Evolutionarily conserved coupling of adaptive and excitable networks mediates eukaryotic chemotaxis

NASA Astrophysics Data System (ADS)

Tang, Ming; Wang, Mingjie; Shi, Changji; Iglesias, Pablo A.; Devreotes, Peter N.; Huang, Chuan-Hsiang

2014-10-01

Numerous models explain how cells sense and migrate towards shallow chemoattractant gradients. Studies show that an excitable signal transduction network acts as a pacemaker that controls the cytoskeleton to drive motility. Here we show that this network is required to link stimuli to actin polymerization and chemotactic motility and we distinguish the various models of chemotaxis. First, signalling activity is suppressed towards the low side in a gradient or following removal of uniform chemoattractant. Second, signalling activities display a rapid shut off and a slower adaptation during which responsiveness to subsequent test stimuli decline. Simulations of various models indicate that these properties require coupled adaptive and excitable networks. Adaptation involves a G-protein-independent inhibitor, as stimulation of cells lacking G-protein function suppresses basal activities. The salient features of the coupled networks were observed for different chemoattractants in Dictyostelium and in human neutrophils, suggesting an evolutionarily conserved mechanism for eukaryotic chemotaxis.

Regulation of Six1 expression by evolutionarily conserved enhancers in tetrapods.

PubMed

Sato, Shigeru; Ikeda, Keiko; Shioi, Go; Nakao, Kazuki; Yajima, Hiroshi; Kawakami, Kiyoshi

2012-08-01

The Six1 homeobox gene plays critical roles in vertebrate organogenesis. Mice deficient for Six1 show severe defects in organs such as skeletal muscle, kidney, thymus, sensory organs and ganglia derived from cranial placodes, and mutations in human SIX1 cause branchio-oto-renal syndrome, an autosomal dominant developmental disorder characterized by hearing loss and branchial defects. The present study was designed to identify enhancers responsible for the dynamic expression pattern of Six1 during mouse embryogenesis. The results showed distinct enhancer activities of seven conserved non-coding sequences (CNSs) retained in tetrapod Six1 loci. The activities were detected in all cranial placodes (excluding the lens placode), dorsal root ganglia, somites, nephrogenic cord, notochord and cranial mesoderm. The major Six1-expression domains during development were covered by the sum of activities of these enhancers, together with the previously identified enhancer for the pre-placodal region and foregut endoderm. Thus, the eight CNSs identified in a series of our study represent major evolutionarily conserved enhancers responsible for the expression of Six1 in tetrapods. The results also confirmed that chick electroporation is a robust means to decipher regulatory information stored in vertebrate genomes. Mutational analysis of the most conserved placode-specific enhancer, Six1-21, indicated that the enhancer integrates a variety of inputs from Sox, Pax, Fox, Six, Wnt/Lef1 and basic helix-loop-helix proteins. Positive autoregulation of Six1 is achieved through the regulation of Six protein-binding sites. The identified Six1 enhancers provide valuable tools to understand the mechanism of Six1 regulation and to manipulate gene expression in the developing embryo, particularly in the sensory organs. Copyright © 2012 Elsevier Inc. All rights reserved.

Identification of Plasmodium falciparum DNA Repair Protein Mre11 with an Evolutionarily Conserved Nuclease Function

PubMed Central

Badugu, Sugith Babu; Nabi, Shaik Abdul; Vaidyam, Pratap; Laskar, Shyamasree; Bhattacharyya, Sunanda; Bhattacharyya, Mrinal Kanti

2015-01-01

The eukaryotic Meiotic Recombination protein 11 (Mre11) plays pivotal roles in the DNA damage response (DDR). Specifically, Mre11 senses and signals DNA double strand breaks (DSB) and facilitates their repair through effector proteins belonging to either homologous recombination (HR) or non-homologous end joining (NHEJ) repair mechanisms. In the human malaria parasite Plasmodium falciparum, HR and alternative-NHEJ have been identified; however, little is known about the upstream factors involved in the DDR of this organism. In this report, we identify a putative ortholog of Mre11 in P. falciparum (PfalMre11) that shares 22% sequence similarity to human Mre11. Homology modeling reveals striking structural resemblance of the predicted PfalMre11 nuclease domain to the nuclease domain of Saccharomyces cerevisiae Mre11 (ScMre11). Complementation analyses reveal functional conservation of PfalMre11 nuclease activity as demonstrated by the ability of the PfalMre11 nuclease domain, in conjunction with the C-terminal domain of ScMre11, to functionally complement an mre11 deficient yeast strain. Functional complementation was virtually abrogated by an amino acid substitution in the PfalMre11 nuclease domain (D398N). PfalMre11 is abundant in the mitotically active trophozoite and schizont stages of P. falciparum and is up-regulated in response to DNA damage, suggesting a role in the DDR. PfalMre11 exhibits physical interaction with PfalRad50. In addition, yeast 2-hybrid studies show that PfalMre11 interacts with ScRad50 and ScXrs2, two important components of the well characterized Mre11-Rad50-Xrs2 complex which is involved in DDR signaling and repair in S. cerevisiae, further supporting a role for PfalMre11 in the DDR. Taken together, these findings provide evidence that PfalMre11 is an evolutionarily conserved component of the DDR in Plasmodium. PMID:25938776

Evolutionarily Conserved Linkage between Enzyme Fold, Flexibility, and Catalysis

PubMed Central

Ramanathan, Arvind; Agarwal, Pratul K.

2011-01-01

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 Å away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme–substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme–substrate interactions, thereby

Evolutionarily conserved linkage between enzyme fold, flexibility, and catalysis.

PubMed

Ramanathan, Arvind; Agarwal, Pratul K

2011-11-01

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 Å away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme-substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme-substrate interactions, thereby impacting

Evolutionarily Conserved Epitopes on Human Immunodeficiency Virus Type 1 (HIV-1) and Feline Immunodeficiency Virus Reverse Transcriptases Detected by HIV-1-Infected Subjects

PubMed Central

Sanou, Missa P.; Roff, Shannon R.; Mennella, Antony; Sleasman, John W.; Rathore, Mobeen H.; Levy, Jay A.

2013-01-01

Anti-human immunodeficiency virus (HIV) cytotoxic T lymphocyte (CTL)-associated epitopes, evolutionarily conserved on both HIV type 1 (HIV-1) and feline immunodeficiency virus (FIV) reverse transcriptases (RT), were identified using gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) and carboxyfluorescein diacetate succinimide ester (CFSE) proliferation assays followed by CTL-associated cytotoxin analysis. The peripheral blood mononuclear cells (PBMC) or T cells from HIV-1-seropositive (HIV+) subjects were stimulated with overlapping RT peptide pools. The PBMC from the HIV+ subjects had more robust IFN-γ responses to the HIV-1 peptide pools than to the FIV peptide pools, except for peptide-pool F3. In contrast, much higher and more frequent CD8+ T-cell proliferation responses were observed with the FIV peptide pools than with the HIV peptide pools. HIV-1-seronegative subjects had no proliferation or IFN-γ responses to the HIV and FIV peptide pools. A total of 24% (40 of 166) of the IFN-γ responses to HIV pools and 43% (23 of 53) of the CD8+ T-cell proliferation responses also correlated to responses to their counterpart FIV pools. Thus, more evolutionarily conserved functional epitopes were identified by T-cell proliferation than by IFN-γ responses. In the HIV+ subjects, peptide-pool F3, but not the HIV H3 counterpart, induced the most IFN-γ and proliferation responses. These reactions to peptide-pool F3 were highly reproducible and persisted over the 1 to 2 years of testing. All five individual peptides and epitopes of peptide-pool F3 induced IFN-γ and/or proliferation responses in addition to inducing CTL-associated cytotoxin responses (perforin, granzyme A, granzyme B). The epitopes inducing polyfunctional T-cell activities were highly conserved among human, simian, feline, and ungulate lentiviruses, which indicated that these epitopes are evolutionarily conserved. These results suggest that FIV peptides could be used in an HIV-1 vaccine

Interaction of MYC with host cell factor-1 is mediated by the evolutionarily conserved Myc box IV motif.

PubMed

Thomas, L R; Foshage, A M; Weissmiller, A M; Popay, T M; Grieb, B C; Qualls, S J; Ng, V; Carboneau, B; Lorey, S; Eischen, C M; Tansey, W P

2016-07-07

The MYC family of oncogenes encodes a set of three related transcription factors that are overexpressed in many human tumors and contribute to the cancer-related deaths of more than 70,000 Americans every year. MYC proteins drive tumorigenesis by interacting with co-factors that enable them to regulate the expression of thousands of genes linked to cell growth, proliferation, metabolism and genome stability. One effective way to identify critical co-factors required for MYC function has been to focus on sequence motifs within MYC that are conserved throughout evolution, on the assumption that their conservation is driven by protein-protein interactions that are vital for MYC activity. In addition to their DNA-binding domains, MYC proteins carry five regions of high sequence conservation known as Myc boxes (Mb). To date, four of the Mb motifs (MbI, MbII, MbIIIa and MbIIIb) have had a molecular function assigned to them, but the precise role of the remaining Mb, MbIV, and the reason for its preservation in vertebrate Myc proteins, is unknown. Here, we show that MbIV is required for the association of MYC with the abundant transcriptional coregulator host cell factor-1 (HCF-1). We show that the invariant core of MbIV resembles the tetrapeptide HCF-binding motif (HBM) found in many HCF-interaction partners, and demonstrate that MYC interacts with HCF-1 in a manner indistinguishable from the prototypical HBM-containing protein VP16. Finally, we show that rationalized point mutations in MYC that disrupt interaction with HCF-1 attenuate the ability of MYC to drive tumorigenesis in mice. Together, these data expose a molecular function for MbIV and indicate that HCF-1 is an important co-factor for MYC.

Interactions between the Nse3 and Nse4 Components of the SMC5-6 Complex Identify Evolutionarily Conserved Interactions between MAGE and EID Families

PubMed Central

Kozakova, Lucie; Liao, Chunyan; Guerineau, Marc; Colnaghi, Rita; Vidot, Susanne; Marek, Jaromir; Bathula, Sreenivas R.; Lehmann, Alan R.; Palecek, Jan

2011-01-01

Background The SMC5-6 protein complex is involved in the cellular response to DNA damage. It is composed of 6–8 polypeptides, of which Nse1, Nse3 and Nse4 form a tight sub-complex. MAGEG1, the mammalian ortholog of Nse3, is the founding member of the MAGE (melanoma-associated antigen) protein family and Nse4 is related to the EID (E1A-like inhibitor of differentiation) family of transcriptional repressors. Methodology/Principal Findings Using site-directed mutagenesis, protein-protein interaction analyses and molecular modelling, we have identified a conserved hydrophobic surface on the C-terminal domain of Nse3 that interacts with Nse4 and identified residues in its N-terminal domain that are essential for interaction with Nse1. We show that these interactions are conserved in the human orthologs. Furthermore, interaction of MAGEG1, the mammalian ortholog of Nse3, with NSE4b, one of the mammalian orthologs of Nse4, results in transcriptional co-activation of the nuclear receptor, steroidogenic factor 1 (SF1). In an examination of the evolutionary conservation of the Nse3-Nse4 interactions, we find that several MAGE proteins can interact with at least one of the NSE4/EID proteins. Conclusions/Significance We have found that, despite the evolutionary diversification of the MAGE family, the characteristic hydrophobic surface shared by all MAGE proteins from yeast to humans mediates its binding to NSE4/EID proteins. Our work provides new insights into the interactions, evolution and functions of the enigmatic MAGE proteins. PMID:21364888

Retinoic acid plays an evolutionarily conserved and biphasic role in pancreas development

PubMed Central

Huang, Wei; Wang, Guangliang; Delaspre, Fabien; Vitery, Maria del Carmen; Beer, Rebecca L.

2015-01-01

As the developing zebrafish pancreas matures, hormone-producing endocrine cells differentiate from pancreatic Notch-responsive cells (PNCs) that reside within the ducts. These new endocrine cells form small clusters known as secondary (2°) islets. We use the formation of 2° islets in the pancreatic tail of the larval zebrafish as a model of β-cell neogenesis. Pharmacological inhibition of Notch signaling leads to precocious endocrine differentiation and the early appearance of 2° islets in the tail of the pancreas. Following a chemical screen, we discovered that blocking the retinoic acid (RA)-signaling pathway also leads to the induction of 2° islets. Conversely, the addition of exogenous RA blocks the differentiation caused by Notch inhibition. In this report we characterize the interaction of these two pathways. We first verified that signaling via both RA and Notch ligands act together to regulate pancreatic progenitor differentiation. We produced a transgenic RA reporter, which demonstrated that PNCs directly respond to RA signaling through the canonical transcriptional pathway. Next, using a genetic lineage tracing approach, we demonstrated these progenitors produce endocrine cells following inhibition of RA signaling. Lastly, inhibition of RA signaling using a cell-type specific inducible cre/lox system revealed that RA signaling acts cell-autonomously in PNCs to regulate their differentiation. Importantly, the action of RA inhibition on endocrine formation is evolutionarily conserved, as shown by the differentiation of human embryonic stem cells in a model of human pancreas development. Together, these results revealed a biphasic function for RA in pancreatogenesis. As previously shown by others, RA initially plays an essential role during embryogenesis as it patterns the endoderm and specifies the pancreatic field. We reveal here that later in development RA is involved in negatively regulating the further differentiation of pancreatic progenitors and

Human growth is associated with distinct patterns of gene expression in evolutionarily conserved networks

PubMed Central

2013-01-01

Background A co-ordinated tissue-independent gene expression profile associated with growth is present in rodent models and this is hypothesised to extend to all mammals. Growth in humans has similarities to other mammals but the return to active long bone growth in the pubertal growth spurt is a distinctly human growth event. The aim of this study was to describe gene expression and biological pathways associated with stages of growth in children and to assess tissue-independent expression patterns in relation to human growth. Results We conducted gene expression analysis on a library of datasets from normal children with age annotation, collated from the NCBI Gene Expression Omnibus (GEO) and EBI Arrayexpress databases. A primary data set was generated using cells of lymphoid origin from normal children; the expression of 688 genes (ANOVA false discovery rate modified p-value, q < 0.1) was associated with age, and subsets of these genes formed clusters that correlated with the phases of growth – infancy, childhood, puberty and final height. Network analysis on these clusters identified evolutionarily conserved growth pathways (NOTCH, VEGF, TGFB, WNT and glucocorticoid receptor – Hyper-geometric test, q < 0.05). The greatest degree of network ‘connectivity’ and hence functional significance was present in infancy (Wilcoxon test, p < 0.05), which then decreased through to adulthood. These observations were confirmed in a separate validation data set from lymphoid tissue. Similar biological pathways were observed to be associated with development-related gene expression in other tissues (conjunctival epithelia, temporal lobe brain tissue and bone marrow) suggesting the existence of a tissue-independent genetic program for human growth and maturation. Conclusions Similar evolutionarily conserved pathways have been associated with gene expression and child growth in multiple tissues. These expression profiles associate with the developmental phases

Cell–cell adhesion in metazoans relies on evolutionarily conserved features of the α-catenin·β-catenin–binding interface

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

Shao, Xiangqiang; Kang, Hyunook; Loveless, Timothy

Stable tissue integrity during embryonic development relies on the function of the cadherin·catenin complex (CCC). The Caenorhabditis elegans CCC is a useful paradigm for analyzing in vivo requirements for specific interactions among the core components of the CCC, and it provides a unique opportunity to examine evolutionarily conserved mechanisms that govern the interaction between α- and β-catenin. HMP-1, unlike its mammalian homolog α-catenin, is constitutively monomeric, and its binding affinity for HMP-2/β-catenin is higher than that of α-catenin for β-catenin. A crystal structure shows that the HMP-1·HMP-2 complex forms a five-helical bundle structure distinct from the structure of the mammalianmore » α-catenin·β-catenin complex. Deletion analysis based on the crystal structure shows that the first helix of HMP-1 is necessary for binding HMP-2 avidly in vitro and for efficient recruitment of HMP-1 to adherens junctions in embryos. HMP-2 Ser-47 and Tyr-69 flank its binding interface with HMP-1, and we show that phosphomimetic mutations at these two sites decrease binding affinity of HMP-1 to HMP-2 by 40–100-fold in vitro. In vivo experiments using HMP-2 S47E and Y69E mutants showed that they are unable to rescue hmp-2(zu364) mutants, suggesting that phosphorylation of HMP-2 on Ser-47 and Tyr-69 could be important for regulating CCC formation in C. elegans. Our data provide novel insights into how cadherin-dependent cell–cell adhesion is modulated in metazoans by conserved elements as well as features unique to specific organisms.« less

Cell–cell adhesion in metazoans relies on evolutionarily conserved features of the α-catenin·β-catenin–binding interface

DOE PAGES

Shao, Xiangqiang; Kang, Hyunook; Loveless, Timothy; ...

2017-08-25

Stable tissue integrity during embryonic development relies on the function of the cadherin·catenin complex (CCC). The Caenorhabditis elegans CCC is a useful paradigm for analyzing in vivo requirements for specific interactions among the core components of the CCC, and it provides a unique opportunity to examine evolutionarily conserved mechanisms that govern the interaction between α- and β-catenin. HMP-1, unlike its mammalian homolog α-catenin, is constitutively monomeric, and its binding affinity for HMP-2/β-catenin is higher than that of α-catenin for β-catenin. A crystal structure shows that the HMP-1·HMP-2 complex forms a five-helical bundle structure distinct from the structure of the mammalianmore » α-catenin·β-catenin complex. Deletion analysis based on the crystal structure shows that the first helix of HMP-1 is necessary for binding HMP-2 avidly in vitro and for efficient recruitment of HMP-1 to adherens junctions in embryos. HMP-2 Ser-47 and Tyr-69 flank its binding interface with HMP-1, and we show that phosphomimetic mutations at these two sites decrease binding affinity of HMP-1 to HMP-2 by 40–100-fold in vitro. In vivo experiments using HMP-2 S47E and Y69E mutants showed that they are unable to rescue hmp-2(zu364) mutants, suggesting that phosphorylation of HMP-2 on Ser-47 and Tyr-69 could be important for regulating CCC formation in C. elegans. Our data provide novel insights into how cadherin-dependent cell–cell adhesion is modulated in metazoans by conserved elements as well as features unique to specific organisms.« less

Evolutionarily conserved mechanisms for the selection and maintenance of behavioural activity.

PubMed

Fiore, Vincenzo G; Dolan, Raymond J; Strausfeld, Nicholas J; Hirth, Frank

2015-12-19

Survival and reproduction entail the selection of adaptive behavioural repertoires. This selection manifests as phylogenetically acquired activities that depend on evolved nervous system circuitries. Lorenz and Tinbergen already postulated that heritable behaviours and their reliable performance are specified by genetically determined programs. Here we compare the functional anatomy of the insect central complex and vertebrate basal ganglia to illustrate their role in mediating selection and maintenance of adaptive behaviours. Comparative analyses reveal that central complex and basal ganglia circuitries share comparable lineage relationships within clusters of functionally integrated neurons. These clusters are specified by genetic mechanisms that link birth time and order to their neuronal identities and functions. Their subsequent connections and associated functions are characterized by similar mechanisms that implement dimensionality reduction and transition through attractor states, whereby spatially organized parallel-projecting loops integrate and convey sensorimotor representations that select and maintain behavioural activity. In both taxa, these neural systems are modulated by dopamine signalling that also mediates memory-like processes. The multiplicity of similarities between central complex and basal ganglia suggests evolutionarily conserved computational mechanisms for action selection. We speculate that these may have originated from ancestral ground pattern circuitries present in the brain of the last common ancestor of insects and vertebrates. © 2015 The Authors.

Evolutionarily conserved mechanisms for the selection and maintenance of behavioural activity

PubMed Central

Fiore, Vincenzo G.; Dolan, Raymond J.; Strausfeld, Nicholas J.; Hirth, Frank

2015-01-01

Survival and reproduction entail the selection of adaptive behavioural repertoires. This selection manifests as phylogenetically acquired activities that depend on evolved nervous system circuitries. Lorenz and Tinbergen already postulated that heritable behaviours and their reliable performance are specified by genetically determined programs. Here we compare the functional anatomy of the insect central complex and vertebrate basal ganglia to illustrate their role in mediating selection and maintenance of adaptive behaviours. Comparative analyses reveal that central complex and basal ganglia circuitries share comparable lineage relationships within clusters of functionally integrated neurons. These clusters are specified by genetic mechanisms that link birth time and order to their neuronal identities and functions. Their subsequent connections and associated functions are characterized by similar mechanisms that implement dimensionality reduction and transition through attractor states, whereby spatially organized parallel-projecting loops integrate and convey sensorimotor representations that select and maintain behavioural activity. In both taxa, these neural systems are modulated by dopamine signalling that also mediates memory-like processes. The multiplicity of similarities between central complex and basal ganglia suggests evolutionarily conserved computational mechanisms for action selection. We speculate that these may have originated from ancestral ground pattern circuitries present in the brain of the last common ancestor of insects and vertebrates. PMID:26554043

Intrinsically disordered proteins drive enamel formation via an evolutionarily conserved self-assembly motif.

PubMed

Wald, Tomas; Spoutil, Frantisek; Osickova, Adriana; Prochazkova, Michaela; Benada, Oldrich; Kasparek, Petr; Bumba, Ladislav; Klein, Ophir D; Sedlacek, Radislav; Sebo, Peter; Prochazka, Jan; Osicka, Radim

2017-02-28

The formation of mineralized tissues is governed by extracellular matrix proteins that assemble into a 3D organic matrix directing the deposition of hydroxyapatite. Although the formation of bones and dentin depends on the self-assembly of type I collagen via the Gly-X-Y motif, the molecular mechanism by which enamel matrix proteins (EMPs) assemble into the organic matrix remains poorly understood. Here we identified a Y/F-x-x-Y/L/F-x-Y/F motif, evolutionarily conserved from the first tetrapods to man, that is crucial for higher order structure self-assembly of the key intrinsically disordered EMPs, ameloblastin and amelogenin. Using targeted mutations in mice and high-resolution imaging, we show that impairment of ameloblastin self-assembly causes disorganization of the enamel organic matrix and yields enamel with disordered hydroxyapatite crystallites. These findings define a paradigm for the molecular mechanism by which the EMPs self-assemble into supramolecular structures and demonstrate that this process is crucial for organization of the organic matrix and formation of properly structured enamel.

Human H/ACA Small Nucleolar RNPs and Telomerase Share Evolutionarily Conserved Proteins NHP2 and NOP10

PubMed Central

Pogacic, Vanda; Dragon, François; Filipowicz, Witold

2000-01-01

The H/ACA small nucleolar RNAs (snoRNAs) are involved in pseudouridylation of pre-rRNAs. In the yeast Saccharomyces cerevisiae, four common proteins are associated with H/ACA snoRNAs: Gar1p, Cbf5p, Nhp2p, and Nop10p. In vitro reconstitution studies showed that four proteins also specifically interact with H/ACA snoRNAs in mammalian cell extracts. Two mammalian proteins, NAP57/dyskerin (the ortholog of Cbf5p) and hGAR1, have been characterized. In this work we describe properties of hNOP10 and hNHP2, human orthologs of yeast Nop10p and Nhp2p, respectively, and further characterize hGAR1. hNOP10 and hNHP2 complement yeast cells depleted of Nhp2p and Nop10p, respectively. Immunoprecipitation experiments with extracts from transfected HeLa cells indicated that epitope-tagged hNOP10 and hNHP2 specifically associate with hGAR1 and H/ACA RNAs; they also interact with the RNA subunit of telomerase, which contains an H/ACA-like domain in its 3′ moiety. Immunofluorescence microscopy experiments showed that hGAR1, hNOP10, and hNHP2 are localized in the dense fibrillar component of the nucleolus and in Cajal (coiled) bodies. Deletion analysis of hGAR1 indicated that its evolutionarily conserved core domain contains all the signals required for localization, but progressive deletions from either the N or the C terminus of the core domain abolish localization in the nucleolus and/or the Cajal bodies. PMID:11074001

Inter-progenitor pool wiring: An evolutionarily conserved strategy that expands neural circuit diversity.

PubMed

Suzuki, Takumi; Sato, Makoto

2017-11-15

Diversification of neuronal types is key to establishing functional variations in neural circuits. The first critical step to generate neuronal diversity is to organize the compartmental domains of developing brains into spatially distinct neural progenitor pools. Neural progenitors in each pool then generate a unique set of diverse neurons through specific spatiotemporal specification processes. In this review article, we focus on an additional mechanism, 'inter-progenitor pool wiring', that further expands the diversity of neural circuits. After diverse types of neurons are generated in one progenitor pool, a fraction of these neurons start migrating toward a remote brain region containing neurons that originate from another progenitor pool. Finally, neurons of different origins are intermingled and eventually form complex but precise neural circuits. The developing cerebral cortex of mammalian brains is one of the best examples of inter-progenitor pool wiring. However, Drosophila visual system development has revealed similar mechanisms in invertebrate brains, suggesting that inter-progenitor pool wiring is an evolutionarily conserved strategy that expands neural circuit diversity. Here, we will discuss how inter-progenitor pool wiring is accomplished in mammalian and fly brain systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Caenorhabditis elegans PRMT-7 and PRMT-9 Are Evolutionarily Conserved Protein Arginine Methyltransferases with Distinct Substrate Specificities.

PubMed

Hadjikyriacou, Andrea; Clarke, Steven G

2017-05-23

Caenorhabditis elegans protein arginine methyltransferases PRMT-7 and PRMT-9 are two evolutionarily conserved enzymes, with distinct orthologs in plants, invertebrates, and vertebrates. Biochemical characterization of these two enzymes reveals that they share much in common with their mammalian orthologs. C. elegans PRMT-7 produces only monomethylarginine (MMA) and preferentially methylates R-X-R motifs in a broad collection of substrates, including human histone peptides and RG-rich peptides. In addition, the activity of the PRMT-7 enzyme is dependent on temperature, the presence of metal ions, and the reducing agent dithiothreitol. C. elegans PRMT-7 has a substrate specificity and a substrate preference different from those of mammalian PRMT7, and the available X-ray crystal structures of the PRMT7 orthologs show differences in active site architecture. C. elegans PRMT-9, on the other hand, produces symmetric dimethylarginine and MMA on SFTB-2, the conserved C. elegans ortholog of human RNA splicing factor SF3B2, indicating a possible role in the regulation of nematode splicing. In contrast to PRMT-7, C. elegans PRMT-9 appears to be biochemically indistinguishable from its human ortholog.

Identification of evolutionarily conserved DNA damage response genes that alter sensitivity to cisplatin

PubMed Central

Gaponova, Anna V.; Deneka, Alexander Y.; Beck, Tim N.; Liu, Hanqing; Andrianov, Gregory; Nikonova, Anna S.; Nicolas, Emmanuelle; Einarson, Margret B.; Golemis, Erica A.; Serebriiskii, Ilya G.

