenic novelties such as domesticates, transgenics, and cancers can alter ecology and evolution in environmental, agricultural, natural resource, public health, and medical systems. The resulting biological changes may either hinder or serve management objectives. For example, biological control and eradication programs are often defeated by unanticipated resistance evolution and by irreversibility of invader impacts. Moreover, eradication may be ill-advised when nonnatives introduce beneficial functions. Thus, contexts that appear to call for eradication may instead demand managed coexistence of natives with nonnatives, and yet applied biologists have not generally considered the need to manage the eco-evolutionary dynamics that commonly result from interactions of natives with nonnatives. Here, I advocate a conciliatory approach to managing systems where novel organisms cannot or should not be eradicated. Conciliatory strategies incorporate benefits of nonnatives to address many practical needs including slowing rates of resistance evolution, promoting evolution of indigenous biological control, cultivating replacement services and novel functions, and managing native–nonnative coevolution. Evolutionary links across disciplines foster cohesion essential for managing the broad impacts of novel biotic systems. Rather than signaling defeat, conciliation biology thus utilizes the predictive power of evolutionary theory to offer diverse and flexible pathways to more sustainable outcomes. PMID:25567967

  20. The Evolutionary Basis of Naturally Diverse Rice Leaves Anatomy.

    PubMed

    Chatterjee, Jolly; Dionora, Jacqueline; Elmido-Mabilangan, Abigail; Wanchana, Samart; Thakur, Vivek; Bandyopadhyay, Anindya; Brar, Darshan S; Quick, William Paul

    2016-01-01

    Rice contains genetically and ecologically diverse wild and cultivated species that show a wide variation in plant and leaf architecture. A systematic characterization of leaf anatomy is essential in understanding the dynamics behind such diversity. Therefore, leaf anatomies of 24 Oryza species spanning 11 genetically diverse rice genomes were studied in both lateral and longitudinal directions and possible evolutionary trends were examined. A significant inter-species variation in mesophyll cells, bundle sheath cells, and vein structure was observed, suggesting precise genetic control over these major rice leaf anatomical traits. Cellular dimensions, measured along three growth axes, were further combined proportionately to construct three-dimensional (3D) leaf anatomy models to compare the relative size and orientation of the major cell types present in a fully expanded leaf. A reconstruction of the ancestral leaf state revealed that the following are the major characteristics of recently evolved rice species: fewer veins, larger and laterally elongated mesophyll cells, with an increase in total mesophyll area and in bundle sheath cell number. A huge diversity in leaf anatomy within wild and domesticated rice species has been portrayed in this study, on an evolutionary context, predicting a two-pronged evolutionary pathway leading to the 'sativa leaf type' that we see today in domesticated species.

  1. On the costs of self-interested economic behavior: how does stinginess get under the skin?

    PubMed

    Dunn, Elizabeth W; Ashton-James, Claire E; Hanson, Margaret D; Aknin, Lara B

    2010-05-01

    The present study examined how financial decisions 'get under the skin'. Participants played an economic game in which they could donate some of their payment to another student. Affect was measured afterward and salivary cortisol was measured before and afterward. Participants who kept more money for themselves reported less positive affect, more negative affect, and more shame. Shame predicted higher levels of post-game cortisol, controlling for pre-game cortisol; stingy economic behavior therefore produced a significant indirect effect on cortisol via shame. Thus, shame and cortisol represent plausible emotional and biological pathways linking everyday decisions with downstream consequences for health.

  2. Rauvomines A and B, Two Monoterpenoid Indole Alkaloids from Rauvolfia vomitoria.

    PubMed

    Zeng, Jun; Zhang, Dong-Bo; Zhou, Pan-Pan; Zhang, Qi-Li; Zhao, Lei; Chen, Jian-Jun; Gao, Kun

    2017-08-04

    Two unusual normonoterpenoid indole alkaloids rauvomine A (1) and rauvomine B (2), together with two known compounds peraksine (3) and alstoyunine A (4), were isolated from the aerial parts of Rauvolfia vomitoria. The structures with absolute configurations of 1 and 2 were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compound 2 is a novel C 18 normonoterpenoid indole alkaloid with a substituted cyclopropane ring that forms an unusual 6/5/6/6/3/5 hexcyclic rearranged ring system. The plausible biogenetic pathways of 1 and 2 were proposed. Compound 2 exhibited significant anti-inflammatory activity.

  3. Magterpenoids A-C, Three Polycyclic Meroterpenoids with PTP1B Inhibitory Activity from the Bark of Magnolia officinalis var. biloba.

    PubMed

    Li, Chuan; Li, Chuang-Jun; Ma, Jie; Chen, Fang-You; Li, Li; Wang, Xiao-Liang; Ye, Fei; Zhang, Dong-Ming

    2018-06-15

    Magterpenoid A (1), possessing a rare 4,6,11-trioxatricyclo[5.3.1.0 1,5 ]undecane framework with an irregular monoterpenoid moiety, magterpenoid B (2), with an unprecedented 6/6/6/6 polycyclic skeleton, and magterpenoid C (3), a novel terpenoid quinone with a C6-C3 unit, were isolated from the bark of Magnolia officinalis var. biloba. Plausible biogenetic pathways of 1-3 are presented. Compounds 1 and 3 exhibited significant PTP1B inhibitory activities with IC 50 values of 1.44 and 0.81 μM, respectively.

  4. Genetic changes associated with testicular cancer susceptibility.

    PubMed

    Pyle, Louise C; Nathanson, Katherine L

    2016-10-01

    Testicular germ cell tumor (TGCT) is a highly heritable cancer primarily affecting young white men. Genome-wide association studies (GWAS) have been particularly effective in identifying multiple common variants with strong contribution to TGCT risk. These loci identified through association studies have implicated multiple genes as associated with TGCT predisposition, many of which are unique among cancer types, and regulate processes such as pluripotency, sex specification, and microtubule assembly. Together these biologically plausible genes converge on pathways involved in male germ cell development and maturation, and suggest that perturbation of them confers susceptibility to TGCT, as a developmental defect of germ cell differentiation. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Down syndrome, RASopathies, and other rare syndromes.

    PubMed

    Kratz, Christian P; Izraeli, Shai

    2017-04-01

    In this article we discuss the occurrence of myeloid neoplasms in patients with a range of syndromes that are due to germline defects of the RAS signaling pathway and in patients with trisomy 21. Both RAS mutations and trisomy 21 are common somatic events contributing to leukemogenis. Thus, the increased leukemia risk observed in children affected by these conditions is biologically highly plausible. Children with myeloid neoplasms in the context of these syndromes require different treatments than children with sporadic myeloid neoplasms and provide an opportunity to study the role of trisomy 21 and RAS signaling during leukemogenesis and development. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Prebiotic NH3 Formation: Insights from Simulations.

    PubMed

    Stirling, András; Rozgonyi, Tamás; Krack, Matthias; Bernasconi, Marco

    2016-02-15

    Simulations of prebiotic NH₃ synthesis from NO₃⁻ and NO₂⁻ on pyrite surfaces under hydrothermal conditions are reported. Ab initio metadynamics calculations have successfully explored the full reaction path which explains earlier experimental observations. We have found that the reaction mechanism can be constructed from stepwise single atom transfers which are compatible with the expected reaction time scales. The roles of the hot-pressurized water and of the pyrite surfaces have been addressed. The mechanistic picture that emerged from the simulations strengthens the theory of chemoautotrophic origin of life by providing plausible reaction pathways for the formation of ammonia within the iron-sulfur-world scenario.

  7. Walking over 4 Gya: Chemical Evolution from Photochemistry to Mineral and Organic Chemistries Leading to an RNA World

    NASA Astrophysics Data System (ADS)

    Kawamura, Kunio; Maurel, Marie-Christine

    2017-09-01

    Here we overview the chemical evolution of RNA molecules from inorganic material through mineral-mediated RNA formation compatible with the plausible early Earth environments. Pathways from the gas-phase reaction to the formation of nucleotides, activation and oligomerization of nucleotides, seem to be compatible with specific environments. However, how these steps interacted is not clear since the chemical conditions are frequently different and can be incompatible between them; thus the products would have migrated from one place to another, suitable for further chemical evolution. In this review, we summarize certain points to scrutinize the RNA World hypothesis.

  8. Mollanol A, a diterpenoid with a new C-nor-D-homograyanane skeleton from the fruits of Rhododendron molle.

    PubMed

    Li, Yong; Liu, Yun-Bao; Liu, Yang-Lan; Wang, Chen; Wu, Lian-Qiu; Li, Li; Ma, Shuang-Gang; Qu, Jing; Yu, Shi-Shan

    2014-08-15

    Two new grayanoids, mollanol A (1) and rhodomollein XXV (2), were isolated from the fruits of Rhododendron molle. Their structures were elucidated by spectroscopic methods and X-ray diffraction analyses. Mollanol A (1) possesses a new C-nor-D-homograyanane carbon skeleton, while rhodomollein XXV (2) is the first example of an 11,16-epoxygrayanane and features a caged oxa-tricyclo[3.3.1.0(3.7)]nonane ring system. Plausible biogenetic pathways for 1 were proposed. Compound 1 exhibited transcriptional activation effects on the xbp1 upstream promoter in IEC-6, 293T, and RAW264.7 cells.

  9. Rhodomollanol A, a Highly Oxygenated Diterpenoid with a 5/7/5/5 Tetracyclic Carbon Skeleton from the Leaves of Rhododendron molle.

    PubMed

    Zhou, Junfei; Zhan, Guanqun; Zhang, Hanqi; Zhang, Qihua; Li, Ying; Xue, Yongbo; Yao, Guangmin

    2017-07-21

    A novel diterpenoid with an unprecedented carbon skeleton, rhodomollanol A (1), and a new grayanane diterpenoid, rhodomollein XXXI (2), were isolated from the leaves of Rhododendron molle. Their structures were elucidated using comprehensive spectroscopic methods and single-crystal X-ray diffraction. Compound 1 possesses a unique cis/trans/trans/cis/cis-fused 3/5/7/5/5/5 hexacyclic ring system featuring a rare 7-oxabicyclo[4.2.1]nonane core decorated with three cyclopentane units. The plausible biosynthetic pathway for 1 was proposed. Compound 1 exhibited moderate PTP1B inhibitory activity.

  10. The protein-protein interaction network of eyestalk, Y-organ and hepatopancreas in Chinese mitten crab Eriocheir sinensis.

    PubMed

    Hao, Tong; Zeng, Zheng; Wang, Bin; Zhang, Yichen; Liu, Yichen; Geng, Xuyun; Sun, Jinsheng

    2014-03-27

    The protein-protein interaction network (PIN) is an effective information tool for understanding the complex biological processes inside the cell and solving many biological problems such as signaling pathway identification and prediction of protein functions. Eriocheir sinensis is a highly-commercial aquaculture species with an unclear proteome background which hinders the construction and development of PIN for E. sinensis. However, in recent years, the development of next-generation deep-sequencing techniques makes it possible to get high throughput data of E. sinensis tanscriptome and subsequently obtain a systematic overview of the protein-protein interaction system. In this work we sequenced the transcriptional RNA of eyestalk, Y-organ and hepatopancreas in E. sinensis and generated a PIN of E. sinensis which included 3,223 proteins and 35,787 interactions. Each protein-protein interaction in the network was scored according to the homology and genetic relationship. The signaling sub-network, representing the signal transduction pathways in E. sinensis, was extracted from the global network, which depicted a global view of the signaling systems in E. sinensis. Seven basic signal transduction pathways were identified in E. sinensis. By investigating the evolution paths of the seven pathways, we found that these pathways got mature in different evolutionary stages. Moreover, the functions of unclassified proteins and unigenes in the PIN of E. sinensis were predicted. Specifically, the functions of 549 unclassified proteins related to 864 unclassified unigenes were assigned, which respectively covered 76% and 73% of all the unclassified proteins and unigenes in the network. The PIN generated in this work is the first large-scale PIN of aquatic crustacean, thereby providing a paradigmatic blueprint of the aquatic crustacean interactome. Signaling sub-network extracted from the global PIN depicts the interaction of different signaling proteins and the evolutionary paths of the identified signal transduction pathways. Furthermore, the function assignment of unclassified proteins based on the PIN offers a new reference in protein function exploration. More importantly, the construction of the E. sinensis PIN provides necessary experience for the exploration of PINs in other aquatic crustacean species.

  11. Search for the Evolution of Steroid Biosynthesis in the Geological Record

    NASA Astrophysics Data System (ADS)

    Brocks, J. J.

    2004-12-01

    To study the evolution of the structure of organisms we can directly examine fossilized shells, skeletons and petrified cells. In contrast, for the tentative reconstruction of the phylogeny of biosynthetic pathways, such as steroid anabolism, we rely entirely on the comparative molecular biology of living organisms. Thus, without fossil evidence, the times in geological history when successive steps of a metabolic pathway evolved remain particularly elusive. Molecular clocks of genes coding for the enzymes involved in a biosynthetic pathway might provide a rough guess when a natural product first appeared in geological time, but they are intrinsically unreliable without calibration points in the distant past. However, it might be possible to trace the evolutionary history of some biosynthetic pathways directly in the geological record by searching for hydrocarbon biomarkers of anabolic intermediates. Biomarkers are molecular fossils of natural products. They often retain the diagnostic carbon skeleton of their biological precursor and remain stable over hundreds of millions of years enclosed in organic-rich sedimentary rocks. Sterane hydrocarbons are particularly abundant biomarkers and potentially suitable for the search of biosynthetic intermediates. Steranes are the fossil equivalents of functionalized steroids found in eukaryotes and certain bacteria. The biosynthesis of typical eukaryotic steroids such as cholesterol (C27), ergosterol (C28) and sitosterol (C29) from the acyclic precursor squalene (C30) involves more than 20 enzymatic steps. The most crucial steps include modification of the carbon skeleton by removal of several methyl groups from the ring system and addition of alkyl groups to the steroid side chain. The evolution of this complex pathway must have occurred over geologically significant periods of time and likely involved several preadaptive intermediates that represented structurally less derived but fully functional lipids. Thus, if a molecular corollary of `ontogeny recapitulates phylogeny' applies, it might be possible to detect a sequence of increasingly modified fossil steroids in the geological record and to create a time frame for the evolution of this fundamental biosynthetic pathway. Here we present first results of an extensive search for the fossil remains of evolutionary intermediate steroids in sedimentary successions of Precambrian age.

  12. A New Acoustic Portal into the Odontocete Ear and Vibrational Analysis of the Tympanoperiotic Complex

    PubMed Central

    Cranford, Ted W.; Krysl, Petr; Amundin, Mats

    2010-01-01

    Global concern over the possible deleterious effects of noise on marine organisms was catalyzed when toothed whales stranded and died in the presence of high intensity sound. The lack of knowledge about mechanisms of hearing in toothed whales prompted our group to study the anatomy and build a finite element model to simulate sound reception in odontocetes. The primary auditory pathway in toothed whales is an evolutionary novelty, compensating for the impedance mismatch experienced by whale ancestors as they moved from hearing in air to hearing in water. The mechanism by which high-frequency vibrations pass from the low density fats of the lower jaw into the dense bones of the auditory apparatus is a key to understanding odontocete hearing. Here we identify a new acoustic portal into the ear complex, the tympanoperiotic complex (TPC) and a plausible mechanism by which sound is transduced into the bony components. We reveal the intact anatomic geometry using CT scanning, and test functional preconceptions using finite element modeling and vibrational analysis. We show that the mandibular fat bodies bifurcate posteriorly, attaching to the TPC in two distinct locations. The smaller branch is an inconspicuous, previously undescribed channel, a cone-shaped fat body that fits into a thin-walled bony funnel just anterior to the sigmoid process of the TPC. The TPC also contains regions of thin translucent bone that define zones of differential flexibility, enabling the TPC to bend in response to sound pressure, thus providing a mechanism for vibrations to pass through the ossicular chain. The techniques used to discover the new acoustic portal in toothed whales, provide a means to decipher auditory filtering, beam formation, impedance matching, and transduction. These tools can also be used to address concerns about the potential deleterious effects of high-intensity sound in a broad spectrum of marine organisms, from whales to fish. PMID:20694149

  13. The "Wow! signal" of the terrestrial genetic code

    NASA Astrophysics Data System (ADS)

    shCherbak, Vladimir I.; Makukov, Maxim A.

    2013-05-01

    It has been repeatedly proposed to expand the scope for SETI, and one of the suggested alternatives to radio is the biological media. Genomic DNA is already used on Earth to store non-biological information. Though smaller in capacity, but stronger in noise immunity is the genetic code. The code is a flexible mapping between codons and amino acids, and this flexibility allows modifying the code artificially. But once fixed, the code might stay unchanged over cosmological timescales; in fact, it is the most durable construct known. Therefore it represents an exceptionally reliable storage for an intelligent signature, if that conforms to biological and thermodynamic requirements. As the actual scenario for the origin of terrestrial life is far from being settled, the proposal that it might have been seeded intentionally cannot be ruled out. A statistically strong intelligent-like "signal" in the genetic code is then a testable consequence of such scenario. Here we show that the terrestrial code displays a thorough precision-type orderliness matching the criteria to be considered an informational signal. Simple arrangements of the code reveal an ensemble of arithmetical and ideographical patterns of the same symbolic language. Accurate and systematic, these underlying patterns appear as a product of precision logic and nontrivial computing rather than of stochastic processes (the null hypothesis that they are due to chance coupled with presumable evolutionary pathways is rejected with P-value < 10-13). The patterns are profound to the extent that the code mapping itself is uniquely deduced from their algebraic representation. The signal displays readily recognizable hallmarks of artificiality, among which are the symbol of zero, the privileged decimal syntax and semantical symmetries. Besides, extraction of the signal involves logically straightforward but abstract operations, making the patterns essentially irreducible to any natural origin. Plausible ways of embedding the signal into the code and possible interpretation of its content are discussed. Overall, while the code is nearly optimized biologically, its limited capacity is used extremely efficiently to pass non-biological information.

  14. A new acoustic portal into the odontocete ear and vibrational analysis of the tympanoperiotic complex.

    PubMed

    Cranford, Ted W; Krysl, Petr; Amundin, Mats

    2010-08-04

    Global concern over the possible deleterious effects of noise on marine organisms was catalyzed when toothed whales stranded and died in the presence of high intensity sound. The lack of knowledge about mechanisms of hearing in toothed whales prompted our group to study the anatomy and build a finite element model to simulate sound reception in odontocetes. The primary auditory pathway in toothed whales is an evolutionary novelty, compensating for the impedance mismatch experienced by whale ancestors as they moved from hearing in air to hearing in water. The mechanism by which high-frequency vibrations pass from the low density fats of the lower jaw into the dense bones of the auditory apparatus is a key to understanding odontocete hearing. Here we identify a new acoustic portal into the ear complex, the tympanoperiotic complex (TPC) and a plausible mechanism by which sound is transduced into the bony components. We reveal the intact anatomic geometry using CT scanning, and test functional preconceptions using finite element modeling and vibrational analysis. We show that the mandibular fat bodies bifurcate posteriorly, attaching to the TPC in two distinct locations. The smaller branch is an inconspicuous, previously undescribed channel, a cone-shaped fat body that fits into a thin-walled bony funnel just anterior to the sigmoid process of the TPC. The TPC also contains regions of thin translucent bone that define zones of differential flexibility, enabling the TPC to bend in response to sound pressure, thus providing a mechanism for vibrations to pass through the ossicular chain. The techniques used to discover the new acoustic portal in toothed whales, provide a means to decipher auditory filtering, beam formation, impedance matching, and transduction. These tools can also be used to address concerns about the potential deleterious effects of high-intensity sound in a broad spectrum of marine organisms, from whales to fish.

  15. Europa's Crust and Ocean: Origin, Composition, and the Prospects for Life

    USGS Publications Warehouse

    Kargel, J.S.; Kaye, J.Z.; Head, J. W.; Marion, G.M.; Sassen, R.; Crowley, J.K.; Ballesteros, O.P.; Grant, S.A.; Hogenboom, D.L.