2017-01-01

Ovarian, head and neck, and other cancers are commonly treated with cisplatin and other DNA damaging cytotoxic agents. Altered DNA damage response (DDR) contributes to resistance of these tumors to chemotherapies, some targeted therapies, and radiation. DDR involves multiple protein complexes and signaling pathways, some of which are evolutionarily ancient and involve protein orthologs conserved from yeast to humans. To identify new regulators of cisplatin-resistance in human tumors, we integrated high throughput and curated datasets describing yeast genes that regulate sensitivity to cisplatin and/or ionizing radiation. Next, we clustered highly validated genes based on chemogenomic profiling, and then mapped orthologs of these genes in expanded genomic networks for multiple metazoans, including humans. This approach identified an enriched candidate set of genes involved in the regulation of resistance to radiation and/or cisplatin in humans. Direct functional assessment of selected candidate genes using RNA interference confirmed their activity in influencing cisplatin resistance, degree of γH2AX focus formation and ATR phosphorylation, in ovarian and head and neck cancer cell lines, suggesting impaired DDR signaling as the driving mechanism. This work enlarges the set of genes that may contribute to chemotherapy resistance and provides a new contextual resource for interpreting next generation sequencing (NGS) genomic profiling of tumors. PMID:27863405

Evolutionarily Conserved, Growth Plate Zone-Specific Regulation of the Matrilin-1 Promoter: L-Sox5/Sox6 and Nfi Factors Bound near TATA Finely Tune Activation by Sox9 ▿

PubMed Central

Nagy, Andrea; Kénesi, Erzsébet; Rentsendorj, Otgonchimeg; Molnár, Annamária; Szénási, Tibor; Sinkó, Ildikó; Zvara, Ágnes; Thottathil Oommen, Sajit; Barta, Endre; Puskás, László G.; Lefebvre, Veronique; Kiss, Ibolya

2011-01-01

To help uncover the mechanisms underlying the staggered expression of cartilage-specific genes in the growth plate, we dissected the transcriptional mechanisms driving expression of the matrilin-1 gene (Matn1). We show that a unique assembly of evolutionarily conserved cis-acting elements in the Matn1 proximal promoter restricts expression to the proliferative and prehypertrophic zones of the growth plate. These elements functionally interact with distal elements and likewise are capable of restricting the domain of activity of a pancartilaginous Col2a1 enhancer. The proximal elements include a Pe1 element binding the chondrogenic L-Sox5, Sox6, and Sox9 proteins, a SI element binding Nfi proteins, and an initiator Ine element binding the Sox trio and other factors. Sox9 binding to Pe1 is indispensable for functional interaction with the distal promoter. Binding of L-Sox5/Sox6 to Ine and Nfib to SI modulates Sox9 transactivation in a protein dose-dependent manner, possibly to enhance Sox9 activity in early stages of chondrogenesis and repress it at later stages. Hence, our data suggest a novel model whereby Sox and Nfi proteins bind to conserved Matn1 proximal elements and functionally interact with each other to finely tune gene expression in specific zones of the cartilage growth plate. PMID:21173167

Cross-species chemogenomic profiling reveals evolutionarily conserved drug mode of action

PubMed Central

Kapitzky, Laura; Beltrao, Pedro; Berens, Theresa J; Gassner, Nadine; Zhou, Chunshui; Wüster, Arthur; Wu, Julie; Babu, M Madan; Elledge, Stephen J; Toczyski, David; Lokey, R Scott; Krogan, Nevan J

2010-01-01

We present a cross-species chemogenomic screening platform using libraries of haploid deletion mutants from two yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe. We screened a set of compounds of known and unknown mode of action (MoA) and derived quantitative drug scores (or D-scores), identifying mutants that are either sensitive or resistant to particular compounds. We found that compound–functional module relationships are more conserved than individual compound–gene interactions between these two species. Furthermore, we observed that combining data from both species allows for more accurate prediction of MoA. Finally, using this platform, we identified a novel small molecule that acts as a DNA damaging agent and demonstrate that its MoA is conserved in human cells. PMID:21179023

An evolutionarily conserved motif in the TAB1 C-terminal region is necessary for interaction with and activation of TAK1 MAPKKK.

PubMed

Ono, K; Ohtomo, T; Sato, S; Sugamata, Y; Suzuki, M; Hisamoto, N; Ninomiya-Tsuji, J; Tsuchiya, M; Matsumoto, K

2001-06-29

TAK1, a member of the MAPKKK family, is involved in the intracellular signaling pathways mediated by transforming growth factor beta, interleukin 1, and Wnt. TAK1 kinase activity is specifically activated by the TAK1-binding protein TAB1. The C-terminal 68-amino acid sequence of TAB1 (TAB1-C68) is sufficient for TAK1 interaction and activation. Analysis of various truncated versions of TAB1-C68 defined a C-terminal 30-amino acid sequence (TAB1-C30) necessary for TAK1 binding and activation. NMR studies revealed that the TAB1-C30 region has a unique alpha-helical structure. We identified a conserved sequence motif, PYVDXA/TXF, in the C-terminal domain of mammalian TAB1, Xenopus TAB1, and its Caenorhabditis elegans homolog TAP-1, suggesting that this motif constitutes a specific TAK1 docking site. Alanine substitution mutagenesis showed that TAB1 Phe-484, located in the conserved motif, is crucial for TAK1 binding and activation. The C. elegans homolog of TAB1, TAP-1, was able to interact with and activate the C. elegans homolog of TAK1, MOM-4. However, the site in TAP-1 corresponding to Phe-484 of TAB1 is an alanine residue (Ala-364), and changing this residue to Phe abrogates the ability of TAP-1 to interact with and activate MOM-4. These results suggest that the Phe or Ala residue within the conserved motif of the TAB1-related proteins is important for interaction with and activation of specific TAK1 MAPKKK family members in vivo.

Asy2/Mer2: an evolutionarily conserved mediator of meiotic recombination, pairing, and global chromosome compaction

PubMed Central

Tessé, Sophie; Bourbon, Henri-Marc; Debuchy, Robert; Budin, Karine; Dubois, Emeline; Liangran, Zhang; Antoine, Romain; Piolot, Tristan; Kleckner, Nancy; Zickler, Denise; Espagne, Eric

2017-01-01

Meiosis is the cellular program by which a diploid cell gives rise to haploid gametes for sexual reproduction. Meiotic progression depends on tight physical and functional coupling of recombination steps at the DNA level with specific organizational features of meiotic-prophase chromosomes. The present study reveals that every step of this coupling is mediated by a single molecule: Asy2/Mer2. We show that Mer2, identified so far only in budding and fission yeasts, is in fact evolutionarily conserved from fungi (Mer2/Rec15/Asy2/Bad42) to plants (PRD3/PAIR1) and mammals (IHO1). In yeasts, Mer2 mediates assembly of recombination–initiation complexes and double-strand breaks (DSBs). This role is conserved in the fungus Sordaria. However, functional analysis of 13 mer2 mutants and successive localization of Mer2 to axis, synaptonemal complex (SC), and chromatin revealed, in addition, three further important functions. First, after DSB formation, Mer2 is required for pairing by mediating homolog spatial juxtaposition, with implications for crossover (CO) patterning/interference. Second, Mer2 participates in the transfer/maintenance and release of recombination complexes to/from the SC central region. Third, after completion of recombination, potentially dependent on SUMOylation, Mer2 mediates global chromosome compaction and post-recombination chiasma development. Thus, beyond its role as a recombinosome–axis/SC linker molecule, Mer2 has important functions in relation to basic chromosome structure. PMID:29021238

Asy2/Mer2: an evolutionarily conserved mediator of meiotic recombination, pairing, and global chromosome compaction.

PubMed

Tessé, Sophie; Bourbon, Henri-Marc; Debuchy, Robert; Budin, Karine; Dubois, Emeline; Liangran, Zhang; Antoine, Romain; Piolot, Tristan; Kleckner, Nancy; Zickler, Denise; Espagne, Eric

2017-09-15

Meiosis is the cellular program by which a diploid cell gives rise to haploid gametes for sexual reproduction. Meiotic progression depends on tight physical and functional coupling of recombination steps at the DNA level with specific organizational features of meiotic-prophase chromosomes. The present study reveals that every step of this coupling is mediated by a single molecule: Asy2/Mer2. We show that Mer2, identified so far only in budding and fission yeasts, is in fact evolutionarily conserved from fungi (Mer2/Rec15/Asy2/Bad42) to plants (PRD3/PAIR1) and mammals (IHO1). In yeasts, Mer2 mediates assembly of recombination-initiation complexes and double-strand breaks (DSBs). This role is conserved in the fungus Sordaria However, functional analysis of 13 mer2 mutants and successive localization of Mer2 to axis, synaptonemal complex (SC), and chromatin revealed, in addition, three further important functions. First, after DSB formation, Mer2 is required for pairing by mediating homolog spatial juxtaposition, with implications for crossover (CO) patterning/interference. Second, Mer2 participates in the transfer/maintenance and release of recombination complexes to/from the SC central region. Third, after completion of recombination, potentially dependent on SUMOylation, Mer2 mediates global chromosome compaction and post-recombination chiasma development. Thus, beyond its role as a recombinosome-axis/SC linker molecule, Mer2 has important functions in relation to basic chromosome structure. © 2017 Tessé et al.; Published by Cold Spring Harbor Laboratory Press.

Control of plant stem cell function by conserved interacting transcriptional regulators

PubMed Central

Zhou, Yun; Liu, Xing; Engstrom, Eric M.; Nimchuk, Zachary L.; Pruneda-Paz, Jose L.; Tarr, Paul T.; Yan, An; Kay, Steve A.; Meyerowitz, Elliot M.

2014-01-01

SUMMARY Plant stem cells in the shoot apical meristem (SAM) and root apical meristem (RAM) provide for postembryonic development of above-ground tissues and roots, respectively, while secondary vascular stem cells sustain vascular development1–4. WUSCHEL (WUS), a homeodomain transcription factor expressed in the rib meristem of the SAM, is a key regulatory factor controlling stem cell populations in the Arabidopsis SAM5–6 and is thought to establish the shoot stem cell niche via a feedback circuit with the CLAVATA3 (CLV3) peptide signaling pathway7. WUSCHEL-RELATED HOMEOBOX5 (WOX5), specifically expressed in root quiescent center (QC), defines QC identity and functions interchangeably with WUS in control of shoot and root stem cell niches8. WOX4, expressed in Arabidopsis procambial cells, defines the vascular stem cell niche9–11. WUS/WOX family proteins are evolutionarily and functionally conserved throughout the plant kingdom12 and emerge as key actors in the specification and maintenance of stem cells within all meristems13. However, the nature of the genetic regime in stem cell niches that centers on WOX gene function has been elusive, and molecular links underlying conserved WUS/WOX function in stem cell niches remain unknown. Here we demonstrate that the Arabidopsis HAIRY MERISTEM (HAM)family transcription regulators act as conserved interacting co-factors with WUS/WOX proteins. HAM and WUS share common targets in vivo and their physical interaction is important in driving downstream transcriptional programs and in promoting shoot stem cell proliferation. Differences in the overlapping expression patterns of WOX and HAM family members underlie the formation of diverse stem cell niche locations, and the HAM family is essential for all of these stem cell niches. These findings establish a new framework for the control of stem cell production during plant development. PMID:25363783

Expression screening using a Medaka cDNA library identifies evolutionarily conserved regulators of the p53/Mdm2 pathway.

PubMed

Zhang, Ping; Kratz, Anne Sophie; Salama, Mohammed; Elabd, Seham; Heinrich, Thorsten; Wittbrodt, Joachim; Blattner, Christine; Davidson, Gary

2015-10-08

The p53 tumor suppressor protein is mainly regulated by alterations in the half-life of the protein, resulting in significant differences in p53 protein levels in cells. The major regulator of this process is Mdm2, which ubiquitinates p53 and targets it for proteasomal degradation. This process can be enhanced or reduced by proteins that associate with p53 or Mdm2 and several proteins have been identified with such an activity. Furthermore, additional ubiquitin ligases for p53 have been identified in recent years. Nevertheless, our understanding of how p53 abundance and Mdm2 activity are regulated remains incomplete. Here we describe a cell culture based overexpression screen to identify evolutionarily conserved regulators of the p53/Mdm2 circuit. The results from this large-scale screening method will contribute to a better understanding of the regulation of these important proteins. Expression screening was based on co-transfection of H1299 cells with pools of cDNA's from a Medaka library together with p53, Mdm2 and, as internal control, Ror2. After cell lysis, SDS-PAGE/WB analysis was used to detect alterations in these proteins. More than one hundred hits that altered the abundance of either p53, Mdm2, or both were identified in the primary screen. Subscreening of the library pools that were identified in the primary screen identified several potential novel regulators of p53 and/or Mdm2. We also tested whether the human orthologues of the Medaka genes regulate p53 and/or Mdm2 abundance. All human orthologues regulated p53 and/or Mdm2 abundance in the same manner as the proteins from Medaka, which underscores the suitability of this screening methodology for the identification of new modifiers of p53 and Mdm2. Despite enormous efforts in the last two decades, many unknown regulators for p53 and Mdm2 abundance are predicted to exist. This cross-species approach to identify evolutionarily conserved regulators demonstrates that our Medaka unigene cDNA library

Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche

USGS Publications Warehouse

Kapp, Friedrich G.; Perlin, Julie R.; Hagedorn, Elliott J.; Gansner, John M.; Schwarz, Daniel E.; O'Connell, Lauren A.; Johnson, Nicholas; Amemiya, Chris; Fisher, David E.; Wolfle, Ute; Trompouki, Eirini; Niemeyer, Charlotte M.; Driever, Wolfgang; Zon, Leonard I.

2018-01-01

Haematopoietic stem and progenitor cells (HSPCs) require a specific microenvironment, the haematopoietic niche, which regulates HSPC behaviour. The location of this niche varies across species, but the evolutionary pressures that drive HSPCs to different microenvironments remain unknown. The niche is located in the bone marrow in adult mammals, whereas it is found in other locations in non-mammalian vertebrates, for example, in the kidney marrow in teleost fish. Here we show that a melanocyte umbrella above the kidney marrow protects HSPCs against ultraviolet light in zebrafish. Because mutants that lack melanocytes have normal steady-state haematopoiesis under standard laboratory conditions, we hypothesized that melanocytes above the stem cell niche protect HSPCs against ultraviolet-light-induced DNA damage. Indeed, after ultraviolet-light irradiation, unpigmented larvae show higher levels of DNA damage in HSPCs, as indicated by staining of cyclobutane pyrimidine dimers and have reduced numbers of HSPCs, as shown by cmyb (also known as myb) expression. The umbrella of melanocytes associated with the haematopoietic niche is highly evolutionarily conserved in aquatic animals, including the sea lamprey, a basal vertebrate. During the transition from an aquatic to a terrestrial environment, HSPCs relocated into the bone marrow, which is protected from ultraviolet light by the cortical bone around the marrow. Our studies reveal that melanocytes above the haematopoietic niche protect HSPCs from ultraviolet-light-induced DNA damage in aquatic vertebrates and suggest that during the transition to terrestrial life, ultraviolet light was an evolutionary pressure affecting the location of the haematopoietic niche.

Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche.

PubMed

Kapp, Friedrich G; Perlin, Julie R; Hagedorn, Elliott J; Gansner, John M; Schwarz, Daniel E; O'Connell, Lauren A; Johnson, Nicholas S; Amemiya, Chris; Fisher, David E; Wölfle, Ute; Trompouki, Eirini; Niemeyer, Charlotte M; Driever, Wolfgang; Zon, Leonard I

2018-06-01

Haematopoietic stem and progenitor cells (HSPCs) require a specific microenvironment, the haematopoietic niche, which regulates HSPC behaviour 1,2 . The location of this niche varies across species, but the evolutionary pressures that drive HSPCs to different microenvironments remain unknown. The niche is located in the bone marrow in adult mammals, whereas it is found in other locations in non-mammalian vertebrates, for example, in the kidney marrow in teleost fish. Here we show that a melanocyte umbrella above the kidney marrow protects HSPCs against ultraviolet light in zebrafish. Because mutants that lack melanocytes have normal steady-state haematopoiesis under standard laboratory conditions, we hypothesized that melanocytes above the stem cell niche protect HSPCs against ultraviolet-light-induced DNA damage. Indeed, after ultraviolet-light irradiation, unpigmented larvae show higher levels of DNA damage in HSPCs, as indicated by staining of cyclobutane pyrimidine dimers and have reduced numbers of HSPCs, as shown by cmyb (also known as myb) expression. The umbrella of melanocytes associated with the haematopoietic niche is highly evolutionarily conserved in aquatic animals, including the sea lamprey, a basal vertebrate. During the transition from an aquatic to a terrestrial environment, HSPCs relocated into the bone marrow, which is protected from ultraviolet light by the cortical bone around the marrow. Our studies reveal that melanocytes above the haematopoietic niche protect HSPCs from ultraviolet-light-induced DNA damage in aquatic vertebrates and suggest that during the transition to terrestrial life, ultraviolet light was an evolutionary pressure affecting the location of the haematopoietic niche.

Evolutionarily conserved gene family important for fat storage

PubMed Central

Kadereit, Bert; Kumar, Pradeep; Wang, Wen-Jun; Miranda, Diego; Snapp, Erik L.; Severina, Nadia; Torregroza, Ingrid; Evans, Todd; Silver, David L.

2008-01-01

The ability to store fat in the form of cytoplasmic triglyceride droplets is conserved from Saccharomyces cerevisiae to humans. Although much is known regarding the composition and catabolism of lipid droplets, the molecular components necessary for the biogenesis of lipid droplets have remained obscure. Here we report the characterization of a conserved gene family important for lipid droplet formation named fat-inducing transcript (FIT). FIT1 and FIT2 are endoplasmic reticulum resident membrane proteins that induce lipid droplet accumulation in cell culture and when expressed in mouse liver. shRNA silencing of FIT2 in 3T3-LI adipocytes prevents accumulation of lipid droplets, and depletion of FIT2 in zebrafish blocks diet-induced accumulation of lipid droplets in the intestine and liver, highlighting an important role for FIT2 in lipid droplet formation in vivo. Together these studies identify and characterize a conserved gene family that is important in the fundamental process of storing fat. PMID:18160536

In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites

PubMed Central

2016-01-01

Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus. Our results provide insight into pigment phenotypes in pythons. PMID:27698666

In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites.

PubMed

Irizarry, Kristopher J L; Bryden, Randall L

2016-01-01

Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus . Our results provide insight into pigment phenotypes in pythons.

Evolutionarily conserved morphogenetic movements at the vertebrate head-trunk interface coordinate the transport and assembly of hypopharyngeal structures.

PubMed

Lours-Calet, Corinne; Alvares, Lucia E; El-Hanfy, Amira S; Gandesha, Saniel; Walters, Esther H; Sobreira, Débora Rodrigues; Wotton, Karl R; Jorge, Erika C; Lawson, Jennifer A; Kelsey Lewis, A; Tada, Masazumi; Sharpe, Colin; Kardon, Gabrielle; Dietrich, Susanne

2014-06-15

The vertebrate head-trunk interface (occipital region) has been heavily remodelled during evolution, and its development is still poorly understood. In extant jawed vertebrates, this region provides muscle precursors for the throat and tongue (hypopharyngeal/hypobranchial/hypoglossal muscle precursors, HMP) that take a stereotype path rostrally along the pharynx and are thought to reach their target sites via active migration. Yet, this projection pattern emerged in jawless vertebrates before the evolution of migratory muscle precursors. This suggests that a so far elusive, more basic transport mechanism must have existed and may still be traceable today. Here we show for the first time that all occipital tissues participate in well-conserved cell movements. These cell movements are spearheaded by the occipital lateral mesoderm and ectoderm that split into two streams. The rostrally directed stream projects along the floor of the pharynx and reaches as far rostrally as the floor of the mandibular arch and outflow tract of the heart. Notably, this stream leads and engulfs the later emerging HMP, neural crest cells and hypoglossal nerve. When we (i) attempted to redirect hypobranchial/hypoglossal muscle precursors towards various attractants, (ii) placed non-migratory muscle precursors into the occipital environment or (iii) molecularly or (iv) genetically rendered muscle precursors non-migratory, they still followed the trajectory set by the occipital lateral mesoderm and ectoderm. Thus, we have discovered evolutionarily conserved morphogenetic movements, driven by the occipital lateral mesoderm and ectoderm, that ensure cell transport and organ assembly at the head-trunk interface. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Evolutionarily conserved morphogenetic movements at the vertebrate head–trunk interface coordinate the transport and assembly of hypopharyngeal structures

PubMed Central

Lours-Calet, Corinne; Alvares, Lucia E.; El-Hanfy, Amira S.; Gandesha, Saniel; Walters, Esther H.; Sobreira, Débora Rodrigues; Wotton, Karl R.; Jorge, Erika C.; Lawson, Jennifer A.; Kelsey Lewis, A.; Tada, Masazumi; Sharpe, Colin; Kardon, Gabrielle; Dietrich, Susanne

2014-01-01

The vertebrate head–trunk interface (occipital region) has been heavily remodelled during evolution, and its development is still poorly understood. In extant jawed vertebrates, this region provides muscle precursors for the throat and tongue (hypopharyngeal/hypobranchial/hypoglossal muscle precursors, HMP) that take a stereotype path rostrally along the pharynx and are thought to reach their target sites via active migration. Yet, this projection pattern emerged in jawless vertebrates before the evolution of migratory muscle precursors. This suggests that a so far elusive, more basic transport mechanism must have existed and may still be traceable today. Here we show for the first time that all occipital tissues participate in well-conserved cell movements. These cell movements are spearheaded by the occipital lateral mesoderm and ectoderm that split into two streams. The rostrally directed stream projects along the floor of the pharynx and reaches as far rostrally as the floor of the mandibular arch and outflow tract of the heart. Notably, this stream leads and engulfs the later emerging HMP, neural crest cells and hypoglossal nerve. When we (i) attempted to redirect hypobranchial/hypoglossal muscle precursors towards various attractants, (ii) placed non-migratory muscle precursors into the occipital environment or (iii) molecularly or (iv) genetically rendered muscle precursors non-migratory, they still followed the trajectory set by the occipital lateral mesoderm and ectoderm. Thus, we have discovered evolutionarily conserved morphogenetic movements, driven by the occipital lateral mesoderm and ectoderm, that ensure cell transport and organ assembly at the head–trunk interface. PMID:24662046

The gibberellin GID1-DELLA signalling module exists in evolutionarily ancient conifers.

PubMed

Du, Ran; Niu, Shihui; Liu, Yang; Sun, Xinrui; Porth, Ilga; El-Kassaby, Yousry A; Li, Wei

2017-11-30

Gibberellins (GAs) participate in controlling various aspects of basic plant growth responses. With the exception of bryophytes, GA signalling in land plants, such as lycophytes, ferns and angiosperms, is mediated via GIBBERELLIN-INSENSITIVE DWARF1 (GID1) and DELLA proteins. To explore whether this GID1-DELLA mechanism is present in pines, we cloned an orthologue (PtGID1) of Arabidopsis AtGID1a and two putative DELLA proteins (PtDPL; PtRGA) from Pinus tabuliformis, a widespread indigenous conifer species in China, and studied their recombinant proteins. PtGID1 shares with AtGID1a the conserved HSL motifs for GA binding and an N-terminal feature that are essential for interaction with DELLA proteins. Indeed, A. thaliana 35S:PtGID1 overexpressors showed a strong GA-hypersensitive phenotype compared to the wild type. Interactions between PtGID1 and PtDELLAs, but also interactions between the conifer-angiosperm counterparts (i.e. between AtGID1 and PtDELLAs and between PtGID1 and AtDELLA), were detected in vivo. This demonstrates that pine has functional GID1-DELLA components. The Δ17-domains within PtDPL and PtRGA were identified as potential interaction sites within PtDELLAs. Our results show that PtGID1 has the ability to interact with DELLA and functions as a GA receptor. Thus, a GA-GID1-DELLA signalling module also operates in evolutionarily ancient conifers.

An evolutionarily conserved NIMA-related kinase directs rhizoid tip growth in the basal land plant Marchantia polymorpha.

PubMed

Otani, Kento; Ishizaki, Kimitsune; Nishihama, Ryuichi; Takatani, Shogo; Kohchi, Takayuki; Takahashi, Taku; Motose, Hiroyasu

2018-03-01

Tip growth is driven by turgor pressure and mediated by the polarized accumulation of cellular materials. How a single polarized growth site is established and maintained is unclear. Here, we analyzed the function of NIMA-related protein kinase 1 (MpNEK1) in the liverwort Marchantia polymorpha In the wild type, rhizoid cells differentiate from the ventral epidermis and elongate through tip growth to form hair-like protrusions. In Mp nek1 knockout mutants, rhizoids underwent frequent changes in growth direction, resulting in a twisted and/or spiral morphology. The functional MpNEK1-Citrine protein fusion localized to microtubule foci in the apical growing region of rhizoids. Mp nek1 knockouts exhibited increases in both microtubule density and bundling in the apical dome of rhizoids. Treatment with the microtubule-stabilizing drug taxol phenocopied the Mp nek1 knockout. These results suggest that MpNEK1 directs tip growth in rhizoids through microtubule organization. Furthermore, MpNEK1 expression rescued ectopic outgrowth of epidermal cells in the Arabidopsis thaliana nek6 mutant, strongly supporting an evolutionarily conserved NEK-dependent mechanism of directional growth. It is possible that such a mechanism contributed to the evolution of the early rooting system in land plants. © 2018. Published by The Company of Biologists Ltd.

An Evolutionarily Conserved Role of Presenilin in Neuronal Protection in the Aging Drosophila Brain.

PubMed

Kang, Jongkyun; Shin, Sarah; Perrimon, Norbert; Shen, Jie

2017-07-01

Mutations in the Presenilin genes are the major genetic cause of Alzheimer's disease. Presenilin and Nicastrin are essential components of γ-secretase, a multi-subunit protease that cleaves Type I transmembrane proteins. Genetic studies in mice previously demonstrated that conditional inactivation of Presenilin or Nicastrin in excitatory neurons of the postnatal forebrain results in memory deficits, synaptic impairment, and age-dependent neurodegeneration. The roles of Drosophila Presenilin ( Psn ) and Nicastrin ( Nct ) in the adult fly brain, however, are unknown. To knockdown (KD) Psn or Nct selectively in neurons of the adult brain, we generated multiple shRNA lines. Using a ubiquitous driver, these shRNA lines resulted in 80-90% reduction of mRNA and pupal lethality-a phenotype that is shared with Psn and Nct mutants carrying nonsense mutations. Furthermore, expression of these shRNAs in the wing disc caused notching wing phenotypes, which are also shared with Psn and Nct mutants. Similar to Nct , neuron-specific Psn KD using two independent shRNA lines led to early mortality and rough eye phenotypes, which were rescued by a fly Psn transgene. Interestingly, conditional KD (cKD) of Psn or Nct in adult neurons using the elav-Gal4 and tubulin-Gal80 ts system caused shortened lifespan, climbing defects, increases in apoptosis, and age-dependent neurodegeneration. Together, these findings demonstrate that, similar to their mammalian counterparts, Drosophila Psn and Nct are required for neuronal survival during aging and normal lifespan, highlighting an evolutionarily conserved role of Presenilin in neuronal protection in the aging brain. Copyright © 2017 by the Genetics Society of America.

Conservation of small RNA pathways in platypus.

PubMed

Murchison, Elizabeth P; Kheradpour, Pouya; Sachidanandam, Ravi; Smith, Carly; Hodges, Emily; Xuan, Zhenyu; Kellis, Manolis; Grützner, Frank; Stark, Alexander; Hannon, Gregory J

2008-06-01

Small RNA pathways play evolutionarily conserved roles in gene regulation and defense from parasitic nucleic acids. The character and expression patterns of small RNAs show conservation throughout animal lineages, but specific animal clades also show variations on these recurring themes, including species-specific small RNAs. The monotremes, with only platypus and four species of echidna as extant members, represent the basal branch of the mammalian lineage. Here, we examine the small RNA pathways of monotremes by deep sequencing of six platypus and echidna tissues. We find that highly conserved microRNA species display their signature tissue-specific expression patterns. In addition, we find a large rapidly evolving cluster of microRNAs on platypus chromosome X1, which is unique to monotremes. Platypus and echidna testes contain a robust Piwi-interacting (piRNA) system, which appears to be participating in ongoing transposon defense.

Drosophila vitelline membrane assembly: A critical role for an evolutionarily conserved cysteine in the “VM domain” of sV23

PubMed Central

Wu, T; Manogaran, A.L; Beauchamp, J.M.; Waring, G.L.

2010-01-01

The vitelline membrane (VM), the oocyte proximal layer of the Drosophila eggshell, contains four major proteins (VMPs) that possess a highly conserved “VM domain” which includes three precisely spaced, evolutionarily conserved, cysteines (CX7CX8C). Focusing on sV23, this study showed that the three cysteines are not functionally equivalent. While substitution mutations at the first (C123S) or third (C140S) cysteines were tolerated, females with a substitution at the second position (C131S) were sterile. Fractionation studies showed sV23 incorporates into a large disulfide linked network well after its secretion ceases, suggesting post-depositional mechanisms are in place to restrict disulfide bond formation until late oogenesis, when the oocyte no longer experiences large volume increases. Affinity chromatography utilizing histidine tagged sV23 alleles revealed small sV23 disulfide linked complexes during the early stages of eggshell formation that included other VMPs, namely sV17 and Vml. The early presence but late loss of these associations in an sV23 double cysteine mutant suggests reorganization of disulfide bonds may underlie the regulated growth of disulfide-linked networks in the vitelline membrane. Found within the context of a putative thioredoxin active site (CXXS) C131, the critical cysteine in sV23, may play an important enzymatic role in isomerizing intermolecular disulfide bonds during eggshell assembly. PMID:20832396

Evolutionarily conserved structural and functional roles of the FYVE domain.

PubMed

Hayakawa, Akira; Hayes, Susan; Leonard, Deborah; Lambright, David; Corvera, Silvia

2007-01-01

The FYVE domain is an approx. 80 amino acid motif that binds to the phosphoinositide PtdIns3P with high specificity and affinity. It is present in 38 predicted gene products within the human genome, but only in 12-13 in Caenorhabditis elegans and Drosophila melanogaster. Eight of these are highly conserved in all three organisms, and they include proteins that have not been characterized in any species. One of these, WDFY2, appears to play an important role in early endocytosis and was revealed in a RNAi (RNA interference) screen in C. elegans. Interestingly, some proteins contain FYVE-like domains in C. elegans and D. melanogaster, but have lost this domain during evolution. One of these is the homologue of Rabatin-5, a protein that, in mammalian cells, binds both Rab5 and Rabex-5, a guanine-nucleotide exchange factor for Rab5. Thus the Rabatin-5 homologue suggests that mechanisms to link PtdIns3P and Rab5 activation developed in evolution. In mammalian cells, these mechanisms are apparent in the existence of proteins that bind PtdIns3P and Rab GTPases, such as EEA1, Rabenosyn-5 and Rabip4'. Despite the comparable ability to bind to PtdIns3P in vitro, FYVE domains display widely variable abilities to interact with endosomes in intact cells. This variation is due to three distinct properties of FYVE domains conferred by residues that are not involved in PtdIns3P head group recognition: These properties are: (i) the propensity to oligomerize, (ii) the ability to insert into the membrane bilayer, and (iii) differing electrostatic interactions with the bilayer surface. The different binding properties are likely to regulate the extent and duration of the interaction of specific FYVE domain-containing proteins with early endosomes, and thereby their biological function.

Conservation of small RNA pathways in platypus

PubMed Central

Murchison, Elizabeth P.; Kheradpour, Pouya; Sachidanandam, Ravi; Smith, Carly; Hodges, Emily; Xuan, Zhenyu; Kellis, Manolis; Grützner, Frank; Stark, Alexander; Hannon, Gregory J.

2008-01-01

Small RNA pathways play evolutionarily conserved roles in gene regulation and defense from parasitic nucleic acids. The character and expression patterns of small RNAs show conservation throughout animal lineages, but specific animal clades also show variations on these recurring themes, including species-specific small RNAs. The monotremes, with only platypus and four species of echidna as extant members, represent the basal branch of the mammalian lineage. Here, we examine the small RNA pathways of monotremes by deep sequencing of six platypus and echidna tissues. We find that highly conserved microRNA species display their signature tissue-specific expression patterns. In addition, we find a large rapidly evolving cluster of microRNAs on platypus chromosome X1, which is unique to monotremes. Platypus and echidna testes contain a robust Piwi-interacting (piRNA) system, which appears to be participating in ongoing transposon defense. PMID:18463306

Microfluidic affinity and ChIP-seq analyses converge on a conserved FOXP2-binding motif in chimp and human, which enables the detection of evolutionarily novel targets.

PubMed

Nelson, Christopher S; Fuller, Chris K; Fordyce, Polly M; Greninger, Alexander L; Li, Hao; DeRisi, Joseph L

2013-07-01

The transcription factor forkhead box P2 (FOXP2) is believed to be important in the evolution of human speech. A mutation in its DNA-binding domain causes severe speech impairment. Humans have acquired two coding changes relative to the conserved mammalian sequence. Despite intense interest in FOXP2, it has remained an open question whether the human protein's DNA-binding specificity and chromatin localization are conserved. Previous in vitro and ChIP-chip studies have provided conflicting consensus sequences for the FOXP2-binding site. Using MITOMI 2.0 microfluidic affinity assays, we describe the binding site of FOXP2 and its affinity profile in base-specific detail for all substitutions of the strongest binding site. We find that human and chimp FOXP2 have similar binding sites that are distinct from previously suggested consensus binding sites. Additionally, through analysis of FOXP2 ChIP-seq data from cultured neurons, we find strong overrepresentation of a motif that matches our in vitro results and identifies a set of genes with FOXP2 binding sites. The FOXP2-binding sites tend to be conserved, yet we identified 38 instances of evolutionarily novel sites in humans. Combined, these data present a comprehensive portrait of FOXP2's-binding properties and imply that although its sequence specificity has been conserved, some of its genomic binding sites are newly evolved.

Microfluidic affinity and ChIP-seq analyses converge on a conserved FOXP2-binding motif in chimp and human, which enables the detection of evolutionarily novel targets

PubMed Central

Nelson, Christopher S.; Fuller, Chris K.; Fordyce, Polly M.; Greninger, Alexander L.; Li, Hao; DeRisi, Joseph L.

2013-01-01

The transcription factor forkhead box P2 (FOXP2) is believed to be important in the evolution of human speech. A mutation in its DNA-binding domain causes severe speech impairment. Humans have acquired two coding changes relative to the conserved mammalian sequence. Despite intense interest in FOXP2, it has remained an open question whether the human protein’s DNA-binding specificity and chromatin localization are conserved. Previous in vitro and ChIP-chip studies have provided conflicting consensus sequences for the FOXP2-binding site. Using MITOMI 2.0 microfluidic affinity assays, we describe the binding site of FOXP2 and its affinity profile in base-specific detail for all substitutions of the strongest binding site. We find that human and chimp FOXP2 have similar binding sites that are distinct from previously suggested consensus binding sites. Additionally, through analysis of FOXP2 ChIP-seq data from cultured neurons, we find strong overrepresentation of a motif that matches our in vitro results and identifies a set of genes with FOXP2 binding sites. The FOXP2-binding sites tend to be conserved, yet we identified 38 instances of evolutionarily novel sites in humans. Combined, these data present a comprehensive portrait of FOXP2’s-binding properties and imply that although its sequence specificity has been conserved, some of its genomic binding sites are newly evolved. PMID:23625967

Evolutionarily conserved proteins MnmE and GidA catalyze the formation of two methyluridine derivatives at tRNA wobble positions

PubMed Central

Moukadiri, Ismaïl; Prado, Silvia; Piera, Julio; Velázquez-Campoy, Adrián; Björk, Glenn R.; Armengod, M.-Eugenia

2009-01-01

The wobble uridine of certain bacterial and mitochondrial tRNAs is modified, at position 5, through an unknown reaction pathway that utilizes the evolutionarily conserved MnmE and GidA proteins. The resulting modification (a methyluridine derivative) plays a critical role in decoding NNG/A codons and reading frame maintenance during mRNA translation. The lack of this tRNA modification produces a pleiotropic phenotype in bacteria and has been associated with mitochondrial encephalomyopathies in humans. In this work, we use in vitro and in vivo approaches to characterize the enzymatic pathway controlled by the Escherichia coli MnmE•GidA complex. Surprisingly, this complex catalyzes two different GTP- and FAD-dependent reactions, which produce 5-aminomethyluridine and 5-carboxymethylamino-methyluridine using ammonium and glycine, respectively, as substrates. In both reactions, methylene-tetrahydrofolate is the most probable source to form the C5-methylene moiety, whereas NADH is dispensable in vitro unless FAD levels are limiting. Our results allow us to reformulate the bacterial MnmE•GidA dependent pathway and propose a novel mechanism for the modification reactions performed by the MnmE and GidA family proteins. PMID:19767610

Interactions among ecosystem stressors and their importance in conservation

PubMed Central

Darling, Emily S.; Brown, Christopher J.

2016-01-01

Interactions between multiple ecosystem stressors are expected to jeopardize biological processes, functions and biodiversity. The scientific community has declared stressor interactions—notably synergies—a key issue for conservation and management. Here, we review ecological literature over the past four decades to evaluate trends in the reporting of ecological interactions (synergies, antagonisms and additive effects) and highlight the implications and importance to conservation. Despite increasing popularity, and ever-finer terminologies, we find that synergies are (still) not the most prevalent type of interaction, and that conservation practitioners need to appreciate and manage for all interaction outcomes, including antagonistic and additive effects. However, it will not be possible to identify the effect of every interaction on every organism's physiology and every ecosystem function because the number of stressors, and their potential interactions, are growing rapidly. Predicting the type of interactions may be possible in the near-future, using meta-analyses, conservation-oriented experiments and adaptive monitoring. Pending a general framework for predicting interactions, conservation management should enact interventions that are robust to uncertainty in interaction type and that continue to bolster biological resilience in a stressful world. PMID:26865306

No strategy is evolutionarily stable in the repeated prisoner's dilemma.

PubMed

Lorberbaum, J

1994-05-21

Following the influential work of Axelrod, the repeated Prisoner's Dilemma game has become the theoretical gold standard for understanding the evolution of co-operative behavior among unrelated individuals. Using the game, several authors have found that a reciprocal strategy known as Tit for Tat (TFT) has done quite well in a wide range of environments. TFT strategists start out co-operating and then do what the other player did on the previous move. Despite the success of TFT and similar strategies in experimental studies of the game, Boyd & Lorberbaum (1987, Nature, Lond. 327, 58) have shown that no pure strategy, including TFT, is evolutionarily stable in the sense that each can be invaded by the joint effect of two invading strategies when long-term interaction occurs in the repeated game and future moves are discounted. Farrell & Ware (1989, Theor. Popul. Biol. 36, 161) have since extended these results to include finite mixes of pure strategies as well. Here, it is proven that no strategy is evolutionarily stable when long-term relationships are maintained in the repeated Prisoner's Dilemma and future moves are discounted. Namely, it is shown each completely probabilistic strategy (i.e. one that both co-operates and defects with positive probability after every sequence of behavior) may be invaded by a single deviant strategy. This completes the proof started by Boyd and Lorberbaum and extended by Farrell and Ware. This paper goes on to prove that no reactive strategy with a memory restricted to the opponent's preceding move is evolutionarily stable when there is no discounting of future moves. This is true despite the success of a more forgiving variant of TFT called GTFT in a recent tournament among reactive strategies conducted by Nowak & Sigmund (1992, Nature 355, 250) where future moves were not discounted. GTFT, for example, may be invaded by a pair of reactive mutants. Since no strategy is evolutionarily stable when future moves are discounted in the

Evolutionarily conserved phenylpropanoid pattern on angiosperm pollen.

PubMed

Fellenberg, Christin; Vogt, Thomas

2015-04-01

The male gametophyte of higher plants appears as a solid box containing the essentials to transmit genetic material to the next generation. These consist of haploid generative cells that are required for reproduction, and an invasive vegetative cell producing the pollen tube, both mechanically protected by a rigid polymer, the pollen wall, and surrounded by a hydrophobic pollen coat. This coat mediates the direct contact to the biotic and abiotic environments. It contains a mixture of compounds required not only for fertilization but also for protection against biotic and abiotic stressors. Among its metabolites, the structural characteristics of two types of phenylpropanoids, hydroxycinnamic acid amides and flavonol glycosides, are highly conserved in Angiosperm pollen. Structural and functional aspects of these compounds will be discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Conservation and variability of West Nile virus proteins.

PubMed

Koo, Qi Ying; Khan, Asif M; Jung, Keun-Ok; Ramdas, Shweta; Miotto, Olivo; Tan, Tin Wee; Brusic, Vladimir; Salmon, Jerome; August, J Thomas

2009-01-01

West Nile virus (WNV) has emerged globally as an increasingly important pathogen for humans and domestic animals. Studies of the evolutionary diversity of the virus over its known history will help to elucidate conserved sites, and characterize their correspondence to other pathogens and their relevance to the immune system. We describe a large-scale analysis of the entire WNV proteome, aimed at identifying and characterizing evolutionarily conserved amino acid sequences. This study, which used 2,746 WNV protein sequences collected from the NCBI GenPept database, focused on analysis of peptides of length 9 amino acids or more, which are immunologically relevant as potential T-cell epitopes. Entropy-based analysis of the diversity of WNV sequences, revealed the presence of numerous evolutionarily stable nonamer positions across the proteome (entropy value of < or = 1). The representation (frequency) of nonamers variant to the predominant peptide at these stable positions was, generally, low (< or = 10% of the WNV sequences analyzed). Eighty-eight fragments of length 9-29 amino acids, representing approximately 34% of the WNV polyprotein length, were identified to be identical and evolutionarily stable in all analyzed WNV sequences. Of the 88 completely conserved sequences, 67 are also present in other flaviviruses, and several have been associated with the functional and structural properties of viral proteins. Immunoinformatic analysis revealed that the majority (78/88) of conserved sequences are potentially immunogenic, while 44 contained experimentally confirmed human T-cell epitopes. This study identified a comprehensive catalogue of completely conserved WNV sequences, many of which are shared by other flaviviruses, and majority are potential epitopes. The complete conservation of these immunologically relevant sequences through the entire recorded WNV history suggests they will be valuable as components of peptide-specific vaccines or other therapeutic

Evolutionarily conserved ELOVL4 gene expression in the vertebrate retina.

PubMed

Lagali, Pamela S; Liu, Jiafan; Ambasudhan, Rajesh; Kakuk, Laura E; Bernstein, Steven L; Seigel, Gail M; Wong, Paul W; Ayyagari, Radha

2003-07-01

The gene elongation of very long chain fatty acids-4 (ELOVL4) has been shown to underlie phenotypically heterogeneous forms of autosomal dominant macular degeneration. In this study, the extent of evolutionary conservation and the existence and localization of retinal expression of this gene was investigated across a wide variety of species. Southern blot analysis of genomic DNA and bioinformatic analysis using the human ELOVL4 cDNA and protein sequences, respectively, were performed to identify species in which ELOVL4 orthologues and/or homologues are present. Retinal RNA and protein extracts derived from different species were assessed by Northern hybridization and immunoblot techniques to assess evolutionary conservation of gene expression. Immunohistochemical analysis of tissue sections prepared from various mammalian retinas was performed to determine the distribution of ELOVL4 and homologous proteins within specific retinal cell layers. The existence of ELOVL4 sequence orthologues and homologues was confirmed by both Southern blot analysis and in silico searches of protein sequence databases. Phylogenetic analysis places ELOVL4 among a large family of known and putative fatty acid elongase proteins. Northern blot analysis revealed the presence of multiple transcripts corresponding to ELOVL4 homologues expressed in the retina of several different mammalian species. Conserved proteins were also detected among retinal extracts of different mammals and were found to localize predominantly to the photoreceptor cell layer within retinal tissue preparations. The ELOVL4 gene is highly conserved throughout evolution and is expressed in the photoreceptor cells of the retina in a variety of different species, which suggests that it plays a critical role in retinal cell biology.

Mitogen-Activated Protein Kinase Signaling in Plant-Interacting Fungi: Distinct Messages from Conserved Messengers[W

PubMed Central

Hamel, Louis-Philippe; Nicole, Marie-Claude; Duplessis, Sébastien; Ellis, Brian E.

2012-01-01

Mitogen-activated protein kinases (MAPKs) are evolutionarily conserved proteins that function as key signal transduction components in fungi, plants, and mammals. During interaction between phytopathogenic fungi and plants, fungal MAPKs help to promote mechanical and/or enzymatic penetration of host tissues, while plant MAPKs are required for activation of plant immunity. However, new insights suggest that MAPK cascades in both organisms do not operate independently but that they mutually contribute to a highly interconnected molecular dialogue between the plant and the fungus. As a result, some pathogenesis-related processes controlled by fungal MAPKs lead to the activation of plant signaling, including the recruitment of plant MAPK cascades. Conversely, plant MAPKs promote defense mechanisms that threaten the survival of fungal cells, leading to a stress response mediated in part by fungal MAPK cascades. In this review, we make use of the genomic data available following completion of whole-genome sequencing projects to analyze the structure of MAPK protein families in 24 fungal taxa, including both plant pathogens and mycorrhizal symbionts. Based on conserved patterns of sequence diversification, we also propose the adoption of a unified fungal MAPK nomenclature derived from that established for the model species Saccharomyces cerevisiae. Finally, we summarize current knowledge of the functions of MAPK cascades in phytopathogenic fungi and highlight the central role played by MAPK signaling during the molecular dialogue between plants and invading fungal pathogens. PMID:22517321

Cellular microbiology and molecular ecology of Legionella-amoeba interaction.

PubMed

Richards, Ashley M; Von Dwingelo, Juanita E; Price, Christopher T; Abu Kwaik, Yousef

2013-05-15

Legionella pneumophila is an aquatic organism that interacts with amoebae and ciliated protozoa as the natural hosts, and this interaction plays a central role in bacterial ecology and infectivity. Upon transmission to humans, L. pneumophila infect and replicate within alveolar macrophages causing pneumonia. Intracellular proliferation of L. pneumophila within the two evolutionarily distant hosts is facilitated by bacterial exploitation of evolutionarily conserved host processes that are targeted by bacterial protein effectors injected into the host cell by the Dot/Icm type VIB translocation system. Although cysteine is semi-essential for humans and essential for amoeba, it is a metabolically favorable source of carbon and energy generation by L. pneumophila. To counteract host limitation of cysteine, L. pneumophila utilizes the AnkB Dot/Icm-translocated F-box effector to promote host proteasomal degradation of polyubiquitinated proteins within amoebae and human cells. Evidence indicates ankB and other Dot/Icm-translocated effector genes have been acquired through inter-kingdom horizontal gene transfer.

Cellular microbiology and molecular ecology of Legionella–amoeba interaction

PubMed Central

Richards, Ashley M.; Von Dwingelo, Juanita E.; Price, Christopher T.; Abu Kwaik, Yousef

2013-01-01

Legionella pneumophila is an aquatic organism that interacts with amoebae and ciliated protozoa as the natural hosts, and this interaction plays a central role in bacterial ecology and infectivity. Upon transmission to humans, L. pneumophila infect and replicate within alveolar macrophages causing pneumonia. Intracellular proliferation of L. pneumophila within the two evolutionarily distant hosts is facilitated by bacterial exploitation of evolutionarily conserved host processes that are targeted by bacterial protein effectors injected into the host cell by the Dot/Icm type VIB translocation system. Although cysteine is semi-essential for humans and essential for amoeba, it is a metabolically favorable source of carbon and energy generation by L. pneumophila. To counteract host limitation of cysteine, L. pneumophila utilizes the AnkB Dot/Icm-translocated F-box effector to promote host proteasomal degradation of polyubiquitinated proteins within amoebae and human cells. Evidence indicates ankB and other Dot/Icm-translocated effector genes have been acquired through inter-kingdom horizontal gene transfer. PMID:23535283

Evolutionary stability of mutualism: interspecific population regulation as an evolutionarily stable strategy

USGS Publications Warehouse

Holland, J. Nathaniel; DeAngelis, Donald L.; Schultz, Stewart T.

2004-01-01

Interspecific mutualisms are often vulnerable to instability because low benefit : cost ratios can rapidly lead to extinction or to the conversion of mutualism to parasite–host or predator–prey interactions. We hypothesize that the evolutionary stability of mutualism can depend on how benefits and costs to one mutualist vary with the population density of its partner, and that stability can be maintained if a mutualist can influence demographic rates and regulate the population density of its partner. We test this hypothesis in a model of mutualism with key features of senita cactus (Pachycereus schottii) – senita moth (Upiga virescens) interactions, in which benefits of pollination and costs of larval seed consumption to plant fitness depend on pollinator density. We show that plants can maximize their fitness by allocating resources to the production of excess flowers at the expense of fruit. Fruit abortion resulting from excess flower production reduces pre–adult survival of the pollinating seed–consumer, and maintains its density beneath a threshold that would destabilize the mutualism. Such a strategy of excess flower production and fruit abortion is convergent and evolutionarily stable against invasion by cheater plants that produce few flowers and abort few to no fruit. This novel mechanism of achieving evolutionarily stable mutualism, namely interspecific population regulation, is qualitatively different from other mechanisms invoking partner choice or selective rewards, and may be a general process that helps to preserve mutualistic interactions in nature.

Evolutionary stability of mutualism: interspecific population regulation as an evolutionarily stable strategy.

PubMed

Holland, J Nathaniel; DeAngelis, Donald L; Schultz, Stewart T

2004-09-07

Interspecific mutualisms are often vulnerable to instability because low benefit : cost ratios can rapidly lead to extinction or to the conversion of mutualism to parasite-host or predator-prey interactions. We hypothesize that the evolutionary stability of mutualism can depend on how benefits and costs to one mutualist vary with the population density of its partner, and that stability can be maintained if a mutualist can influence demographic rates and regulate the population density of its partner. We test this hypothesis in a model of mutualism with key features of senita cactus (Pachycereus schottii)-senita moth (Upiga virescens) interactions, in which benefits of pollination and costs of larval seed consumption to plant fitness depend on pollinator density. We show that plants can maximize their fitness by allocating resources to the production of excess flowers at the expense of fruit. Fruit abortion resulting from excess flower production reduces pre-adult survival of the pollinating seed-consumer, and maintains its density beneath a threshold that would destabilize the mutualism. Such a strategy of excess flower production and fruit abortion is convergent and evolutionarily stable against invasion by cheater plants that produce few flowers and abort few to no fruit. This novel mechanism of achieving evolutionarily stable mutualism, namely interspecific population regulation, is qualitatively different from other mechanisms invoking partner choice or selective rewards, and may be a general process that helps to preserve mutualistic interactions in nature.

Structures of pyruvate kinases display evolutionarily divergent allosteric strategies

PubMed Central

Morgan, Hugh P.; Zhong, Wenhe; McNae, Iain W.; Michels, Paul A. M.; Fothergill-Gilmore, Linda A.; Walkinshaw, Malcolm D.

2014-01-01

The transition between the inactive T-state (apoenzyme) and active R-state (effector bound enzyme) of Trypanosoma cruzi pyruvate kinase (PYK) is accompanied by a symmetrical 8° rigid body rocking motion of the A- and C-domain cores in each of the four subunits, coupled with the formation of additional salt bridges across two of the four subunit interfaces. These salt bridges provide increased tetramer stability correlated with an enhanced specificity constant (kcat/S0.5). A detailed kinetic and structural comparison between the potential drug target PYKs from the pathogenic protists T. cruzi, T. brucei and Leishmania mexicana shows that their allosteric mechanism is conserved. By contrast, a structural comparison of trypanosomatid PYKs with the evolutionarily divergent PYKs of humans and of bacteria shows that they have adopted different allosteric strategies. The underlying principle in each case is to maximize (kcat/S0.5) by stabilizing and rigidifying the tetramer in an active R-state conformation. However, bacterial and mammalian PYKs have evolved alternative ways of locking the tetramers together. In contrast to the divergent allosteric mechanisms, the PYK active sites are highly conserved across species. Selective disruption of the varied allosteric mechanisms may therefore provide a useful approach for the design of species-specific inhibitors. PMID:26064527

Fragile X mental retardation protein has a unique, evolutionarily conserved neuronal function not shared with FXR1P or FXR2P

PubMed Central

Coffee, R. Lane; Tessier, Charles R.; Woodruff, Elvin A.; Broadie, Kendal

2010-01-01

SUMMARY Fragile X syndrome (FXS), resulting solely from the loss of function of the human fragile X mental retardation 1 (hFMR1) gene, is the most common heritable cause of mental retardation and autism disorders, with syndromic defects also in non-neuronal tissues. In addition, the human genome encodes two closely related hFMR1 paralogs: hFXR1 and hFXR2. The Drosophila genome, by contrast, encodes a single dFMR1 gene with close sequence homology to all three human genes. Drosophila that lack the dFMR1 gene (dfmr1 null mutants) recapitulate FXS-associated molecular, cellular and behavioral phenotypes, suggesting that FMR1 function has been conserved, albeit with specific functions possibly sub-served by the expanded human gene family. To test evolutionary conservation, we used tissue-targeted transgenic expression of all three human genes in the Drosophila disease model to investigate function at (1) molecular, (2) neuronal and (3) non-neuronal levels. In neurons, dfmr1 null mutants exhibit elevated protein levels that alter the central brain and neuromuscular junction (NMJ) synaptic architecture, including an increase in synapse area, branching and bouton numbers. Importantly, hFMR1 can, comparably to dFMR1, fully rescue both the molecular and cellular defects in neurons, whereas hFXR1 and hFXR2 provide absolutely no rescue. For non-neuronal requirements, we assayed male fecundity and testes function. dfmr1 null mutants are effectively sterile owing to disruption of the 9+2 microtubule organization in the sperm tail. Importantly, all three human genes fully and equally rescue mutant fecundity and spermatogenesis defects. These results indicate that FMR1 gene function is evolutionarily conserved in neural mechanisms and cannot be compensated by either FXR1 or FXR2, but that all three proteins can substitute for each other in non-neuronal requirements. We conclude that FMR1 has a neural-specific function that is distinct from its paralogs, and that the unique FMR1

Evolutionarily diverse SYP1 Qa-SNAREs jointly sustain pollen tube growth in Arabidopsis.