    2000-01-01

    We have considered a wide array of scenarios for Europa's chemical evolution in an attempt to explain the presence of ice and hydrated materials on its surface and to understand the physical and chemical nature of any ocean that may lie below. We postulate that, following formation of the jovian system, the europan evolutionary sequence has as its major links: (a) initial carbonaceous chondrite rock, (b) global primordial aqueous differentiation and formation of an impure primordial hydrous crust, (c) brine evolution and intracrustal differentiation, (d) degassing of Europa's mantle and gas venting, (e) hydrothermal processes, and (f) chemical surface alteration. Our models were developed in the context of constraints provided by Galileo imaging, near infrared reflectance spectroscopy, and gravity and magnetometer data. Low-temperature aqueous differentiation from a carbonaceous CI or CM chondrite precursor, without further chemical processing, would result in a crust/ocean enriched in magnesium sulfate and sodium sulfate, consistent with Galileo spectroscopy. Within the bounds of this simple model, a wide range of possible layered structures may result; the final state depends on the details of intracrustal differentiation. Devolatilization of the rocky mantle and hydrothermal brine reactions could have produced very different ocean/crust compositions, e.g., an ocean/crust of sodium carbonate or sulfuric acid, or a crust containing abundant clathrate hydrates. Realistic chemical-physical evolution scenarios differ greatly in detailed predictions, but they generally call for a highly impure and chemically layered crust. Some of these models could lead also to lateral chemical heterogeneities by diapiric upwellings and/or cryovolcanism. We describe some plausible geological consequences of the physical-chemical structures predicted from these scenarios. These predicted consequences and observed aspects of Europa's geology may serve as a basis for further analys is and discrimination among several alternative scenarios. Most chemical pathways could support viable ecosystems based on analogy with the metabolic and physiological versatility of terrestrial microorganisms. ?? 2000 Academic Press.

  16. Induced vibrations facilitate traversal of cluttered obstacles

    NASA Astrophysics Data System (ADS)

    Thoms, George; Yu, Siyuan; Kang, Yucheng; Li, Chen

    When negotiating cluttered terrains such as grass-like beams, cockroaches and legged robots with rounded body shapes most often rolled their bodies to traverse narrow gaps between beams. Recent locomotion energy landscape modeling suggests that this locomotor pathway overcomes the lowest potential energy barriers. Here, we tested the hypothesis that body vibrations induced by intermittent leg-ground contact facilitate obstacle traversal by allowing exploration of locomotion energy landscape to find this lowest barrier pathway. To mimic a cockroach / legged robot pushing against two adjacent blades of grass, we developed an automated robotic system to move an ellipsoidal body into two adjacent beams, and varied body vibrations by controlling an oscillation actuator. A novel gyroscope mechanism allowed the body to freely rotate in response to interaction with the beams, and an IMU and cameras recorded the motion of the body and beams. We discovered that body vibrations facilitated body rolling, significantly increasing traversal probability and reducing traversal time (P <0.0001, ANOVA). Traversal probability increased with and traversal time decreased with beam separation. These results confirmed our hypothesis and support the plausibility of locomotion energy landscapes for understanding the formation of locomotor pathways in complex 3-D terrains.

  17. Applying NGS Data to Find Evolutionary Network Biomarkers from the Early and Late Stages of Hepatocellular Carcinoma

    PubMed Central

    Wu, Chia-Chou; Lin, Chih-Lung; Chen, Ting-Shou

    2015-01-01

    Hepatocellular carcinoma (HCC) is a major liver tumor (~80%), besides hepatoblastomas, angiosarcomas, and cholangiocarcinomas. In this study, we used a systems biology approach to construct protein-protein interaction networks (PPINs) for early-stage and late-stage liver cancer. By comparing the networks of these two stages, we found that the two networks showed some common mechanisms and some significantly different mechanisms. To obtain differential network structures between cancer and noncancer PPINs, we constructed cancer PPIN and noncancer PPIN network structures for the two stages of liver cancer by systems biology method using NGS data from cancer cells and adjacent noncancer cells. Using carcinogenesis relevance values (CRVs), we identified 43 and 80 significant proteins and their PPINs (network markers) for early-stage and late-stage liver cancer. To investigate the evolution of network biomarkers in the carcinogenesis process, a primary pathway analysis showed that common pathways of the early and late stages were those related to ordinary cancer mechanisms. A pathway specific to the early stage was the mismatch repair pathway, while pathways specific to the late stage were the spliceosome pathway, lysine degradation pathway, and progesterone-mediated oocyte maturation pathway. This study provides a new direction for cancer-targeted therapies at different stages. PMID:26366411

  18. The Mevalonate Pathway and Innate Immune Hyper-Responsiveness in the Pathogenesis of COPD and Lung Cancer: Potential for Chemoprevention.

    PubMed

    Young, Robert P; Hopkins, Raewyn J

    2017-01-01

    Current evidence suggests that persisting and/or exaggerated inflammation in the lungs initiated by smoking, and up-regulated through genetic susceptibility, may result in lung remodelling and impaired repair. The mevalonate pathway, through its modifying effects on innate immune responsiveness, may be involved in these processes providing a plausible pathogenic link between the development of chronic obstructive pulmonary disease (COPD) and lung cancer. The mevalonate pathway, mediates these effects through important intra-cellular signalling molecules called guanine phosphate transferases (GTPases) such as Rho-A. Smoke exposure activates cell surface proteins which, through the mediating influence of GTPases, then modify the activation of NFkB and its downstream effects on genes underlying innate immunity, neutrophilic inflammation and carcinogenesis. The mevalonate pathway is readily and substantially modified by inhibition of the enzyme 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMGCo-A) reductase. This enzyme controls the rate limiting step of the mevalonate pathway and is subject to inhibition by statin drugs and small chain fatty acids derived from high dietary fibre intake. Thus inhibiting the mevelonate pathway, and dampening the innate immune response to smoking, may play a critical role in modifying pulmonary inflammation and lung remodelling. Such an action might slow the progression of COPD and reduce the tendency to the development of lung cancer. This review examines the pre-clinical and clinical data suggesting that HMGCoA-reductase inhibition and it's modification of the mevalonate pathway, may have a chemo-preventive effect on lung cancer, particularly in patients with COPD where pulmonary inflammation is increased and the risk of lung cancer is greatest. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Diet and Colorectal Cancer: Analysis of a Candidate Pathway Using SNPS, Haplotypes, and Multi-Gene Assessment

    PubMed Central

    Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Caan, Bette J.; Potter, John D.; Wolff, Roger K.

    2012-01-01

    There is considerable biologic plausibility to the hypothesis that genetic variability in pathways involved in insulin signaling and energy homeostasis may modulate dietary risk associated with colorectal cancer. We utilized data from 2 population-based case-control studies of colon (n = 1,574 cases, 1,970 controls) and rectal (n = 791 cases, 999 controls) cancer to evaluate genetic variation in candidate SNPs identified from 9 genes in a candidate pathway: PDK1, RP6KA1, RPS6KA2, RPS6KB1, RPS6KB2, PTEN, FRAP1 (mTOR), TSC1, TSC2, Akt1, PIK3CA, and PRKAG2 with dietary intake of total energy, carbohydrates, fat, and fiber. We employed SNP, haplotype, and multiple-gene analysis to evaluate associations. PDK1 interacted with dietary fat for both colon and rectal cancer and with dietary carbohydrates for colon cancer. Statistically significant interaction with dietary carbohydrates and rectal cancer was detected by haplotype analysis of PDK1. Evaluation of dietary interactions with multiple genes in this candidate pathway showed several interactions with pairs of genes: Akt1 and PDK1, PDK1 and PTEN, PDK1 and TSC1, and PRKAG2 and PTEN. Analyses show that genetic variation influences risk of colorectal cancer associated with diet and illustrate the importance of evaluating dietary interactions beyond the level of single SNPs or haplotypes when a biologically relevant candidate pathway is examined. PMID:21999454

  20. THE ADVERSE OUTCOME PATHWAY (AOP) FRAMEWORK ...

    EPA Pesticide Factsheets

    An Adverse Outcome Pathway (AOP) represents the organization of current and newly acquired knowledge of biological pathways. These pathways contain a series of nodes (Key Events, KEs) that when sufficiently altered influence the next node on the pathway, beginning from an Molecular Initiating Event (MIE), through intermediate KEs, ending in an Adverse Outcome (AO) which may be used as a basis for decision making. A KE is a measurable biological change, and is linked with other KEs via Key Event Relationships (KERs). A given KE may be involved in several AOPs, leading to a plausible network of biological changes that are involved in an organism’s response to an external stressor. When describing an AOP, five guiding principles have been proposed [1]: 1) an AOP is not specific to a single external stressor, 2) AOPs are modular, with KEs and KERs that can be used in several AOPs, 3) a single AOP is the unit of development, 4) most biological responses will be the result of networks of AOPs, and 5) AOPs will be modified as more biological knowledge becomes available. The collaborative development of AOPs is recommended to be performed using the AOP-Wiki (https://aopwiki.org), which is an effort between the European Commission – DG Joint Research Centre (JRC) and U.S. Environmental Protection Agency (EPA). The Wiki is one part of a larger OECD-sponsored AOP Knowledgebase effort, which is a repository for all AOPs developed as part of the Organization for Economic

  1. Resolving Conflicts Between Syntax and Plausibility in Sentence Comprehension

    PubMed Central

    Andrews, Glenda; Ogden, Jessica E.; Halford, Graeme S.

    2017-01-01

    Comprehension of plausible and implausible object- and subject-relative clause sentences with and without prepositional phrases was examined. Undergraduates read each sentence then evaluated a statement as consistent or inconsistent with the sentence. Higher acceptance of consistent than inconsistent statements indicated reliance on syntactic analysis. Higher acceptance of plausible than implausible statements reflected reliance on semantic plausibility. There was greater reliance on semantic plausibility and lesser reliance on syntactic analysis for more complex object-relatives and sentences with prepositional phrases than for less complex subject-relatives and sentences without prepositional phrases. Comprehension accuracy and confidence were lower when syntactic analysis and semantic plausibility yielded conflicting interpretations. The conflict effect on comprehension was significant for complex sentences but not for less complex sentences. Working memory capacity predicted resolution of the syntax-plausibility conflict in more and less complex items only when sentences and statements were presented sequentially. Fluid intelligence predicted resolution of the conflict in more and less complex items under sequential and simultaneous presentation. Domain-general processes appear to be involved in resolving syntax-plausibility conflicts in sentence comprehension. PMID:28458748

  2. Counterfactual Plausibility and Comparative Similarity.

    PubMed

    Stanley, Matthew L; Stewart, Gregory W; Brigard, Felipe De

    2017-05-01

    Counterfactual thinking involves imagining hypothetical alternatives to reality. Philosopher David Lewis (1973, 1979) argued that people estimate the subjective plausibility that a counterfactual event might have occurred by comparing an imagined possible world in which the counterfactual statement is true against the current, actual world in which the counterfactual statement is false. Accordingly, counterfactuals considered to be true in possible worlds comparatively more similar to ours are judged as more plausible than counterfactuals deemed true in possible worlds comparatively less similar. Although Lewis did not originally develop his notion of comparative similarity to be investigated as a psychological construct, this study builds upon his idea to empirically investigate comparative similarity as a possible psychological strategy for evaluating the perceived plausibility of counterfactual events. More specifically, we evaluate judgments of comparative similarity between episodic memories and episodic counterfactual events as a factor influencing people's judgments of plausibility in counterfactual simulations, and we also compare it against other factors thought to influence judgments of counterfactual plausibility, such as ease of simulation and prior simulation. Our results suggest that the greater the perceived similarity between the original memory and the episodic counterfactual event, the greater the perceived plausibility that the counterfactual event might have occurred. While similarity between actual and counterfactual events, ease of imagining, and prior simulation of the counterfactual event were all significantly related to counterfactual plausibility, comparative similarity best captured the variance in ratings of counterfactual plausibility. Implications for existing theories on the determinants of counterfactual plausibility are discussed. Copyright © 2016 Cognitive Science Society, Inc.

  3. Evolutionary developmental explanations of gender differences in interpersonal conflict: A response to Trnka (2013).

    PubMed

    Ingram, Gordon P D

    2013-07-27

    In focusing on gender differences in anger expression, Trnka (2013) provides a useful complement to the article by Ingram et al., (2012) analyzing gender differences in children's narratives about peer conflict. I agree that gender differences in anger are more likely to be the result of differential socialization processes regarding the expression of anger than by innate differences in the experience of anger. Gender differences in intersexual anger and aggression are likely to be affected by the social context, and especially whether a female is interacting with a romantic partner or an unknown male. The implication of socialization in anger expression raises the possibility that culture plays a causal role in encouraging cooperative breeding by inhibiting inter-female aggressive displays. Another of Trnka's proposals, that the expression of anger contributes to reconciliation and inhibits long-term relationship damage, is intuitively plausible and supported by the research literature, but not by data from the current study.

  4. CMCpy: Genetic Code-Message Coevolution Models in Python

    PubMed Central

    Becich, Peter J.; Stark, Brian P.; Bhat, Harish S.; Ardell, David H.

    2013-01-01

    Code-message coevolution (CMC) models represent coevolution of a genetic code and a population of protein-coding genes (“messages”). Formally, CMC models are sets of quasispecies coupled together for fitness through a shared genetic code. Although CMC models display plausible explanations for the origin of multiple genetic code traits by natural selection, useful modern implementations of CMC models are not currently available. To meet this need we present CMCpy, an object-oriented Python API and command-line executable front-end that can reproduce all published results of CMC models. CMCpy implements multiple solvers for leading eigenpairs of quasispecies models. We also present novel analytical results that extend and generalize applications of perturbation theory to quasispecies models and pioneer the application of a homotopy method for quasispecies with non-unique maximally fit genotypes. Our results therefore facilitate the computational and analytical study of a variety of evolutionary systems. CMCpy is free open-source software available from http://pypi.python.org/pypi/CMCpy/. PMID:23532367

  5. Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study

    PubMed Central

    Catanzaro, Daniele; Schäffer, Alejandro A.; Schwartz, Russell

    2016-01-01

    Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with Synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints. PMID:26353381

  6. The molecular and mathematical basis of Waddington's epigenetic landscape: a framework for post-Darwinian biology?

    PubMed

    Huang, Sui

    2012-02-01

    The Neo-Darwinian concept of natural selection is plausible when one assumes a straightforward causation of phenotype by genotype. However, such simple 1:1 mapping must now give place to the modern concepts of gene regulatory networks and gene expression noise. Both can, in the absence of genetic mutations, jointly generate a diversity of inheritable randomly occupied phenotypic states that could also serve as a substrate for natural selection. This form of epigenetic dynamics challenges Neo-Darwinism. It needs to incorporate the non-linear, stochastic dynamics of gene networks. A first step is to consider the mathematical correspondence between gene regulatory networks and Waddington's metaphoric 'epigenetic landscape', which actually represents the quasi-potential function of global network dynamics. It explains the coexistence of multiple stable phenotypes within one genotype. The landscape's topography with its attractors is shaped by evolution through mutational re-wiring of regulatory interactions - offering a link between genetic mutation and sudden, broad evolutionary changes. Copyright © 2012 WILEY Periodicals, Inc.

  7. Origins and spread of fluted-point technology in the Canadian Ice-Free Corridor and eastern Beringia.

    PubMed

    Smith, Heather L; Goebel, Ted

    2018-04-17

    Fluted projectile points have long been recognized as the archaeological signature of early humans dispersing throughout the Western Hemisphere; however, we still lack a clear understanding of their appearance in the interior "Ice-Free Corridor" of western Canada and eastern Beringia. To solve this problem, we conducted a geometric morphometric shape analysis and a phylogenetic analysis of technological traits on fluted points from the archaeological records of northern Alaska and Yukon, in combination with artifacts from further south in Canada, the Great Plains, and eastern United States to investigate the plausibility of historical relatedness and evolutionary patterns in the spread of fluted-point technology in the latest Pleistocene and earliest Holocene. Results link morphologies and technologies of Clovis, certain western Canadian, and northern fluted points, suggesting that fluting technology arrived in the Arctic from a proximate source in the interior Ice-Free Corridor and ultimately from the earliest populations in temperate North America, complementing new genomic models explaining the peopling of the Americas.

  8. Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study.

    PubMed

    Catanzaro, Daniele; Shackney, Stanley E; Schaffer, Alejandro A; Schwartz, Russell

    2016-01-01

    Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints.

  9. A test of multiple hypotheses for the species richness gradient of South American owls.

    PubMed

    Diniz-Filho, José Alexandre Felizola; Rangel, Thiago F L V B; Hawkins, Bradford A

    2004-08-01

    Many mechanisms have been proposed to explain broad scale spatial patterns in species richness. In this paper, we evaluate five explanations for geographic gradients in species richness, using South American owls as a model. We compared the explanatory power of contemporary climate, landcover diversity, spatial climatic heterogeneity, evolutionary history, and area. An important aspect of our analyses is that very different hypotheses, such as history and area, can be quantified at the same observation scale and, consequently can be incorporated into a single analytical framework. Both area effects and owl phylogenetic history were poorly associated with richness, whereas contemporary climate, climatic heterogeneity at the mesoscale and landcover diversity explained ca. 53% of the variation in species richness. We conclude that both climate and environmental heterogeneity should be retained as plausible explanations for the diversity gradient. Turnover rates and scaling effects, on the other hand, although perhaps useful for detecting faunal changes and beta diversity at local and regional scales, are not strong explanations for the owl diversity gradient.

  10. Hot horizontal branch stars: Predictions for mass loss. Winds, rotation, and the low gravity problem

    NASA Astrophysics Data System (ADS)

    Vink, Jorick S.; Cassisi, Santi

    2002-09-01

    We predict mass-loss rates for the late evolutionary phases of low-mass stars, with special emphasis on the consequences for the morphology of the Horizontal Branch (HB). We show that the computed rates, as predicted by the most plausible mechanism of radiation pressure on spectral lines, are too low to produce EHB/sdB stars. This invalidates the scenario recently outlined by Yong et al. (2000) to create these objects by mass loss on the HB. We argue, however, that mass loss plays a role in the distribution of rotational velocities of hot HB stars, and may - together with the enhancement of heavy element abundances due to radiative levitation - provide an explanation for the so-called ``low gravity'' problem. The mass loss recipe derived for hot HB (and extreme HB, sdB, sdOB) stars may also be applied to post-HB (AGB-manqué, UV-bright) stars over a range in effective temperatures between 12 500-40 000 K.

  11. Risks for Life on Habitable Planets from Superflares of Their Host Stars

    NASA Astrophysics Data System (ADS)

    Lingam, Manasvi; Loeb, Abraham

    2017-10-01

    We explore some of the ramifications arising from superflares on the evolutionary history of Earth, other planets in the solar system, and exoplanets. We propose that the most powerful superflares can serve as plausible drivers of extinction events, and that their periodicity corresponds to certain patterns in the terrestrial fossil diversity record. On the other hand, weaker superflares may play a positive role in enabling the origin of life through the formation of key organic compounds. Superflares could also prove to be quite detrimental to the evolution of complex life on present-day Mars and exoplanets in the habitable zone of M- and K-dwarfs. We conclude that the risk posed by superflares has not been sufficiently appreciated, and that humanity might potentially witness a superflare event in the next ˜ {10}3 years, leading to devastating economic and technological losses. In light of the many uncertainties and assumptions associated with our analysis, we recommend that these results should be viewed with due caution.

  12. X-Ray Probes of Cosmic Star-Formation History

    NASA Technical Reports Server (NTRS)

    Ghosh, Pranab; White, Nicholas E.

    2001-01-01

    In a previous paper we point out that the X-ray luminosity L(sub x) of a galaxy is driven by the evolution of its X-ray binary population and that the profile of L(sub x) with redshift can both serve as a diagnostic probe of the Star Formation Rate (SFR) profile and constrain evolutionary models for X-ray binaries. We update our previous work using a suite of more recently developed SFR profiles that span the currently plausible range. The first Chandra deep imaging results on L(sub x)-evolution are beginning to probe the SFR profile of bright spirals and the early results are consistent with predictions based on current SFR models. Using these new SFR profiles the resolution of the "birthrate problem" of lowmass X-ray binaries (LMXBs) and recycled, millisecond pulsars in terms of an evolving global SFR is more complete. We also discuss the possible impact of the variations in the SFR profile of individual galaxies.