PubMed

Slane, Daniel; Reichardt, Ilka; El Kasmi, Farid; Bayer, Martin; Jürgens, Gerd

2017-11-01

Intracellular membrane fusion is effected by SNARE proteins that reside on adjacent membranes and form bridging trans-SNARE complexes. Qa-SNARE members of the Arabidopsis SYP1 family are involved in membrane fusion at the plasma membrane or during cell plate formation. Three SYP1 family members have been classified as pollen-specific as inferred from gene expression profiling studies, and two of them, SYP124 and SYP125, are confined to angiosperms. The SYP124 gene appears genetically unstable, whereas its sister gene SYP125 shows essentially no variation among Arabidopsis accessions. The third pollen-specific member SYP131 is sister to SYP132, which appears evolutionarily conserved in the plant lineage. Although evolutionarily diverse, the three SYP1 proteins are functionally overlapping in that only the triple mutant syp124 syp125 syp131 shows a specific and severe male gametophytic defect. While pollen development and germination appear normal, pollen tube growth is arrested during passage through the style. Our results suggest that angiosperm pollen tubes employ a combination of ancient and modern Qa-SNARE proteins to sustain their growth-promoting membrane dynamics during the reproductive process. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

An efficient algorithm for pairwise local alignment of protein interaction networks

DOE PAGES

Chen, Wenbin; Schmidt, Matthew; Tian, Wenhong; ...

2015-04-01

Recently, researchers seeking to understand, modify, and create beneficial traits in organisms have looked for evolutionarily conserved patterns of protein interactions. Their conservation likely means that the proteins of these conserved functional modules are important to the trait's expression. In this paper, we formulate the problem of identifying these conserved patterns as a graph optimization problem, and develop a fast heuristic algorithm for this problem. We compare the performance of our network alignment algorithm to that of the MaWISh algorithm [Koyuturk M, Kim Y, Topkara U, Subramaniam S, Szpankowski W, Grama A, Pairwise alignment of protein interaction networks, J Computmore » Biol 13(2): 182-199, 2006.], which bases its search algorithm on a related decision problem formulation. We find that our algorithm discovers conserved modules with a larger number of proteins in an order of magnitude less time. In conclusion, the protein sets found by our algorithm correspond to known conserved functional modules at comparable precision and recall rates as those produced by the MaWISh algorithm.« less

Genome-Wide Identification of Evolutionarily Conserved Alternative Splicing Events in Flowering Plants

PubMed Central

Chamala, Srikar; Feng, Guanqiao; Chavarro, Carolina; Barbazuk, W. Brad

2015-01-01

Alternative splicing (AS) plays important roles in many plant functions, but its conservation across the plant kingdom is not known. We describe a methodology to identify AS events and identify conserved AS events across large phylogenetic distances using RNA-Seq datasets. We applied this methodology to transcriptome data from nine angiosperms including Amborella, the single sister species to all other extant flowering plants. AS events within 40–70% of the expressed multi-exonic genes per species were found, 27,120 of which are conserved among two or more of the taxa studied. While many events are species specific, many others are shared across long evolutionary distances suggesting they have functional significance. Conservation of AS event data provides an estimate of the number of ancestral AS events present at each node of the tree representing the nine species studied. Furthermore, the presence or absence of AS isoforms between species with different whole genome duplication (WGD) histories provides the opportunity to examine the impact of WDG on AS potential. Examining AS in gene families identifies those with high rates of AS, and conservation can distinguish ancient events vs. recent or species specific adaptations. The MADS-box and SR protein families are found to represent families with low and high occurrences of AS, respectively, yet their AS events were likely present in the MRCA of angiosperms. PMID:25859541

The Evolutionarily Conserved Protein LAS1 Is Required for Pre-rRNA Processing at Both Ends of ITS2

PubMed Central

Schillewaert, Stéphanie; Wacheul, Ludivine; Lhomme, Frédéric

2012-01-01

Ribosome synthesis entails the formation of mature rRNAs from long precursor molecules, following a complex pre-rRNA processing pathway. Why the generation of mature rRNA ends is so complicated is unclear. Nor is it understood how pre-rRNA processing is coordinated at distant sites on pre-rRNA molecules. Here we characterized, in budding yeast and human cells, the evolutionarily conserved protein Las1. We found that, in both species, Las1 is required to process ITS2, which separates the 5.8S and 25S/28S rRNAs. In yeast, Las1 is required for pre-rRNA processing at both ends of ITS2. It is required for Rrp6-dependent formation of the 5.8S rRNA 3′ end and for Rat1-dependent formation of the 25S rRNA 5′ end. We further show that the Rat1-Rai1 5′-3′ exoribonuclease (exoRNase) complex functionally connects processing at both ends of the 5.8S rRNA. We suggest that pre-rRNA processing is coordinated at both ends of 5.8S rRNA and both ends of ITS2, which are brought together by pre-rRNA folding, by an RNA processing complex. Consistently, we note the conspicuous presence of ∼7- or 8-nucleotide extensions on both ends of 5.8S rRNA precursors and at the 5′ end of pre-25S RNAs suggestive of a protected spacer fragment of similar length. PMID:22083961

An Evolutionarily Conserved DOF-CONSTANS Module Controls Plant Photoperiodic Signaling.

PubMed

Lucas-Reina, Eva; Romero-Campero, Francisco J; Romero, José M; Valverde, Federico

2015-06-01

The response to daylength is a crucial process that evolved very early in plant evolution, entitling the early green eukaryote to predict seasonal variability and attune its physiological responses to the environment. The photoperiod responses evolved into the complex signaling pathways that govern the angiosperm floral transition today. The Chlamydomonas reinhardtii DNA-Binding with One Finger (CrDOF) gene controls transcription in a photoperiod-dependent manner, and its misexpression influences algal growth and viability. In short days, CrDOF enhances CrCO expression, a homolog of plant CONSTANS (CO), by direct binding to its promoter, while it reduces the expression of cell division genes in long days independently of CrCO. In Arabidopsis (Arabidopsis thaliana), transgenic plants overexpressing CrDOF show floral delay and reduced expression of the photoperiodic genes CO and FLOWERING LOCUS T. The conservation of the DOF-CO module during plant evolution could be an important clue to understanding diversification by the inheritance of conserved gene toolkits in key developmental programs. © 2015 American Society of Plant Biologists. All Rights Reserved.

In vivo screening reveals interactions between Drosophila Manf and genes involved in the mitochondria and the ubiquinone synthesis pathway.

PubMed

Lindström, Riitta; Lindholm, Päivi; Palgi, Mari; Saarma, Mart; Heino, Tapio I

2017-06-02

Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) and Cerebral Dopamine Neurotrophic Factor (CDNF) form an evolutionarily conserved family of neurotrophic factors. Orthologues for MANF/CDNF are the only neurotrophic factors as yet identified in invertebrates with conserved amino acid sequence. Previous studies indicate that mammalian MANF and CDNF support and protect brain dopaminergic system in non-cell-autonomous manner. However, MANF has also been shown to function intracellularly in the endoplasmic reticulum. To date, the knowledge on the interacting partners of MANF/CDNF and signaling pathways they activate is rudimentary. Here, we have employed the Drosophila genetics to screen for potential interaction partners of Drosophila Manf (DmManf) in vivo. We first show that DmManf plays a role in the development of Drosophila wing. We exploited this function by using Drosophila UAS-RNAi lines and discovered novel genetic interactions of DmManf with genes known to function in the mitochondria. We also found evidence of an interaction between DmManf and the Drosophila homologue encoding Ku70, the closest structural homologue of SAP domain of mammalian MANF. In addition to the previously known functions of MANF/CDNF protein family, DmManf also interacts with mitochondria-related genes. Our data supports the functional importance of these evolutionarily significant proteins and provides new insights for the future studies.

Evolutionarily conserved coding properties of auditory neurons across grasshopper species

PubMed Central

Neuhofer, Daniela; Wohlgemuth, Sandra; Stumpner, Andreas; Ronacher, Bernhard

2008-01-01

We investigated encoding properties of identified auditory interneurons in two not closely related grasshopper species (Acrididae). The neurons can be homologized on the basis of their similar morphologies and physiologies. As test stimuli, we used the species-specific stridulation signals of Chorthippus biguttulus, which evidently are not relevant for the other species, Locusta migratoria. We recorded spike trains produced in response to these signals from several neuron types at the first levels of the auditory pathway in both species. Using a spike train metric to quantify differences between neuronal responses, we found a high similarity in the responses of homologous neurons: interspecific differences between the responses of homologous neurons in the two species were not significantly larger than intraspecific differences (between several specimens of a neuron in one species). These results suggest that the elements of the thoracic auditory pathway have been strongly conserved during the evolutionary divergence of these species. According to the ‘efficient coding’ hypothesis, an adaptation of the thoracic auditory pathway to the specific needs of acoustic communication could be expected. We conclude that there must have been stabilizing selective forces at work that conserved coding characteristics and prevented such an adaptation. PMID:18505715

Dissociation of Paramyxovirus Interferon Evasion Activities: Universal and Virus-Specific Requirements for Conserved V Protein Amino Acids in MDA5 Interference ▿

PubMed Central

Ramachandran, Aparna; Horvath, Curt M.

2010-01-01

The V protein of the paramyxovirus subfamily Paramyxovirinae is an important virulence factor that can interfere with host innate immunity by inactivating the cytosolic pathogen recognition receptor MDA5. This interference is a result of a protein-protein interaction between the highly conserved carboxyl-terminal domain of the V protein and the helicase domain of MDA5. The V protein C-terminal domain (CTD) is an evolutionarily conserved 49- to 68-amino-acid region that coordinates two zinc atoms per protein chain. Site-directed mutagenesis of conserved residues in the V protein CTD has revealed both universal and virus-specific requirements for zinc coordination in MDA5 engagement and has also identified other conserved residues as critical for MDA5 interaction and interference. Mutation of these residues produces V proteins that are specifically defective for MDA5 interference and not impaired in targeting STAT1 for proteasomal degradation via the VDC ubiquitin ligase complex. Results demonstrate that mutation of conserved charged residues in the V proteins of Nipah virus, measles virus, and mumps virus also abolishes MDA5 interaction. These findings clearly define molecular determinants for MDA5 inhibition by the paramyxovirus V proteins. PMID:20719949

An Evolutionarily Conserved SoxB-Hdac2 Crosstalk Regulates Neurogenesis in a Cnidarian.

PubMed

Flici, Hakima; Schnitzler, Christine E; Millane, R Cathriona; Govinden, Graham; Houlihan, Amy; Boomkamp, Stephanie D; Shen, Sanbing; Baxevanis, Andreas D; Frank, Uri

2017-02-07

SoxB transcription factors and histone deacetylases (HDACs) are each major players in the regulation of neurogenesis, but a functional link between them has not been previously demonstrated. Here, we show that SoxB2 and Hdac2 act together to regulate neurogenesis in the cnidarian Hydractinia echinata during tissue homeostasis and head regeneration. We find that misexpression of SoxB genes modifies the number of neural cells in all life stages and interferes with head regeneration. Hdac2 was co-expressed with SoxB2, and its downregulation phenocopied SoxB2 knockdown. We also show that SoxB2 and Hdac2 promote each other's transcript levels, but Hdac2 counteracts this amplification cycle by deacetylating and destabilizing SoxB2 protein. Finally, we present evidence for conservation of these interactions in human neural progenitors. We hypothesize that crosstalk between SoxB transcription factors and Hdac2 is an ancient feature of metazoan neurogenesis and functions to stabilize the correct levels of these multifunctional proteins. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Global priorities for conserving the evolutionary history of sharks, rays and chimaeras.

PubMed

Stein, R William; Mull, Christopher G; Kuhn, Tyler S; Aschliman, Neil C; Davidson, Lindsay N K; Joy, Jeffrey B; Smith, Gordon J; Dulvy, Nicholas K; Mooers, Arne O

2018-02-01

In an era of accelerated biodiversity loss and limited conservation resources, systematic prioritization of species and places is essential. In terrestrial vertebrates, evolutionary distinctness has been used to identify species and locations that embody the greatest share of evolutionary history. We estimate evolutionary distinctness for a large marine vertebrate radiation on a dated taxon-complete tree for all 1,192 chondrichthyan fishes (sharks, rays and chimaeras) by augmenting a new 610-species molecular phylogeny using taxonomic constraints. Chondrichthyans are by far the most evolutionarily distinct of all major radiations of jawed vertebrates-the average species embodies 26 million years of unique evolutionary history. With this metric, we identify 21 countries with the highest richness, endemism and evolutionary distinctness of threatened species as targets for conservation prioritization. On average, threatened chondrichthyans are more evolutionarily distinct-further motivating improved conservation, fisheries management and trade regulation to avoid significant pruning of the chondrichthyan tree of life.

Conserved mRNA-binding proteomes in eukaryotic organisms.

PubMed

Matia-González, Ana M; Laing, Emma E; Gerber, André P

2015-12-01

RNA-binding proteins (RBPs) are essential for post-transcriptional regulation of gene expression. Recent high-throughput screens have dramatically increased the number of experimentally identified RBPs; however, comprehensive identification of RBPs within living organisms is elusive. Here we describe the repertoire of 765 and 594 proteins that reproducibly interact with polyadenylated mRNAs in Saccharomyces cerevisiae and Caenorhabditis elegans, respectively. Furthermore, we report the differential association of mRNA-binding proteins (mRPBs) upon induction of apoptosis in C. elegans L4-stage larvae. Strikingly, most proteins composing mRBPomes, including components of early metabolic pathways and the proteasome, are evolutionarily conserved between yeast and C. elegans. We speculate, on the basis of our evidence that glycolytic enzymes bind distinct glycolytic mRNAs, that enzyme-mRNA interactions relate to an ancient mechanism for post-transcriptional coordination of metabolic pathways that perhaps was established during the transition from the early 'RNA world' to the 'protein world'.

Conservation of hot regions in protein-protein interaction in evolution.

PubMed

Hu, Jing; Li, Jiarui; Chen, Nansheng; Zhang, Xiaolong

2016-11-01

The hot regions of protein-protein interactions refer to the active area which formed by those most important residues to protein combination process. With the research development on protein interactions, lots of predicted hot regions can be discovered efficiently by intelligent computing methods, while performing biology experiments to verify each every prediction is hardly to be done due to the time-cost and the complexity of the experiment. This study based on the research of hot spot residue conservations, the proposed method is used to verify authenticity of predicted hot regions that using machine learning algorithm combined with protein's biological features and sequence conservation, though multiple sequence alignment, module substitute matrix and sequence similarity to create conservation scoring algorithm, and then using threshold module to verify the conservation tendency of hot regions in evolution. This research work gives an effective method to verify predicted hot regions in protein-protein interactions, which also provides a useful way to deeply investigate the functional activities of protein hot regions. Copyright © 2016. Published by Elsevier Inc.

Body weight-dependent troponin T alternative splicing is evolutionarily conserved from insects to mammals and is partially impaired in skeletal muscle of obese rats.

PubMed

Schilder, Rudolf J; Kimball, Scot R; Marden, James H; Jefferson, Leonard S

2011-05-01

Do animals know at a physiological level how much they weigh, and, if so, do they make homeostatic adjustments in response to changes in body weight? Skeletal muscle is a likely tissue for such plasticity, as weight-bearing muscles receive mechanical feedback regarding body weight and consume ATP in order to generate forces sufficient to counteract gravity. Using rats, we examined how variation in body weight affected alternative splicing of fast skeletal muscle troponin T (Tnnt3), a component of the thin filament that regulates the actin-myosin interaction during contraction and modulates force output. In response to normal growth and experimental body weight increases, alternative splicing of Tnnt3 in rat gastrocnemius muscle was adjusted in a quantitative fashion. The response depended on weight per se, as externally attached loads had the same effect as an equal change in actual body weight. Examining the association between Tnnt3 alternative splicing and ATP consumption rate, we found that the Tnnt3 splice form profile had a significant association with nocturnal energy expenditure, independently of effects of weight. For a subset of the Tnnt3 splice forms, obese Zucker rats failed to make the same adjustments; that is, they did not show the same relationship between body weight and the relative abundance of five Tnnt3 β splice forms (i.e. Tnnt3 β2-β5 and β8), four of which showed significant effects on nocturnal energy expenditure in Sprague-Dawley rats. Heavier obese Zucker rats displayed certain splice form relative abundances (e.g. Tnnt3 β3) characteristic of much lighter, lean animals, resulting in a mismatch between body weight and muscle molecular composition. Consequently, we suggest that body weight-inappropriate skeletal muscle Tnnt3 expression in obesity is a candidate mechanism for muscle weakness and reduced mobility. Weight-dependent quantitative variation in Tnnt3 alternative splicing appears to be an evolutionarily conserved feature of

Violation of an Evolutionarily Conserved Immunoglobulin Diversity Gene Sequence Preference Promotes Production of dsDNA-Specific IgG Antibodies

PubMed Central

Silva-Sanchez, Aaron; Liu, Cun Ren; Vale, Andre M.; Khass, Mohamed; Kapoor, Pratibha; Elgavish, Ada; Ivanov, Ivaylo I.; Ippolito, Gregory C.; Schelonka, Robert L.; Schoeb, Trenton R.; Burrows, Peter D.; Schroeder, Harry W.

2015-01-01

Variability in the developing antibody repertoire is focused on the third complementarity determining region of the H chain (CDR-H3), which lies at the center of the antigen binding site where it often plays a decisive role in antigen binding. The power of VDJ recombination and N nucleotide addition has led to the common conception that the sequence of CDR-H3 is unrestricted in its variability and random in its composition. Under this view, the immune response is solely controlled by somatic positive and negative clonal selection mechanisms that act on individual B cells to promote production of protective antibodies and prevent the production of self-reactive antibodies. This concept of a repertoire of random antigen binding sites is inconsistent with the observation that diversity (DH) gene segment sequence content by reading frame (RF) is evolutionarily conserved, creating biases in the prevalence and distribution of individual amino acids in CDR-H3. For example, arginine, which is often found in the CDR-H3 of dsDNA binding autoantibodies, is under-represented in the commonly used DH RFs rearranged by deletion, but is a frequent component of rarely used inverted RF1 (iRF1), which is rearranged by inversion. To determine the effect of altering this germline bias in DH gene segment sequence on autoantibody production, we generated mice that by genetic manipulation are forced to utilize an iRF1 sequence encoding two arginines. Over a one year period we collected serial serum samples from these unimmunized, specific pathogen-free mice and found that more than one-fifth of them contained elevated levels of dsDNA-binding IgG, but not IgM; whereas mice with a wild type DH sequence did not. Thus, germline bias against the use of arginine enriched DH sequence helps to reduce the likelihood of producing self-reactive antibodies. PMID:25706374

Evolutionarily Conserved nodE, nodO, T1SS, and Hydrogenase System in Rhizobia of Astragalus membranaceus and Caragana intermedia.

PubMed

Yan, Hui; Xie, Jian Bo; Ji, Zhao Jun; Yuan, Na; Tian, Chang Fu; Ji, Shou Kun; Wu, Zhong Yu; Zhong, Liang; Chen, Wen Xin; Du, Zheng Lin; Wang, En Tao; Chen, Wen Feng

2017-01-01

Mesorhizobium species are the main microsymbionts associated with the medicinal or sand-fixation plants Astragalus membranaceus and Caragana intermedia (AC) in temperate regions of China, while all the Mesorhizobium strains isolated from each of these plants could nodulate both of them. However, Rhizobium yanglingense strain CCBAU01603 could nodulate AC plants and it's a high efficiency symbiotic and competitive strain with Caragana . Therefore, the common features shared by these symbiotic rhizobia in genera of Mesorhizobium and Rhizobium still remained undiscovered. In order to study the genomic background influencing the host preference of these AC symbiotic strains, the whole genomes of two ( M. silamurunense CCBAU01550, M. silamurunense CCBAU45272) and five representative strains ( M. septentrionale CCBAU01583, M. amorphae CCBAU01570, M. caraganae CCBAU01502, M. temperatum CCBAU01399, and R. yanglingense CCBAU01603) originally isolated from AC plants were sequenced, respectively. As results, type III secretion systems (T3SS) of AC rhizobia evolved in an irregular pattern, while an evolutionarily specific region including nodE, nodO , T1SS, and a hydrogenase system was detected to be conserved in all these AC rhizobia. Moreover, nodO was verified to be prevalently distributed in other AC rhizobia and was presumed as a factor affecting the nodule formation process. In conclusion, this research interpreted the multifactorial features of the AC rhizobia that may be associated with their host specificity at cross-nodulation group, including nodE, nodZ , T1SS as the possible main determinants; and nodO , hydrogenase system, and T3SS as factors regulating the bacteroid formation or nitrogen fixation efficiency.

Effects of threat management interactions on conservation priorities.

PubMed

Auerbach, Nancy A; Wilson, Kerrie A; Tulloch, Ayesha I T; Rhodes, Jonathan R; Hanson, Jeffrey O; Possingham, Hugh P

2015-12-01

Decisions need to be made about which biodiversity management actions are undertaken to mitigate threats and about where these actions are implemented. However, management actions can interact; that is, the cost, benefit, and feasibility of one action can change when another action is undertaken. There is little guidance on how to explicitly and efficiently prioritize management for multiple threats, including deciding where to act. Integrated management could focus on one management action to abate a dominant threat or on a strategy comprising multiple actions to abate multiple threats. Furthermore management could be undertaken at sites that are in close proximity to reduce costs. We used cost-effectiveness analysis to prioritize investments in fire management, controlling invasive predators, and reducing grazing pressure in a bio-diverse region of southeastern Queensland, Australia. We compared outcomes of 5 management approaches based on different assumptions about interactions and quantified how investment needed, benefits expected, and the locations prioritized for implementation differed when interactions were taken into account. Managing for interactions altered decisions about where to invest and in which actions to invest and had the potential to deliver increased investment efficiency. Differences in high priority locations and actions were greatest between the approaches when we made different assumptions about how management actions deliver benefits through threat abatement: either all threats must be managed to conserve species or only one management action may be required. Threatened species management that does not consider interactions between actions may result in misplaced investments or misguided expectations of the effort required to mitigate threats to species. © 2015 The Authors. Conservation Biology published by Wiley Periodicals, Inc., on behalf of Society for Conservation Biology.

Evolutionarily conserved heterogeneous nuclear ribonucleoprotein (hnRNP) A/B proteins functionally interact with human and Drosophila TAR DNA-binding protein 43 (TDP-43).

PubMed

Romano, Maurizio; Buratti, Emanuele; Romano, Giulia; Klima, Raffaella; Del Bel Belluz, Lisa; Stuani, Cristiana; Baralle, Francisco; Feiguin, Fabian

2014-03-07

Human TDP-43 represents the main component of neuronal inclusions found in patients with neurodegenerative diseases, especially frontotemporal lobar degeneration and amyotrophic lateral sclerosis. In vitro and in vivo studies have shown that the TAR DNA-binding protein 43 (TDP-43) Drosophila ortholog (TBPH) can biochemically and functionally overlap the properties of the human factor. The recent direct implication of the human heterogeneous nuclear ribonucleoproteins (hnRNPs) A2B1 and A1, known TDP-43 partners, in the pathogenesis of multisystem proteinopathy and amyotrophic lateral sclerosis supports the hypothesis that the physical and functional interplay between TDP-43 and hnRNP A/B orthologs might play a crucial role in the pathogenesis of neurodegenerative diseases. To test this hypothesis and further validate the fly system as a useful model to study this type of diseases, we have now characterized human TDP-43 and Drosophila TBPH similarity in terms of protein-protein interaction pathways. In this work we show that TDP-43 and TBPH share the ability to associate in vitro with Hrp38/Hrb98DE/CG9983, the fruit fly ortholog of the human hnRNP A1/A2 factors. Interestingly, the protein regions of TDP-43 and Hrp38 responsible for reciprocal interactions are conserved through evolution. Functionally, experiments in HeLa cells demonstrate that TDP-43 is necessary for the inhibitory activity of Hrp38 on splicing. Finally, Drosophila in vivo studies show that Hrp38 deficiency produces locomotive defects and life span shortening in TDP-43 with and without animals. These results suggest that hnRNP protein levels can play a modulatory role on TDP-43 functions.

The drug target genes show higher evolutionary conservation than non-target genes.

PubMed

Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

2016-01-26

Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

Evolutionarily conserved intracellular gate of voltage-dependent sodium channels

NASA Astrophysics Data System (ADS)

Oelstrom, Kevin; Goldschen-Ohm, Marcel P.; Holmgren, Miguel; Chanda, Baron

2014-03-01

Members of the voltage-gated ion channel superfamily (VGIC) regulate ion flux and generate electrical signals in excitable cells by opening and closing pore gates. The location of the gate in voltage-gated sodium channels, a founding member of this superfamily, remains unresolved. Here we explore the chemical modification rates of introduced cysteines along the S6 helix of domain IV in an inactivation-removed background. We find that state-dependent accessibility is demarcated by an S6 hydrophobic residue; substituted cysteines above this site are not modified by charged thiol reagents when the channel is closed. These accessibilities are consistent with those inferred from open- and closed-state structures of prokaryotic sodium channels. Our findings suggest that an intracellular gate composed of a ring of hydrophobic residues is not only responsible for regulating access to the pore of sodium channels, but is also a conserved feature within canonical members of the VGIC superfamily.

Nuclear Pore Complexes: Global Conservation and Local Variation.

PubMed

Holzer, Guillaume; Antonin, Wolfram

2018-06-04

Nuclear pore complexes are the transport gates to the nucleus. Most proteins forming these huge complexes are evolutionarily conserved, as is the eightfold symmetry of these complexes. A new study reporting the structure of the yeast nuclear pore complex now shows striking differences from its human counterpart. Copyright © 2018 Elsevier Ltd. All rights reserved.

Case study of building of conservation coalitions to conserve ecological interactions.

PubMed

Chen, Gao; Luo, Shihong; Mei, Nianshu; Shen, Dingfang; Sun, Weibang

2015-12-01

We engaged experts in various fields of study (pollination ecology, chemical ecology, and ethnobotany), invited community participation, and provided environmental education in an effort to conserve an endangered birthwort (Aristolochia delavayi) and a vulnerable pipevine swallowtail (Byasa daemonius). Scientists studied the uptake and sequestration of the secondary metabolites aristolochic acids from A. delavayi leaves by different stages of pipevine swallowtail as a defense mechanism; low fruit set of the myophilous A. delavayi due to pollinator limitation; and the emission of chemical signals that attract parasitic wasps by the prepupae of B. daemonius. The results of these studies were part of an education program delivered by personnel of non-governmental organizations. The program was devised to deliver information to the public about the health risks of consuming A. delavayi individuals (aristolochic-acid-associated cancers) and to establish a bridge between the public and scientific research. Following delivery of the program, the behavior of residents changed considerably. Community residents were involved in management activities, including participation in a program to promote understanding of ecological interactions between A. delavayi and B. daemonius; designing an in situ conservation site; monitoring A. delavayi and B. daemonius individuals; and promoting the natural fruit set of A. delavayi by scattering animal excrement to attract fly pollinators. The integration of scientific information and community participation appears to have resulted in an increase in abundance of threatened A. delavayi and B. daemonius populations. We believe the involvement of local people in conservation is necessary for successful species conservation. © 2015 Society for Conservation Biology.

Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes

PubMed Central

Wuttke, Daniel; Connor, Richard; Vora, Chintan; Craig, Thomas; Li, Yang; Wood, Shona; Vasieva, Olga; Shmookler Reis, Robert; Tang, Fusheng; de Magalhães, João Pedro

2012-01-01

Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR. We called these DR–essential genes and identified more than 100 in model organisms such as yeast, worms, flies, and mice. In order for other researchers to benefit from this first curated list of genes essential for DR, we established an online database called GenDR (http://genomics.senescence.info/diet/). To dissect the interactions of DR–essential genes and discover the underlying lifespan-extending mechanisms, we then used a variety of network and systems biology approaches to analyze the gene network of DR. We show that DR–essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR–essential genes. In budding yeast, we predicted nine genes related to vacuolar functions; we show experimentally that mutations deleting eight of those genes prevent the life-extending effects of DR. Three of these mutants (OPT2, FRE6, and RCR2) had extended lifespan under ad libitum, indicating that the lack of further longevity under DR is not caused by a general compromise of fitness. These results demonstrate how network analyses of DR using GenDR can be used to make phenotypically relevant predictions. Moreover, gene-regulatory circuits reveal that the DR–induced transcriptional signature in yeast involves nutrient-sensing, stress responses and meiotic transcription factors. Finally, comparing the influence of gene expression changes during DR on the interactomes of multiple

IAA-Ala Resistant3, an Evolutionarily Conserved Target of miR167, Mediates Arabidopsis Root Architecture Changes during High Osmotic Stress[W

PubMed Central

Kinoshita, Natsuko; Wang, Huan; Kasahara, Hiroyuki; Liu, Jun; MacPherson, Cameron; Machida, Yasunori; Kamiya, Yuji; Hannah, Matthew A.; Chua, Nam-Hai

2012-01-01

The functions of microRNAs and their target mRNAs in Arabidopsis thaliana development have been widely documented; however, roles of stress-responsive microRNAs and their targets are not as well understood. Using small RNA deep sequencing and ATH1 microarrays to profile mRNAs, we identified IAA-Ala Resistant3 (IAR3) as a new target of miR167a. As expected, IAR3 mRNA was cleaved at the miR167a complementary site and under high osmotic stress miR167a levels decreased, whereas IAR3 mRNA levels increased. IAR3 hydrolyzes an inactive form of auxin (indole-3-acetic acid [IAA]-alanine) and releases bioactive auxin (IAA), a central phytohormone for root development. In contrast with the wild type, iar3 mutants accumulated reduced IAA levels and did not display high osmotic stress–induced root architecture changes. Transgenic plants expressing a cleavage-resistant form of IAR3 mRNA accumulated high levels of IAR3 mRNAs and showed increased lateral root development compared with transgenic plants expressing wild-type IAR3. Expression of an inducible noncoding RNA to sequester miR167a by target mimicry led to an increase in IAR3 mRNA levels, further confirming the inverse relationship between the two partners. Sequence comparison revealed the miR167 target site on IAR3 mRNA is conserved in evolutionarily distant plant species. Finally, we showed that IAR3 is required for drought tolerance. PMID:22960911

The evolutionarily conserved transcription factor PRDM12 controls sensory neuron development and pain perception.

PubMed

Nagy, Vanja; Cole, Tiffany; Van Campenhout, Claude; Khoung, Thang M; Leung, Calvin; Vermeiren, Simon; Novatchkova, Maria; Wenzel, Daniel; Cikes, Domagoj; Polyansky, Anton A; Kozieradzki, Ivona; Meixner, Arabella; Bellefroid, Eric J; Neely, G Gregory; Penninger, Josef M

2015-01-01

PR homology domain-containing member 12 (PRDM12) belongs to a family of conserved transcription factors implicated in cell fate decisions. Here we show that PRDM12 is a key regulator of sensory neuronal specification in Xenopus. Modeling of human PRDM12 mutations that cause hereditary sensory and autonomic neuropathy (HSAN) revealed remarkable conservation of the mutated residues in evolution. Expression of wild-type human PRDM12 in Xenopus induced the expression of sensory neuronal markers, which was reduced using various human PRDM12 mutants. In Drosophila, we identified Hamlet as the functional PRDM12 homolog that controls nociceptive behavior in sensory neurons. Furthermore, expression analysis of human patient fibroblasts with PRDM12 mutations uncovered possible downstream target genes. Knockdown of several of these target genes including thyrotropin-releasing hormone degrading enzyme (TRHDE) in Drosophila sensory neurons resulted in altered cellular morphology and impaired nociception. These data show that PRDM12 and its functional fly homolog Hamlet are evolutionary conserved master regulators of sensory neuronal specification and play a critical role in pain perception. Our data also uncover novel pathways in multiple species that regulate evolutionary conserved nociception.

An Evolutionarily Conserved DOF-CONSTANS Module Controls Plant Photoperiodic Signaling1[OPEN

PubMed Central

2015-01-01

The response to daylength is a crucial process that evolved very early in plant evolution, entitling the early green eukaryote to predict seasonal variability and attune its physiological responses to the environment. The photoperiod responses evolved into the complex signaling pathways that govern the angiosperm floral transition today. The Chlamydomonas reinhardtii DNA-Binding with One Finger (CrDOF) gene controls transcription in a photoperiod-dependent manner, and its misexpression influences algal growth and viability. In short days, CrDOF enhances CrCO expression, a homolog of plant CONSTANS (CO), by direct binding to its promoter, while it reduces the expression of cell division genes in long days independently of CrCO. In Arabidopsis (Arabidopsis thaliana), transgenic plants overexpressing CrDOF show floral delay and reduced expression of the photoperiodic genes CO and FLOWERING LOCUS T. The conservation of the DOF-CO module during plant evolution could be an important clue to understanding diversification by the inheritance of conserved gene toolkits in key developmental programs. PMID:25897001

Conservation and diversification of Msx protein in metazoan evolution.

PubMed

Takahashi, Hirokazu; Kamiya, Akiko; Ishiguro, Akira; Suzuki, Atsushi C; Saitou, Naruya; Toyoda, Atsushi; Aruga, Jun

2008-01-01

Msx (/msh) family genes encode homeodomain (HD) proteins that control ontogeny in many animal species. We compared the structures of Msx genes from a wide range of Metazoa (Porifera, Cnidaria, Nematoda, Arthropoda, Tardigrada, Platyhelminthes, Mollusca, Brachiopoda, Annelida, Echiura, Echinodermata, Hemichordata, and Chordata) to gain an understanding of the role of these genes in phylogeny. Exon-intron boundary analysis suggested that the position of the intron located N-terminally to the HDs was widely conserved in all the genes examined, including those of cnidarians. Amino acid (aa) sequence comparison revealed 3 new evolutionarily conserved domains, as well as very strong conservation of the HDs. Two of the three domains were associated with Groucho-like protein binding in both a vertebrate and a cnidarian Msx homolog, suggesting that the interaction between Groucho-like proteins and Msx proteins was established in eumetazoan ancestors. Pairwise comparison among the collected HDs and their C-flanking aa sequences revealed that the degree of sequence conservation varied depending on the animal taxa from which the sequences were derived. Highly conserved Msx genes were identified in the Vertebrata, Cephalochordata, Hemichordata, Echinodermata, Mollusca, Brachiopoda, and Anthozoa. The wide distribution of the conserved sequences in the animal phylogenetic tree suggested that metazoan ancestors had already acquired a set of conserved domains of the current Msx family genes. Interestingly, although strongly conserved sequences were recovered from the Vertebrata, Cephalochordata, and Anthozoa, the sequences from the Urochordata and Hydrozoa showed weak conservation. Because the Vertebrata-Cephalochordata-Urochordata and Anthozoa-Hydrozoa represent sister groups in the Chordata and Cnidaria, respectively, Msx sequence diversification may have occurred differentially in the course of evolution. We speculate that selective loss of the conserved domains in Msx family

The binary protein-protein interaction landscape of Escherichia coli

PubMed Central

Rajagopala, Seesandra V.; Vlasblom, James; Arnold, Roland; Franca-Koh, Jonathan; Pakala, Suman B.; Phanse, Sadhna; Ceol, Arnaud; Häuser, Roman; Siszler, Gabriella; Wuchty, Stefan; Emili, Andrew; Babu, Mohan; Aloy, Patrick; Pieper, Rembert; Uetz, Peter

2014-01-01

Efforts to map the Escherichia coli interactome have identified several hundred macromolecular complexes, but direct binary protein-protein interactions (PPIs) have not been surveyed on a large scale. Here we performed yeast two-hybrid screens of 3,305 baits against 3,606 preys (~70% of the E. coli proteome) in duplicate to generate a map of 2,234 interactions, approximately doubling the number of known binary PPIs in E. coli. Integration of binary PPIs and genetic interactions revealed functional dependencies among components involved in cellular processes, including envelope integrity, flagellum assembly and protein quality control. Many of the binary interactions that could be mapped within multi-protein complexes were informative regarding internal topology and indicated that interactions within complexes are significantly more conserved than those interactions connecting different complexes. This resource will be useful for inferring bacterial gene function and provides a draft reference of the basic physical wiring network of this evolutionarily significant model microbe. PMID:24561554

Indole: An evolutionarily conserved influencer of behavior across kingdoms

USDA-ARS?s Scientific Manuscript database

Indole, which is produced from the breakdown of the essential amino acid tryptophan, is a key environmental cue that is used by many organisms. But why is its use so ubiquitous, and how does it function to modulate interactions among such diverse organisms? Here, we review the literature to addres...

Evolution and Conservation of Plant NLR Functions

PubMed Central

Jacob, Florence; Vernaldi, Saskia; Maekawa, Takaki

2013-01-01

In plants and animals, nucleotide-binding domain and leucine-rich repeats (NLR)-containing proteins play pivotal roles in innate immunity. Despite their similar biological functions and protein architecture, comparative genome-wide analyses of NLRs and genes encoding NLR-like proteins suggest that plant and animal NLRs have independently arisen in evolution. Furthermore, the demonstration of interfamily transfer of plant NLR functions from their original species to phylogenetically distant species implies evolutionary conservation of the underlying immune principle across plant taxonomy. In this review we discuss plant NLR evolution and summarize recent insights into plant NLR-signaling mechanisms, which might constitute evolutionarily conserved NLR-mediated immune mechanisms. PMID:24093022

Quantitative functional characterization of conserved molecular interactions in the active site of mannitol 2-dehydrogenase

PubMed Central

Lucas, James E; Siegel, Justin B

2015-01-01

Enzyme active site residues are often highly conserved, indicating a significant role in function. In this study we quantitate the functional contribution for all conserved molecular interactions occurring within a Michaelis complex for mannitol 2-dehydrogenase derived from Pseudomonas fluorescens (pfMDH). Through systematic mutagenesis of active site residues, we reveal that the molecular interactions in pfMDH mediated by highly conserved residues not directly involved in reaction chemistry can be as important to catalysis as those directly involved in the reaction chemistry. This quantitative analysis of the molecular interactions within the pfMDH active site provides direct insight into the functional role of each molecular interaction, several of which were unexpected based on canonical sequence conservation and structural analyses. PMID:25752240

Conservation implications of anthropogenic impacts on visual communication and camouflage.

PubMed

Delhey, Kaspar; Peters, Anne

2017-02-01

Anthropogenic environmental impacts can disrupt the sensory environment of animals and affect important processes from mate choice to predator avoidance. Currently, these effects are best understood for auditory and chemosensory modalities, and recent reviews highlight their importance for conservation. We examined how anthropogenic changes to the visual environment (ambient light, transmission, and backgrounds) affect visual communication and camouflage and considered the implications of these effects for conservation. Human changes to the visual environment can increase predation risk by affecting camouflage effectiveness, lead to maladaptive patterns of mate choice, and disrupt mutualistic interactions between pollinators and plants. Implications for conservation are particularly evident for disrupted camouflage due to its tight links with survival. The conservation importance of impaired visual communication is less documented. The effects of anthropogenic changes on visual communication and camouflage may be severe when they affect critical processes such as pollination or species recognition. However, when impaired mate choice does not lead to hybridization, the conservation consequences are less clear. We suggest that the demographic effects of human impacts on visual communication and camouflage will be particularly strong when human-induced modifications to the visual environment are evolutionarily novel (i.e., very different from natural variation); affected species and populations have low levels of intraspecific (genotypic and phenotypic) variation and behavioral, sensory, or physiological plasticity; and the processes affected are directly related to survival (camouflage), species recognition, or number of offspring produced, rather than offspring quality or attractiveness. Our findings suggest that anthropogenic effects on the visual environment may be of similar importance relative to conservation as anthropogenic effects on other sensory modalities

A predicted protein interactome identifies conserved global networks and disease resistance subnetworks in maize

PubMed Central

Musungu, Bryan; Bhatnagar, Deepak; Brown, Robert L.; Fakhoury, Ahmad M.; Geisler, Matt

2015-01-01

Interactomes are genome-wide roadmaps of protein-protein interactions. They have been produced for humans, yeast, the fruit fly, and Arabidopsis thaliana and have become invaluable tools for generating and testing hypotheses. A predicted interactome for Zea mays (PiZeaM) is presented here as an aid to the research community for this valuable crop species. PiZeaM was built using a proven method of interologs (interacting orthologs) that were identified using both one-to-one and many-to-many orthology between genomes of maize and reference species. Where both maize orthologs occurred for an experimentally determined interaction in the reference species, we predicted a likely interaction in maize. A total of 49,026 unique interactions for 6004 maize proteins were predicted. These interactions are enriched for processes that are evolutionarily conserved, but include many otherwise poorly annotated proteins in maize. The predicted maize interactions were further analyzed by comparing annotation of interacting proteins, including different layers of ontology. A map of pairwise gene co-expression was also generated and compared to predicted interactions. Two global subnetworks were constructed for highly conserved interactions. These subnetworks showed clear clustering of proteins by function. Another subnetwork was created for disease response using a bait and prey strategy to capture interacting partners for proteins that respond to other organisms. Closer examination of this subnetwork revealed the connectivity between biotic and abiotic hormone stress pathways. We believe PiZeaM will provide a useful tool for the prediction of protein function and analysis of pathways for Z. mays researchers and is presented in this paper as a reference tool for the exploration of protein interactions in maize. PMID:26089837

An evolutionarily conserved gene family encodes proton-selective ion channels.

PubMed

Tu, Yu-Hsiang; Cooper, Alexander J; Teng, Bochuan; Chang, Rui B; Artiga, Daniel J; Turner, Heather N; Mulhall, Eric M; Ye, Wenlei; Smith, Andrew D; Liman, Emily R

2018-03-02

Ion channels form the basis for cellular electrical signaling. Despite the scores of genetically identified ion channels selective for other monatomic ions, only one type of proton-selective ion channel has been found in eukaryotic cells. By comparative transcriptome analysis of mouse taste receptor cells, we identified Otopetrin1 (OTOP1), a protein required for development of gravity-sensing otoconia in the vestibular system, as forming a proton-selective ion channel. We found that murine OTOP1 is enriched in acid-detecting taste receptor cells and is required for their zinc-sensitive proton conductance. Two related murine genes, Otop2 and Otop3 , and a Drosophila ortholog also encode proton channels. Evolutionary conservation of the gene family and its widespread tissue distribution suggest a broad role for proton channels in physiology and pathophysiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

The conserved role of Krox-20 in directing Hox gene expression during vertebrate hindbrain segmentation.

PubMed

Nonchev, S; Maconochie, M; Vesque, C; Aparicio, S; Ariza-McNaughton, L; Manzanares, M; Maruthainar, K; Kuroiwa, A; Brenner, S; Charnay, P; Krumlauf, R

1996-09-03

Transient segmentation in the hindbrain is a fundamental morphogenetic phenomenon in the vertebrate embryo, and the restricted expression of subsets of Hox genes in the developing rhombomeric units and their derivatives is linked with regional specification. Here we show that patterning of the vertebrate hindbrain involves the direct upregulation of the chicken and pufferfish group 2 paralogous genes, Hoxb-2 and Hoxa-2, in rhombomeres 3 and 5 (r3 and r5) by the zinc finger gene Krox-20. We identified evolutionarily conserved r3/r5 enhancers that contain high affinity Krox-20. binding sites capable of mediating transactivation by Krox-20. In addition to conservation of binding sites critical for Krox-20 activity in the chicken Hoxa-2 and pufferfish Hoxb-2 genes, the r3/r5 enhancers are also characterized by the presence of a number of identical motifs likely to be involved in cooperative interactions with Krox-20 during the process of hindbrain patterning in vertebrates.

Evolutionarily stable learning schedules and cumulative culture in discrete generation models.

PubMed

Aoki, Kenichi; Wakano, Joe Yuichiro; Lehmann, Laurent

2012-06-01

Individual learning (e.g., trial-and-error) and social learning (e.g., imitation) are alternative ways of acquiring and expressing the appropriate phenotype in an environment. The optimal choice between using individual learning and/or social learning may be dictated by the life-stage or age of an organism. Of special interest is a learning schedule in which social learning precedes individual learning, because such a schedule is apparently a necessary condition for cumulative culture. Assuming two obligatory learning stages per discrete generation, we obtain the evolutionarily stable learning schedules for the three situations where the environment is constant, fluctuates between generations, or fluctuates within generations. During each learning stage, we assume that an organism may target the optimal phenotype in the current environment by individual learning, and/or the mature phenotype of the previous generation by oblique social learning. In the absence of exogenous costs to learning, the evolutionarily stable learning schedules are predicted to be either pure social learning followed by pure individual learning ("bang-bang" control) or pure individual learning at both stages ("flat" control). Moreover, we find for each situation that the evolutionarily stable learning schedule is also the one that optimizes the learned phenotype at equilibrium. Copyright © 2012 Elsevier Inc. All rights reserved.

Similarity-based gene detection: using COGs to find evolutionarily-conserved ORFs.

PubMed

Powell, Bradford C; Hutchison, Clyde A

2006-01-19

Experimental verification of gene products has not kept pace with the rapid growth of microbial sequence information. However, existing annotations of gene locations contain sufficient information to screen for probable errors. Furthermore, comparisons among genomes become more informative as more genomes are examined. We studied all open reading frames (ORFs) of at least 30 codons from the genomes of 27 sequenced bacterial strains. We grouped the potential peptide sequences encoded from the ORFs by forming Clusters of Orthologous Groups (COGs). We used this grouping in order to find homologous relationships that would not be distinguishable from noise when using simple BLAST searches. Although COG analysis was initially developed to group annotated genes, we applied it to the task of grouping anonymous DNA sequences that may encode proteins. "Mixed COGs" of ORFs (clusters in which some sequences correspond to annotated genes and some do not) are attractive targets when seeking errors of gene prediction. Examination of mixed COGs reveals some situations in which genes appear to have been missed in current annotations and a smaller number of regions that appear to have been annotated as gene loci erroneously. This technique can also be used to detect potential pseudogenes or sequencing errors. Our method uses an adjustable parameter for degree of conservation among the studied genomes (stringency). We detail results for one level of stringency at which we found 83 potential genes which had not previously been identified, 60 potential pseudogenes, and 7 sequences with existing gene annotations that are probably incorrect. Systematic study of sequence conservation offers a way to improve existing annotations by identifying potentially homologous regions where the annotation of the presence or absence of a gene is inconsistent among genomes.

Similarity-based gene detection: using COGs to find evolutionarily-conserved ORFs

PubMed Central

Powell, Bradford C; Hutchison, Clyde A

2006-01-01

Background Experimental verification of gene products has not kept pace with the rapid growth of microbial sequence information. However, existing annotations of gene locations contain sufficient information to screen for probable errors. Furthermore, comparisons among genomes become more informative as more genomes are examined. We studied all open reading frames (ORFs) of at least 30 codons from the genomes of 27 sequenced bacterial strains. We grouped the potential peptide sequences encoded from the ORFs by forming Clusters of Orthologous Groups (COGs). We used this grouping in order to find homologous relationships that would not be distinguishable from noise when using simple BLAST searches. Although COG analysis was initially developed to group annotated genes, we applied it to the task of grouping anonymous DNA sequences that may encode proteins. Results "Mixed COGs" of ORFs (clusters in which some sequences correspond to annotated genes and some do not) are attractive targets when seeking errors of gene predicion. Examination of mixed COGs reveals some situations in which genes appear to have been missed in current annotations and a smaller number of regions that appear to have been annotated as gene loci erroneously. This technique can also be used to detect potential pseudogenes or sequencing errors. Our method uses an adjustable parameter for degree of conservation among the studied genomes (stringency). We detail results for one level of stringency at which we found 83 potential genes which had not previously been identified, 60 potential pseudogenes, and 7 sequences with existing gene annotations that are probably incorrect. Conclusion Systematic study of sequence conservation offers a way to improve existing annotations by identifying potentially homologous regions where the annotation of the presence or absence of a gene is inconsistent among genomes. PMID:16423288

H2B ubiquitination: Conserved molecular mechanism, diverse physiologic functions of the E3 ligase during meiosis.

PubMed

Wang, Liying; Cao, Chunwei; Wang, Fang; Zhao, Jianguo; Li, Wei

2017-09-03

RNF20/Bre1 mediated H2B ubiquitination (H2Bub) has various physiologic functions. Recently, we found that H2Bub participates in meiotic recombination by promoting chromatin relaxation during meiosis. We then analyzed the phylogenetic relationships among the E3 ligase for H2Bub, its E2 Rad6 and their partner WW domain-containing adaptor with a coiled-coil (WAC) or Lge1, and found that the molecular mechanism underlying H2Bub is evolutionarily conserved from yeast to mammals. However, RNF20 has diverse physiologic functions in different organisms, which might be caused by the evolutionary divergency of their domain/motif architectures. In the current extra view, we not only elucidate the evolutionarily conserved molecular mechanism underlying H2Bub, but also discuss the diverse physiologic functions of RNF20 during meiosis.

Blue reflectance in tarantulas is evolutionarily conserved despite nanostructural diversity

PubMed Central

Hsiung, Bor-Kai; Deheyn, Dimitri D.; Shawkey, Matthew D.; Blackledge, Todd A.

2015-01-01

Slight shifts in arrangement within biological photonic nanostructures can produce large color differences, and sexual selection often leads to high color diversity in clades with structural colors. We use phylogenetic reconstruction, electron microscopy, spectrophotometry, and optical modeling to show an opposing pattern of nanostructural diversification accompanied by unusual conservation of blue color in tarantulas (Araneae: Theraphosidae). In contrast to other clades, blue coloration in phylogenetically distant tarantulas peaks within a narrow 20-nm region around 450 nm. Both quasi-ordered and multilayer nanostructures found in different tarantulas produce this blue color. Thus, even within monophyletic lineages, tarantulas have evolved strikingly similar blue coloration through divergent mechanisms. The poor color perception and lack of conspicuous display during courtship of tarantulas argue that these colors are not sexually selected. Therefore, our data contrast with sexual selection that typically produces a diverse array of colors with a single structural mechanism by showing that natural selection on structural color in tarantulas resulted in convergence on similar color through diverse structural mechanisms. PMID:26702433

RNA polymerase II conserved protein domains as platforms for protein-protein interactions

PubMed Central

García-López, M Carmen

2011-01-01

RNA polymerase II establishes many protein-protein interactions with transcriptional regulators to coordinate gene expression, but little is known about protein domains involved in the contact with them. We use a new approach to look for conserved regions of the RNA pol II of S. cerevisiae located at the surface of the structure of the complex, hypothesizing that they might be involved in the interaction with transcriptional regulators. We defined five different conserved domains and demonstrate that all of them make contact with transcriptional regulators. PMID:21922063

Interacting Social and Environmental Predictors for the Spatial Distribution of Conservation Lands

PubMed Central

Baldwin, Robert F.; Leonard, Paul B.

2015-01-01

Conservation decisions should be evaluated for how they meet conservation goals at multiple spatial extents. Conservation easements are land use decisions resulting from a combination of social and environmental conditions. An emerging area of research is the evaluation of spatial distribution of easements and their spatial correlates. We tested the relative influence of interacting social and environmental variables on the spatial distribution of conservation easements by ownership category and conservation status. For the Appalachian region of the United States, an area with a long history of human occupation and complex land uses including public-private conservation, we found that settlement, economic, topographic, and environmental data associated with spatial distribution of easements (N = 4813). Compared to random locations, easements were more likely to be found in lower elevations, in areas of greater agricultural productivity, farther from public protected areas, and nearer other human features. Analysis of ownership and conservation status revealed sources of variation, with important differences between local and state government ownerships relative to non-governmental organizations (NGOs), and among U.S. Geological Survey (USGS) GAP program status levels. NGOs were more likely to have easements nearer protected areas, and higher conservation status, while local governments held easements closer to settlement, and on lands of greater agricultural potential. Logistic interactions revealed environmental variables having effects modified by social correlates, and the strongest predictors overall were social (distance to urban area, median household income, housing density, distance to land trust office). Spatial distribution of conservation lands may be affected by geographic area of influence of conservation groups, suggesting that multi-scale conservation planning strategies may be necessary to satisfy local and regional needs for reserve networks. Our

Interacting Social and Environmental Predictors for the Spatial Distribution of Conservation Lands.

PubMed

Baldwin, Robert F; Leonard, Paul B

2015-01-01

Conservation decisions should be evaluated for how they meet conservation goals at multiple spatial extents. Conservation easements are land use decisions resulting from a combination of social and environmental conditions. An emerging area of research is the evaluation of spatial distribution of easements and their spatial correlates. We tested the relative influence of interacting social and environmental variables on the spatial distribution of conservation easements by ownership category and conservation status. For the Appalachian region of the United States, an area with a long history of human occupation and complex land uses including public-private conservation, we found that settlement, economic, topographic, and environmental data associated with spatial distribution of easements (N = 4813). Compared to random locations, easements were more likely to be found in lower elevations, in areas of greater agricultural productivity, farther from public protected areas, and nearer other human features. Analysis of ownership and conservation status revealed sources of variation, with important differences between local and state government ownerships relative to non-governmental organizations (NGOs), and among U.S. Geological Survey (USGS) GAP program status levels. NGOs were more likely to have easements nearer protected areas, and higher conservation status, while local governments held easements closer to settlement, and on lands of greater agricultural potential. Logistic interactions revealed environmental variables having effects modified by social correlates, and the strongest predictors overall were social (distance to urban area, median household income, housing density, distance to land trust office). Spatial distribution of conservation lands may be affected by geographic area of influence of conservation groups, suggesting that multi-scale conservation planning strategies may be necessary to satisfy local and regional needs for reserve networks. Our

Establishment and Usability Evaluation of an Interactive AR Learning System on Conservation of Fish

ERIC Educational Resources Information Center

Lin, Hao-Chiang Koong; Hsieh, Min-Chai; Wang, Cheng-Hung; Sie, Zong-Yuan; Chang, Shei-Hsi

2011-01-01

In this study, we develop an interactive AR Learning System based on Augmented Reality and interactive touch-screen. The learning content knowledge is about conservation of fish in Taiwan. The system combines the game by the concept of AR book which allows children to learn about the importance of conservation of fish. A mechanism is designed to…

An evolutionary analysis identifies a conserved pentapeptide stretch containing the two essential lysine residues for rice L-myo-inositol 1-phosphate synthase catalytic activity

PubMed Central

Basak, Papri; Maitra-Majee, Susmita; Das, Jayanta Kumar; Mukherjee, Abhishek; Ghosh Dastidar, Shubhra; Pal Choudhury, Pabitra

2017-01-01

A molecular evolutionary analysis of a well conserved protein helps to determine the essential amino acids in the core catalytic region. Based on the chemical properties of amino acid residues, phylogenetic analysis of a total of 172 homologous sequences of a highly conserved enzyme, L-myo-inositol 1-phosphate synthase or MIPS from evolutionarily diverse organisms was performed. This study revealed the presence of six phylogenetically conserved blocks, out of which four embrace the catalytic core of the functional protein. Further, specific amino acid modifications targeting the lysine residues, known to be important for MIPS catalysis, were performed at the catalytic site of a MIPS from monocotyledonous model plant, Oryza sativa (OsMIPS1). Following this study, OsMIPS mutants with deletion or replacement of lysine residues in the conserved blocks were made. Based on the enzyme kinetics performed on the deletion/replacement mutants, phylogenetic and structural comparison with the already established crystal structures from non-plant sources, an evolutionarily conserved peptide stretch was identified at the active pocket which contains the two most important lysine residues essential for catalytic activity. PMID:28950028

Phylogenetically-informed priorities for amphibian conservation.