  13. Phenotypic landscape inference reveals multiple evolutionary paths to C4 photosynthesis

    PubMed Central

    Williams, Ben P; Johnston, Iain G; Covshoff, Sarah; Hibberd, Julian M

    2013-01-01

    C4 photosynthesis has independently evolved from the ancestral C3 pathway in at least 60 plant lineages, but, as with other complex traits, how it evolved is unclear. Here we show that the polyphyletic appearance of C4 photosynthesis is associated with diverse and flexible evolutionary paths that group into four major trajectories. We conducted a meta-analysis of 18 lineages containing species that use C3, C4, or intermediate C3–C4 forms of photosynthesis to parameterise a 16-dimensional phenotypic landscape. We then developed and experimentally verified a novel Bayesian approach based on a hidden Markov model that predicts how the C4 phenotype evolved. The alternative evolutionary histories underlying the appearance of C4 photosynthesis were determined by ancestral lineage and initial phenotypic alterations unrelated to photosynthesis. We conclude that the order of C4 trait acquisition is flexible and driven by non-photosynthetic drivers. This flexibility will have facilitated the convergent evolution of this complex trait. DOI: http://dx.doi.org/10.7554/eLife.00961.001 PMID:24082995

  14. Origin and Evolutionary Alteration of the Mitochondrial Import System in Eukaryotic Lineages

    PubMed Central

    Fukasawa, Yoshinori; Oda, Toshiyuki; Tomii, Kentaro

    2017-01-01

    Abstract Protein transport systems are fundamentally important for maintaining mitochondrial function. Nevertheless, mitochondrial protein translocases such as the kinetoplastid ATOM complex have recently been shown to vary in eukaryotic lineages. Various evolutionary hypotheses have been formulated to explain this diversity. To resolve any contradiction, estimating the primitive state and clarifying changes from that state are necessary. Here, we present more likely primitive models of mitochondrial translocases, specifically the translocase of the outer membrane (TOM) and translocase of the inner membrane (TIM) complexes, using scrutinized phylogenetic profiles. We then analyzed the translocases’ evolution in eukaryotic lineages. Based on those results, we propose a novel evolutionary scenario for diversification of the mitochondrial transport system. Our results indicate that presequence transport machinery was mostly established in the last eukaryotic common ancestor, and that primitive translocases already had a pathway for transporting presequence-containing proteins. Moreover, secondary changes including convergent and migrational gains of a presequence receptor in TOM and TIM complexes, respectively, likely resulted from constrained evolution. The nature of a targeting signal can constrain alteration to the protein transport complex. PMID:28369657

  15. Preserving the evolutionary potential of floras in biodiversity hotspots.

    PubMed

    Forest, Félix; Grenyer, Richard; Rouget, Mathieu; Davies, T Jonathan; Cowling, Richard M; Faith, Daniel P; Balmford, Andrew; Manning, John C; Procheş, Serban; van der Bank, Michelle; Reeves, Gail; Hedderson, Terry A J; Savolainen, Vincent

    2007-02-15

    One of the biggest challenges for conservation biology is to provide conservation planners with ways to prioritize effort. Much attention has been focused on biodiversity hotspots. However, the conservation of evolutionary process is now also acknowledged as a priority in the face of global change. Phylogenetic diversity (PD) is a biodiversity index that measures the length of evolutionary pathways that connect a given set of taxa. PD therefore identifies sets of taxa that maximize the accumulation of 'feature diversity'. Recent studies, however, concluded that taxon richness is a good surrogate for PD. Here we show taxon richness to be decoupled from PD, using a biome-wide phylogenetic analysis of the flora of an undisputed biodiversity hotspot--the Cape of South Africa. We demonstrate that this decoupling has real-world importance for conservation planning. Finally, using a database of medicinal and economic plant use, we demonstrate that PD protection is the best strategy for preserving feature diversity in the Cape. We should be able to use PD to identify those key regions that maximize future options, both for the continuing evolution of life on Earth and for the benefit of society.

  16. An evolutionary firefly algorithm for the estimation of nonlinear biological model parameters.

    PubMed

    Abdullah, Afnizanfaizal; Deris, Safaai; Anwar, Sohail; Arjunan, Satya N V

    2013-01-01

    The development of accurate computational models of biological processes is fundamental to computational systems biology. These models are usually represented by mathematical expressions that rely heavily on the system parameters. The measurement of these parameters is often difficult. Therefore, they are commonly estimated by fitting the predicted model to the experimental data using optimization methods. The complexity and nonlinearity of the biological processes pose a significant challenge, however, to the development of accurate and fast optimization methods. We introduce a new hybrid optimization method incorporating the Firefly Algorithm and the evolutionary operation of the Differential Evolution method. The proposed method improves solutions by neighbourhood search using evolutionary procedures. Testing our method on models for the arginine catabolism and the negative feedback loop of the p53 signalling pathway, we found that it estimated the parameters with high accuracy and within a reasonable computation time compared to well-known approaches, including Particle Swarm Optimization, Nelder-Mead, and Firefly Algorithm. We have also verified the reliability of the parameters estimated by the method using an a posteriori practical identifiability test.

  17. An Evolutionary Firefly Algorithm for the Estimation of Nonlinear Biological Model Parameters

    PubMed Central

    Abdullah, Afnizanfaizal; Deris, Safaai; Anwar, Sohail; Arjunan, Satya N. V.

    2013-01-01

    The development of accurate computational models of biological processes is fundamental to computational systems biology. These models are usually represented by mathematical expressions that rely heavily on the system parameters. The measurement of these parameters is often difficult. Therefore, they are commonly estimated by fitting the predicted model to the experimental data using optimization methods. The complexity and nonlinearity of the biological processes pose a significant challenge, however, to the development of accurate and fast optimization methods. We introduce a new hybrid optimization method incorporating the Firefly Algorithm and the evolutionary operation of the Differential Evolution method. The proposed method improves solutions by neighbourhood search using evolutionary procedures. Testing our method on models for the arginine catabolism and the negative feedback loop of the p53 signalling pathway, we found that it estimated the parameters with high accuracy and within a reasonable computation time compared to well-known approaches, including Particle Swarm Optimization, Nelder-Mead, and Firefly Algorithm. We have also verified the reliability of the parameters estimated by the method using an a posteriori practical identifiability test. PMID:23469172

  18. Conditional Selection of Genomic Alterations Dictates Cancer Evolution and Oncogenic Dependencies.

    PubMed

    Mina, Marco; Raynaud, Franck; Tavernari, Daniele; Battistello, Elena; Sungalee, Stephanie; Saghafinia, Sadegh; Laessle, Titouan; Sanchez-Vega, Francisco; Schultz, Nikolaus; Oricchio, Elisa; Ciriello, Giovanni

    2017-08-14

    Cancer evolves through the emergence and selection of molecular alterations. Cancer genome profiling has revealed that specific events are more or less likely to be co-selected, suggesting that the selection of one event depends on the others. However, the nature of these evolutionary dependencies and their impact remain unclear. Here, we designed SELECT, an algorithmic approach to systematically identify evolutionary dependencies from alteration patterns. By analyzing 6,456 genomes from multiple tumor types, we constructed a map of oncogenic dependencies associated with cellular pathways, transcriptional readouts, and therapeutic response. Finally, modeling of cancer evolution shows that alteration dependencies emerge only under conditional selection. These results provide a framework for the design of strategies to predict cancer progression and therapeutic response. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Understanding sequence similarity and framework analysis between centromere proteins using computational biology.

    PubMed

    Doss, C George Priya; Chakrabarty, Chiranjib; Debajyoti, C; Debottam, S

    2014-11-01

    Certain mysteries pointing toward their recruitment pathways, cell cycle regulation mechanisms, spindle checkpoint assembly, and chromosome segregation process are considered the centre of attraction in cancer research. In modern times, with the established databases, ranges of computational platforms have provided a platform to examine almost all the physiological and biochemical evidences in disease-associated phenotypes. Using existing computational methods, we have utilized the amino acid residues to understand the similarity within the evolutionary variance of different associated centromere proteins. This study related to sequence similarity, protein-protein networking, co-expression analysis, and evolutionary trajectory of centromere proteins will speed up the understanding about centromere biology and will create a road map for upcoming researchers who are initiating their work of clinical sequencing using centromere proteins.

  20. Gene regulatory and signaling networks exhibit distinct topological distributions of motifs

    NASA Astrophysics Data System (ADS)

    Ferreira, Gustavo Rodrigues; Nakaya, Helder Imoto; Costa, Luciano da Fontoura

    2018-04-01

    The biological processes of cellular decision making and differentiation involve a plethora of signaling pathways and gene regulatory circuits. These networks in turn exhibit a multitude of motifs playing crucial parts in regulating network activity. Here we compare the topological placement of motifs in gene regulatory and signaling networks and observe that it suggests different evolutionary strategies in motif distribution for distinct cellular subnetworks.

  1. Characterization of a novel oxyfluorfen-degrading bacterial strain Chryseobacterium aquifrigidense and its biochemical degradation pathway.

    PubMed

    Zhao, Huanhuan; Xu, Jun; Dong, Fengshou; Liu, Xingang; Wu, Yanbing; Wu, Xiaohu; Zheng, Yongquan

    2016-08-01

    Persistent use of the diphenyl ether herbicides oxyfluorfen may seriously increase the health risks and ecological safety problems. A newly bacterium R-21 isolated from active soil was able to degrade and utilize oxyfluorfen as the sole carbon source. R-21 was identified as Chryseobacterium aquifrigidense by morphology, physiobiochemical characteristics, and genetic analysis. Under the optimum cultural conditions (pH 6.9, temperature 33.4 °C, and inoculum size 0.2 g L(-1)), R-21 could degrade 92.1 % of oxyfluorfen at 50 mg L(-1) within 5 days. During oxyfluorfen degradation, six metabolites were detected and identified by atmospheric pressure gas chromatography coupled to quadrupole-time of flight mass spectrometry and ultra-performance liquid chromatography coupled to quadrupole-time of flight mass spectrometry, and a plausible degradation pathway was deduced. Strain R-21 is a promising potential in bioremediation of oxyfluorfen-contaminated environments.

  2. Antioxidative mechanisms in chlorogenic acid.

    PubMed

    Tošović, Jelena; Marković, Svetlana; Dimitrić Marković, Jasmina M; Mojović, Miloš; Milenković, Dejan

    2017-12-15

    Although chlorogenic acid (5CQA) is an important ingredient of various foods and beverages, mechanisms of its antioxidative action have not been fully clarified. Besides electron spin resonance experiment, this study includes thermodynamic and mechanistic investigations of the hydrogen atom transfer (HAT), radical adduct formation (RAF), sequential proton loss electron transfer (SPLET), and single electron transfer - proton transfer (SET-PT) mechanisms of 5CQA in benzene, ethanol, and water solutions. The calculations were performed using the M06-2X/6-311++G(d,p) level of theory and CPCM solvation model. It was found that SET-PT is not a plausible antioxidative mechanism of 5CQA. RAF pathways are faster, but HAT yields thermodynamically more stable radical products, indicating that in acidic and neutral media 5CQA can take either HAT or RAF pathways. In basic environment (e.g. at physiological pH) SPLET is the likely antioxidative mechanism of 5CQA with extremely high rate. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. The abandoned ice sheet base at Camp Century, Greenland, in a warming climate

    NASA Astrophysics Data System (ADS)

    Colgan, William; Machguth, Horst; MacFerrin, Mike; Colgan, Jeff D.; As, Dirk; MacGregor, Joseph A.

    2016-08-01

    In 1959 the U.S. Army Corps of Engineers built Camp Century beneath the surface of the northwestern Greenland Ice Sheet. There they studied the feasibility of deploying ballistic missiles within the ice sheet. The base and its wastes were abandoned with minimal decommissioning in 1967, under the assumption they would be preserved for eternity by perpetually accumulating snowfall. Here we show that a transition in ice sheet surface mass balance at Camp Century from net accumulation to net ablation is plausible within the next 75 years, under a business-as-usual anthropogenic emissions scenario (Representative Concentration Pathway 8.5). Net ablation would guarantee the eventual remobilization of physical, chemical, biological, and radiological wastes abandoned at the site. While Camp Century and four other contemporaneous ice sheet bases were legally established under a Danish-U.S. treaty, the potential remobilization of their abandoned wastes, previously regarded as sequestered, represents an entirely new pathway of political dispute resulting from climate change.

  4. The Abandoned Ice Sheet Base at Camp Century, Greenland, in a Warming Climate

    NASA Technical Reports Server (NTRS)

    Colgan, William; Machguth, Horst; Macferrin, Mike; Colgan, Jeff D.; Van As, Dirk; Macgregor, Joseph A.

    2016-01-01

    In 1959 the U.S. Army Corps of Engineers built Camp Century beneath the surface of the northwestern Greenland Ice Sheet. There they studied the feasibility of deploying ballistic missiles within the ice sheet. The base and its wastes were abandoned with minimal decommissioning in 1967, under the assumption they would be preserved for eternity by perpetually accumulating snowfall. Here we show that a transition in ice sheet surface mass balance at Camp Century from net accumulation to net ablation is plausible within the next 75years, under a business-as-usual anthropogenic emissions scenario (Representative Concentration Pathway 8.5). Net ablation would guarantee the eventual remobilization of physical, chemical, biological, and radiological wastes abandoned at the site. While Camp Century and four other contemporaneous ice sheet bases were legally established under a Danish-U.S. treaty, the potential remobilization of their abandoned wastes, previously regarded as sequestered, represents an entirely new pathway of political dispute resulting from climate change.

  5. Subcutaneous white adipocytes express a light sensitive signaling pathway mediated via a melanopsin/TRPC channel axis.

    PubMed

    Ondrusova, Katarina; Fatehi, Mohammad; Barr, Amy; Czarnecka, Zofia; Long, Wentong; Suzuki, Kunimasa; Campbell, Scott; Philippaert, Koenraad; Hubert, Matthew; Tredget, Edward; Kwan, Peter; Touret, Nicolas; Wabitsch, Martin; Lee, Kevin Y; Light, Peter E

    2017-11-27

    Subcutaneous white adipose tissue (scWAT) is the major fat depot in humans and is a central player in regulating whole body metabolism. Skin exposure to UV wavelengths from sunlight is required for Vitamin D synthesis and pigmentation, although it is plausible that longer visible wavelengths that penetrate the skin may regulate scWAT function. In this regard, we discovered a novel blue light-sensitive current in human scWAT that is mediated by melanopsin coupled to transient receptor potential canonical cation channels. This pathway is activated at physiological intensities of light that penetrate the skin on a sunny day. Daily exposure of differentiated adipocytes to blue light resulted in decreased lipid droplet size, increased basal lipolytic rate and alterations in adiponectin and leptin secretion. Our results suggest that scWAT function may be directly under the influence of ambient sunlight exposure and may have important implications for our current understanding of adipocyte biology. (150 words).

  6. Constructing xylose-assimilating pathways in Pediococcus acidilactici for high titer d-lactic acid fermentation from corn stover feedstock.

    PubMed

    Qiu, Zhongyang; Gao, Qiuqiang; Bao, Jie

    2017-12-01

    Xylose-assimilating pathway was constructed in a d-lactic acid producing Pediococcus acidilactici strain and evolutionary adapted to yield a co-fermentation strain P. acidilactici ZY15 with 97.3g/L of d-lactic acid and xylose conversion of 92.6% obtained in the high solids content simultaneous saccharification and co-fermentation (SSCF) of dry dilute acid pretreated and biodetoxified corn stover feedstock. The heterologous genes encoding xylose isomerase (xylA) and xylulokinase (xylB) were screened and integrated into the P. acidilactici chromosome. The metabolic flux to acetic acid in phosphoketolase pathway was re-directed to pentose phosphate pathway by substituting the endogenous phosphoketolase gene (pkt) with the heterologous transketolase (tkt) and transaldolase (tal) genes. The xylose-assimilating ability of the newly constructed P. acidilactici strain was significantly improved by adaptive evolution. This study provided an important strain and process prototype for high titer d-lactic acid production from lignocellulose feedstock with efficient xylose assimilation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. A New Strategy to Control and Eradicate "Undruggable" Oncogenic K-RAS-Driven Pancreatic Cancer: Molecular Insights and Core Principles Learned from Developmental and Evolutionary Biology.

    PubMed

    Van Sciver, Robert E; Lee, Michael P; Lee, Caroline Dasom; Lafever, Alex C; Svyatova, Elizaveta; Kanda, Kevin; Colliver, Amber L; Siewertsz van Reesema, Lauren L; Tang-Tan, Angela M; Zheleva, Vasilena; Bwayi, Monicah N; Bian, Minglei; Schmidt, Rebecca L; Matrisian, Lynn M; Petersen, Gloria M; Tang, Amy H

    2018-05-14

    Oncogenic K-RAS mutations are found in virtually all pancreatic cancers, making K-RAS one of the most targeted oncoproteins for drug development in cancer therapies. Despite intense research efforts over the past three decades, oncogenic K-RAS has remained largely "undruggable". Rather than targeting an upstream component of the RAS signaling pathway (i.e., EGFR/HER2) and/or the midstream effector kinases (i.e., RAF/MEK/ERK/PI3K/mTOR), we propose an alternative strategy to control oncogenic K-RAS signal by targeting its most downstream signaling module, Seven-In-Absentia Homolog (SIAH). SIAH E3 ligase controls the signal output of oncogenic K-RAS hyperactivation that drives unchecked cell proliferation, uncontrolled tumor growth, and rapid cancer cell dissemination in human pancreatic cancer. Therefore, SIAH is an ideal therapeutic target as it is an extraordinarily conserved downstream signaling gatekeeper indispensable for proper RAS signaling. Guided by molecular insights and core principles obtained from developmental and evolutionary biology, we propose an anti-SIAH-centered anti-K-RAS strategy as a logical and alternative anticancer strategy to dampen uncontrolled K-RAS hyperactivation and halt tumor growth and metastasis in pancreatic cancer. The clinical utility of developing SIAH as both a tumor-specific and therapy-responsive biomarker, as well as a viable anti-K-RAS drug target, is logically simple and conceptually innovative. SIAH clearly constitutes a major tumor vulnerability and K-RAS signaling bottleneck in pancreatic ductal adenocarcinoma (PDAC). Given the high degree of evolutionary conservation in the K-RAS/SIAH signaling pathway, an anti-SIAH-based anti-PDAC therapy will synergize with covalent K-RAS inhibitors and direct K-RAS targeted initiatives to control and eradicate pancreatic cancer in the future.

  8. Low Frequency Variants, Collapsed Based on Biological Knowledge, Uncover Complexity of Population Stratification in 1000 Genomes Project Data

    PubMed Central

    Moore, Carrie B.; Wallace, John R.; Wolfe, Daniel J.; Frase, Alex T.; Pendergrass, Sarah A.; Weiss, Kenneth M.; Ritchie, Marylyn D.

    2013-01-01

    Analyses investigating low frequency variants have the potential for explaining additional genetic heritability of many complex human traits. However, the natural frequencies of rare variation between human populations strongly confound genetic analyses. We have applied a novel collapsing method to identify biological features with low frequency variant burden differences in thirteen populations sequenced by the 1000 Genomes Project. Our flexible collapsing tool utilizes expert biological knowledge from multiple publicly available database sources to direct feature selection. Variants were collapsed according to genetically driven features, such as evolutionary conserved regions, regulatory regions genes, and pathways. We have conducted an extensive comparison of low frequency variant burden differences (MAF<0.03) between populations from 1000 Genomes Project Phase I data. We found that on average 26.87% of gene bins, 35.47% of intergenic bins, 42.85% of pathway bins, 14.86% of ORegAnno regulatory bins, and 5.97% of evolutionary conserved regions show statistically significant differences in low frequency variant burden across populations from the 1000 Genomes Project. The proportion of bins with significant differences in low frequency burden depends on the ancestral similarity of the two populations compared and types of features tested. Even closely related populations had notable differences in low frequency burden, but fewer differences than populations from different continents. Furthermore, conserved or functionally relevant regions had fewer significant differences in low frequency burden than regions under less evolutionary constraint. This degree of low frequency variant differentiation across diverse populations and feature elements highlights the critical importance of considering population stratification in the new era of DNA sequencing and low frequency variant genomic analyses. PMID:24385916

  9. Radiation hybrid mapping of genes in the lithium-sensitive wnt signaling pathway.

    PubMed

    Rhoads, A R; Karkera, J D; Detera-Wadleigh, S D

    1999-09-01

    Lithium, an effective drug in the treatment of bipolar disorder, has been proposed to disrupt the Wnt signaling pathway. To facilitate analysis of the possible involvement of elements of the Wnt pathway in human bipolar disorder, a high resolution radiation hybrid mapping (RHM) of these genes was performed. A fine physical location has been obtained for Wnt 7A, frizzled 3, 4 and 5, dishevelled 1, 2 and 3, GSK3beta, axin, alpha-catenin, the Armadillo repeat-containing genes (delta-catenin and ARVCF), and a frizzled-like protein (frpHE) using the Stanford Human Genome Center (SHGC) G3 panel. Most of these genes were previously mapped by fluorescence in situ hybridization (FISH). Frizzled 4, axin and frpHE did not have a previous chromosomal assignment and were linked by RHM to chromosome markers, SHGC-35131 at 11q22.1, NIB1488 at 16p13.3 and D7S2919 at 7p15.2, respectively. Interestingly, some of these genes were found to map within potential regions underlying susceptibility to bipolar disorder and schizophrenia as well as disorders of neurodevelopmental origin. This alternative approach of establishing the precise location of selected genetic components of a candidate pathway and determining if they map within previously defined susceptibility loci should help to identify plausible candidate genes that warrant further analysis through association and mutational scanning.

  10. Potential pathways by which maternal second-hand smoke exposure during pregnancy causes full-term low birth weight.

    PubMed

    Niu, Zhongzheng; Xie, Chuanbo; Wen, Xiaozhong; Tian, Fuying; Yuan, Shixin; Jia, Deqin; Chen, Wei-Qing

    2016-04-29

    It is well documented that maternal exposure to second-hand smoke (SHS) during pregnancy causes low birth weight (LBW), but its mechanism remains unknown. This study explored the potential pathways. We enrolled 195 pregnant women who delivered full-term LBW newborns, and 195 who delivered full-term normal birth weight newborns as the controls. After controlling for maternal age, education level, family income, pre-pregnant body mass index, newborn gender and gestational age, logistic regression analysis revealed that LBW was significantly and positively associated with maternal exposure to SHS during pregnancy, lower placental weight, TNF-α and IL-1β, and that SHS exposure was significantly associated with lower placental weight, TNF-α and IL-1β. Structural equation modelling identified two plausible pathways by which maternal exposure to SHS during pregnancy might cause LBW. First, SHS exposure induced the elevation of TNF-α, which might directly increase the risk of LBW by transmission across the placenta. Second, SHS exposure first increased maternal secretion of IL-1β and TNF-α, which then triggered the secretion of VCAM-1; both TNF-α and VCAM-1 were significantly associated with lower placental weight, thus increasing the risk of LBW. In conclusion, maternal exposure to SHS during pregnancy may lead to LBW through the potential pathways of maternal inflammation and lower placental weight.

  11. Long-term smoking alters abundance of over half of the proteome in bronchoalveolar lavage cell in smokers with normal spirometry, with effects on molecular pathways associated with COPD.

    PubMed

    Yang, Mingxing; Kohler, Maxie; Heyder, Tina; Forsslund, Helena; Garberg, Hilde K; Karimi, Reza; Grunewald, Johan; Berven, Frode S; Magnus Sköld, C; Wheelock, Åsa M

    2018-03-08

    Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort. Multivariate statistical modeling, multivariate correlations with clinical data, and pathway enrichment analysis were performed. Smoking exerted a significant impact on the BAL cell proteome, with more than 500 proteins representing 15 molecular pathways altered due to smoking. The majority of these alterations occurred in a gender-independent manner. The phagosomal- and leukocyte trans endothelial migration (LTM) pathways significantly correlated with FEV 1 /FVC as well as the percentage of CD8 + T-cells and CD8 + CD69 + T-cells in smokers. The correlations to clinical parameters in healthy never-smokers were minor. The significant correlations of proteins in the phagosome- and LTM pathways with activated cytotoxic T-cells (CD69+) and the level of airway obstruction (FEV 1 /FVC) in smokers, both hallmarks of COPD, suggests that these two pathways may play a role in the molecular events preceding the development of COPD in susceptible smokers. Both pathways were found to be further dysregulated in COPD patients from the same cohort, thereby providing further support to this hypothesis. Given that not all smokers develop COPD in spite of decades of smoking, it is also plausible that some of the molecular pathways associated with response to smoking exert protective mechanisms to smoking-related pathologies in resilient individuals. ClinicalTrials.gov identifier NCT02627872 ; Retrospectively registered on December 9, 2015.

  12. MOLECULAR GAS EVOLUTION ACROSS A SPIRAL ARM IN M51

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Egusa, Fumi; Scoville, Nick; Koda, Jin, E-mail: fegusa@ir.isas.jaxa.jp

    We present sensitive and high angular resolution CO(1-0) data obtained by the Combined Array for Research in Millimeter-wave Astronomy observations toward the nearby grand-design spiral galaxy M51. The angular resolution of 0.''7 corresponds to 30 pc, which is similar to the typical size of giant molecular clouds (GMCs), and the sensitivity is also high enough to detect typical GMCs. Within the 1' field of view centered on a spiral arm, a number of GMC-scale structures are detected as clumps. However, only a few clumps are found to be associated with each giant molecular association (GMA) and more than 90% ofmore » the total flux is resolved out in our data. Considering the high sensitivity and resolution of our data, these results indicate that GMAs are not mere confusion with GMCs but plausibly smooth structures. In addition, we have found that the most massive clumps are located downstream of the spiral arm, which suggests that they are at a later stage of molecular cloud evolution across the arm and plausibly are cores of GMAs. By comparing with H{alpha} and Pa{alpha} images, most of these cores are found to have nearby star-forming regions. We thus propose an evolutionary scenario for the interstellar medium, in which smaller molecular clouds collide to form smooth GMAs at spiral arm regions and then star formation is triggered in the GMA cores. Our new CO data have revealed the internal structure of GMAs at GMC scales, finding the most massive substructures on the downstream side of the arm in close association with the brightest H II regions.« less

  13. RECOVERY OF THE CANDIDATE PROTOPLANET HD 100546 b WITH GEMINI/NICI AND DETECTION OF ADDITIONAL (PLANET-INDUCED?) DISK STRUCTURE AT SMALL SEPARATIONS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Currie, Thayne; Kudo, Tomoyuki; Muto, Takayuki

    2014-12-01

    We report the first independent, second epoch (re-)detection of a directly imaged protoplanet candidate. Using L' high-contrast imaging of HD 100546 taken with the Near-Infrared Coronagraph and Imager on Gemini South, we recover ''HD 100546 b'' with a position and brightness consistent with the original Very Large Telescope/NAos-COnica detection from Quanz et al., although data obtained after 2013 will be required to decisively demonstrate common proper motion. HD 100546 b may be spatially resolved, up to ≈12-13 AU in diameter, and is embedded in a finger of thermal IR-bright, polarized emission extending inward to at least 0.''3. Standard hot-start models implymore » a mass of ≈15 M{sub J} . However, if HD 100546 b is newly formed or made visible by a circumplanetary disk, both of which are plausible, its mass is significantly lower (e.g., 1-7 M{sub J} ). Additionally, we discover a thermal IR-bright disk feature, possibly a spiral density wave, at roughly the same angular separation as HD 100546 b but 90° away. Our interpretation of this feature as a spiral arm is not decisive, but modeling analyses using spiral density wave theory implies a wave launching point exterior to ≈0.''45 embedded within the visible disk structure: plausibly evidence for a second, hitherto unseen, wide-separation planet. With one confirmed protoplanet candidate and evidence for one to two others, HD 100546 is an important evolutionary precursor to intermediate-mass stars with multiple super-Jovian planets at moderate/wide separations like HR 8799.« less

  14. Rapid evolution of piRNA pathway in the teleost fish: implication for an adaptation to transposon diversity.

    PubMed

    Yi, Minhan; Chen, Feng; Luo, Majing; Cheng, Yibin; Zhao, Huabin; Cheng, Hanhua; Zhou, Rongjia

    2014-05-19

    The Piwi-interacting RNA (piRNA) pathway is responsible for germline specification, gametogenesis, transposon silencing, and genome integrity. Transposable elements can disrupt genome and its functions. However, piRNA pathway evolution and its adaptation to transposon diversity in the teleost fish remain unknown. This article unveils evolutionary scene of piRNA pathway and its association with diverse transposons by systematically comparative analysis on diverse teleost fish genomes. Selective pressure analysis on piRNA pathway and miRNA/siRNA (microRNA/small interfering RNA) pathway genes between teleosts and mammals showed an accelerated evolution of piRNA pathway genes in the teleost lineages, and positive selection on functional PAZ (Piwi/Ago/Zwille) and Tudor domains involved in the Piwi-piRNA/Tudor interaction, suggesting that the amino acid substitutions are adaptive to their functions in piRNA pathway in the teleost fish species. Notably five piRNA pathway genes evolved faster in the swamp eel, a kind of protogynous hermaphrodite fish, than the other teleosts, indicating a differential evolution of piRNA pathway between the swamp eel and other gonochoristic fishes. In addition, genome-wide analysis showed higher diversity of transposons in the teleost fish species compared with mammals. Our results suggest that rapidly evolved piRNA pathway in the teleost fish is likely to be involved in the adaption to transposon diversity. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  15. Evolutionary bottlenecks in brackish water habitats drive the colonization of fresh water by stingrays.

    PubMed

    Kirchhoff, K N; Hauffe, T; Stelbrink, B; Albrecht, C; Wilke, T

    2017-08-01

    Species richness in freshwater bony fishes depends on two main processes: the transition into and the diversification within freshwater habitats. In contrast to bony fishes, only few cartilaginous fishes, mostly stingrays (Myliobatoidei), were able to colonize fresh water. Respective transition processes have been mainly assessed from a physiological and morphological perspective, indicating that the freshwater lifestyle is strongly limited by the ability to perform osmoregulatory adaptations. However, the transition history and the effect of physiological constraints on the diversification in stingrays remain poorly understood. Herein, we estimated the geographic pathways of freshwater colonization and inferred the mode of habitat transitions. Further, we assessed habitat-related speciation rates in a time-calibrated phylogenetic framework to understand factors driving the transition of stingrays into and the diversification within fresh water. Using South American and Southeast Asian freshwater taxa as model organisms, we found one independent freshwater colonization event by stingrays in South America and at least three in Southeast Asia. We revealed that vicariant processes most likely caused freshwater transition during the time of major marine incursions. The habitat transition rates indicate that brackish water species switch preferably back into marine than forth into freshwater habitats. Moreover, our results showed significantly lower diversification rates in brackish water lineages, whereas freshwater and marine lineages exhibit similar rates. Thus, brackish water habitats may have functioned as evolutionary bottlenecks for the colonization of fresh water by stingrays, probably because of the higher variability of environmental conditions in brackish water. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  16. When plausibility manipulations work: an examination of their role in the development of false beliefs and memories.

    PubMed

    Bays, Rebecca B; Zabrucky, Karen M; Gagne, Phill

    2012-01-01

    In the current study we examined whether prevalence information and imagery encoding influence participants' general plausibility, personal plausibility, belief, and memory ratings for suggested childhood events. Results showed decreases in general and personal plausibility ratings for low prevalence events when encoding instructions were not elaborate; however, instructions to repeatedly imagine suggested events elicited personal plausibility increases for low-prevalence events, evidence that elaborate imagery negated the effect of our prevalence manipulation. We found no evidence of imagination inflation or false memory construction. We discuss critical differences in researchers' manipulations of plausibility and imagery that may influence results of false memory studies in the literature. In future research investigators should focus on the specific nature of encoding instructions when examining the development of false memories.

  17. Molecular population genetics of the insulin/TOR signal transduction pathway: a network-level analysis in Drosophila melanogaster.

    PubMed

    Alvarez-Ponce, David; Guirao-Rico, Sara; Orengo, Dorcas J; Segarra, Carmen; Rozas, Julio; Aguadé, Montserrat

    2012-01-01

    The IT-insulin/target of rapamycin (TOR)-signal transduction pathway is a relatively well-characterized pathway that plays a central role in fundamental biological processes. Network-level analyses of DNA divergence in Drosophila and vertebrates have revealed a clear gradient in the levels of purifying selection along this pathway, with the downstream genes being the most constrained. Remarkably, this feature does not result from factors known to affect selective constraint such as gene expression, codon bias, protein length, and connectivity. The present work aims to establish whether the selective constraint gradient detected along the IT pathway at the between-species level can also be observed at a shorter time scale. With this purpose, we have surveyed DNA polymorphism in Drosophila melanogaster and divergence from D. simulans along the IT pathway. Our network-level analysis shows that DNA polymorphism exhibits the same polarity in the strength of purifying selection as previously detected at the divergence level. This equivalent feature detected both within species and between closely and distantly related species points to the action of a general mechanism, whose action is neither organism specific nor evolutionary time dependent. The detected polarity would be, therefore, intrinsic to the IT pathway architecture and function.

  18. Antagonizing retinoic acid and FGF/MAPK pathways control posterior body patterning in the invertebrate chordate Ciona intestinalis.

    PubMed

    Pasini, Andrea; Manenti, Raoul; Rothbächer, Ute; Lemaire, Patrick

    2012-01-01

    Vertebrate embryos exploit the mutual inhibition between the RA and FGF signalling pathways to coordinate the proliferative elongation of the main body axis with the progressive patterning and differentiation of its neuroectodermal and paraxial mesodermal structures. The evolutionary history of this patterning system is still poorly understood. Here, we investigate the role played by the RA and FGF/MAPK signals during the development of the tail structures in the tunicate Ciona intestinalis, an invertebrate chordate belonging to the sister clade of vertebrates, in which the prototypical chordate body plan is established through very derived morphogenetic processes. Ciona embryos are constituted of few cells and develop according to a fixed lineage; elongation of the tail occurs largely by rearrangement of postmitotic cells; mesoderm segmentation and somitogenesis are absent. We show that in the Ciona embryo, the antagonism of the RA and FGF/MAPK signals is required to control the anteroposterior patterning of the tail epidermis. We also demonstrate that the RA, FGF/MAPK and canonical Wnt pathways control the anteroposterior patterning of the tail peripheral nervous system, and reveal the existence of distinct subpopulations of caudal epidermal neurons with different responsiveness to the RA, FGF/MAPK and canonical Wnt signals. Our data provide the first demonstration that the use of the antagonism between the RA and FGF signals to pattern the main body axis predates the emergence of vertebrates and highlight the evolutionary plasticity of this patterning strategy, showing that in different chordates it can be used to pattern different tissues within the same homologous body region.

  19. Evolutionary and functional perspectives on signaling from neuronal surface to nucleus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cohen, Samuel M.; Li, Boxing; Tsien, Richard W., E-mail: richard.tsien@nyumc.org

    2015-04-24

    Reliance on Ca{sup 2+} signaling has been well-preserved through the course of evolution. While the complexity of Ca{sup 2+} signaling pathways has increased, activation of transcription factors including CREB by Ca{sup 2+}/CaM-dependent kinases (CaMKs) has remained critical for long-term plasticity. In C. elegans, the CaMK family is made up of only three members, and CREB phosphorylation is mediated by CMK-1, the homologue of CaMKI. CMK-1 nuclear translocation directly regulates adaptation of thermotaxis behavior in response to changes in the environment. In mammals, the CaMK family has been expanded from three to ten members, enabling specialization of individual elements of amore » signal transduction pathway and increased reliance on the CaMKII subfamily. This increased complexity enables private line communication between Ca{sup 2+} sources at the cell surface and specific cellular targets. Using both new and previously published data, we review the mechanism of a γCaMKII-CaM nuclear translocation. This intricate pathway depends on a specific role for multiple Ca{sup 2+}/CaM-dependent kinases and phosphatases: α/βCaMKII phosphorylates γCaMKII to trap CaM; CaN dephosphorylates γCaMKII to dispatch it to the nucleus; and PP2A induces CaM release from γCaMKII so that CaMKK and CaMKIV can trigger CREB phosphorylation. Thus, while certain basic elements have been conserved from C. elegans, evolutionary modifications offer opportunities for targeted communication, regulation of key nodes and checkpoints, and greater specificity and flexibility in signaling.« less

  20. Evolutionary Aspects and Regulation of Tetrapyrrole Biosynthesis in Cyanobacteria under Aerobic and Anaerobic Environments

    PubMed Central

    Fujita, Yuichi; Tsujimoto, Ryoma; Aoki, Rina

    2015-01-01

    Chlorophyll a (Chl) is a light-absorbing tetrapyrrole pigment that is essential for photosynthesis. The molecule is produced from glutamate via a complex biosynthetic pathway comprised of at least 15 enzymatic steps. The first half of the Chl pathway is shared with heme biosynthesis, and the latter half, called the Mg-branch, is specific to Mg-containing Chl a. Bilin pigments, such as phycocyanobilin, are additionally produced from heme, so these light-harvesting pigments also share many common biosynthetic steps with Chl biosynthesis. Some of these common steps in the biosynthetic pathways of heme, Chl and bilins require molecular oxygen for catalysis, such as oxygen-dependent coproporphyrinogen III oxidase. Cyanobacteria thrive in diverse environments in terms of oxygen levels. To cope with Chl deficiency caused by low-oxygen conditions, cyanobacteria have developed elaborate mechanisms to maintain Chl production, even under microoxic environments. The use of enzymes specialized for low-oxygen conditions, such as oxygen-independent coproporphyrinogen III oxidase, constitutes part of a mechanism adapted to low-oxygen conditions. Another mechanism adaptive to hypoxic conditions is mediated by the transcriptional regulator ChlR that senses low oxygen and subsequently activates the transcription of genes encoding enzymes that work under low-oxygen tension. In diazotrophic cyanobacteria, this multilayered regulation also contributes in Chl biosynthesis by supporting energy production for nitrogen fixation that also requires low-oxygen conditions. We will also discuss the evolutionary implications of cyanobacterial tetrapyrrole biosynthesis and regulation, because low oxygen-type enzymes also appear to be evolutionarily older than oxygen-dependent enzymes. PMID:25830590

  1. Primates, Lice and Bacteria: Speciation and Genome Evolution in the Symbionts of Hominid Lice

    PubMed Central

    Allen, Julie M.; Nguyen, Nam-Phuong; Vachaspati, Pranjal; Quicksall, Zachary S.; Warnow, Tandy; Mugisha, Lawrence; Johnson, Kevin P.; Reed, David L.

    2017-01-01

    Abstract Insects with restricted diets rely on symbiotic bacteria to provide essential metabolites missing in their diet. The blood-sucking lice are obligate, host-specific parasites of mammals and are themselves host to symbiotic bacteria. In human lice, these bacterial symbionts supply the lice with B-vitamins. Here, we sequenced the genomes of symbiotic and heritable bacterial of human, chimpanzee, gorilla, and monkey lice and used phylogenomics to investigate their evolutionary relationships. We find that these symbionts have a phylogenetic history reflecting the louse phylogeny, a finding contrary to previous reports of symbiont replacement. Examination of the highly reduced symbiont genomes (0.53–0.57 Mb) reveals much of the genomes are dedicated to vitamin synthesis. This is unchanged in the smallest symbiont genome and one that appears to have been reorganized. Specifically, symbionts from human lice, chimpanzee lice, and gorilla lice carry a small plasmid that encodes synthesis of vitamin B5, a vitamin critical to the bacteria-louse symbiosis. This plasmid is absent in an old world monkey louse symbiont, where this pathway is on its primary chromosome. This suggests the unique genomic configuration brought about by the plasmid is not essential for symbiosis, but once obtained, it has persisted for up to 25 My. We also find evidence that human, chimpanzee, and gorilla louse endosymbionts have lost a pathway for synthesis of vitamin B1, whereas the monkey louse symbiont has retained this pathway. It is unclear whether these changes are adaptive, but they may point to evolutionary responses of louse symbionts to shifts in primate biology. PMID:28419279

  2. Modeling the evolution of protein domain architectures using maximum parsimony.

    PubMed

    Fong, Jessica H; Geer, Lewis Y; Panchenko, Anna R; Bryant, Stephen H

    2007-02-09

    Domains are basic evolutionary units of proteins and most proteins have more than one domain. Advances in domain modeling and collection are making it possible to annotate a large fraction of known protein sequences by a linear ordering of their domains, yielding their architecture. Protein domain architectures link evolutionarily related proteins and underscore their shared functions. Here, we attempt to better understand this association by identifying the evolutionary pathways by which extant architectures may have evolved. We propose a model of evolution in which architectures arise through rearrangements of inferred precursor architectures and acquisition of new domains. These pathways are ranked using a parsimony principle, whereby scenarios requiring the fewest number of independent recombination events, namely fission and fusion operations, are assumed to be more likely. Using a data set of domain architectures present in 159 proteomes that represent all three major branches of the tree of life allows us to estimate the history of over 85% of all architectures in the sequence database. We find that the distribution of rearrangement classes is robust with respect to alternative parsimony rules for inferring the presence of precursor architectures in ancestral species. Analyzing the most parsimonious pathways, we find 87% of architectures to gain complexity over time through simple changes, among which fusion events account for 5.6 times as many architectures as fission. Our results may be used to compute domain architecture similarities, for example, based on the number of historical recombination events separating them. Domain architecture "neighbors" identified in this way may lead to new insights about the evolution of protein function.

  3. Modeling the Evolution of Protein Domain Architectures Using Maximum Parsimony

    PubMed Central

    Fong, Jessica H.; Geer, Lewis Y.; Panchenko, Anna R.; Bryant, Stephen H.