PubMed

Isaac, Nick J B; Redding, David W; Meredith, Helen M; Safi, Kamran

2012-01-01

The amphibian decline and extinction crisis demands urgent action to prevent further large numbers of species extinctions. Lists of priority species for conservation, based on a combination of species' threat status and unique contribution to phylogenetic diversity, are one tool for the direction and catalyzation of conservation action. We describe the construction of a near-complete species-level phylogeny of 5713 amphibian species, which we use to create a list of evolutionarily distinct and globally endangered species (EDGE list) for the entire class Amphibia. We present sensitivity analyses to test the robustness of our priority list to uncertainty in species' phylogenetic position and threat status. We find that both sources of uncertainty have only minor impacts on our 'top 100' list of priority species, indicating the robustness of the approach. By contrast, our analyses suggest that a large number of Data Deficient species are likely to be high priorities for conservation action from the perspective of their contribution to the evolutionary history.

Electric Double-Layer Interaction between Dissimilar Charge-Conserved Conducting Plates.

PubMed

Chan, Derek Y C

2015-09-15

Small metallic particles used in forming nanostructured to impart novel optical, catalytic, or tribo-rheological can be modeled as conducting particles with equipotential surfaces that carry a net surface charge. The value of the surface potential will vary with the separation between interacting particles, and in the absence of charge-transfer or electrochemical reactions across the particle surface, the total charge of each particle must also remain constant. These two physical conditions require the electrostatic boundary condition for metallic nanoparticles to satisfy an equipotential whole-of-particle charge conservation constraint that has not been studied previously. This constraint gives rise to a global charge conserved constant potential boundary condition that results in multibody effects in the electric double-layer interaction that are either absent or are very small in the familiar constant potential or constant charge or surface electrochemical equilibrium condition.

Scaffolding protein RanBPM and its interactions in diverse signaling pathways in health and disease.

PubMed

Das, Soumyadip; Haq, Saba; Ramakrishna, Suresh

2018-04-01

Ran-binding protein in the microtubule-organizing center (RanBPM) is an evolutionarily conserved, nucleocytoplasmic scaffolding protein involved in various cellular processes and several signal transduction pathways. RanBPM has a crucial role in mediating disease pathology by interacting with diverse proteins to regulate their functions. Previously, we compiled diverse cellular functions of RanBPM. Since then the functions of RanBPM have increased exponentially. In this article, we have updated the functions of RanBPM through its manifold interactions that have been investigated to date, according to their roles in protein stability, transcriptional activity, cellular development, neurobiology, and the cell cycle. Our review provides a complete guide on RanBPM interactors, the physiological role of RanBPM in cellular functions, and potential applications in disease therapeutics.

Adaptive evolutionary conservation: towards a unified concept for defining conservation units.

PubMed

Fraser, D J; Bernatchez, L

2001-12-01

Recent years have seen a debate over various methods that could objectively prioritize conservation value below the species level. Most prominent among these has been the evolutionarily significant unit (ESU). We reviewed ESU concepts with the aim of proposing a more unified concept that would reconcile opposing views. Like species concepts, conflicting ESU concepts are all essentially aiming to define the same thing: segments of species whose divergence can be measured or evaluated by putting differential emphasis on the role of evolutionary forces at varied temporal scales. Thus, differences between ESU concepts lie more in the criteria used to define the ESUs themselves rather than in their fundamental essence. We provide a context-based framework for delineating ESUs which circumvents much of this situation. Rather than embroil in a befuddled debate over an optimal criterion, the key to a solution is accepting that differing criteria will work more dynamically than others and can be used alone or in combination depending on the situation. These assertions constitute the impetus behind adaptive evolutionary conservation.

Evolutionary and structural analyses of alpha-papillomavirus capsid proteins yields novel insights into L2 structure and interaction with L1

PubMed Central

Lowe, John; Panda, Debasis; Rose, Suzanne; Jensen, Ty; Hughes, Willie A; Tso, For Yue; Angeletti, Peter C

2008-01-01

Background PVs (PV) are small, non-enveloped, double-stranded DNA viruses that have been identified as the primary etiological agent for cervical cancer and their potential for malignant transformation in mucosal tissue has a large impact on public health. The PV family Papillomaviridae is organized into multiple genus based on sequential parsimony, host range, tissue tropism, and histology. We focused this analysis on the late gene products, major (L1) and minor (L2) capsid proteins from the family Papillomaviridae genus Alpha-papillomavirus. Alpha-PVs preferentially infect oral and anogenital mucosa of humans and primates with varied risk of oncogenic transformation. Development of evolutionary associations between PVs will likely provide novel information to assist in clarifying the currently elusive relationship between PV and its microenvironment (i.e., the single infected cell) and macro environment (i.e., the skin tissue). We attempt to identify the regions of the major capsid proteins as well as minor capsid proteins of alpha-papillomavirus that have been evolutionarily conserved, and define regions that are under constant selective pressure with respect to the entire family of viruses. Results This analysis shows the loops of L1 are in fact the most variable regions among the alpha-PVs. We also identify regions of L2, involved in interaction with L1, as evolutionarily conserved among the members of alpha- PVs. Finally, a predicted three-dimensional model was generated to further elucidate probable aspects of the L1 and L2 interaction. PMID:19087355

Conservation Genetics of the Philippine Tarsier: Cryptic Genetic Variation Restructures Conservation Priorities for an Island Archipelago Primate

PubMed Central

Brown, Rafe M.; Weghorst, Jennifer A.; Olson, Karen V.; Duya, Mariano R. M.; Barley, Anthony J.; Duya, Melizar V.; Shekelle, Myron; Neri-Arboleda, Irene; Esselstyn, Jacob A.; Dominy, Nathaniel J.; Ong, Perry S.; Moritz, Gillian L.; Luczon, Adrian; Diesmos, Mae Lowe L.; Diesmos, Arvin C.; Siler, Cameron D.

2014-01-01

Establishment of conservation priorities for primates is a particular concern in the island archipelagos of Southeast Asia, where rates of habitat destruction are among the highest in the world. Conservation programs require knowledge of taxonomic diversity to ensure success. The Philippine tarsier is a flagship species that promotes environmental awareness and a thriving ecotourism economy in the Philippines. However, assessment of its conservation status has been impeded by taxonomic uncertainty, a paucity of field studies, and a lack of vouchered specimens and genetic samples available for study in biodiversity repositories. Consequently, conservation priorities are unclear. In this study we use mitochondrial and nuclear DNA to empirically infer geographic partitioning of genetic variation and to identify evolutionarily distinct lineages for conservation action. The distribution of Philippine tarsier genetic diversity is neither congruent with expectations based on biogeographical patterns documented in other Philippine vertebrates, nor does it agree with the most recent Philippine tarsier taxonomic arrangement. We identify three principal evolutionary lineages that do not correspond to the currently recognized subspecies, highlight the discovery of a novel cryptic and range-restricted subcenter of genetic variation in an unanticipated part of the archipelago, and identify additional geographically structured genetic variation that should be the focus of future studies and conservation action. Conservation of this flagship species necessitates establishment of protected areas and targeted conservation programs within the range of each genetically distinct variant of the Philippine tarsier. PMID:25136854

Evolutionarily stable range limits set by interspecific competition.

PubMed

Price, Trevor D; Kirkpatrick, Mark

2009-04-22

A combination of abiotic and biotic factors probably restricts the range of many species. Recent evolutionary models and tests of those models have asked how a gradual change in environmental conditions can set the range limit, with a prominent idea being that gene flow disrupts local adaptation. We investigate how biotic factors, explicitly competition for limited resources, result in evolutionarily stable range limits even in the absence of the disruptive effect of gene flow. We model two competing species occupying different segments of the resource spectrum. If one segment of the resource spectrum declines across space, a species that specializes on that segment can be driven to extinction, even though in the absence of competition it would evolve to exploit other abundant resources and so be saved. The result is that a species range limit is set in both evolutionary and ecological time, as the resources associated with its niche decline. Factors promoting this outcome include: (i) inherent gaps in the resource distribution, (ii) relatively high fitness of the species when in its own niche, and low fitness in the alternative niche, even when resource abundances are similar in each niche, (iii) strong interspecific competition, and (iv) asymmetric interspecific competition. We suggest that these features are likely to be common in multispecies communities, thereby setting evolutionarily stable range limits.

Evolutionarily stable range limits set by interspecific competition

PubMed Central

Price, Trevor D.; Kirkpatrick, Mark

2009-01-01

A combination of abiotic and biotic factors probably restricts the range of many species. Recent evolutionary models and tests of those models have asked how a gradual change in environmental conditions can set the range limit, with a prominent idea being that gene flow disrupts local adaptation. We investigate how biotic factors, explicitly competition for limited resources, result in evolutionarily stable range limits even in the absence of the disruptive effect of gene flow. We model two competing species occupying different segments of the resource spectrum. If one segment of the resource spectrum declines across space, a species that specializes on that segment can be driven to extinction, even though in the absence of competition it would evolve to exploit other abundant resources and so be saved. The result is that a species range limit is set in both evolutionary and ecological time, as the resources associated with its niche decline. Factors promoting this outcome include: (i) inherent gaps in the resource distribution, (ii) relatively high fitness of the species when in its own niche, and low fitness in the alternative niche, even when resource abundances are similar in each niche, (iii) strong interspecific competition, and (iv) asymmetric interspecific competition. We suggest that these features are likely to be common in multispecies communities, thereby setting evolutionarily stable range limits. PMID:19324813

Conserved conformational selection mechanism of Hsp70 chaperone-substrate interactions

PubMed Central

Velyvis, Algirdas; Zoltsman, Guy; Rosenzweig, Rina; Bouvignies, Guillaume

2018-01-01

Molecular recognition is integral to biological function and frequently involves preferred binding of a molecule to one of several exchanging ligand conformations in solution. In such a process the bound structure can be selected from the ensemble of interconverting ligands a priori (conformational selection, CS) or may form once the ligand is bound (induced fit, IF). Here we focus on the ubiquitous and conserved Hsp70 chaperone which oversees the integrity of the cellular proteome through its ATP-dependent interaction with client proteins. We directly quantify the flux along CS and IF pathways using solution NMR spectroscopy that exploits a methyl TROSY effect and selective isotope-labeling methodologies. Our measurements establish that both bacterial and human Hsp70 chaperones interact with clients by selecting the unfolded state from a pre-existing array of interconverting structures, suggesting a conserved mode of client recognition among Hsp70s and highlighting the importance of molecular dynamics in this recognition event. PMID:29460778

Conservation priorities when species interact: the Noah's Ark metaphor revisited.

PubMed

Courtois, Pierre; Figuieres, Charles; Mulier, Chloé

2014-01-01

This note incorporates ecological interactions into the Noah's Ark problem. In doing so, we arrive at a general model for ranking in situ conservation projects accounting for species interrelations and provide an operational cost-effectiveness method for the selection of best preserving diversity projects under a limited budget constraint.

Phylogenetic analysis of conservation priorities for aquatic mammals and their terrestrial relatives, with a comparison of methods.

PubMed

May-Collado, Laura J; Agnarsson, Ingi

2011-01-01

Habitat loss and overexploitation are among the primary factors threatening populations of many mammal species. Recently, aquatic mammals have been highlighted as particularly vulnerable. Here we test (1) if aquatic mammals emerge as more phylogenetically urgent conservation priorities than their terrestrial relatives, and (2) if high priority species are receiving sufficient conservation effort. We also compare results among some phylogenetic conservation methods. A phylogenetic analysis of conservation priorities for all 620 species of Cetartiodactyla and Carnivora, including most aquatic mammals. Conservation priority ranking of aquatic versus terrestrial species is approximately proportional to their diversity. However, nearly all obligated freshwater cetartiodactylans are among the top conservation priority species. Further, ∼74% and 40% of fully aquatic cetartiodactylans and carnivores, respectively, are either threatened or data deficient, more so than their terrestrial relatives. Strikingly, only 3% of all 'high priority' species are thought to be stable. An overwhelming 97% of these species thus either show decreasing population trends (87%) or are insufficiently known (10%). Furthermore, a disproportional number of highly evolutionarily distinct species are experiencing population decline, thus, such species should be closely monitored even if not currently threatened. Comparison among methods reveals that exact species ranking differs considerably among methods, nevertheless, most top priority species consistently rank high under any method. While we here favor one approach, we also suggest that a consensus approach may be useful when methods disagree. These results reinforce prior findings, suggesting there is an urgent need to gather basic conservation data for aquatic mammals, and special conservation focus is needed on those confined to freshwater. That evolutionarily distinct--and thus 'biodiverse'--species are faring relatively poorly is alarming

Phylogenetic Analysis of Conservation Priorities for Aquatic Mammals and Their Terrestrial Relatives, with a Comparison of Methods

PubMed Central

May-Collado, Laura J.; Agnarsson, Ingi

2011-01-01

Background Habitat loss and overexploitation are among the primary factors threatening populations of many mammal species. Recently, aquatic mammals have been highlighted as particularly vulnerable. Here we test (1) if aquatic mammals emerge as more phylogenetically urgent conservation priorities than their terrestrial relatives, and (2) if high priority species are receiving sufficient conservation effort. We also compare results among some phylogenetic conservation methods. Methodology/Principal Findings A phylogenetic analysis of conservation priorities for all 620 species of Cetartiodactyla and Carnivora, including most aquatic mammals. Conservation priority ranking of aquatic versus terrestrial species is approximately proportional to their diversity. However, nearly all obligated freshwater cetartiodactylans are among the top conservation priority species. Further, ∼74% and 40% of fully aquatic cetartiodactylans and carnivores, respectively, are either threatened or data deficient, more so than their terrestrial relatives. Strikingly, only 3% of all ‘high priority’ species are thought to be stable. An overwhelming 97% of these species thus either show decreasing population trends (87%) or are insufficiently known (10%). Furthermore, a disproportional number of highly evolutionarily distinct species are experiencing population decline, thus, such species should be closely monitored even if not currently threatened. Comparison among methods reveals that exact species ranking differs considerably among methods, nevertheless, most top priority species consistently rank high under any method. While we here favor one approach, we also suggest that a consensus approach may be useful when methods disagree. Conclusions/Significance These results reinforce prior findings, suggesting there is an urgent need to gather basic conservation data for aquatic mammals, and special conservation focus is needed on those confined to freshwater. That evolutionarily distinct�

Conservation Priorities when Species Interact: The Noah's Ark Metaphor Revisited

PubMed Central

Courtois, Pierre; Figuieres, Charles; Mulier, Chloé

2014-01-01

This note incorporates ecological interactions into the Noah's Ark problem. In doing so, we arrive at a general model for ranking in situ conservation projects accounting for species interrelations and provide an operational cost-effectiveness method for the selection of best preserving diversity projects under a limited budget constraint. PMID:25181514

INCENP Centromere and Spindle Targeting: Identification of Essential Conserved Motifs and Involvement of Heterochromatin Protein HP1

PubMed Central

Ainsztein, Alexandra M.; Kandels-Lewis, Stefanie E.; Mackay, Alastair M.; Earnshaw, William C.

1998-01-01

The inner centromere protein (INCENP) has a modular organization, with domains required for chromosomal and cytoskeletal functions concentrated near the amino and carboxyl termini, respectively. In this study we have identified an autonomous centromere- and midbody-targeting module in the amino-terminal 68 amino acids of INCENP. Within this module, we have identified two evolutionarily conserved amino acid sequence motifs: a 13–amino acid motif that is required for targeting to centromeres and transfer to the spindle, and an 11–amino acid motif that is required for transfer to the spindle by molecules that have targeted previously to the centromere. To begin to understand the mechanisms of INCENP function in mitosis, we have performed a yeast two-hybrid screen for interacting proteins. These and subsequent in vitro binding experiments identify a physical interaction between INCENP and heterochromatin protein HP1Hsα. Surprisingly, this interaction does not appear to be involved in targeting INCENP to the centromeric heterochromatin, but may instead have a role in its transfer from the chromosomes to the anaphase spindle. PMID:9864353

An evolutionarily young defense metabolite influences the root growth of plants via the ancient TOR signaling pathway.

PubMed

Malinovsky, Frederikke Gro; Thomsen, Marie-Louise F; Nintemann, Sebastian J; Jagd, Lea Møller; Bourgine, Baptiste; Burow, Meike; Kliebenstein, Daniel J

2017-12-12

To optimize fitness a plant should monitor its metabolism to appropriately control growth and defense. Primary metabolism can be measured by the universally conserved TOR (Target of Rapamycin) pathway to balance growth and development with the available energy and nutrients. Recent work suggests that plants may measure defense metabolites to potentially provide a strategy ensuring fast reallocation of resources to coordinate plant growth and defense. There is little understanding of mechanisms enabling defense metabolite signaling. To identify mechanisms of defense metabolite signaling, we used glucosinolates, an important class of plant defense metabolites. We report novel signaling properties specific to one distinct glucosinolate, 3-hydroxypropylglucosinolate across plants and fungi. This defense metabolite, or derived compounds, reversibly inhibits root growth and development. 3-hydroxypropylglucosinolate signaling functions via genes in the ancient TOR pathway. If this event is not unique, this raises the possibility that other evolutionarily new plant metabolites may link to ancient signaling pathways.

An evolutionarily young defense metabolite influences the root growth of plants via the ancient TOR signaling pathway

PubMed Central

Malinovsky, Frederikke Gro; Thomsen, Marie-Louise F; Nintemann, Sebastian J; Jagd, Lea Møller; Bourgine, Baptiste; Burow, Meike

2017-01-01

To optimize fitness a plant should monitor its metabolism to appropriately control growth and defense. Primary metabolism can be measured by the universally conserved TOR (Target of Rapamycin) pathway to balance growth and development with the available energy and nutrients. Recent work suggests that plants may measure defense metabolites to potentially provide a strategy ensuring fast reallocation of resources to coordinate plant growth and defense. There is little understanding of mechanisms enabling defense metabolite signaling. To identify mechanisms of defense metabolite signaling, we used glucosinolates, an important class of plant defense metabolites. We report novel signaling properties specific to one distinct glucosinolate, 3-hydroxypropylglucosinolate across plants and fungi. This defense metabolite, or derived compounds, reversibly inhibits root growth and development. 3-hydroxypropylglucosinolate signaling functions via genes in the ancient TOR pathway. If this event is not unique, this raises the possibility that other evolutionarily new plant metabolites may link to ancient signaling pathways. PMID:29231169

An Abundant Evolutionarily Conserved CSB-PiggyBac Fusion Protein Expressed in Cockayne Syndrome

PubMed Central

Newman, John C.; Bailey, Arnold D.; Fan, Hua-Ying; Pavelitz, Thomas; Weiner, Alan M.

2008-01-01

Cockayne syndrome (CS) is a devastating progeria most often caused by mutations in the CSB gene encoding a SWI/SNF family chromatin remodeling protein. Although all CSB mutations that cause CS are recessive, the complete absence of CSB protein does not cause CS. In addition, most CSB mutations are located beyond exon 5 and are thought to generate only C-terminally truncated protein fragments. We now show that a domesticated PiggyBac-like transposon PGBD3, residing within intron 5 of the CSB gene, functions as an alternative 3′ terminal exon. The alternatively spliced mRNA encodes a novel chimeric protein in which CSB exons 1–5 are joined in frame to the PiggyBac transposase. The resulting CSB-transposase fusion protein is as abundant as CSB protein itself in a variety of human cell lines, and continues to be expressed by primary CS cells in which functional CSB is lost due to mutations beyond exon 5. The CSB-transposase fusion protein has been highly conserved for at least 43 Myr since the divergence of humans and marmoset, and appears to be subject to selective pressure. The human genome contains over 600 nonautonomous PGBD3-related MER85 elements that were dispersed when the PGBD3 transposase was last active at least 37 Mya. Many of these MER85 elements are associated with genes which are involved in neuronal development, and are known to be regulated by CSB. We speculate that the CSB-transposase fusion protein has been conserved for host antitransposon defense, or to modulate gene regulation by MER85 elements, but may cause CS in the absence of functional CSB protein. PMID:18369450

Conserved regions of ribonucleoprotein ribonuclease MRP are involved in interactions with its substrate

PubMed Central

Esakova, Olga; Perederina, Anna; Berezin, Igor; Krasilnikov, Andrey S.

2013-01-01

Ribonuclease (RNase) MRP is a ubiquitous and essential site-specific eukaryotic endoribonuclease involved in the metabolism of a wide range of RNA molecules. RNase MRP is a ribonucleoprotein with a large catalytic RNA moiety that is closely related to the RNA component of RNase P, and multiple proteins, most of which are shared with RNase P. Here, we report the results of an ultraviolet-cross-linking analysis of interactions between a photoreactive RNase MRP substrate and the Saccharomyces cerevisiae RNase MRP holoenzyme. The results show that the substrate interacts with phylogenetically conserved RNA elements universally found in all enzymes of the RNase P/MRP family, as well as with a phylogenetically conserved RNA region that is unique to RNase MRP, and demonstrate that four RNase MRP protein components, all shared with RNase P, interact with the substrate. Implications for the structural organization of RNase MRP and the roles of its components are discussed. PMID:23700311

Conserved regions of ribonucleoprotein ribonuclease MRP are involved in interactions with its substrate.

PubMed

Esakova, Olga; Perederina, Anna; Berezin, Igor; Krasilnikov, Andrey S

2013-08-01

Ribonuclease (RNase) MRP is a ubiquitous and essential site-specific eukaryotic endoribonuclease involved in the metabolism of a wide range of RNA molecules. RNase MRP is a ribonucleoprotein with a large catalytic RNA moiety that is closely related to the RNA component of RNase P, and multiple proteins, most of which are shared with RNase P. Here, we report the results of an ultraviolet-cross-linking analysis of interactions between a photoreactive RNase MRP substrate and the Saccharomyces cerevisiae RNase MRP holoenzyme. The results show that the substrate interacts with phylogenetically conserved RNA elements universally found in all enzymes of the RNase P/MRP family, as well as with a phylogenetically conserved RNA region that is unique to RNase MRP, and demonstrate that four RNase MRP protein components, all shared with RNase P, interact with the substrate. Implications for the structural organization of RNase MRP and the roles of its components are discussed.

BMP, Wnt and FGF signals are integrated through evolutionarily conserved enhancers to achieve robust expression of Pax3 and Zic genes at the zebrafish neural plate border

PubMed Central

Garnett, Aaron T.; Square, Tyler A.; Medeiros, Daniel M.

2012-01-01

Neural crest cells generate a range of cells and tissues in the vertebrate head and trunk, including peripheral neurons, pigment cells, and cartilage. Neural crest cells arise from the edges of the nascent central nervous system, a domain called the neural plate border (NPB). NPB induction is known to involve the BMP, Wnt and FGF signaling pathways. However, little is known about how these signals are integrated to achieve temporally and spatially specific expression of genes in NPB cells. Furthermore, the timing and relative importance of these signals in NPB formation appears to differ between vertebrate species. Here, we use heat-shock overexpression and chemical inhibitors to determine whether, and when, BMP, Wnt and FGF signaling are needed for expression of the NPB specifiers pax3a and zic3 in zebrafish. We then identify four evolutionarily conserved enhancers from the pax3a and zic3 loci and test their response to BMP, Wnt and FGF perturbations. We find that all three signaling pathways are required during gastrulation for the proper expression of pax3a and zic3 in the zebrafish NPB. We also find that, although the expression patterns driven by the pax3a and zic3 enhancers largely overlap, they respond to different combinations of BMP, Wnt and FGF signals. Finally, we show that the combination of the two pax3a enhancers is less susceptible to signaling perturbations than either enhancer alone. Taken together, our results reveal how BMPs, FGFs and Wnts act cooperatively and redundantly through partially redundant enhancers to achieve robust, specific gene expression in the zebrafish NPB. PMID:23034628

Structural Dynamics Investigation of Human Family 1 & 2 Cystatin-Cathepsin L1 Interaction: A Comparison of Binding Modes.

PubMed

Nandy, Suman Kumar; Seal, Alpana

2016-01-01

Cystatin superfamily is a large group of evolutionarily related proteins involved in numerous physiological activities through their inhibitory activity towards cysteine proteases. Despite sharing the same cystatin fold, and inhibiting cysteine proteases through the same tripartite edge involving highly conserved N-terminal region, L1 and L2 loop; cystatins differ widely in their inhibitory affinity towards C1 family of cysteine proteases and molecular details of these interactions are still elusive. In this study, inhibitory interactions of human family 1 & 2 cystatins with cathepsin L1 are predicted and their stability and viability are verified through protein docking & comparative molecular dynamics. An overall stabilization effect is observed in all cystatins on complex formation. Complexes are mostly dominated by van der Waals interaction but the relative participation of the conserved regions varied extensively. While van der Waals contacts prevail in L1 and L2 loop, N-terminal segment chiefly acts as electrostatic interaction site. In fact the comparative dynamics study points towards the instrumental role of L1 loop in directing the total interaction profile of the complex either towards electrostatic or van der Waals contacts. The key amino acid residues surfaced via interaction energy, hydrogen bonding and solvent accessible surface area analysis for each cystatin-cathepsin L1 complex influence the mode of binding and thus control the diverse inhibitory affinity of cystatins towards cysteine proteases.

Structural Dynamics Investigation of Human Family 1 & 2 Cystatin-Cathepsin L1 Interaction: A Comparison of Binding Modes

PubMed Central

Nandy, Suman Kumar; Seal, Alpana

2016-01-01

Cystatin superfamily is a large group of evolutionarily related proteins involved in numerous physiological activities through their inhibitory activity towards cysteine proteases. Despite sharing the same cystatin fold, and inhibiting cysteine proteases through the same tripartite edge involving highly conserved N-terminal region, L1 and L2 loop; cystatins differ widely in their inhibitory affinity towards C1 family of cysteine proteases and molecular details of these interactions are still elusive. In this study, inhibitory interactions of human family 1 & 2 cystatins with cathepsin L1 are predicted and their stability and viability are verified through protein docking & comparative molecular dynamics. An overall stabilization effect is observed in all cystatins on complex formation. Complexes are mostly dominated by van der Waals interaction but the relative participation of the conserved regions varied extensively. While van der Waals contacts prevail in L1 and L2 loop, N-terminal segment chiefly acts as electrostatic interaction site. In fact the comparative dynamics study points towards the instrumental role of L1 loop in directing the total interaction profile of the complex either towards electrostatic or van der Waals contacts. The key amino acid residues surfaced via interaction energy, hydrogen bonding and solvent accessible surface area analysis for each cystatin-cathepsin L1 complex influence the mode of binding and thus control the diverse inhibitory affinity of cystatins towards cysteine proteases. PMID:27764212

Complex interactions amongst N-cadherin, DLAR, and Liprin-α regulate Drosophila photoreceptor axon targeting

PubMed Central

Prakash, Saurabh; Maclendon, Helen; Dubreuil, Catherine I.; Ghose, Aurnab; Hwa, Jennifer; Dennehy, Kelly A.; Tomalty, Katharine M.H.; Clark, Kelsey; Van Vactor, David; Clandinin, Thomas R.