    2007-01-01

    Domains are basic evolutionary units of proteins and most proteins have more than one domain. Advances in domain modeling and collection are making it possible to annotate a large fraction of known protein sequences by a linear ordering of their domains, yielding their architecture. Protein domain architectures link evolutionarily related proteins and underscore their shared functions. Here, we attempt to better understand this association by identifying the evolutionary pathways by which extant architectures may have evolved. We propose a model of evolution in which architectures arise through rearrangements of inferred precursor architectures and acquisition of new domains. These pathways are ranked using a parsimony principle, whereby scenarios requiring the fewest number of independent recombination events, namely fission and fusion operations, are assumed to be more likely. Using a data set of domain architectures present in 159 proteomes that represent all three major branches of the tree of life allows us to estimate the history of over 85% of all architectures in the sequence database. We find that the distribution of rearrangement classes is robust with respect to alternative parsimony rules for inferring the presence of precursor architectures in ancestral species. Analyzing the most parsimonious pathways, we find 87% of architectures to gain complexity over time through simple changes, among which fusion events account for 5.6 times as many architectures as fission. Our results may be used to compute domain architecture similarities, for example, based on the number of historical recombination events separating them. Domain architecture “neighbors” identified in this way may lead to new insights about the evolution of protein function. PMID:17166515

  4. Repeated cis-regulatory tuning of a metabolic bottleneck gene during evolution.

    PubMed

    Kuang, Meihua Christina; Kominek, Jacek; Alexander, William G; Cheng, Jan-Fang; Wrobel, Russell L; Hittinger, Chris Todd

    2018-05-21

    Repeated evolutionary events imply underlying genetic constraints that can make evolutionary mechanisms predictable. Morphological traits are thought to evolve frequently through cis-regulatory changes because these mechanisms bypass constraints in pleiotropic genes that are reused during development. In contrast, the constraints acting on metabolic traits during evolution are less well studied. Here we show how a metabolic bottleneck gene has repeatedly adopted similar cis-regulatory solutions during evolution, likely due to its pleiotropic role integrating flux from multiple metabolic pathways. Specifically, the genes encoding phosphoglucomutase activity (PGM1/PGM2), which connect GALactose catabolism to glycolysis, have gained and lost direct regulation by the transcription factor Gal4 several times during yeast evolution. Through targeted mutations of predicted Gal4-binding sites in yeast genomes, we show this galactose-mediated regulation of PGM1/2 supports vigorous growth on galactose in multiple yeast species, including Saccharomyces uvarum and Lachancea kluyveri. Furthermore, the addition of galactose-inducible PGM1 alone is sufficient to improve the growth on galactose of multiple species that lack this regulation, including Saccharomyces cerevisiae. The strong association between regulation of PGM1/2 by Gal4 even enables remarkably accurate predictions of galactose growth phenotypes between closely related species. This repeated mode of evolution suggests that this specific cis-regulatory connection is a common way that diverse yeasts can govern flux through the pathway, likely due to the constraints imposed by this pleiotropic bottleneck gene. Since metabolic pathways are highly interconnected, we argue that cis-regulatory evolution might be widespread at pleiotropic genes that control metabolic bottlenecks and intersections.

  5. Power Systems of the Future: A 21st Century Power Partnership Thought Leadership Report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zinaman, Owen; Miller, Mackay; Adil, Ali

    This report summarizes key forces driving transformation in the power sector around the world, presents a framework for evaluating decisions regarding extent and pace of change, and defines pathways for transformation. Powerful trends in technology, policy environments, financing, and business models are driving change in power sectors globally. In light of these trends, the question is no longer whether power systems will be transformed, but rather how these transformations will occur. Three approaches to policy and technology decision-making can guide these transformations: adaptive, reconstructive, and evolutionary. Within these approaches, we explore the five pathways that have emerged as viable modelsmore » for power system transformation.« less

  6. Temperature-Dependent Sex Determination under Rapid Anthropogenic Environmental Change: Evolution at a Turtle's Pace?

    PubMed

    Refsnider, Jeanine M; Janzen, Fredric J

    2016-01-01

    Organisms become adapted to their environment by evolving through natural selection, a process that generally transpires over many generations. Currently, anthropogenically driven environmental changes are occurring orders of magnitude faster than they did prior to human influence, which could potentially outpace the ability of some organisms to adapt. Here, we focus on traits associated with temperature-dependent sex determination (TSD), a classic polyphenism, in a model turtle species to address the evolutionary potential of species with TSD to respond to rapid climate change. We show, first, that sex-ratio outcomes in species with TSD are sensitive to climatic variation. We then identify the evolutionary potential, in terms of heritability, of TSD and quantify the evolutionary potential of 3 key traits involved in TSD: pivotal temperature, maternal nest-site choice, and nesting phenology. We find that these traits display different patterns of adaptive potential: pivotal temperature exhibits moderate heritable variation, whereas nest-site choice and nesting phenology, with considerable phenotypic plasticity, have only modest evolutionary potential to alter sex ratios. Therefore, the most likely response of species with TSD to anthropogenically induced climate change may be a combination of microevolution in thermal sensitivity of the sex-determining pathway and of plasticity in maternal nesting behavior. © The American Genetic Association. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Helminths and Cancers From the Evolutionary Perspective.

    PubMed

    Scholte, Larissa L S; Pascoal-Xavier, Marcelo A; Nahum, Laila A

    2018-01-01

    Helminths include free-living and parasitic Platyhelminthes and Nematoda which infect millions of people worldwide. Some Platyhelminthes species of blood flukes ( Schistosoma haematobium, Schistosoma japonicum , and Schistosoma mansoni ) and liver flukes ( Clonorchis sinensis and Opisthorchis viverrini ) are known to be involved in human cancers. Other helminths are likely to be carcinogenic. Our main goals are to summarize the current knowledge of human cancers caused by Platyhelminthes, point out some helminth and human biomarkers identified so far, and highlight the potential contributions of phylogenetics and molecular evolution to cancer research. Human cancers caused by helminth infection include cholangiocarcinoma, colorectal hepatocellular carcinoma, squamous cell carcinoma, and urinary bladder cancer. Chronic inflammation is proposed as a common pathway for cancer initiation and development. Furthermore, different bacteria present in gastric, colorectal, and urogenital microbiomes might be responsible for enlarging inflammatory and fibrotic responses in cancers. Studies have suggested that different biomarkers are involved in helminth infection and human cancer development; although, the detailed mechanisms remain under debate. Different helminth proteins have been studied by different approaches. However, their evolutionary relationships remain unsolved. Here, we illustrate the strengths of homology identification and function prediction of uncharacterized proteins from genome sequencing projects based on an evolutionary framework. Together, these approaches may help identifying new biomarkers for disease diagnostics and intervention measures. This work has potential applications in the field of phylomedicine (evolutionary medicine) and may contribute to parasite and cancer research.

  8. Human drivers of ecological and evolutionary dynamics in emerging and disappearing infectious disease systems.

    PubMed

    Rogalski, Mary A; Gowler, Camden D; Shaw, Clara L; Hufbauer, Ruth A; Duffy, Meghan A

    2017-01-19

    Humans have contributed to the increased frequency and severity of emerging infectious diseases, which pose a significant threat to wild and domestic species, as well as human health. This review examines major pathways by which humans influence parasitism by altering (co)evolutionary interactions between hosts and parasites on ecological timescales. There is still much to learn about these interactions, but a few well-studied cases show that humans influence disease emergence every step of the way. Human actions significantly increase dispersal of host, parasite and vector species, enabling greater frequency of infection in naive host populations and host switches. Very dense host populations resulting from urbanization and agriculture can drive the evolution of more virulent parasites and, in some cases, more resistant host populations. Human activities that reduce host genetic diversity or impose abiotic stress can impair the ability of hosts to adapt to disease threats. Further, evolutionary responses of hosts and parasites can thwart disease management and biocontrol efforts. Finally, in rare cases, humans influence evolution by eradicating an infectious disease. If we hope to fully understand the factors driving disease emergence and potentially control these epidemics we must consider the widespread influence of humans on host and parasite evolutionary trajectories.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'. © 2016 The Author(s).

  9. Evolutionary Diversification of Alanine Transaminases in Yeast: Catabolic Specialization and Biosynthetic Redundancy.

    PubMed

    Escalera-Fanjul, Ximena; Campero-Basaldua, Carlos; Colón, Maritrini; González, James; Márquez, Dariel; González, Alicia

    2017-01-01

    Gene duplication is one of the major evolutionary mechanisms providing raw material for the generation of genes with new or modified functions. The yeast Saccharomyces cerevisiae originated after an allopolyploidization event, which involved mating between two different ancestral yeast species. ScALT1 and ScALT2 codify proteins with 65% identity, which were proposed to be paralogous alanine transaminases. Further analysis of their physiological role showed that while ScALT1 encodes an alanine transaminase which constitutes the main pathway for alanine biosynthesis and the sole pathway for alanine catabolism, Sc Alt2 does not display alanine transaminase activity and is not involved in alanine metabolism. Moreover, phylogenetic studies have suggested that ScALT1 and ScALT2 come from each one of the two parental strains which gave rise to the ancestral hybrid. The present work has been aimed to the understanding of the properties of the ancestral type Lacchancea kluyveri LkALT1 and Kluyveromyces lactis KlALT1 , alanine transaminases in order to better understand the ScALT1 and ScALT2 evolutionary history. These ancestral -type species were chosen since they harbor ALT1 genes, which are related to ScALT2. Presented results show that, although LkALT1 and KlALT1 constitute ScALT1 orthologous genes, encoding alanine transaminases, both yeasts display Lk Alt1 and Kl Alt1 independent alanine transaminase activity and additional unidentified alanine biosynthetic and catabolic pathway(s). Furthermore, phenotypic analysis of null mutants uncovered the fact that Kl Alt1 and Lk Alt1 have an additional role, not related to alanine metabolism but is necessary to achieve wild type growth rate. Our study shows that the ancestral alanine transaminase function has been retained by the ScALT1 encoded enzyme, which has specialized its catabolic character, while losing the alanine independent role observed in the ancestral type enzymes. The fact that Sc Alt2 conserves 64% identity with Lk Alt1 and 66% with Kl Alt1, suggests that Sc Alt2 diversified after the ancestral hybrid was formed. ScALT2 functional diversification resulted in loss of both alanine transaminase activity and the additional alanine-independent Lk Alt1 function, since ScALT2 did not complement the Lkalt1Δ phenotype. It can be concluded that LkALT1 and KlLALT1 functional role as alanine transaminases was delegated to ScALT1 , while ScALT2 lost this role during diversification.

  10. Evolutionary Diversification of Alanine Transaminases in Yeast: Catabolic Specialization and Biosynthetic Redundancy

    PubMed Central

    Escalera-Fanjul, Ximena; Campero-Basaldua, Carlos; Colón, Maritrini; González, James; Márquez, Dariel; González, Alicia

    2017-01-01

    Gene duplication is one of the major evolutionary mechanisms providing raw material for the generation of genes with new or modified functions. The yeast Saccharomyces cerevisiae originated after an allopolyploidization event, which involved mating between two different ancestral yeast species. ScALT1 and ScALT2 codify proteins with 65% identity, which were proposed to be paralogous alanine transaminases. Further analysis of their physiological role showed that while ScALT1 encodes an alanine transaminase which constitutes the main pathway for alanine biosynthesis and the sole pathway for alanine catabolism, ScAlt2 does not display alanine transaminase activity and is not involved in alanine metabolism. Moreover, phylogenetic studies have suggested that ScALT1 and ScALT2 come from each one of the two parental strains which gave rise to the ancestral hybrid. The present work has been aimed to the understanding of the properties of the ancestral type Lacchancea kluyveri LkALT1 and Kluyveromyces lactis KlALT1, alanine transaminases in order to better understand the ScALT1 and ScALT2 evolutionary history. These ancestral -type species were chosen since they harbor ALT1 genes, which are related to ScALT2. Presented results show that, although LkALT1 and KlALT1 constitute ScALT1 orthologous genes, encoding alanine transaminases, both yeasts display LkAlt1 and KlAlt1 independent alanine transaminase activity and additional unidentified alanine biosynthetic and catabolic pathway(s). Furthermore, phenotypic analysis of null mutants uncovered the fact that KlAlt1 and LkAlt1 have an additional role, not related to alanine metabolism but is necessary to achieve wild type growth rate. Our study shows that the ancestral alanine transaminase function has been retained by the ScALT1 encoded enzyme, which has specialized its catabolic character, while losing the alanine independent role observed in the ancestral type enzymes. The fact that ScAlt2 conserves 64% identity with LkAlt1 and 66% with KlAlt1, suggests that ScAlt2 diversified after the ancestral hybrid was formed. ScALT2 functional diversification resulted in loss of both alanine transaminase activity and the additional alanine-independent LkAlt1 function, since ScALT2 did not complement the Lkalt1Δ phenotype. It can be concluded that LkALT1 and KlLALT1 functional role as alanine transaminases was delegated to ScALT1, while ScALT2 lost this role during diversification. PMID:28694796

  11. A feedback model of visual attention.

    PubMed

    Spratling, M W; Johnson, M H

    2004-03-01

    Feedback connections are a prominent feature of cortical anatomy and are likely to have a significant functional role in neural information processing. We present a neural network model of cortical feedback that successfully simulates neurophysiological data associated with attention. In this domain, our model can be considered a more detailed, and biologically plausible, implementation of the biased competition model of attention. However, our model is more general as it can also explain a variety of other top-down processes in vision, such as figure/ground segmentation and contextual cueing. This model thus suggests that a common mechanism, involving cortical feedback pathways, is responsible for a range of phenomena and provides a unified account of currently disparate areas of research.

  12. Callistrilones A and B, Triketone-Phloroglucinol-Monoterpene Hybrids with a New Skeleton from Callistemon rigidus.

    PubMed

    Cao, Jia-Qing; Huang, Xiao-Jun; Li, Yu-Ting; Wang, Ying; Wang, Lei; Jiang, Ren-Wang; Ye, Wen-Cai

    2016-01-04

    The first triketone-phloroglucinol-monoterpene hybrids, callistrilones A and B (1 and 2), along with a postulated biosynthetic intermediate (3) were isolated from the leaves of Callistemon rigidus. Compounds 1 and 2 featured a new carbon skeleton with an unprecedented [1]benzofuro[2,3-a]xanthene or [1]benzofuro[3,2-b]xanthene pentacyclic ring system composed of three kinds of building blocks. Their structures and absolute configurations were elucidated by spectroscopic analysis, X-ray diffraction, and electronic circular dichroism (ECD) calculations. A plausible biogenetic pathway for the new compounds is also proposed. Compound 1 exhibited moderate antibacterial activity against Gram-positive bacteria including multiresistant strains.

  13. Tunnel junction based memristors as artificial synapses

    PubMed Central

    Thomas, Andy; Niehörster, Stefan; Fabretti, Savio; Shepheard, Norman; Kuschel, Olga; Küpper, Karsten; Wollschläger, Joachim; Krzysteczko, Patryk; Chicca, Elisabetta

    2015-01-01

    We prepared magnesia, tantalum oxide, and barium titanate based tunnel junction structures and investigated their memristive properties. The low amplitudes of the resistance change in these types of junctions are the major obstacle for their use. Here, we increased the amplitude of the resistance change from 10% up to 100%. Utilizing the memristive properties, we looked into the use of the junction structures as artificial synapses. We observed analogs of long-term potentiation, long-term depression and spike-time dependent plasticity in these simple two terminal devices. Finally, we suggest a possible pathway of these devices toward their integration in neuromorphic systems for storing analog synaptic weights and supporting the implementation of biologically plausible learning mechanisms. PMID:26217173

  14. A role for neurotransmission and neurodevelopment in attention-deficit/hyperactivity disorder

    PubMed Central

    2009-01-01

    Attention-deficit/hyperactivity disorder (ADHD) has a moderate to high genetic component, probably due to many genes with small effects. Several susceptibility genes have been suggested on the basis of hypotheses that catecholaminergic pathways in the brain are responsible for ADHD. However, many negative association findings have been reported, indicating a limited success for investigations using this approach. The results from genome-wide association studies have suggested that genes related to general brain functions rather than specific aspects of the disorder may contribute to its development. Plausible biological hypotheses linked to neurotransmission and neurodevelopment in general and common to different psychiatric conditions need to be considered when defining candidate genes for ADHD association studies. PMID:19930624

  15. Scale-Free Distribution of Avian Influenza Outbreaks

    NASA Astrophysics Data System (ADS)

    Small, Michael; Walker, David M.; Tse, Chi Kong

    2007-11-01

    Using global case data for the period from 25 November 2003 to 10 March 2007, we construct a network of plausible transmission pathways for the spread of avian influenza among domestic and wild birds. The network structure we obtain is complex and exhibits scale-free (although not necessarily small-world) properties. Communities within this network are connected with a distribution of links with infinite variance. Hence, the disease transmission model does not exhibit a threshold and so the infection will continue to propagate even with very low transmissibility. Consequentially, eradication with methods applicable to locally homogeneous populations is not possible. Any control measure needs to focus explicitly on the hubs within this network structure.

  16. Vibrational resonance, allostery, and activation in rhodopsin-like G protein-coupled receptors

    PubMed Central

    Woods, Kristina N.; Pfeffer, Jürgen; Dutta, Arpana; Klein-Seetharaman, Judith

    2016-01-01

    G protein-coupled receptors are a large family of membrane proteins activated by a variety of structurally diverse ligands making them highly adaptable signaling molecules. Despite recent advances in the structural biology of this protein family, the mechanism by which ligands induce allosteric changes in protein structure and dynamics for its signaling function remains a mystery. Here, we propose the use of terahertz spectroscopy combined with molecular dynamics simulation and protein evolutionary network modeling to address the mechanism of activation by directly probing the concerted fluctuations of retinal ligand and transmembrane helices in rhodopsin. This approach allows us to examine the role of conformational heterogeneity in the selection and stabilization of specific signaling pathways in the photo-activation of the receptor. We demonstrate that ligand-induced shifts in the conformational equilibrium prompt vibrational resonances in the protein structure that link the dynamics of conserved interactions with fluctuations of the active-state ligand. The connection of vibrational modes creates an allosteric association of coupled fluctuations that forms a coherent signaling pathway from the receptor ligand-binding pocket to the G-protein activation region. Our evolutionary analysis of rhodopsin-like GPCRs suggest that specific allosteric sites play a pivotal role in activating structural fluctuations that allosterically modulate functional signals. PMID:27849063

  17. Large-scale gene function analysis with the PANTHER classification system.

    PubMed

    Mi, Huaiyu; Muruganujan, Anushya; Casagrande, John T; Thomas, Paul D

    2013-08-01

    The PANTHER (protein annotation through evolutionary relationship) classification system (http://www.pantherdb.org/) is a comprehensive system that combines gene function, ontology, pathways and statistical analysis tools that enable biologists to analyze large-scale, genome-wide data from sequencing, proteomics or gene expression experiments. The system is built with 82 complete genomes organized into gene families and subfamilies, and their evolutionary relationships are captured in phylogenetic trees, multiple sequence alignments and statistical models (hidden Markov models or HMMs). Genes are classified according to their function in several different ways: families and subfamilies are annotated with ontology terms (Gene Ontology (GO) and PANTHER protein class), and sequences are assigned to PANTHER pathways. The PANTHER website includes a suite of tools that enable users to browse and query gene functions, and to analyze large-scale experimental data with a number of statistical tests. It is widely used by bench scientists, bioinformaticians, computer scientists and systems biologists. In the 2013 release of PANTHER (v.8.0), in addition to an update of the data content, we redesigned the website interface to improve both user experience and the system's analytical capability. This protocol provides a detailed description of how to analyze genome-wide experimental data with the PANTHER classification system.

  18. The reformulation of emotional security theory: the role of children's social defense in developmental psychopathology.

    PubMed

    Davies, Patrick T; Martin, Meredith J

    2013-11-01

    Although children's security in the context of the interparental relationship has been identified as a key explanatory mechanism in pathways between family discord and child psychopathology, little is known about the inner workings of emotional security as a goal system. Thus, the objective of this paper is to describe how our reformulation of emotional security theory within an ethological and evolutionary framework may advance the characterization of the architecture and operation of emotional security and, in the process, cultivate sustainable growing points in developmental psychopathology. The first section of the paper describes how children's security in the interparental relationship is organized around a distinctive behavioral system designed to defend against interpersonal threat. Building on this evolutionary foundation for emotional security, the paper offers an innovative taxonomy for identifying qualitatively different ways children try to preserve their security and its innovative implications for more precisely informing understanding of the mechanisms in pathways between family and developmental precursors and children's trajectories of mental health. In the final section, the paper highlights the potential of the reformulation of emotional security theory to stimulate new generations of research on understanding how children defend against social threats in ecologies beyond the interparental dyad, including both familial and extrafamilial settings.

  19. The Reformulation of Emotional Security Theory: The Role of Children’s Social Defense in Developmental Psychopathology

    PubMed Central

    Davies, Patrick T.; Martin, Meredith J.