2009-01-01

The formation of stable adhesive contacts between pre- and post-synaptic neurons represents the initial step in synapse assembly. The cell adhesion molecule N-cadherin, the receptor tyrosine phosphatase DLAR, and the scaffolding molecule Liprin-α play critical, evolutionarily conserved roles in this process. However, how these proteins signal to the growth cone, and are themselves regulated, remains poorly understood. Using Drosophila photoreceptors (R cells) as a model, we evaluate genetic and physical interactions among these three proteins. We demonstrate that DLAR function in this context is independent of phosphatase activity, but requires interactions mediated by its intracellular domain. Genetic studies reveal both positive and, surprisingly, inhibitory interactions amongst all three genes. These observations are corroborated by biochemical studies demonstrating that DLAR physically associates via its phosphatase domain with N-cadherin in Drosophila embryos. Together, these data demonstrate that N-cadherin, DLAR, and Liprin-α function in a complex to regulate adhesive interactions between pre- and post-synaptic cells, and provide a novel mechanism for controlling the activity of liprin-α in the developing growth cone. PMID:19766621

Conservation and Evolutionary Dynamics of the agr Cell-to-Cell Communication System across Firmicutes▿ †

PubMed Central

Wuster, Arthur; Babu, M. Madan

2008-01-01

We present evidence that the agr cell-to-cell communication system is present across firmicutes, including the human pathogen Clostridium perfringens. Although we find that the agr system is evolutionarily conserved and that the general functions which it regulates are similar in different species, the individual regulated genes are not the same. This suggests that the regulatory network controlled by agr is dynamic and evolves rapidly. PMID:17933897

Evolutionarily conserved odorant receptor function questions ecological context of octenol role in mosquitoes

PubMed Central

Dekel, Amir; Pitts, Ronald J.; Yakir, Esther; Bohbot, Jonathan D.

2016-01-01

Olfaction is a key insect adaptation to a wide range of habitats. In the last thirty years, the detection of octenol by blood-feeding insects has been primarily understood in the context of animal host-seeking. The recent discovery of a conserved octenol receptor gene in the strictly nectar-feeding elephant mosquito Toxorhynchites amboinensis (TaOr8) suggests a different biological role. Here, we show that TaOR8 is a functional ortholog of its counterparts in blood-feeding mosquitoes displaying selectivity towards the (R)-enantiomer of octenol and susceptibility to the insect repellent DEET. These findings suggest that while the function of OR8 has been maintained throughout mosquito evolution, the context in which this receptor is operating has diverged in blood and nectar-feeding mosquitoes. PMID:27849027

A mammalian germ cell-specific RNA-binding protein interacts with ubiquitously expressed proteins involved in splice site selection

NASA Astrophysics Data System (ADS)

Elliott, David J.; Bourgeois, Cyril F.; Klink, Albrecht; Stévenin, James; Cooke, Howard J.

2000-05-01

RNA-binding motif (RBM) genes are found on all mammalian Y chromosomes and are implicated in spermatogenesis. Within human germ cells, RBM protein shows a similar nuclear distribution to components of the pre-mRNA splicing machinery. To address the function of RBM, we have used protein-protein interaction assays to test for possible physical interactions between these proteins. We find that RBM protein directly interacts with members of the SR family of splicing factors and, in addition, strongly interacts with itself. We have mapped the protein domains responsible for mediating these interactions and expressed the mouse RBM interaction region as a bacterial fusion protein. This fusion protein can pull-down several functionally active SR protein species from cell extracts. Depletion and add-back experiments indicate that these SR proteins are the only splicing factors bound by RBM which are required for the splicing of a panel of pre-mRNAs. Our results suggest that RBM protein is an evolutionarily conserved mammalian splicing regulator which operates as a germ cell-specific cofactor for more ubiquitously expressed pre-mRNA splicing activators.

Physical and functional interactions between Drosophila TRAF2 and Pelle kinase contribute to Dorsal activation.

PubMed

Shen, B; Liu, H; Skolnik, E Y; Manley, J L

2001-07-17

Signaling through the Toll receptor is required for dorsal/ventral polarity in Drosophila embryos, and also plays an evolutionarily conserved role in the immune response. Upon ligand binding, Toll appears to multimerize and activate the associated kinase, Pelle. However, the immediate downstream targets of Pelle have not been identified. Here we show that Drosophila tumor necrosis factor receptor-associated factor 2 (dTRAF2), a homologue of human TRAF6, physically and functionally interacts with Pelle, and is phosphorylated by Pelle in vitro. Importantly, dTRAF2 and Pelle cooperate to activate Dorsal synergistically in cotransfected Schneider cells. Deletion of the C-terminal TRAF domain of dTRAF2 enhances Dorsal activation, perhaps reflecting the much stronger interaction of the mutant protein with phosphorylated, active Pelle. Taken together, our results indicate that Pelle and dTRAF2 physically and functionally interact, and that the TRAF domain acts as a regulator of this interaction. dTRAF2 thus appears to be a downstream target of Pelle. We discuss these results in the context of Toll signaling in flies and mammals.

Identification of evolutionarily conserved Momordica charantia microRNAs using computational approach and its utility in phylogeny analysis.

PubMed

Thirugnanasambantham, Krishnaraj; Saravanan, Subramanian; Karikalan, Kulandaivelu; Bharanidharan, Rajaraman; Lalitha, Perumal; Ilango, S; HairulIslam, Villianur Ibrahim

2015-10-01

Momordica charantia (bitter gourd, bitter melon) is a monoecious Cucurbitaceae with anti-oxidant, anti-microbial, anti-viral and anti-diabetic potential. Molecular studies on this economically valuable plant are very essential to understand its phylogeny and evolution. MicroRNAs (miRNAs) are conserved, small, non-coding RNA with ability to regulate gene expression by bind the 3' UTR region of target mRNA and are evolved at different rates in different plant species. In this study we have utilized homology based computational approach and identified 27 mature miRNAs for the first time from this bio-medically important plant. The phylogenetic tree developed from binary data derived from the data on presence/absence of the identified miRNAs were noticed to be uncertain and biased. Most of the identified miRNAs were highly conserved among the plant species and sequence based phylogeny analysis of miRNAs resolved the above difficulties in phylogeny approach using miRNA. Predicted gene targets of the identified miRNAs revealed their importance in regulation of plant developmental process. Reported miRNAs held sequence conservation in mature miRNAs and the detailed phylogeny analysis of pre-miRNA sequences revealed genus specific segregation of clusters. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluating Interactions of Forest Conservation Policies on Avoided Deforestation

PubMed Central

Robalino, Juan; Sandoval, Catalina; Barton, David N.; Chacon, Adriana; Pfaff, Alexander

2015-01-01

We estimate the effects on deforestation that have resulted from policy interactions between parks and payments and between park buffers and payments in Costa Rica between 2000 and 2005. We show that the characteristics of the areas where protected and unprotected lands are located differ significantly. Additionally, we find that land characteristics of each of the policies and of the places where they interact also differ significantly. To adequately estimate the effects of the policies and their interactions, we use matching methods. Matching is implemented not only to define adequate control groups, as in previous research, but also to define those groups of locations under the influence of policies that are comparable to each other. We find that it is more effective to locate parks and payments away from each other, rather than in the same location or near each other. The high levels of enforcement inside both parks and lands with payments, and the presence of conservation spillovers that reduce deforestation near parks, significantly reduce the potential impact of combining these two policies. PMID:25909323

Evaluating interactions of forest conservation policies on avoided deforestation.

PubMed

Robalino, Juan; Sandoval, Catalina; Barton, David N; Chacon, Adriana; Pfaff, Alexander

2015-01-01

We estimate the effects on deforestation that have resulted from policy interactions between parks and payments and between park buffers and payments in Costa Rica between 2000 and 2005. We show that the characteristics of the areas where protected and unprotected lands are located differ significantly. Additionally, we find that land characteristics of each of the policies and of the places where they interact also differ significantly. To adequately estimate the effects of the policies and their interactions, we use matching methods. Matching is implemented not only to define adequate control groups, as in previous research, but also to define those groups of locations under the influence of policies that are comparable to each other. We find that it is more effective to locate parks and payments away from each other, rather than in the same location or near each other. The high levels of enforcement inside both parks and lands with payments, and the presence of conservation spillovers that reduce deforestation near parks, significantly reduce the potential impact of combining these two policies.

Conservation Below the Species Level: Suitable Evolutionarily Significant Units among Mountain Vipers (the Montivipera raddei complex) in Iran.

PubMed

Behrooz, Roozbeh; Kaboli, Mohammad; Arnal, Véronique; Nazarizadeh, Masoud; Asadi, Atefeh; Salmanian, Amin; Ahmadi, Mohsen; Montgelard, Claudine

2018-05-11

Northern and western mountains of Iran are among the most important biodiversity and endemism hot spots for reptiles in the Middle East. Among herpetofauna, the montivipers represent an emblematic and fragmented endemic group for which estimating their level of genetic differentiation and defining conservation priorities is urgently needed. Here, we present the most comprehensive phylogenetic study on the Montivipera raddei species group comprising all 5 known taxa, among which 3 are endemic to Iran. Based on 2 mitochondrial genes, phylogenetic and phylogeographic analyses revealed 3 major lineages each presenting very contrasting distribution areas. The Iranian montivipers are highly structured in clades showing low genetic diversity and corresponding to high altitude summits. Molecular dating revealed the role of Quaternary paleo-climatic oscillations and altitudinal movements of montivipers in shaping genetic diversity and differentiation of these sky-island taxa. In addition, the best scenario of historical biogeography allowed identifying 3 possible refugial areas in Iran most likely arising by vicariance. Based on our mitochondrial results and pending additional data, we recognize 3 candidate species among the M. raddei complex: M. raddei, Montivipera latifii, and Montivipera kuhrangica that are coherent with their geographical distribution. We propose that the most appropriate evolutionary significant units for conservation of the montivipers are represented by 13 units among which 6 are recognized as high priority. Finally, we suggest some recommendations to the IUCN as well as to the Iranian conservation policies with respect to conservation prioritization.

Multi-scale coarse-graining of non-conservative interactions in molecular liquids

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

Izvekov, Sergei, E-mail: sergiy.izvyekov.civ@mail.mil; Rice, Betsy M.

2014-03-14

A new bottom-up procedure for constructing non-conservative (dissipative and stochastic) interactions for dissipative particle dynamics (DPD) models is described and applied to perform hierarchical coarse-graining of a polar molecular liquid (nitromethane). The distant-dependent radial and shear frictions in functional-free form are derived consistently with a chosen form for conservative interactions by matching two-body force-velocity and three-body velocity-velocity correlations along the microscopic trajectories of the centroids of Voronoi cells (clusters), which represent the dissipative particles within the DPD description. The Voronoi tessellation is achieved by application of the K-means clustering algorithm at regular time intervals. Consistently with a notion of many-bodymore » DPD, the conservative interactions are determined through the multi-scale coarse-graining (MS-CG) method, which naturally implements a pairwise decomposition of the microscopic free energy. A hierarchy of MS-CG/DPD models starting with one molecule per Voronoi cell and up to 64 molecules per cell is derived. The radial contribution to the friction appears to be dominant for all models. As the Voronoi cell sizes increase, the dissipative forces rapidly become confined to the first coordination shell. For Voronoi cells of two and more molecules the time dependence of the velocity autocorrelation function becomes monotonic and well reproduced by the respective MS-CG/DPD models. A comparative analysis of force and velocity correlations in the atomistic and CG ensembles indicates Markovian behavior with as low as two molecules per dissipative particle. The models with one and two molecules per Voronoi cell yield transport properties (diffusion and shear viscosity) that are in good agreement with the atomistic data. The coarser models produce slower dynamics that can be appreciably attributed to unaccounted dissipation introduced by regular Voronoi re-partitioning as well as by larger

Comparative interactomics: analysis of arabidopsis 14-3-3 complexes reveals highly conserved 14-3-3 interactions between humans and plants.

PubMed

Paul, Anna-Lisa; Liu, Li; McClung, Scott; Laughner, Beth; Chen, Sixue; Ferl, Robert J

2009-04-01

As a first step in the broad characterization of plant 14-3-3 multiprotein complexes in vivo, stringent and specific antibody affinity purification was used to capture 14-3-3s together with their interacting proteins from extracts of Arabidopsis cell suspension cultures. Approximately 120 proteins were identified as potential in vivo 14-3-3 interacting proteins by mass spectrometry of the recovered complexes. Comparison of the proteins in this data set with the 14-3-3 interacting proteins from a similar study in human embryonic kidney cell cultures revealed eight interacting proteins that likely represent reasonably abundant, fundamental 14-3-3 interaction complexes that are highly conserved across all eukaryotes. The Arabidopsis 14-3-3 interaction data set was also compared to a yeast in vivo 14-3-3 interaction data set. Four 14-3-3 interacting proteins are conserved in yeast, humans, and Arabidopsis. Comparisons of the data sets based on biochemical function revealed many additional similarities in the human and Arabidopsis data sets that represent conserved functional interactions, while also leaving many proteins uniquely identified in either Arabidopsis or human cells. In particular, the Arabidopsis interaction data set is enriched for proteins involved in metabolism.

ERp57 interacts with conserved cysteine residues in the MHC class I peptide-binding groove.

PubMed

Antoniou, Antony N; Santos, Susana G; Campbell, Elaine C; Lynch, Sarah; Arosa, Fernando A; Powis, Simon J

2007-05-15

The oxidoreductase ERp57 is a component of the major histocompatibility complex (MHC) class I peptide-loading complex. ERp57 can interact directly with MHC class I molecules, however, little is known about which of the cysteine residues within the MHC class I molecule are relevant to this interaction. MHC class I molecules possess conserved disulfide bonds between cysteines 101-164, and 203-259 in the peptide-binding and alpha3 domain, respectively. By studying a series of mutants of these conserved residues, we demonstrate that ERp57 predominantly associates with cysteine residues in the peptide-binding domain, thus indicating ERp57 has direct access to the peptide-binding groove of MHC class I molecules during assembly.

An orthosteric inhibitor of the RAS-SOS interaction.

PubMed

Nickerson, Seth; Joy, Stephen T; Arora, Paramjit S; Bar-Sagi, Dafna

2013-01-01

Rat sarcoma (RAS) proteins are signaling nodes that transduce extracellular cues into precise alterations in cellular physiology by engaging effector pathways. RAS signaling thus regulates diverse cell processes including proliferation, migration, differentiation, and survival. Owing to this central role in governing mitogenic signals, RAS pathway components are often dysregulated in human diseases. Targeted therapy of RAS pathways has generally not been successful, largely because of the robust biochemistry of the targets and their multifaceted network of molecular regulators. The rate-limiting step of RAS activation is Son of Sevenless (SOS)-mediated nucleotide exchange involving a single evolutionarily conserved catalytic helix from SOS. Structure function data of this mechanism provided a strong platform to design an SOS-derived, helically constrained peptide mimic as an inhibitor of the RAS-SOS interaction. In this chapter, we review RAS-SOS signaling dynamics and present evidence supporting the novel paradigm of inhibiting their interaction as a therapeutic strategy. We then describe a method of generating helically constrained peptide mimics of protein surfaces, which we have employed to inhibit the RAS-SOS active site interaction. The biochemical and functional properties of this SOS mimic support the premise that inhibition of RAS-nucleotide exchange can effectively block RAS activation and downstream signaling. © 2013 Elsevier Inc. All rights reserved.

Evolutionary conservation of regulatory elements in vertebrate HOX gene clusters

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

Santini, Simona; Boore, Jeffrey L.; Meyer, Axel

2003-12-31

Due to their high degree of conservation, comparisons of DNA sequences among evolutionarily distantly-related genomes permit to identify functional regions in noncoding DNA. Hox genes are optimal candidate sequences for comparative genome analyses, because they are extremely conserved in vertebrates and occur in clusters. We aligned (Pipmaker) the nucleotide sequences of HoxA clusters of tilapia, pufferfish, striped bass, zebrafish, horn shark, human and mouse (over 500 million years of evolutionary distance). We identified several highly conserved intergenic sequences, likely to be important in gene regulation. Only a few of these putative regulatory elements have been previously described as being involvedmore » in the regulation of Hox genes, while several others are new elements that might have regulatory functions. The majority of these newly identified putative regulatory elements contain short fragments that are almost completely conserved and are identical to known binding sites for regulatory proteins (Transfac). The conserved intergenic regions located between the most rostrally expressed genes in the developing embryo are longer and better retained through evolution. We document that presumed regulatory sequences are retained differentially in either A or A clusters resulting from a genome duplication in the fish lineage. This observation supports both the hypothesis that the conserved elements are involved in gene regulation and the Duplication-Deletion-Complementation model.« less

Identifying all moiety conservation laws in genome-scale metabolic networks.

PubMed

De Martino, Andrea; De Martino, Daniele; Mulet, Roberto; Pagnani, Andrea

2014-01-01

The stoichiometry of a metabolic network gives rise to a set of conservation laws for the aggregate level of specific pools of metabolites, which, on one hand, pose dynamical constraints that cross-link the variations of metabolite concentrations and, on the other, provide key insight into a cell's metabolic production capabilities. When the conserved quantity identifies with a chemical moiety, extracting all such conservation laws from the stoichiometry amounts to finding all non-negative integer solutions of a linear system, a programming problem known to be NP-hard. We present an efficient strategy to compute the complete set of integer conservation laws of a genome-scale stoichiometric matrix, also providing a certificate for correctness and maximality of the solution. Our method is deployed for the analysis of moiety conservation relationships in two large-scale reconstructions of the metabolism of the bacterium E. coli, in six tissue-specific human metabolic networks, and, finally, in the human reactome as a whole, revealing that bacterial metabolism could be evolutionarily designed to cover broader production spectra than human metabolism. Convergence to the full set of moiety conservation laws in each case is achieved in extremely reduced computing times. In addition, we uncover a scaling relation that links the size of the independent pool basis to the number of metabolites, for which we present an analytical explanation.

The conservation pattern of short linear motifs is highly correlated with the function of interacting protein domains.

PubMed

Ren, Siyuan; Yang, Guang; He, Youyu; Wang, Yiguo; Li, Yixue; Chen, Zhengjun

2008-10-01

Many well-represented domains recognize primary sequences usually less than 10 amino acids in length, called Short Linear Motifs (SLiMs). Accurate prediction of SLiMs has been difficult because they are short (often < 10 amino acids) and highly degenerate. In this study, we combined scoring matrixes derived from peptide library and conservation analysis to identify protein classes enriched of functional SLiMs recognized by SH2, SH3, PDZ and S/T kinase domains. Our combined approach revealed that SLiMs are highly conserved in proteins from functional classes that are known to interact with a specific domain, but that they are not conserved in most other protein groups. We found that SLiMs recognized by SH2 domains were highly conserved in receptor kinases/phosphatases, adaptor molecules, and tyrosine kinases/phosphatases, that SLiMs recognized by SH3 domains were highly conserved in cytoskeletal and cytoskeletal-associated proteins, that SLiMs recognized by PDZ domains were highly conserved in membrane proteins such as channels and receptors, and that SLiMs recognized by S/T kinase domains were highly conserved in adaptor molecules, S/T kinases/phosphatases, and proteins involved in transcription or cell cycle control. We studied Tyr-SLiMs recognized by SH2 domains in more detail, and found that SH2-recognized Tyr-SLiMs on the cytoplasmic side of membrane proteins are more highly conserved than those on the extra-cellular side. Also, we found that SH2-recognized Tyr-SLiMs that are associated with SH3 motifs and a tyrosine kinase phosphorylation motif are more highly conserved. The interactome of protein domains is reflected by the evolutionary conservation of SLiMs recognized by these domains. Combining scoring matrixes derived from peptide libraries and conservation analysis, we would be able to find those protein groups that are more likely to interact with specific domains.

Motivational Systems in Adolescence: Possible Implications for Age Differences in Substance Abuse and Other Risk-Taking Behaviors

ERIC Educational Resources Information Center

Doremus-Fitzwater, Tamara L.; Varlinskaya, Elena I.; Spear, Linda P.

2010-01-01

Adolescence is an evolutionarily conserved developmental phase characterized by hormonal, physiological, neural and behavioral alterations evident widely across mammalian species. For instance, adolescent rats, like their human counterparts, exhibit elevations in peer-directed social interactions, risk-taking/novelty seeking and drug and alcohol…

The juxtamembrane regions of human receptor tyrosine kinases exhibit conserved interaction sites with anionic lipids

PubMed Central

Hedger, George; Sansom, Mark S. P.; Koldsø, Heidi

2015-01-01

Receptor tyrosine kinases (RTKs) play a critical role in diverse cellular processes and their activity is regulated by lipids in the surrounding membrane, including PIP2 (phosphatidylinositol-4,5-bisphosphate) in the inner leaflet, and GM3 (monosialodihexosylganglioside) in the outer leaflet. However, the precise details of the interactions at the molecular level remain to be fully characterised. Using a multiscale molecular dynamics simulation approach, we comprehensively characterise anionic lipid interactions with all 58 known human RTKs. Our results demonstrate that the juxtamembrane (JM) regions of RTKs are critical for inducing clustering of anionic lipids, including PIP2, both in simple asymmetric bilayers, and in more complex mixed membranes. Clustering is predominantly driven by interactions between a conserved cluster of basic residues within the first five positions of the JM region, and negatively charged lipid headgroups. This highlights a conserved interaction pattern shared across the human RTK family. In particular predominantly the N-terminal residues of the JM region are involved in the interactions with PIP2, whilst residues within the distal JM region exhibit comparatively less lipid specificity. Our results suggest that JM–lipid interactions play a key role in RTK structure and function, and more generally in the nanoscale organisation of receptor-containing cell membranes. PMID:25779975

A regulon conserved in monocot and dicot plants defines a functional module in antifungal plant immunity

PubMed Central

Humphry, Matt; Bednarek, Paweł; Kemmerling, Birgit; Koh, Serry; Stein, Mónica; Göbel, Ulrike; Stüber, Kurt; Piślewska-Bednarek, Mariola; Loraine, Ann; Schulze-Lefert, Paul; Somerville, Shauna; Panstruga, Ralph

2010-01-01

At least two components that modulate plant resistance against the fungal powdery mildew disease are ancient and have been conserved since the time of the monocot–dicot split (≈200 Mya). These components are the seven transmembrane domain containing MLO/MLO2 protein and the syntaxin ROR2/PEN1, which act antagonistically and have been identified in the monocot barley (Hordeum vulgare) and the dicot Arabidopsis thaliana, respectively. Additionally, syntaxin-interacting N-ethylmaleimide sensitive factor adaptor protein receptor proteins (VAMP721/722 and SNAP33/34) as well as a myrosinase (PEN2) and an ABC transporter (PEN3) contribute to antifungal resistance in both barley and/or Arabidopsis. Here, we show that these genetically defined defense components share a similar set of coexpressed genes in the two plant species, comprising a statistically significant overrepresentation of gene products involved in regulation of transcription, posttranslational modification, and signaling. Most of the coexpressed Arabidopsis genes possess a common cis-regulatory element that may dictate their coordinated expression. We exploited gene coexpression to uncover numerous components in Arabidopsis involved in antifungal defense. Together, our data provide evidence for an evolutionarily conserved regulon composed of core components and clade/species-specific innovations that functions as a module in plant innate immunity. PMID:21098265

Lariat sequencing in a unicellular yeast identifies regulated alternative splicing of exons that are evolutionarily conserved with humans.

PubMed

Awan, Ali R; Manfredo, Amanda; Pleiss, Jeffrey A

2013-07-30

Alternative splicing is a potent regulator of gene expression that vastly increases proteomic diversity in multicellular eukaryotes and is associated with organismal complexity. Although alternative splicing is widespread in vertebrates, little is known about the evolutionary origins of this process, in part because of the absence of phylogenetically conserved events that cross major eukaryotic clades. Here we describe a lariat-sequencing approach, which offers high sensitivity for detecting splicing events, and its application to the unicellular fungus, Schizosaccharomyces pombe, an organism that shares many of the hallmarks of alternative splicing in mammalian systems but for which no previous examples of exon-skipping had been demonstrated. Over 200 previously unannotated splicing events were identified, including examples of regulated alternative splicing. Remarkably, an evolutionary analysis of four of the exons identified here as subject to skipping in S. pombe reveals high sequence conservation and perfect length conservation with their homologs in scores of plants, animals, and fungi. Moreover, alternative splicing of two of these exons have been documented in multiple vertebrate organisms, making these the first demonstrations of identical alternative-splicing patterns in species that are separated by over 1 billion y of evolution.

REMARKS ON COMPOUND MODELS, CONSERVED CURRENTS AND WEAK INTERACTIONS

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

Mayer, M.E.

A discussion is given of some implications of a symmetry principle, conjectured by Gamba, Marshak, and Okubo (GMO), in connection with the compound models for elementary particles, and the interpretation of weak interactions by a heavy vector meson coupled to the conserved V and A currents of the fermions. GMO observed that, for weak interactions, the three baryons LAMBDA deg , n, p are equivalent to the leptons mu /sup -/, e/sup -/, nu in the sense that any reaction permitted or observed for one of the groups is permitted for the other and conversely, no reaction forbidden for onemore » is observed in the other. This permitted the extension of the notions of isospin and strangeness to leptons and led to the expression of the electric charge in terms of the isospin projection, T/sub 3/, and the baryon and lepton numbers B and L:. Q = T/sub 3/ + 1/2(S+ B -- L). (B.O.G.)« less

A nuclear DNA perspective on delineating evolutionarily significant lineages in polyploids: the case of the endangered shortnose sturgeon (Acipenser brevirostrum)

USGS Publications Warehouse

King, Timothy L.; Henderson, Anne P.; Kynard, Boyd E.; Kieffer, Micah C.; Peterson, Douglas L.; Aunins, Aaron W.; Brown, Bonnie L.

2014-01-01

The shortnose sturgeon, Acipenser brevirostrum, oft considered a phylogenetic relic, is listed as an “endangered species threatened with extinction” in the US and “Vulnerable” on the IUCN Red List. Effective conservation of A. brevirostrum depends on understanding its diversity and evolutionary processes, yet challenges associated with the polyploid nature of its nuclear genome have heretofore limited population genetic analysis to maternally inherited haploid characters. We developed a suite of polysomic microsatellite DNA markers and characterized a sample of 561 shortnose sturgeon collected from major extant populations along the North American Atlantic coast. The 181 alleles observed at 11 loci were scored as binary loci and the data were subjected to multivariate ordination, Bayesian clustering, hierarchical partitioning of variance, and among-population distance metric tests. The methods uncovered moderately high levels of gene diversity suggesting population structuring across and within three metapopulations (Northeast, Mid-Atlantic, and Southeast) that encompass seven demographically discrete and evolutionarily distinct lineages. The predicted groups are consistent with previously described behavioral patterns, especially dispersal and migration, supporting the interpretation that A. brevirostrum exhibit adaptive differences based on watershed. Combined with results of prior genetic (mitochondrial DNA) and behavioral studies, the current work suggests that dispersal is an important factor in maintaining genetic diversity in A. brevirostrum and that the basic unit for conservation management is arguably the local population.