    2014-01-01

    Although children’s security in the context of the interparental relationship has been identified as a key explanatory mechanism in pathways between family discord and child psychopathology, little is known about the inner workings of emotional security as a goal system. Accordingly, the objective of this paper is to describe how our reformulation of emotional security theory (EST-R) within an ethological and evolutionary framework may advance the characterization of the architecture and operation of emotional security and, in the process, cultivate sustainable growing points in developmental psychopathology. The first section of the paper describes how children’s security in the interparental relationship is organized around a distinctive behavioral system designed to defend against interpersonal threat. Building on this evolutionary foundation for emotional security, the paper offers an innovative taxonomy for identifying qualitatively different ways children try to preserve their security and its innovative implications for more precisely informing understanding of the mechanisms in pathways between family and developmental precursors and children’s trajectories of mental health. In the final section, the paper highlights the potential of EST-R to stimulate new generations of research on understanding how children defend against social threats in ecologies beyond the interparental dyad, including both familial and extrafamilial settings. PMID:24342849

  20. Optimal time points sampling in pathway modelling.

    PubMed

    Hu, Shiyan

    2004-01-01

    Modelling cellular dynamics based on experimental data is at the heart of system biology. Considerable progress has been made to dynamic pathway modelling as well as the related parameter estimation. However, few of them gives consideration for the issue of optimal sampling time selection for parameter estimation. Time course experiments in molecular biology rarely produce large and accurate data sets and the experiments involved are usually time consuming and expensive. Therefore, to approximate parameters for models with only few available sampling data is of significant practical value. For signal transduction, the sampling intervals are usually not evenly distributed and are based on heuristics. In the paper, we investigate an approach to guide the process of selecting time points in an optimal way to minimize the variance of parameter estimates. In the method, we first formulate the problem to a nonlinear constrained optimization problem by maximum likelihood estimation. We then modify and apply a quantum-inspired evolutionary algorithm, which combines the advantages of both quantum computing and evolutionary computing, to solve the optimization problem. The new algorithm does not suffer from the morass of selecting good initial values and being stuck into local optimum as usually accompanied with the conventional numerical optimization techniques. The simulation results indicate the soundness of the new method.

  1. Kinetics and structural features of dimeric glutamine-dependent bacterial NAD+ synthetases suggest evolutionary adaptation to available metabolites.

    PubMed

    Santos, Adrian Richard Schenberger; Gerhardt, Edileusa Cristina Marques; Moure, Vivian Rotuno; Pedrosa, Fábio Oliveira; Souza, Emanuel Maltempi; Diamanti, Riccardo; Högbom, Martin; Huergo, Luciano Fernandes

    2018-05-11

    NADH (NAD + ) and its reduced form NADH serve as cofactors for a variety of oxidoreductases that participate in many metabolic pathways. NAD + also is used as substrate by ADP-ribosyl transferases and by sirtuins. NAD + biosynthesis is one of the most fundamental biochemical pathways in nature, and the ubiquitous NAD + synthetase (NadE) catalyzes the final step in this biosynthetic route. Two different classes of NadE have been described to date: dimeric single-domain ammonium-dependent NadE NH3 and octameric glutamine-dependent NadE Gln , and the presence of multiple NadE isoforms is relatively common in prokaryotes. Here, we identified a novel dimeric group of NadE Gln in bacteria. Substrate preferences and structural analyses suggested that dimeric NadE Gln enzymes may constitute evolutionary intermediates between dimeric NadE NH3 and octameric NadE Gln The characterization of additional NadE isoforms in the diazotrophic bacterium Azospirillum brasilense along with the determination of intracellular glutamine levels in response to an ammonium shock led us to propose a model in which these different NadE isoforms became active accordingly to the availability of nitrogen. These data may explain the selective pressures that support the coexistence of multiple isoforms of NadE in some prokaryotes. © 2018 Santos et al.

  2. Selective autophagy: ubiquitin-mediated recognition and beyond.

    PubMed

    Kraft, Claudine; Peter, Matthias; Hofmann, Kay

    2010-09-01

    Eukaryotic cells use autophagy and the ubiquitin-proteasome system as their major protein degradation pathways. Whereas the ubiquitin-proteasome system is involved in the rapid degradation of proteins, autophagy pathways can selectively remove protein aggregates and damaged or excess organelles. Proteasome-mediated degradation requires previous ubiquitylation of the cargo, which is then recognized by ubiquitin receptors directing it to 26S proteasomes. Although autophagy has long been viewed as a random cytoplasmic degradation system, the involvement of ubiquitin as a specificity factor for selective autophagy is rapidly emerging. Recent evidence also suggests active crosstalk between proteasome-mediated degradation and selective autophagy. Here, we discuss the molecular mechanisms that link autophagy and the proteasome system, as well as the emerging roles of ubiquitin and ubiquitin-binding proteins in selective autophagy. On the basis of the evolutionary history of autophagic ubiquitin receptors, we propose a common origin for metazoan ubiquitin-dependent autophagy and the cytoplasm-to-vacuole targeting pathway of yeast.

  3. Enterohemorrhagic Escherichia coli senses low biotin status in the large intestine for colonization and infection

    PubMed Central

    Yang, Bin; Feng, Lu; Wang, Fang; Wang, Lei

    2015-01-01

    Enterohemorrhagic Escherichia coli (EHEC) is an important foodborne pathogen that infects humans by colonizing the large intestine. Here we identify a virulence-regulating pathway in which the biotin protein ligase BirA signals to the global regulator Fur, which in turn activates LEE (locus of enterocyte effacement) genes to promote EHEC adherence in the low-biotin large intestine. LEE genes are repressed in the high-biotin small intestine, thus preventing adherence and ensuring selective colonization of the large intestine. The presence of this pathway in all nine EHEC serotypes tested indicates that it is an important evolutionary strategy for EHEC. The pathway is incomplete in closely related small-intestinal enteropathogenic E. coli due to the lack of the Fur response to BirA. Mice fed with a biotin-rich diet show significantly reduced EHEC adherence, indicating that biotin might be useful to prevent EHEC infection in humans. PMID:25791315

  4. Transient visual pathway critical for normal development of primate grasping behavior.

    PubMed

    Mundinano, Inaki-Carril; Fox, Dylan M; Kwan, William C; Vidaurre, Diego; Teo, Leon; Homman-Ludiye, Jihane; Goodale, Melvyn A; Leopold, David A; Bourne, James A

    2018-02-06

    An evolutionary hallmark of anthropoid primates, including humans, is the use of vision to guide precise manual movements. These behaviors are reliant on a specialized visual input to the posterior parietal cortex. Here, we show that normal primate reaching-and-grasping behavior depends critically on a visual pathway through the thalamic pulvinar, which is thought to relay information to the middle temporal (MT) area during early life and then swiftly withdraws. Small MRI-guided lesions to a subdivision of the inferior pulvinar subnucleus (PIm) in the infant marmoset monkey led to permanent deficits in reaching-and-grasping behavior in the adult. This functional loss coincided with the abnormal anatomical development of multiple cortical areas responsible for the guidance of actions. Our study reveals that the transient retino-pulvinar-MT pathway underpins the development of visually guided manual behaviors in primates that are crucial for interacting with complex features in the environment.

  5. Evolution of a flipped pathway creates metabolic innovation in tomato trichomes through BAHD enzyme promiscuity.

    PubMed

    Fan, Pengxiang; Miller, Abigail M; Liu, Xiaoxiao; Jones, A Daniel; Last, Robert L

    2017-12-12

    Plants produce hundreds of thousands of structurally diverse specialized metabolites via multistep biosynthetic networks, including compounds of ecological and therapeutic importance. These pathways are restricted to specific plant groups, and are excellent systems for understanding metabolic evolution. Tomato and other plants in the nightshade family synthesize protective acylated sugars in the tip cells of glandular trichomes on stems and leaves. We describe a metabolic innovation in wild tomato species that contributes to acylsucrose structural diversity. A small number of amino acid changes in two acylsucrose acyltransferases alter their acyl acceptor preferences, resulting in reversal of their order of reaction and increased product diversity. This study demonstrates how small numbers of amino acid changes in multiple pathway enzymes can lead to diversification of specialized metabolites in plants. It also highlights the power of a combined genetic, genomic and in vitro biochemical approach to identify the evolutionary mechanisms leading to metabolic novelty.

  6. Rab protein evolution and the history of the eukaryotic endomembrane system

    PubMed Central

    Brighouse, Andrew; Dacks, Joel B.

    2010-01-01

    Spectacular increases in the quantity of sequence data genome have facilitated major advances in eukaryotic comparative genomics. By exploiting homology with classical model organisms, this makes possible predictions of pathways and cellular functions currently impossible to address in intractable organisms. Echoing realization that core metabolic processes were established very early following evolution of life on earth, it is now emerging that many eukaryotic cellular features, including the endomembrane system, are ancient and organized around near-universal principles. Rab proteins are key mediators of vesicle transport and specificity, and via the presence of multiple paralogues, alterations in interaction specificity and modification of pathways, contribute greatly to the evolution of complexity of membrane transport. Understanding system-level contributions of Rab proteins to evolutionary history provides insight into the multiple processes sculpting cellular transport pathways and the exciting challenges that we face in delving further into the origins of membrane trafficking specificity. PMID:20582450

  7. Agrobacterium Mediated Transient Gene Silencing (AMTS) in Stevia rebaudiana: Insights into Steviol Glycoside Biosynthesis Pathway

    PubMed Central

    Guleria, Praveen; Yadav, Sudesh Kumar

    2013-01-01

    Background Steviol glycoside biosynthesis pathway has emerged as bifurcation from ent-kaurenoic acid, substrate of methyl erythritol phosphate pathway that also leads to gibberellin biosynthesis. However, the genetic regulation of steviol glycoside biosynthesis has not been studied. So, in present study RNA interference (RNAi) based Agrobacterium mediated transient gene silencing (AMTS) approach was followed. SrKA13H and three SrUGTs (SrUGT85C2, SrUGT74G1 and SrUGT76G1) genes encoding ent-kaurenoic acid-13 hydroxylase and three UDP glycosyltransferases of steviol glycoside biosynthesis pathway were silenced in Stevia rebaudiana to understand its molecular mechanism and association with gibberellins. Methodology/Principal Findings RNAi mediated AMTS of SrKA13H and three SrUGTs has significantly reduced the expression of targeted endogenous genes as well as total steviol glycoside accumulation. While gibberellins (GA3) content was significantly enhanced on AMTS of SrUGT85C2 and SrKA13H. Silencing of SrKA13H and SrUGT85C2 was found to block the metabolite flux of steviol glycoside pathway and shifted it towards GA3 biosynthesis. Further, molecular docking of three SrUGT proteins has documented highest affinity of SrUGT76G1 for the substrates of alternate pathways synthesizing steviol glycosides. This could be a plausible reason for maximum reduction in steviol glycoside content on silencing of SrUGT76G1 than other genes. Conclusions SrKA13H and SrUGT85C2 were identified as regulatory genes influencing carbon flux between steviol glycoside and gibberellin biosynthesis. This study has also documented the existence of alternate steviol glycoside biosynthesis route. PMID:24023961

  8. Expression of Wnt pathway genes in polyps and medusa-like structures of Ectopleura larynx (Cnidaria: Hydrozoa).

    PubMed

    Nawrocki, Annalise M; Cartwright, Paulyn

    2013-01-01

    The canonical Wnt signaling pathway is conserved in its role in axial patterning throughout Metazoa. In some hydrozoans (Phylum Cnidaria), Wnt signaling is implicated in oral-aboral patterning of the different life cycle stages-the planula, polyp and medusa. Unlike most hydrozoans, members of Aplanulata lack a planula larva and the polyp instead develops directly from a brooded or encysted embryo. The Aplanulata species Ectopleura larynx broods such embryos within gonophores. These gonophores are truncated medusae that remain attached to the polyps from which they bud, and retain evolutionary remnants of medusa structures. In E. larynx, gonophores differ between males and females in their degree of medusa truncation, making them an ideal system for examining truncated medusa development. Using next-generation sequencing, we isolated genes from Wnt signaling pathways and examined their expression in E. larynx. Our data are consistent with the Wnt pathway being involved in axial patterning of the polyp and truncated medusa. Changes in the spatial expression of Wnt pathway genes are correlated with the development of different oral structures in male and female gonophores. The absence of expression of components of the Wnt pathway and presence of a Wnt pathway antagonist SFRP in the developing anterior end of the gonophore suggest that downregulation of the Wnt pathway could play a role in medusa reduction in E. larynx. © 2013 Wiley Periodicals, Inc.

  9. Macro-evolutionary studies of cultural diversity: a review of empirical studies of cultural transmission and cultural adaptation.

    PubMed

    Mace, Ruth; Jordan, Fiona M

    2011-02-12

    A growing body of theoretical and empirical research has examined cultural transmission and adaptive cultural behaviour at the individual, within-group level. However, relatively few studies have tried to examine proximate transmission or test ultimate adaptive hypotheses about behavioural or cultural diversity at a between-societies macro-level. In both the history of anthropology and in present-day work, a common approach to examining adaptive behaviour at the macro-level has been through correlating various cultural traits with features of ecology. We discuss some difficulties with simple ecological associations, and then review cultural phylogenetic studies that have attempted to go beyond correlations to understand the underlying cultural evolutionary processes. We conclude with an example of a phylogenetically controlled approach to understanding proximate transmission pathways in Austronesian cultural diversity.

  10. Evolutionary rewiring of bacterial regulatory networks

    PubMed Central

    Taylor, Tiffany B.; Mulley, Geraldine; McGuffin, Liam J.; Johnson, Louise J.; Brockhurst, Michael A.; Arseneault, Tanya; Silby, Mark W.; Jackson, Robert W.

    2015-01-01

    Bacteria have evolved complex regulatory networks that enable integration of multiple intracellular and extracellular signals to coordinate responses to environmental changes. However, our knowledge of how regulatory systems function and evolve is still relatively limited. There is often extensive homology between components of different networks, due to past cycles of gene duplication, divergence, and horizontal gene transfer, raising the possibility of cross-talk or redundancy. Consequently, evolutionary resilience is built into gene networks - homology between regulators can potentially allow rapid rescue of lost regulatory function across distant regions of the genome. In our recent study [Taylor, et al. Science (2015), 347(6225)] we find that mutations that facilitate cross-talk between pathways can contribute to gene network evolution, but that such mutations come with severe pleiotropic costs. Arising from this work are a number of questions surrounding how this phenomenon occurs. PMID:28357301

  11. Clonal Evolution of Glioblastoma under Therapy

    PubMed Central

    Wang, Jiguang; Cazzato, Emanuela; Ladewig, Erik; Frattini, Veronique; Rosenbloom, Daniel I. S.; Zairis, Sakellarios; Abate, Francesco; Liu, Zhaoqi; Elliott, Oliver; Shin, Yong-Jae; Lee, Jin-Ku; Lee, In-Hee; Park, Woong-Yang; Eoli, Marica; Blumberg, Andrew J.; Lasorella, Anna; Nam, Do-Hyun; Finocchiaro, Gaetano; Iavarone, Antonio; Rabadan, Raul

    2017-01-01

    Glioblastoma (GBM) constitutes the most common and aggressive primary brain tumor. To better understand how GBM evolves we analyzed longitudinal genomic and transcriptomic data of 114 patients. The analysis reveals a highly branched evolutionary pattern in which 63% of patients experience expression-based subtype changes. The branching pattern together with estimates of evolutionary rates suggest that the relapse associated clone typically preexisted years before diagnosis. 15% of tumors present hypermutations at relapse in highly expressed genes with a clear mutational signature. We find that 11% of recurrent tumors harbor mutations in LTBP4, a protein binding to TGF-β. Silencing LTBP4 in GBM cells leads to TGF-β activity suppression and decreased proliferation. In IDH1-wild-type recurrent GBM, high LTBP4 expression is associated with worse prognosis, highlighting the TGF-β pathway as a potential therapeutic target in GBM. PMID:27270107

  12. Macro-evolutionary studies of cultural diversity: a review of empirical studies of cultural transmission and cultural adaptation

    PubMed Central

    Mace, Ruth; Jordan, Fiona M.

    2011-01-01

    A growing body of theoretical and empirical research has examined cultural transmission and adaptive cultural behaviour at the individual, within-group level. However, relatively few studies have tried to examine proximate transmission or test ultimate adaptive hypotheses about behavioural or cultural diversity at a between-societies macro-level. In both the history of anthropology and in present-day work, a common approach to examining adaptive behaviour at the macro-level has been through correlating various cultural traits with features of ecology. We discuss some difficulties with simple ecological associations, and then review cultural phylogenetic studies that have attempted to go beyond correlations to understand the underlying cultural evolutionary processes. We conclude with an example of a phylogenetically controlled approach to understanding proximate transmission pathways in Austronesian cultural diversity. PMID:21199844

  13. Phenotypic plasticity, the Baldwin effect, and the speeding up of evolution: the computational roots of an illusion.

    PubMed

    Santos, Mauro; Szathmáry, Eörs; Fontanari, José F

    2015-04-21

    An increasing number of dissident voices claim that the standard neo-Darwinian view of genes as 'leaders' and phenotypes as 'followers' during the process of adaptive evolution should be turned on its head. This idea is older than the rediscovery of Mendel's laws of inheritance, with the turn-of-the-twentieth-century notion eventually labeled as the 'Baldwin effect' as one of the many ways in which the standard neo-Darwinian view can be turned around. A condition for this effect is that environmentally induced variation such as phenotypic plasticity or learning is crucial for the initial establishment of a trait. This gives the additional time for natural selection to act on genetic variation and the adaptive trait can be eventually encoded in the genotype. An influential paper published in the late 1980s claimed the Baldwin effect to happen in computer simulations, and avowed that it was crucial to solve a difficult adaptive task. This generated much excitement among scholars in various disciplines that regard neo-Darwinian accounts to explain the evolutionary emergence of high-order phenotypic traits such as consciousness or language almost hopeless. Here, we use analytical and computational approaches to show that a standard population genetics treatment can easily crack what the scientific community has granted as an unsolvable adaptive problem without learning. Evolutionary psychologists and linguists have invoked the (claimed) Baldwin effect to make wild assertions that should not be taken seriously. What the Baldwin effect needs are plausible case-histories. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Evolutionary escalation: the bat-moth arms race.

    PubMed

    Ter Hofstede, Hannah M; Ratcliffe, John M

    2016-06-01

    Echolocation in bats and high-frequency hearing in their insect prey make bats and insects an ideal system for studying the sensory ecology and neuroethology of predator-prey interactions. Here, we review the evolutionary history of bats and eared insects, focusing on the insect order Lepidoptera, and consider the evidence for antipredator adaptations and predator counter-adaptations. Ears evolved in a remarkable number of body locations across insects, with the original selection pressure for ears differing between groups. Although cause and effect are difficult to determine, correlations between hearing and life history strategies in moths provide evidence for how these two variables influence each other. We consider life history variables such as size, sex, circadian and seasonal activity patterns, geographic range and the composition of sympatric bat communities. We also review hypotheses on the neural basis for anti-predator behaviours (such as evasive flight and sound production) in moths. It is assumed that these prey adaptations would select for counter-adaptations in predatory bats. We suggest two levels of support for classifying bat traits as counter-adaptations: traits that allow bats to eat more eared prey than expected based on their availability in the environment provide a low level of support for counter-adaptations, whereas traits that have no other plausible explanation for their origination and maintenance than capturing defended prey constitute a high level of support. Specific predator counter-adaptations include calling at frequencies outside the sensitivity range of most eared prey, changing the pattern and frequency of echolocation calls during prey pursuit, and quiet, or 'stealth', echolocation. © 2016. Published by The Company of Biologists Ltd.

  15. An algebraic hypothesis about the primeval genetic code architecture.

    PubMed

    Sánchez, Robersy; Grau, Ricardo

    2009-09-01

    A plausible architecture of an ancient genetic code is derived from an extended base triplet vector space over the Galois field of the extended base alphabet {D,A,C,G,U}, where symbol D represents one or more hypothetical bases with unspecific pairings. We hypothesized that the high degeneration of a primeval genetic code with five bases and the gradual origin and improvement of a primeval DNA repair system could make possible the transition from ancient to modern genetic codes. Our results suggest that the Watson-Crick base pairing G identical with C and A=U and the non-specific base pairing of the hypothetical ancestral base D used to define the sum and product operations are enough features to determine the coding constraints of the primeval and the modern genetic code, as well as, the transition from the former to the latter. Geometrical and algebraic properties of this vector space reveal that the present codon assignment of the standard genetic code could be induced from a primeval codon assignment. Besides, the Fourier spectrum of the extended DNA genome sequences derived from the multiple sequence alignment suggests that the called period-3 property of the present coding DNA sequences could also exist in the ancient coding DNA sequences. The phylogenetic analyses achieved with metrics defined in the N-dimensional vector space (B(3))(N) of DNA sequences and with the new evolutionary model presented here also suggest that an ancient DNA coding sequence with five or more bases does not contradict the expected evolutionary history.

  16. Coordinated rates of evolution between interacting plastid and nuclear genes in Geraniaceae.

    PubMed

    Zhang, Jin; Ruhlman, Tracey A; Sabir, Jamal; Blazier, J Chris; Jansen, Robert K

    2015-03-01

    Although gene coevolution has been widely observed within individuals and between different organisms, rarely has this phenomenon been investigated within a phylogenetic framework. The Geraniaceae is an attractive system in which to study plastid-nuclear genome coevolution due to the highly elevated evolutionary rates in plastid genomes. In plants, the plastid-encoded RNA polymerase (PEP) is a protein complex composed of subunits encoded by both plastid (rpoA, rpoB, rpoC1, and rpoC2) and nuclear genes (sig1-6). We used transcriptome and genomic data for 27 species of Geraniales in a systematic evaluation of coevolution between genes encoding subunits of the PEP holoenzyme. We detected strong correlations of dN (nonsynonymous substitutions) but not dS (synonymous substitutions) within rpoB/sig1 and rpoC2/sig2, but not for other plastid/nuclear gene pairs, and identified the correlation of dN/dS ratio between rpoB/C1/C2 and sig1/5/6, rpoC1/C2 and sig2, and rpoB/C2 and sig3 genes. Correlated rates between interacting plastid and nuclear sequences across the Geraniales could result from plastid-nuclear genome coevolution. Analyses of coevolved amino acid positions suggest that structurally mediated coevolution is not the major driver of plastid-nuclear coevolution. The detection of strong correlation of evolutionary rates between SIG and RNAP genes suggests a plausible explanation for plastome-genome incompatibility in Geraniaceae. © 2015 American Society of Plant Biologists. All rights reserved.

  17. The inflated radii of M dwarfs in the Pleiades

    NASA Astrophysics Data System (ADS)

    Jackson, R. J.; Deliyannis, Constantine P.; Jeffries, R. D.

    2018-05-01

    Rotation periods obtained with the Kepler satellite have been combined with precise measurements of projected rotation velocity from the WIYN 3.5-m telescope to determine the distribution of projected radii for several hundred low-mass (0.1 ≤ M/M⊙ ≤ 0.8), fast-rotating members of the Pleiades cluster. A maximum likelihood modelling technique, that takes account of observational uncertainties, selection effects and censored data, and considers the effects of differential rotation and unresolved binarity, has been used to find that the average radius of these stars is 14 ± 2 per cent larger at a given luminosity than predicted by current evolutionary models of Dotter et al. and Baraffe et al. The same models are a reasonable match to the interferometric radii of older, magnetically inactive field M dwarfs, suggesting that the over-radius may be associated with the young, magnetically active nature of the Pleiades objects. No evidence is found for any change in this over-radius above and below the boundary marking the transition to full convection. Published evolutionary models that incorporate either the effects of magnetic inhibition of convection or the blocking of flux by dark star-spots do not individually explain the radius inflation, but a combination of the two effects might. The distribution of projected radii is consistent with the adopted hypothesis of a random spatial orientation of spin axes; strong alignments of the spin vectors into cones with an opening semi-angle <30° can be ruled out. Any plausible but weaker alignment would increase the inferred over-radius.

  18. Exploratory Application of Neuropharmacometabolomics in Severe Childhood Traumatic Brain Injury.

    PubMed

    Hagos, Fanuel T; Empey, Philip E; Wang, Pengcheng; Ma, Xiaochao; Poloyac, Samuel M; Bayır, Hülya; Kochanek, Patrick M; Bell, Michael J; Clark, Robert S B

    2018-05-07

    To employ metabolomics-based pathway and network analyses to evaluate the cerebrospinal fluid metabolome after severe traumatic brain injury in children and the capacity of combination therapy with probenecid and N-acetylcysteine to impact glutathione-related and other pathways and networks, relative to placebo treatment. Analysis of cerebrospinal fluid obtained from children enrolled in an Institutional Review Board-approved, randomized, placebo-controlled trial of a combination of probenecid and N-acetylcysteine after severe traumatic brain injury (Trial Registration NCT01322009). Thirty-six-bed PICU in a university-affiliated children's hospital. Twelve children 2-18 years old after severe traumatic brain injury and five age-matched control subjects. Probenecid (25 mg/kg) and N-acetylcysteine (140 mg/kg) or placebo administered via naso/orogastric tube. The cerebrospinal fluid metabolome was analyzed in samples from traumatic brain injury patients 24 hours after the first dose of drugs or placebo and control subjects. Feature detection, retention time, alignment, annotation, and principal component analysis and statistical analysis were conducted using XCMS-online. The software "mummichog" was used for pathway and network analyses. A two-component principal component analysis revealed clustering of each of the groups, with distinct metabolomics signatures. Several novel pathways with plausible mechanistic involvement in traumatic brain injury were identified. A combination of metabolomics and pathway/network analyses showed that seven glutathione-centered pathways and two networks were enriched in the cerebrospinal fluid of traumatic brain injury patients treated with probenecid and N-acetylcysteine versus placebo-treated patients. Several additional pathways/networks consisting of components that are known substrates of probenecid-inhibitable transporters were also identified, providing additional mechanistic validation. This proof-of-concept neuropharmacometabolomics assessment reveals alterations in known and previously unidentified metabolic pathways and supports therapeutic target engagement of the combination of probenecid and N-acetylcysteine treatment after severe traumatic brain injury in children.

  19. Reconstruction of metabolic pathways for the cattle genome

    PubMed Central

    Seo, Seongwon; Lewin, Harris A

    2009-01-01

    Background Metabolic reconstruction of microbial, plant and animal genomes is a necessary step toward understanding the evolutionary origins of metabolism and species-specific adaptive traits. The aims of this study were to reconstruct conserved metabolic pathways in the cattle genome and to identify metabolic pathways with missing genes and proteins. The MetaCyc database and PathwayTools software suite were chosen for this work because they are widely used and easy to implement. Results An amalgamated cattle genome database was created using the NCBI and Ensembl cattle genome databases (based on build 3.1) as data sources. PathwayTools was used to create a cattle-specific pathway genome database, which was followed by comprehensive manual curation for the reconstruction of metabolic pathways. The curated database, CattleCyc 1.0, consists of 217 metabolic pathways. A total of 64 mammalian-specific metabolic pathways were modified from the reference pathways in MetaCyc, and two pathways previously identified but missing from MetaCyc were added. Comparative analysis of metabolic pathways revealed the absence of mammalian genes for 22 metabolic enzymes whose activity was reported in the literature. We also identified six human metabolic protein-coding genes for which the cattle ortholog is missing from the sequence assembly. Conclusion CattleCyc is a powerful tool for understanding the biology of ruminants and other cetartiodactyl species. In addition, the approach used to develop CattleCyc provides a framework for the metabolic reconstruction of other newly sequenced mammalian genomes. It is clear that metabolic pathway analysis strongly reflects the quality of the underlying genome annotations. Thus, having well-annotated genomes from many mammalian species hosted in BioCyc will facilitate the comparative analysis of metabolic pathways among different species and a systems approach to comparative physiology. PMID:19284618

  20. The autophagy interaction network of the aging model Podospora anserina.

    PubMed

    Philipp, Oliver; Hamann, Andrea; Osiewacz, Heinz D; Koch, Ina

    2017-03-27

    Autophagy is a conserved molecular pathway involved in the degradation and recycling of cellular components. It is active either as response to starvation or molecular damage. Evidence is emerging that autophagy plays a key role in the degradation of damaged cellular components and thereby affects aging and lifespan control. In earlier studies, it was found that autophagy in the aging model Podospora anserina acts as a longevity assurance mechanism. However, only little is known about the individual components controlling autophagy in this aging model. Here, we report a biochemical and bioinformatics study to detect the protein-protein interaction (PPI) network of P. anserina combining experimental and theoretical methods. We constructed the PPI network of autophagy in P. anserina based on the corresponding networks of yeast and human. We integrated PaATG8 interaction partners identified in an own yeast two-hybrid analysis using ATG8 of P. anserina as bait. Additionally, we included age-dependent transcriptome data. The resulting network consists of 89 proteins involved in 186 interactions. We applied bioinformatics approaches to analyze the network topology and to prove that the network is not random, but exhibits biologically meaningful properties. We identified hub proteins which play an essential role in the network as well as seven putative sub-pathways, and interactions which are likely to be evolutionary conserved amongst species. We confirmed that autophagy-associated genes are significantly often up-regulated and co-expressed during aging of P. anserina. With the present study, we provide a comprehensive biological network of the autophagy pathway in P. anserina comprising PPI and gene expression data. It is based on computational prediction as well as experimental data. We identified sub-pathways, important hub proteins, and evolutionary conserved interactions. The network clearly illustrates the relation of autophagy to aging processes and enables further specific studies to understand autophagy and aging in P. anserina as well as in other systems.

  1. Metabolic network prediction through pairwise rational kernels.

    PubMed

    Roche-Lima, Abiel; Domaratzki, Michael; Fristensky, Brian

    2014-09-26

    Metabolic networks are represented by the set of metabolic pathways. Metabolic pathways are a series of biochemical reactions, in which the product (output) from one reaction serves as the substrate (input) to another reaction. Many pathways remain incompletely characterized. One of the major challenges of computational biology is to obtain better models of metabolic pathways. Existing models are dependent on the annotation of the genes. This propagates error accumulation when the pathways are predicted by incorrectly annotated genes. Pairwise classification methods are supervised learning methods used to classify new pair of entities. Some of these classification methods, e.g., Pairwise Support Vector Machines (SVMs), use pairwise kernels. Pairwise kernels describe similarity measures between two pairs of entities. Using pairwise kernels to handle sequence data requires long processing times and large storage. Rational kernels are kernels based on weighted finite-state transducers that represent similarity measures between sequences or automata. They have been effectively used in problems that handle large amount of sequence information such as protein essentiality, natural language processing and machine translations. We create a new family of pairwise kernels using weighted finite-state transducers (called Pairwise Rational Kernel (PRK)) to predict metabolic pathways from a variety of biological data. PRKs take advantage of the simpler representations and faster algorithms of transducers. Because raw sequence data can be used, the predictor model avoids the errors introduced by incorrect gene annotations. We then developed several experiments with PRKs and Pairwise SVM to validate our methods using the metabolic network of Saccharomyces cerevisiae. As a result, when PRKs are used, our method executes faster in comparison with other pairwise kernels. Also, when we use PRKs combined with other simple kernels that include evolutionary information, the accuracy values have been improved, while maintaining lower construction and execution times. The power of using kernels is that almost any sort of data can be represented using kernels. Therefore, completely disparate types of data can be combined to add power to kernel-based machine learning methods. When we compared our proposal using PRKs with other similar kernel, the execution times were decreased, with no compromise of accuracy. We also proved that by combining PRKs with other kernels that include evolutionary information, the accuracy can also also be improved. As our proposal can use any type of sequence data, genes do not need to be properly annotated, avoiding accumulation errors because of incorrect previous annotations.

  2. Bacterial pathogenesis of plants: future challenges from a microbial perspective: Challenges in Bacterial Molecular Plant Pathology.

    PubMed

    Pfeilmeier, Sebastian; Caly, Delphine L; Malone, Jacob G

    2016-10-01

    Plant infection is a complicated process. On encountering a plant, pathogenic microorganisms must first adapt to life on the epiphytic surface, and survive long enough to initiate an infection. Responsiveness to the environment is critical throughout infection, with intracellular and community-level signal transduction pathways integrating environmental signals and triggering appropriate responses in the bacterial population. Ultimately, phytopathogens must migrate from the epiphytic surface into the plant tissue using motility and chemotaxis pathways. This migration is coupled with overcoming the physical and chemical barriers to entry into the plant apoplast. Once inside the plant, bacteria use an array of secretion systems to release phytotoxins and protein effectors that fulfil diverse pathogenic functions (Fig. ) (Melotto and Kunkel, ; Phan Tran et al., ). As our understanding of the pathways and mechanisms underpinning plant pathogenicity increases, a number of central research challenges are emerging that will profoundly shape the direction of research in the future. We need to understand the bacterial phenotypes that promote epiphytic survival and surface adaptation in pathogenic bacteria. How do these pathways function in the context of the plant-associated microbiome, and what impact does this complex microbial community have on the onset and severity of plant infections? The huge importance of bacterial signal transduction to every stage of plant infection is becoming increasingly clear. However, there is a great deal to learn about how these signalling pathways function in phytopathogenic bacteria, and the contribution they make to various aspects of plant pathogenicity. We are increasingly able to explore the structural and functional diversity of small-molecule natural products from plant pathogens. We need to acquire a much better understanding of the production, deployment, functional redundancy and physiological roles of these molecules. Type III secretion systems (T3SSs) are important and well-studied contributors to bacterial disease. Several key unanswered questions will shape future investigations of these systems. We need to define the mechanism of hierarchical and temporal control of effector secretion. For successful infection, effectors need to interact with host components to exert their function. Advanced biochemical, proteomic and cell biological techniques will enable us to study the function of effectors inside the host cell in more detail and on a broader scale. Population genomics analyses provide insight into evolutionary adaptation processes of phytopathogens. The determination of the diversity and distribution of type III effectors (T3Es) and other virulence genes within and across pathogenic species, pathovars and strains will allow us to understand how pathogens adapt to specific hosts, the evolutionary pathways available to them, and the possible future directions of the evolutionary arms race between effectors and molecular plant targets. Although pathogenic bacteria employ a host of different virulence and proliferation strategies, as a result of the space constraints, this review focuses mainly on the hemibiotrophic pathogens. We discuss the process of plant infection from the perspective of these important phytopathogens, and highlight new approaches to address the outstanding challenges in this important and fast-moving field. © 2016 The Authors. Molecular Plant Pathology Published by British Society for Plant Pathology and John Wiley & Sons Ltd.

  3. Evolutionary History of Assassin Bugs (Insecta: Hemiptera: Reduviidae): Insights from Divergence Dating and Ancestral State Reconstruction

    PubMed Central

    Hwang, Wei Song; Weirauch, Christiane

    2012-01-01

    Assassin bugs are one of the most successful clades of predatory animals based on their species numbers (∼6,800 spp.) and wide distribution in terrestrial ecosystems. Various novel prey capture strategies and remarkable prey specializations contribute to their appeal as a model to study evolutionary pathways involved in predation. Here, we reconstruct the most comprehensive reduviid phylogeny (178 taxa, 18 subfamilies) to date based on molecular data (5 markers). This phylogeny tests current hypotheses on reduviid relationships emphasizing the polyphyletic Reduviinae and the blood-feeding, disease-vectoring Triatominae, and allows us, for the first time in assassin bugs, to reconstruct ancestral states of prey associations and microhabitats. Using a fossil-calibrated molecular tree, we estimated divergence times for key events in the evolutionary history of Reduviidae. Our results indicate that the polyphyletic Reduviinae fall into 11–14 separate clades. Triatominae are paraphyletic with respect to the reduviine genus Opisthacidius in the maximum likelihood analyses; this result is in contrast to prior hypotheses that found Triatominae to be monophyletic or polyphyletic and may be due to the more comprehensive taxon and character sampling in this study. The evolution of blood-feeding may thus have occurred once or twice independently among predatory assassin bugs. All prey specialists evolved from generalist ancestors, with multiple evolutionary origins of termite and ant specializations. A bark-associated life style on tree trunks is ancestral for most of the lineages of Higher Reduviidae; living on foliage has evolved at least six times independently. Reduviidae originated in the Middle Jurassic (178 Ma), but significant lineage diversification only began in the Late Cretaceous (97 Ma). The integration of molecular phylogenetics with fossil and life history data as presented in this paper provides insights into the evolutionary history of reduviids and clears the way for in-depth evolutionary hypothesis testing in one of the most speciose clades of predators. PMID:23029072

  4. The temporal characteristics of the early and late stages of the L- and M-cone pathways that signal color

    PubMed Central

    Petrova, Daniela; Henning, G. Bruce; Stockman, Andrew

    2013-01-01

    Flickering long-wavelength light appears more yellow than steady light of the same average intensity. The hue change is consistent with distortion of the visual signal at some nonlinear site (or sites) that produces temporal components not present in the original stimulus (known as distortion products). We extracted the temporal attenuation characteristics of the early (prenonlinearity) and late (post-nonlinearity) filter stages in the L- and M-cone chromatic pathway by varying the input stimulus to manipulate the distortion products and the measuring of the observers' sensitivity to them. The early, linear, filter stage acts like a band-pass filter peaking at 10–15 Hz with substantial sensitivity losses at both lower and higher frequencies. Its characteristics are consistent with nonlinearity being early in the visual pathway but following surround inhibition. The late stage, in contrast, acts like a low-pass filter with a cutoff frequency around 3 Hz. The response of the early stage speeds up with radiance, but the late stage does not. A plausible site for the nonlinearity, which modelling suggests may be smoothly compressive but with a hard limit at high input levels, is after surround inhibition from the horizontal cells. PMID:23457358

  5. Applying Aggregate Exposure Pathway and Adverse Outcome ...

    EPA Pesticide Factsheets

    Hazard assessment for nanomaterials often involves applying in vitro dose-response data to estimate potential health risks that arise from exposure to products that contain nanomaterials. However, much uncertainty is inherent in relating bioactivities observed in an in vitro system to the perturbations of biological mechanisms that lead to apical adverse health outcomes in living organisms. The Adverse Outcome Pathway (AOP) framework addresses this uncertainty by acting as a scaffold onto which in vitro toxicity testing and other data can be arranged to aid in the interpretation of these results in terms of biologically-relevant responses, as an AOP connects an upstream molecular initiating event (MIE) to a downstream adverse outcome. In addition to hazard assessment, risk estimation also requires reconciling in vitro concentrations sufficient to produce bioactivity with in vivo concentrations that can trigger a MIE at the relevant biological target. Such target site exposures (TSEs) can be estimated by integrating pharmacokinetic considerations with environmental and exposure factors. Environmental and exposure data have been historically scattered in various resources, such as monitoring data for air pollutants or exposure models for specific chemicals. The Aggregate Exposure Pathway (AEP) framework is introduced to organize existing knowledge concerning biologically, chemically, and physically plausible, as well as empirically supported, links between the i

  6. Requirement for Pectin Methyl Esterase and Preference for Fragmented over Native Pectins for Wall-associated Kinase-activated, EDS1/PAD4-dependent Stress Response in Arabidopsis*

    PubMed Central

    Kohorn, Bruce D.; Kohorn, Susan L.; Saba, Nicholas J.; Martinez, Victoriano Meco

    2014-01-01

    The wall-associated kinases (WAKs) have a cytoplasmic protein kinase domain that spans the plasma membrane and binds pectin in the extracellular matrix of plants. WAKs are required for cell expansion during Arabidopsis seedling development but are also an integral part of the response to pathogens and stress that present oligogalacturonides (OGs), which subsequently bind to WAKs and activate a MPK6 (mitogen-activated protein kinase)-dependent pathway. It was unclear how WAKs distinguish native pectin polymers and OGs to activate one or the other of these two pathways. A dominant allele of WAK2 constitutively activates the stress response, and we show here that the effect is dependent upon EDS1 and PAD4, transcriptional activators involved in the pathogen response. Moreover, the WAK2 dominant allele is suppressed by a null allele of a pectin methyl esterase (PME3) whose activity normally leads to cross-linking of pectins in the cell wall. Although OGs activate a transcriptional response in wild type, the response is enhanced in a pme3/pme3 null, consistent with a competition by OG and native polymers for activation of WAKs. This provides a plausible mechanism for WAKs to distinguish an expansion from a stress pathway. PMID:24855660

  7. Pregnancy outcome and ultraviolet radiation; A systematic review

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Megaw, Lauren, E-mail: lauren.megaw@ed.ac.uk

    Background: Season and vitamin D are indirect and direct correlates of ultraviolet (UV) radiation and are associated with pregnancy outcomes. Further to producing vitamin D, UV has positive effects on cardiovascular and immune health that may support a role for UV directly benefitting pregnancy. Objectives: To investigate the effects of UV exposure on pregnancy; specifically fetal growth, preterm birth and hypertensive complications. Methods: We conducted a systematic review of Medline, EMBASE, DoPHER, Global Health, ProQuest Public Health, AustHealth Informit, SCOPUS and Google Scholar to identify 537 citations, 8 of which are included in this review. This review was registered onmore » PROSPERO and a. narrative synthesis is presented following PRISMA guidance. Results: All studies were observational and assessed at high risk of bias. Higher first trimester UV was associated with and improved fetal growth and increased hypertension in pregnancy. Interpretation is limited by study design and quality. Meta-analysis was precluded by the variety of outcomes and methods. Discussion: The low number of studies and risk of bias limit the validity of any conclusions. Environmental health methodological issues are discussed with consideration given to design and analytical improvements to further address this reproductive environmental health question. Conclusions: The evidence for UV having benefits for pregnancy hypertension and fetal growth is limited by the methodological approaches utilized. Future epidemiological efforts should focus on improving the methods of modeling and linking widely available environmental data to reproductive health outcomes. - Highlights: • Biologically plausible pathways support an association between ultraviolet radiation (UV) and pregnancy outcomes. • This study is the first systematic review of prevailing literature on the relationship between UV and singleton pregnancy outcomes. • It focuses on both substantive findings and the methodologies that were used. • Only seven studies met the search criteria and these were methodologically heterogeneous demonstrating a paucity of evidence. • Given the plausibility of the UV pathway, more studies examining this hypothesis are needed.« less

  8. Evolution of branched regulatory genetic pathways: directional selection on pleiotropic loci accelerates developmental system drift.

    PubMed

    Johnson, Norman A; Porter, Adam H

    2007-01-01

    Developmental systems are regulated by a web of interacting loci. One common and useful approach in studying the evolution of development is to focus on classes of interacting elements within these systems. Here, we use individual-based simulations to study the evolution of traits controlled by branched developmental pathways involving three loci, where one locus regulates two different traits. We examined the system under a variety of selective regimes. In the case where one branch was under stabilizing selection and the other under directional selection, we observed "developmental system drift": the trait under stabilizing selection showed little phenotypic change even though the loci underlying that trait showed considerable evolutionary divergence. This occurs because the pleiotropic locus responds to directional selection and compensatory mutants are then favored in the pathway under stabilizing selection. Though developmental system drift may be caused by other mechanisms, it seems likely that it is accelerated by the same underlying genetic mechanism as that producing the Dobzhansky-Muller incompatibilities that lead to speciation in both linear and branched pathways. We also discuss predictions of our model for developmental system drift and how different selective regimes affect probabilities of speciation in the branched pathway system.

  9. Wnt signal transduction pathways: modules, development and evolution.

    PubMed

    Nayak, Losiana; Bhattacharyya, Nitai P; De, Rajat K

    2016-08-01

    Wnt signal transduction pathway (Wnt STP) is a crucial intracellular pathway mainly due to its participation in important biological processes, functions, and diseases, i.e., embryonic development, stem-cell management, and human cancers among others. This is why Wnt STP is one of the highest researched signal transduction pathways. Study and analysis of its origin, expansion and gradual development to the present state as found in humans is one aspect of Wnt research. The pattern of development and evolution of the Wnt STP among various species is not clear till date. A phylogenetic tree created from Wnt STPs of multiple species may address this issue. In this respect, we construct a phylogenetic tree from modules of Wnt STPs of diverse species. We term it as the 'Module Tree'. A module is nothing but a self-sufficient minimally-dependent subset of the original Wnt STP. Authenticity of the module tree is tested by comparing it with the two reference trees. The module tree performs better than an alternative phylogenetic tree constructed from pathway topology of Wnt STPs. Moreover, an evolutionary emergence pattern of the Wnt gene family is created and the module tree is tallied with it to showcase the significant resemblances.

  10. Pathways from education to fertility decline: a multi-site comparative study

    PubMed Central

    Colleran, Heidi

    2016-01-01

    Women's education has emerged as a central predictor of fertility decline, but the many ways that education affects fertility have not been subject to detailed comparative investigation. Taking an evolutionary biosocial approach, we use structural equation modelling to examine potential pathways between education and fertility including: infant/child mortality, women's participation in the labour market, husband's education, social network influences, and contraceptive use or knowledge across three very different contexts: Matlab, Bangladesh; San Borja, Bolivia; and rural Poland. Using a comparable set of variables, we show that the pathways by which education affects fertility differ in important ways, yet also show key similarities. For example, we find that across all three contexts, education is associated with delayed age at first birth via increasing women's labour-force participation, but this pathway only influences fertility in rural Poland. In Matlab and San Borja, education is associated with lower local childhood mortality, which influences fertility, but this pathway is not important in rural Poland. Similarities across sites suggest that there are common elements in how education drives demographic transitions cross-culturally, but the differences suggest that local socioecologies also play an important role in the relationship between education and fertility decline. PMID:27022083

  11. Origin and Evolutionary Alteration of the Mitochondrial Import System in Eukaryotic Lineages.

    PubMed

    Fukasawa, Yoshinori; Oda, Toshiyuki; Tomii, Kentaro; Imai, Kenichiro

    2017-07-01

    Protein transport systems are fundamentally important for maintaining mitochondrial function. Nevertheless, mitochondrial protein translocases such as the kinetoplastid ATOM complex have recently been shown to vary in eukaryotic lineages. Various evolutionary hypotheses have been formulated to explain this diversity. To resolve any contradiction, estimating the primitive state and clarifying changes from that state are necessary. Here, we present more likely primitive models of mitochondrial translocases, specifically the translocase of the outer membrane (TOM) and translocase of the inner membrane (TIM) complexes, using scrutinized phylogenetic profiles. We then analyzed the translocases' evolution in eukaryotic lineages. Based on those results, we propose a novel evolutionary scenario for diversification of the mitochondrial transport system. Our results indicate that presequence transport machinery was mostly established in the last eukaryotic common ancestor, and that primitive translocases already had a pathway for transporting presequence-containing proteins. Moreover, secondary changes including convergent and migrational gains of a presequence receptor in TOM and TIM complexes, respectively, likely resulted from constrained evolution. The nature of a targeting signal can constrain alteration to the protein transport complex. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  12. Molecular evolution of nitrogen assimilatory enzymes in marine prasinophytes.

    PubMed

    Ghoshroy, Sohini; Robertson, Deborah L

    2015-01-01

    Nitrogen assimilation is a highly regulated process requiring metabolic coordination of enzymes and pathways in the cytosol, chloroplast, and mitochondria. Previous studies of prasinophyte genomes revealed that genes encoding nitrate and ammonium transporters have a complex evolutionary history involving both vertical and horizontal transmission. Here we examine the evolutionary history of well-conserved nitrogen-assimilating enzymes to determine if a similar complex history is observed. Phylogenetic analyses suggest that genes encoding glutamine synthetase (GS) III in the prasinophytes evolved by horizontal gene transfer from a member of the heterokonts. In contrast, genes encoding GSIIE, a canonical vascular plant and green algal enzyme, were found in the Micromonas genomes but have been lost from Ostreococcus. Phylogenetic analyses placed the Micromonas GSIIs in a larger chlorophyte/vascular plant clade; a similar topology was observed for ferredoxin-dependent nitrite reductase (Fd-NiR), indicating the genes encoding GSII and Fd-NiR in these prasinophytes evolved via vertical transmission. Our results show that genes encoding the nitrogen-assimilating enzymes in Micromonas and Ostreococcus have been differentially lost and as well as recruited from different evolutionary lineages, suggesting that the regulation of nitrogen assimilation in prasinophytes will differ from other green algae.

  13. The C(4) plant lineages of planet Earth.

    PubMed

    Sage, Rowan F; Christin, Pascal-Antoine; Edwards, Erika J

    2011-05-01

    Using isotopic screens, phylogenetic assessments, and 45 years of physiological data, it is now possible to identify most of the evolutionary lineages expressing the C(4) photosynthetic pathway. Here, 62 recognizable lineages of C(4) photosynthesis are listed. Thirty-six lineages (60%) occur in the eudicots. Monocots account for 26 lineages, with a minimum of 18 lineages being present in the grass family and six in the sedge family. Species exhibiting the C(3)-C(4) intermediate type of photosynthesis correspond to 21 lineages. Of these, 9 are not immediately associated with any C(4) lineage, indicating that they did not share common C(3)-C(4) ancestors with C(4) species and are instead an independent line. The geographic centre of origin for 47 of the lineages could be estimated. These centres tend to cluster in areas corresponding to what are now arid to semi-arid regions of southwestern North America, south-central South America, central Asia, northeastern and southern Africa, and inland Australia. With 62 independent lineages, C(4) photosynthesis has to be considered one of the most convergent of the complex evolutionary phenomena on planet Earth, and is thus an outstanding system to study the mechanisms of evolutionary adaptation.

  14. The evolution of photosynthesis...again?

    PubMed

    Rothschild, Lynn J

    2008-08-27

    'Replaying the tape' is an intriguing 'would it happen again?' exercise. With respect to broad evolutionary innovations, such as photosynthesis, the answers are central to our search for life elsewhere. Photosynthesis permits a large planetary biomass on Earth. Specifically, oxygenic photosynthesis has allowed an oxygenated atmosphere and the evolution of large metabolically demanding creatures, including ourselves. There are at least six prerequisites for the evolution of biological carbon fixation: a carbon-based life form; the presence of inorganic carbon; the availability of reductants; the presence of light; a light-harvesting mechanism to convert the light energy into chemical energy; and carboxylating enzymes. All were present on the early Earth. To provide the evolutionary pressure, organic carbon must be a scarce resource in contrast to inorganic carbon. The probability of evolving a carboxylase is approached by creating an inventory of carbon-fixation enzymes and comparing them, leading to the conclusion that carbon fixation in general is basic to life and has arisen multiple times. Certainly, the evolutionary pressure to evolve new pathways for carbon fixation would have been present early in evolution. From knowledge about planetary systems and extraterrestrial chemistry, if organic carbon-based life occurs elsewhere, photosynthesis -- although perhaps not oxygenic photosynthesis -- would also have evolved.

  15. Evolutionary Importance of the Intramolecular Pathways of Hydrolysis of Phosphate Ester Mixed Anhydrides with Amino Acids and Peptides

    NASA Astrophysics Data System (ADS)

    Liu, Ziwei; Beaufils, Damien; Rossi, Jean-Christophe; Pascal, Robert

    2014-12-01

    Aminoacyl adenylates (aa-AMPs) constitute essential intermediates of protein biosynthesis. Their polymerization in aqueous solution has often been claimed as a potential route to abiotic peptides in spite of a highly efficient CO2-promoted pathway of hydrolysis. Here we investigate the efficiency and relevance of this frequently overlooked pathway from model amino acid phosphate mixed anhydrides including aa-AMPs. Its predominance was demonstrated at CO2 concentrations matching that of physiological fluids or that of the present-day ocean, making a direct polymerization pathway unlikely. By contrast, the occurrence of the CO2-promoted pathway was observed to increase the efficiency of peptide bond formation owing to the high reactivity of the N-carboxyanhydride (NCA) intermediate. Even considering CO2 concentrations in early Earth liquid environments equivalent to present levels, mixed anhydrides would have polymerized predominantly through NCAs. The issue of a potential involvement of NCAs as biochemical metabolites could even be raised. The formation of peptide-phosphate mixed anhydrides from 5(4H)-oxazolones (transiently formed through prebiotically relevant peptide activation pathways) was also observed as well as the occurrence of the reverse cyclization process in the reactions of these mixed anhydrides. These processes constitute the core of a reaction network that could potentially have evolved towards the emergence of translation.

  16. The nuclear genome of Rhazya stricta and the evolution of alkaloid diversity in a medically relevant clade of Apocynaceae

    PubMed Central

    Sabir, Jamal S. M.; Jansen, Robert K.; Arasappan, Dhivya; Calderon, Virginie; Noutahi, Emmanuel; Zheng, Chunfang; Park, Seongjun; Sabir, Meshaal J.; Baeshen, Mohammed N.; Hajrah, Nahid H.; Khiyami, Mohammad A.; Baeshen, Nabih A.; Obaid, Abdullah Y.; Al-Malki, Abdulrahman L.; Sankoff, David; El-Mabrouk, Nadia; Ruhlman, Tracey A.

    2016-01-01

    Alkaloid accumulation in plants is activated in response to stress, is limited in distribution and specific alkaloid repertoires are variable across taxa. Rauvolfioideae (Apocynaceae, Gentianales) represents a major center of structural expansion in the monoterpenoid indole alkaloids (MIAs) yielding thousands of unique molecules including highly valuable chemotherapeutics. The paucity of genome-level data for Apocynaceae precludes a deeper understanding of MIA pathway evolution hindering the elucidation of remaining pathway enzymes and the improvement of MIA availability in planta or in vitro. We sequenced the nuclear genome of Rhazya stricta (Apocynaceae, Rauvolfioideae) and present this high quality assembly in comparison with that of coffee (Rubiaceae, Coffea canephora, Gentianales) and others to investigate the evolution of genome-scale features. The annotated Rhazya genome was used to develop the community resource, RhaCyc, a metabolic pathway database. Gene family trees were constructed to identify homologs of MIA pathway genes and to examine their evolutionary history. We found that, unlike Coffea, the Rhazya lineage has experienced many structural rearrangements. Gene tree analyses suggest recent, lineage-specific expansion and diversification among homologs encoding MIA pathway genes in Gentianales and provide candidate sequences with the potential to close gaps in characterized pathways and support prospecting for new MIA production avenues. PMID:27653669

  17. The nuclear genome of Rhazya stricta and the evolution of alkaloid diversity in a medically relevant clade of Apocynaceae.

    PubMed

    Sabir, Jamal S M; Jansen, Robert K; Arasappan, Dhivya; Calderon, Virginie; Noutahi, Emmanuel; Zheng, Chunfang; Park, Seongjun; Sabir, Meshaal J; Baeshen, Mohammed N; Hajrah, Nahid H; Khiyami, Mohammad A; Baeshen, Nabih A; Obaid, Abdullah Y; Al-Malki, Abdulrahman L; Sankoff, David; El-Mabrouk, Nadia; Ruhlman, Tracey A

    2016-09-22

    Alkaloid accumulation in plants is activated in response to stress, is limited in distribution and specific alkaloid repertoires are variable across taxa. Rauvolfioideae (Apocynaceae, Gentianales) represents a major center of structural expansion in the monoterpenoid indole alkaloids (MIAs) yielding thousands of unique molecules including highly valuable chemotherapeutics. The paucity of genome-level data for Apocynaceae precludes a deeper understanding of MIA pathway evolution hindering the elucidation of remaining pathway enzymes and the improvement of MIA availability in planta or in vitro. We sequenced the nuclear genome of Rhazya stricta (Apocynaceae, Rauvolfioideae) and present this high quality assembly in comparison with that of coffee (Rubiaceae, Coffea canephora, Gentianales) and others to investigate the evolution of genome-scale features. The annotated Rhazya genome was used to develop the community resource, RhaCyc, a metabolic pathway database. Gene family trees were constructed to identify homologs of MIA pathway genes and to examine their evolutionary history. We found that, unlike Coffea, the Rhazya lineage has experienced many structural rearrangements. Gene tree analyses suggest recent, lineage-specific expansion and diversification among homologs encoding MIA pathway genes in Gentianales and provide candidate sequences with the potential to close gaps in characterized pathways and support prospecting for new MIA production avenues.

  18. The evolutionary life cycle of the polysaccharide biosynthetic gene cluster based on the Sphingomonadaceae.

    PubMed

    Wu, Mengmeng; Huang, Haidong; Li, Guoqiang; Ren, Yi; Shi, Zhong; Li, Xiaoyan; Dai, Xiaohui; Gao, Ge; Ren, Mengnan; Ma, Ting

    2017-04-21

    Although clustering of genes from the same metabolic pathway is a widespread phenomenon, the evolution of the polysaccharide biosynthetic gene cluster remains poorly understood. To determine the evolution of this pathway, we identified a scattered production pathway of the polysaccharide sanxan by Sphingomonas sanxanigenens NX02, and compared the distribution of genes between sphingan-producing and other Sphingomonadaceae strains. This allowed us to determine how the scattered sanxan pathway developed, and how the polysaccharide gene cluster evolved. Our findings suggested that the evolution of microbial polysaccharide biosynthesis gene clusters is a lengthy cyclic process comprising cluster 1 → scatter → cluster 2. The sanxan biosynthetic pathway proved the existence of a dispersive process. We also report the complete genome sequence of NX02, in which we identified many unstable genetic elements and powerful secretion systems. Furthermore, nine enzymes for the formation of activated precursors, four glycosyltransferases, four acyltransferases, and four polymerization and export proteins were identified. These genes were scattered in the NX02 genome, and the positive regulator SpnA of sphingans synthesis could not regulate sanxan production. Finally, we concluded that the evolution of the sanxan pathway was independent. NX02 evolved naturally as a polysaccharide producing strain over a long-time evolution involving gene acquisitions and adaptive mutations.

  19. How robust is a robust policy? A comparative analysis of alternative robustness metrics for supporting robust decision analysis.

    NASA Astrophysics Data System (ADS)

    Kwakkel, Jan; Haasnoot, Marjolijn

    2015-04-01

    In response to climate and socio-economic change, in various policy domains there is increasingly a call for robust plans or policies. That is, plans or policies that performs well in a very large range of plausible futures. In the literature, a wide range of alternative robustness metrics can be found. The relative merit of these alternative conceptualizations of robustness has, however, received less attention. Evidently, different robustness metrics can result in different plans or policies being adopted. This paper investigates the consequences of several robustness metrics on decision making, illustrated here by the design of a flood risk management plan. A fictitious case, inspired by a river reach in the Netherlands is used. The performance of this system in terms of casualties, damages, and costs for flood and damage mitigation actions is explored using a time horizon of 100 years, and accounting for uncertainties pertaining to climate change and land use change. A set of candidate policy options is specified up front. This set of options includes dike raising, dike strengthening, creating more space for the river, and flood proof building and evacuation options. The overarching aim is to design an effective flood risk mitigation strategy that is designed from the outset to be adapted over time in response to how the future actually unfolds. To this end, the plan will be based on the dynamic adaptive policy pathway approach (Haasnoot, Kwakkel et al. 2013) being used in the Dutch Delta Program. The policy problem is formulated as a multi-objective robust optimization problem (Kwakkel, Haasnoot et al. 2014). We solve the multi-objective robust optimization problem using several alternative robustness metrics, including both satisficing robustness metrics and regret based robustness metrics. Satisficing robustness metrics focus on the performance of candidate plans across a large ensemble of plausible futures. Regret based robustness metrics compare the performance of a candidate plan with the performance of other candidate plans across a large ensemble of plausible futures. Initial results suggest that the simplest satisficing metric, inspired by the signal to noise ratio, results in very risk averse solutions. Other satisficing metrics, which handle the average performance and the dispersion around the average separately, provide substantial additional insights into the trade off between the average performance, and the dispersion around this average. In contrast, the regret-based metrics enhance insight into the relative merits of candidate plans, while being less clear on the average performance or the dispersion around this performance. These results suggest that it is beneficial to use multiple robustness metrics when doing a robust decision analysis study. Haasnoot, M., J. H. Kwakkel, W. E. Walker and J. Ter Maat (2013). "Dynamic Adaptive Policy Pathways: A New Method for Crafting Robust Decisions for a Deeply Uncertain World." Global Environmental Change 23(2): 485-498. Kwakkel, J. H., M. Haasnoot and W. E. Walker (2014). "Developing Dynamic Adaptive Policy Pathways: A computer-assisted approach for developing adaptive strategies for a deeply uncertain world." Climatic Change.

  20. Pilgrims sailing the Titanic: plausibility effects on memory for misinformation.

    PubMed

    Hinze, Scott R; Slaten, Daniel G; Horton, William S; Jenkins, Ryan; Rapp, David N

    2014-02-01

    People rely on information they read even when it is inaccurate (Marsh, Meade, & Roediger, Journal of Memory and Language 49:519-536, 2003), but how ubiquitous is this phenomenon? In two experiments, we investigated whether this tendency to encode and rely on inaccuracies from text might be influenced by the plausibility of misinformation. In Experiment 1, we presented stories containing inaccurate plausible statements (e.g., "The Pilgrims' ship was the Godspeed"), inaccurate implausible statements (e.g., . . . the Titanic), or accurate statements (e.g., . . . the Mayflower). On a subsequent test of general knowledge, participants relied significantly less on implausible than on plausible inaccuracies from the texts but continued to rely on accurate information. In Experiment 2, we replicated these results with the addition of a think-aloud procedure to elicit information about readers' noticing and evaluative processes for plausible and implausible misinformation. Participants indicated more skepticism and less acceptance of implausible than of plausible inaccuracies. In contrast, they often failed to notice, completely ignored, and at times even explicitly accepted the misinformation provided by plausible lures. These results offer insight into the conditions under which reliance on inaccurate information occurs and suggest potential mechanisms that may underlie reported misinformation effects.

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