A nuclear DNA perspective on delineating evolutionarily significant lineages in polyploids: the case of the endangered shortnose sturgeon (Acipenser brevirostrum).

PubMed

King, Tim L; Henderson, Anne P; Kynard, Boyd E; Kieffer, Micah C; Peterson, Douglas L; Aunins, Aaron W; Brown, Bonnie L

2014-01-01

The shortnose sturgeon, Acipenser brevirostrum, oft considered a phylogenetic relic, is listed as an "endangered species threatened with extinction" in the US and "Vulnerable" on the IUCN Red List. Effective conservation of A. brevirostrum depends on understanding its diversity and evolutionary processes, yet challenges associated with the polyploid nature of its nuclear genome have heretofore limited population genetic analysis to maternally inherited haploid characters. We developed a suite of polysomic microsatellite DNA markers and characterized a sample of 561 shortnose sturgeon collected from major extant populations along the North American Atlantic coast. The 181 alleles observed at 11 loci were scored as binary loci and the data were subjected to multivariate ordination, Bayesian clustering, hierarchical partitioning of variance, and among-population distance metric tests. The methods uncovered moderately high levels of gene diversity suggesting population structuring across and within three metapopulations (Northeast, Mid-Atlantic, and Southeast) that encompass seven demographically discrete and evolutionarily distinct lineages. The predicted groups are consistent with previously described behavioral patterns, especially dispersal and migration, supporting the interpretation that A. brevirostrum exhibit adaptive differences based on watershed. Combined with results of prior genetic (mitochondrial DNA) and behavioral studies, the current work suggests that dispersal is an important factor in maintaining genetic diversity in A. brevirostrum and that the basic unit for conservation management is arguably the local population.

Conserved Sequence Preferences Contribute to Substrate Recognition by the Proteasome*

PubMed Central

Yu, Houqing; Singh Gautam, Amit K.; Wilmington, Shameika R.; Wylie, Dennis; Martinez-Fonts, Kirby; Kago, Grace; Warburton, Marie; Chavali, Sreenivas; Inobe, Tomonao; Finkelstein, Ilya J.; Babu, M. Madan

2016-01-01

The proteasome has pronounced preferences for the amino acid sequence of its substrates at the site where it initiates degradation. Here, we report that modulating these sequences can tune the steady-state abundance of proteins over 2 orders of magnitude in cells. This is the same dynamic range as seen for inducing ubiquitination through a classic N-end rule degron. The stability and abundance of His3 constructs dictated by the initiation site affect survival of yeast cells and show that variation in proteasomal initiation can affect fitness. The proteasome's sequence preferences are linked directly to the affinity of the initiation sites to their receptor on the proteasome and are conserved between Saccharomyces cerevisiae, Schizosaccharomyces pombe, and human cells. These findings establish that the sequence composition of unstructured initiation sites influences protein abundance in vivo in an evolutionarily conserved manner and can affect phenotype and fitness. PMID:27226608

MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution

PubMed Central

Huang, Shouxiong; Martin, Emmanuel; Kim, Sojung; Yu, Lawrence; Soudais, Claire; Fremont, Daved H.; Lantz, Olivier; Hansen, Ted H.

2009-01-01

Several nonclassical major histocompatibilty antigens (class Ib molecules) have emerged as key players in the early immune response to pathogens or stress. Class Ib molecules activate subsets of T cells that mount effector responses before the adaptive immune system, and thus are called innate T cells. MR1 is a novel class Ib molecule with properties highly suggestive of its regulation of mucosal immunity. The Mr1 gene is evolutionarily conserved, is non-Mhc linked, and controls the development of mucosal-associated invariant T (MAIT) cells. MAIT cells preferentially reside in the gut, and their development is dependent on commensal microbiota. Although these properties suggest that MAIT cells function as innate T cells in the mucosa, this has been difficult to test, due to the (i) paucity of MAIT cells that display MR1-specific activation in vitro and (ii) lack of knowledge of whether or not MR1 presents antigen. Here we show that both mouse and human MAIT cells display a high level of cross-reactivity on mammalian MR1 orthologs, but with differences consistent with limited ligand discrimination. Furthermore, acid eluates from recombinant or cellular MR1 proteins enhance MAIT cell activation in an MR1-specific and cross-species manner. Our findings demonstrate that the presentation pathway of MR1 to MAIT cells is highly evolutionarily conserved. PMID:19416870

Secondary metabolites in plant innate immunity: conserved function of divergent chemicals.

PubMed

Piasecka, Anna; Jedrzejczak-Rey, Nicolas; Bednarek, Paweł

2015-05-01

Plant secondary metabolites carry out numerous functions in interactions between plants and a broad range of other organisms. Experimental evidence strongly supports the indispensable contribution of many constitutive and pathogen-inducible phytochemicals to plant innate immunity. Extensive studies on model plant species, particularly Arabidopsis thaliana, have brought significant advances in our understanding of the molecular mechanisms underpinning pathogen-triggered biosynthesis and activation of defensive secondary metabolites. However, despite the proven significance of secondary metabolites in plant response to pathogenic microorganisms, little is known about the precise mechanisms underlying their contribution to plant immunity. This insufficiency concerns information on the dynamics of cellular and subcellular localization of defensive phytochemicals during the encounters with microbial pathogens and precise knowledge on their mode of action. As many secondary metabolites are characterized by their in vitro antimicrobial activity, these compounds were commonly considered to function in plant defense as in planta antibiotics. Strikingly, recent experimental evidence suggests that at least some of these compounds alternatively may be involved in controlling several immune responses that are evolutionarily conserved in the plant kingdom, including callose deposition and programmed cell death. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Positioning of centrioles is a conserved readout of Frizzled planar cell polarity signalling

PubMed Central

Carvajal-Gonzalez, Jose Maria; Roman, Angel-Carlos; Mlodzik, Marek

2016-01-01

Planar cell polarity (PCP) signalling is a well-conserved developmental pathway regulating cellular orientation during development. An evolutionarily conserved pathway readout is not established and, moreover, it is thought that PCP mediated cellular responses are tissue-specific. A key PCP function in vertebrates is to regulate coordinated centriole/cilia positioning, a function that has not been associated with PCP in Drosophila. Here we report instructive input of Frizzled-PCP (Fz/PCP) signalling into polarized centriole positioning in Drosophila wings. We show that centrioles are polarized in pupal wing cells as a readout of PCP signalling, with both gain and loss-of-function Fz/PCP signalling affecting centriole polarization. Importantly, loss or gain of centrioles does not affect Fz/PCP establishment, implicating centriolar positioning as a conserved PCP-readout, likely downstream of PCP-regulated actin polymerization. Together with vertebrate data, these results suggest a unifying model of centriole/cilia positioning as a common downstream effect of PCP signalling from flies to mammals. PMID:27021213

Positioning of centrioles is a conserved readout of Frizzled planar cell polarity signalling.

PubMed

Carvajal-Gonzalez, Jose Maria; Roman, Angel-Carlos; Mlodzik, Marek

2016-03-29

Planar cell polarity (PCP) signalling is a well-conserved developmental pathway regulating cellular orientation during development. An evolutionarily conserved pathway readout is not established and, moreover, it is thought that PCP mediated cellular responses are tissue-specific. A key PCP function in vertebrates is to regulate coordinated centriole/cilia positioning, a function that has not been associated with PCP in Drosophila. Here we report instructive input of Frizzled-PCP (Fz/PCP) signalling into polarized centriole positioning in Drosophila wings. We show that centrioles are polarized in pupal wing cells as a readout of PCP signalling, with both gain and loss-of-function Fz/PCP signalling affecting centriole polarization. Importantly, loss or gain of centrioles does not affect Fz/PCP establishment, implicating centriolar positioning as a conserved PCP-readout, likely downstream of PCP-regulated actin polymerization. Together with vertebrate data, these results suggest a unifying model of centriole/cilia positioning as a common downstream effect of PCP signalling from flies to mammals.

CORECLUST: identification of the conserved CRM grammar together with prediction of gene regulation.

PubMed

Nikulova, Anna A; Favorov, Alexander V; Sutormin, Roman A; Makeev, Vsevolod J; Mironov, Andrey A

2012-07-01

Identification of transcriptional regulatory regions and tracing their internal organization are important for understanding the eukaryotic cell machinery. Cis-regulatory modules (CRMs) of higher eukaryotes are believed to possess a regulatory 'grammar', or preferred arrangement of binding sites, that is crucial for proper regulation and thus tends to be evolutionarily conserved. Here, we present a method CORECLUST (COnservative REgulatory CLUster STructure) that predicts CRMs based on a set of positional weight matrices. Given regulatory regions of orthologous and/or co-regulated genes, CORECLUST constructs a CRM model by revealing the conserved rules that describe the relative location of binding sites. The constructed model may be consequently used for the genome-wide prediction of similar CRMs, and thus detection of co-regulated genes, and for the investigation of the regulatory grammar of the system. Compared with related methods, CORECLUST shows better performance at identification of CRMs conferring muscle-specific gene expression in vertebrates and early-developmental CRMs in Drosophila.

On the relationship between residue structural environment and sequence conservation in proteins.

PubMed

Liu, Jen-Wei; Lin, Jau-Ji; Cheng, Chih-Wen; Lin, Yu-Feng; Hwang, Jenn-Kang; Huang, Tsun-Tsao

2017-09-01

Residues that are crucial to protein function or structure are usually evolutionarily conserved. To identify the important residues in protein, sequence conservation is estimated, and current methods rely upon the unbiased collection of homologous sequences. Surprisingly, our previous studies have shown that the sequence conservation is closely correlated with the weighted contact number (WCN), a measure of packing density for residue's structural environment, calculated only based on the C α positions of a protein structure. Moreover, studies have shown that sequence conservation is correlated with environment-related structural properties calculated based on different protein substructures, such as a protein's all atoms, backbone atoms, side-chain atoms, or side-chain centroid. To know whether the C α atomic positions are adequate to show the relationship between residue environment and sequence conservation or not, here we compared C α atoms with other substructures in their contributions to the sequence conservation. Our results show that C α positions are substantially equivalent to the other substructures in calculations of various measures of residue environment. As a result, the overlapping contributions between C α atoms and the other substructures are high, yielding similar structure-conservation relationship. Take the WCN as an example, the average overlapping contribution to sequence conservation is 87% between C α and all-atom substructures. These results indicate that only C α atoms of a protein structure could reflect sequence conservation at the residue level. © 2017 Wiley Periodicals, Inc.

Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions.

PubMed

Hill, W D; Davies, G; Harris, S E; Hagenaars, S P; Liewald, D C; Penke, L; Gale, C R; Deary, I J

2016-12-13

Differences in general cognitive function have been shown to be partly heritable and to show genetic correlations with several psychiatric and physical disease states. However, to date, few single-nucleotide polymorphisms (SNPs) have demonstrated genome-wide significance, hampering efforts aimed at determining which genetic variants are most important for cognitive function and which regions drive the genetic associations between cognitive function and disease states. Here, we combine multiple large genome-wide association study (GWAS) data sets, from the CHARGE cognitive consortium (n=53 949) and UK Biobank (n=36 035), to partition the genome into 52 functional annotations and an additional 10 annotations describing tissue-specific histone marks. Using stratified linkage disequilibrium score regression we show that, in two measures of cognitive function, SNPs associated with cognitive function cluster in regions of the genome that are under evolutionary negative selective pressure. These conserved regions contained ~2.6% of the SNPs from each GWAS but accounted for ~40% of the SNP-based heritability. The results suggest that the search for causal variants associated with cognitive function, and those variants that exert a pleiotropic effect between cognitive function and health, will be facilitated by examining these enriched regions.

The conservation pattern of short linear motifs is highly correlated with the function of interacting protein domains

PubMed Central

Ren, Siyuan; Yang, Guang; He, Youyu; Wang, Yiguo; Li, Yixue; Chen, Zhengjun

2008-01-01

Background Many well-represented domains recognize primary sequences usually less than 10 amino acids in length, called Short Linear Motifs (SLiMs). Accurate prediction of SLiMs has been difficult because they are short (often < 10 amino acids) and highly degenerate. In this study, we combined scoring matrixes derived from peptide library and conservation analysis to identify protein classes enriched of functional SLiMs recognized by SH2, SH3, PDZ and S/T kinase domains. Results Our combined approach revealed that SLiMs are highly conserved in proteins from functional classes that are known to interact with a specific domain, but that they are not conserved in most other protein groups. We found that SLiMs recognized by SH2 domains were highly conserved in receptor kinases/phosphatases, adaptor molecules, and tyrosine kinases/phosphatases, that SLiMs recognized by SH3 domains were highly conserved in cytoskeletal and cytoskeletal-associated proteins, that SLiMs recognized by PDZ domains were highly conserved in membrane proteins such as channels and receptors, and that SLiMs recognized by S/T kinase domains were highly conserved in adaptor molecules, S/T kinases/phosphatases, and proteins involved in transcription or cell cycle control. We studied Tyr-SLiMs recognized by SH2 domains in more detail, and found that SH2-recognized Tyr-SLiMs on the cytoplasmic side of membrane proteins are more highly conserved than those on the extra-cellular side. Also, we found that SH2-recognized Tyr-SLiMs that are associated with SH3 motifs and a tyrosine kinase phosphorylation motif are more highly conserved. Conclusion The interactome of protein domains is reflected by the evolutionary conservation of SLiMs recognized by these domains. Combining scoring matrixes derived from peptide libraries and conservation analysis, we would be able to find those protein groups that are more likely to interact with specific domains. PMID:18828911

FEZ2 has acquired additional protein interaction partners relative to FEZ1: functional and evolutionary implications.

PubMed

Alborghetti, Marcos R; Furlan, Ariane S; Kobarg, Jörg

2011-03-08

The FEZ (fasciculation and elongation protein zeta) family designation was purposed by Bloom and Horvitz by genetic analysis of C. elegans unc-76. Similar human sequences were identified in the expressed sequence tag database as FEZ1 and FEZ2. The unc-76 function is necessary for normal axon fasciculation and is required for axon-axon interactions. Indeed, the loss of UNC-76 function results in defects in axonal transport. The human FEZ1 protein has been shown to rescue defects caused by unc-76 mutations in nematodes, indicating that both UNC-76 and FEZ1 are evolutionarily conserved in their function. Until today, little is known about FEZ2 protein function. Using the yeast two-hybrid system we demonstrate here conserved evolutionary features among orthologs and non-conserved features between paralogs of the FEZ family of proteins, by comparing the interactome profiles of the C-terminals of human FEZ1, FEZ2 and UNC-76 from C. elegans. Furthermore, we correlate our data with an analysis of the molecular evolution of the FEZ protein family in the animal kingdom. We found that FEZ2 interacted with 59 proteins and that of these only 40 interacted with FEZ1. Of the 40 FEZ1 interacting proteins, 36 (90%), also interacted with UNC-76 and none of the 19 FEZ2 specific proteins interacted with FEZ1 or UNC-76. This together with the duplication of unc-76 gene in the ancestral line of chordates suggests that FEZ2 is in the process of acquiring new additional functions. The results provide also an explanation for the dramatic difference between C. elegans and D. melanogaster unc-76 mutants on one hand, which cause serious defects in the nervous system, and the mouse FEZ1 -/- knockout mice on the other, which show no morphological and no strong behavioural phenotype. Likely, the ubiquitously expressed FEZ2 can completely compensate the lack of neuronal FEZ1, since it can interact with all FEZ1 interacting proteins and additional 19 proteins.

FEZ2 Has Acquired Additional Protein Interaction Partners Relative to FEZ1: Functional and Evolutionary Implications

PubMed Central

Alborghetti, Marcos R.; Furlan, Ariane S.; Kobarg, Jörg

2011-01-01

Background The FEZ (fasciculation and elongation protein zeta) family designation was purposed by Bloom and Horvitz by genetic analysis of C. elegans unc-76. Similar human sequences were identified in the expressed sequence tag database as FEZ1 and FEZ2. The unc-76 function is necessary for normal axon fasciculation and is required for axon-axon interactions. Indeed, the loss of UNC-76 function results in defects in axonal transport. The human FEZ1 protein has been shown to rescue defects caused by unc-76 mutations in nematodes, indicating that both UNC-76 and FEZ1 are evolutionarily conserved in their function. Until today, little is known about FEZ2 protein function. Methodology/Principal Findings Using the yeast two-hybrid system we demonstrate here conserved evolutionary features among orthologs and non-conserved features between paralogs of the FEZ family of proteins, by comparing the interactome profiles of the C-terminals of human FEZ1, FEZ2 and UNC-76 from C. elegans. Furthermore, we correlate our data with an analysis of the molecular evolution of the FEZ protein family in the animal kingdom. Conclusions/Significance We found that FEZ2 interacted with 59 proteins and that of these only 40 interacted with FEZ1. Of the 40 FEZ1 interacting proteins, 36 (90%), also interacted with UNC-76 and none of the 19 FEZ2 specific proteins interacted with FEZ1 or UNC-76. This together with the duplication of unc-76 gene in the ancestral line of chordates suggests that FEZ2 is in the process of acquiring new additional functions. The results provide also an explanation for the dramatic difference between C. elegans and D. melanogaster unc-76 mutants on one hand, which cause serious defects in the nervous system, and the mouse FEZ1 -/- knockout mice on the other, which show no morphological and no strong behavioural phenotype. Likely, the ubiquitously expressed FEZ2 can completely compensate the lack of neuronal FEZ1, since it can interact with all FEZ1 interacting

Zygote arrest 1 (Zar1) is an evolutionarily conserved gene expressed in vertebrate ovaries.

PubMed

Wu, Xuemei; Wang, Pei; Brown, Christopher A; Zilinski, Carolyn A; Matzuk, Martin M

2003-09-01

Zygote arrest 1 (ZAR1) is an ovary-specific maternal factor that plays essential roles during the oocyte-to-embryo transition. In mice, the Zar1 mRNA is detected as a 1.4-kilobase (kb) transcript that is synthesized exclusively in growing oocytes. To further understand the functions of ZAR1, we have cloned the orthologous Zar1 cDNA and/or genes for mouse, rat, human, frog, zebrafish, and pufferfish. The entire mouse Zar1 gene and a related pseudogene span approximately 4.0 kb, contain four exons, and map to adjacent loci on mouse chromosome 5. The human ZAR1 orthologous gene similarly consists of four exons and resides on human chromosome 4p12, which is syntenic with the mouse Zar1 chromosomal locus. Rat (Rattus norvegicus) and pufferfish (Fugu rubripes) Zar1 genes were recognized by database mining and deduced protein alignment analysis. The rat Zar1 gene also maps to a region that is syntenic with the mouse Zar1 gene locus on rat chromosome 14. Frog (Xenopus laevis) and zebrafish (Danio rerio) Zar1 orthologs were cloned by reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends analysis of ovarian mRNA. Unlike mouse and human, the frog Zar1 is detected in multiple tissues, including lung, muscle, and ovary. The Zar1 mRNA appears in the cytoplasm of oocytes and persists until the tailbud stage during frog embryogenesis. Mouse, rat, human, frog, zebrafish, and pufferfish Zar1 genes encode proteins of 361, 361, 424, 295, 329, and 320 amino acids, respectively, and share 50.8%-88.1% amino acid identity. Regions of the N-termini of these ZAR1 orthologs show high sequence identity among these various proteins. However, the C-terminal 103 amino acids of these proteins, encoded by exons 2-4, contain an atypical eight-cysteine Plant Homeo Domain motif and are highly conserved, sharing 80.6%-98.1% identity among these species. These findings suggest that the carboxyl-termini of these ZAR1 proteins contain an important functional domain that is

Fenced and Fragmented: Conservation Value of Managed Metapopulations

PubMed Central

Miller, Susan M.; Harper, Cindy K.; Bloomer, Paulette; Hofmeyr, Jennifer; Funston, Paul J.

2015-01-01

Population fragmentation is threatening biodiversity worldwide. Species that once roamed vast areas are increasingly being conserved in small, isolated areas. Modern management approaches must adapt to ensure the continued survival and conservation value of these populations. In South Africa, a managed metapopulation approach has been adopted for several large carnivore species, all protected in isolated, relatively small, reserves that are fenced. As far as possible these approaches are based on natural metapopulation structures. In this network, over the past 25 years, African lions (Panthera leo) were reintroduced into 44 fenced reserves with little attention given to maintaining genetic diversity. To examine the situation, we investigated the current genetic provenance and diversity of these lions. We found that overall genetic diversity was similar to that in a large national park, and included a mixture of four different southern African evolutionarily significant units (ESUs). This mixing of ESUs, while not ideal, provides a unique opportunity to study the impact of mixing ESUs over the long term. We propose a strategic managed metapopulation plan to ensure the maintenance of genetic diversity and improve the long-term conservation value of these lions. This managed metapopulation approach could be applied to other species under similar ecological constraints around the globe. PMID:26699333

The Mediator complex of Caenorhabditis elegans: insights into the developmental and physiological roles of a conserved transcriptional coregulator

PubMed Central

Grants, Jennifer M.; Goh, Grace Y. S.; Taubert, Stefan

2015-01-01

The Mediator multiprotein complex (‘Mediator’) is an important transcriptional coregulator that is evolutionarily conserved throughout eukaryotes. Although some Mediator subunits are essential for the transcription of all protein-coding genes, others influence the expression of only subsets of genes and participate selectively in cellular signaling pathways. Here, we review the current knowledge of Mediator subunit function in the nematode Caenorhabditis elegans, a metazoan in which established and emerging genetic technologies facilitate the study of developmental and physiological regulation in vivo. In this nematode, unbiased genetic screens have revealed critical roles for Mediator components in core developmental pathways such as epidermal growth factor (EGF) and Wnt/β-catenin signaling. More recently, important roles for C. elegans Mediator subunits have emerged in the regulation of lipid metabolism and of systemic stress responses, engaging conserved transcription factors such as nuclear hormone receptors (NHRs). We emphasize instances where similar functions for individual Mediator subunits exist in mammals, highlighting parallels between Mediator subunit action in nematode development and in human cancer biology. We also discuss a parallel between the association of the Mediator subunit MED12 with several human disorders and the role of its C. elegans ortholog mdt-12 as a regulatory hub that interacts with numerous signaling pathways. PMID:25634893

On Nash Equilibrium and Evolutionarily Stable States That Are Not Characterised by the Folk Theorem

PubMed Central

Li, Jiawei; Kendall, Graham

2015-01-01

In evolutionary game theory, evolutionarily stable states are characterised by the folk theorem because exact solutions to the replicator equation are difficult to obtain. It is generally assumed that the folk theorem, which is the fundamental theory for non-cooperative games, defines all Nash equilibria in infinitely repeated games. Here, we prove that Nash equilibria that are not characterised by the folk theorem do exist. By adopting specific reactive strategies, a group of players can be better off by coordinating their actions in repeated games. We call it a type-k equilibrium when a group of k players coordinate their actions and they have no incentive to deviate from their strategies simultaneously. The existence and stability of the type-k equilibrium in general games is discussed. This study shows that the sets of Nash equilibria and evolutionarily stable states have greater cardinality than classic game theory has predicted in many repeated games. PMID:26288088

Conserved intergenic sequences revealed by CTAG-profiling in Salmonella: thermodynamic modeling for function prediction

NASA Astrophysics Data System (ADS)

Tang, Le; Zhu, Songling; Mastriani, Emilio; Fang, Xin; Zhou, Yu-Jie; Li, Yong-Guo; Johnston, Randal N.; Guo, Zheng; Liu, Gui-Rong; Liu, Shu-Lin

2017-03-01

Highly conserved short sequences help identify functional genomic regions and facilitate genomic annotation. We used Salmonella as the model to search the genome for evolutionarily conserved regions and focused on the tetranucleotide sequence CTAG for its potentially important functions. In Salmonella, CTAG is highly conserved across the lineages and large numbers of CTAG-containing short sequences fall in intergenic regions, strongly indicating their biological importance. Computer modeling demonstrated stable stem-loop structures in some of the CTAG-containing intergenic regions, and substitution of a nucleotide of the CTAG sequence would radically rearrange the free energy and disrupt the structure. The postulated degeneration of CTAG takes distinct patterns among Salmonella lineages and provides novel information about genomic divergence and evolution of these bacterial pathogens. Comparison of the vertically and horizontally transmitted genomic segments showed different CTAG distribution landscapes, with the genome amelioration process to remove CTAG taking place inward from both terminals of the horizontally acquired segment.

Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions

PubMed Central

Hill, W D; Davies, G; Harris, S E; Hagenaars, S P; Davies, Gail; Deary, Ian J; Debette, Stephanie; Verbaas, Carla I; Bressler, Jan; Schuur, Maaike; Smith, Albert V; Bis, Joshua C; Bennett, David A; Ikram, M Arfan; Launer, Lenore J; Fitzpatrick, Annette L; Seshadri, Sudha; van Duijn, Cornelia M; Mosley Jr, Thomas H; Liewald, D C; Penke, L; Gale, C R; Deary, I J

2016-01-01

Differences in general cognitive function have been shown to be partly heritable and to show genetic correlations with several psychiatric and physical disease states. However, to date, few single-nucleotide polymorphisms (SNPs) have demonstrated genome-wide significance, hampering efforts aimed at determining which genetic variants are most important for cognitive function and which regions drive the genetic associations between cognitive function and disease states. Here, we combine multiple large genome-wide association study (GWAS) data sets, from the CHARGE cognitive consortium (n=53 949) and UK Biobank (n=36 035), to partition the genome into 52 functional annotations and an additional 10 annotations describing tissue-specific histone marks. Using stratified linkage disequilibrium score regression we show that, in two measures of cognitive function, SNPs associated with cognitive function cluster in regions of the genome that are under evolutionary negative selective pressure. These conserved regions contained ~2.6% of the SNPs from each GWAS but accounted for ~40% of the SNP-based heritability. The results suggest that the search for causal variants associated with cognitive function, and those variants that exert a pleiotropic effect between cognitive function and health, will be facilitated by examining these enriched regions. PMID:27959336

The evolutionarily conserved G protein-coupled receptor SREB2/GPR85 influences brain size, behavior, and vulnerability to schizophrenia.

PubMed

Matsumoto, Mitsuyuki; Straub, Richard E; Marenco, Stefano; Nicodemus, Kristin K; Matsumoto, Shun-Ichiro; Fujikawa, Akihiko; Miyoshi, Sosuke; Shobo, Miwako; Takahashi, Shinji; Yarimizu, Junko; Yuri, Masatoshi; Hiramoto, Masashi; Morita, Shuji; Yokota, Hiroyuki; Sasayama, Takeshi; Terai, Kazuhiro; Yoshino, Masayasu; Miyake, Akira; Callicott, Joseph H; Egan, Michael F; Meyer-Lindenberg, Andreas; Kempf, Lucas; Honea, Robyn; Vakkalanka, Radha Krishna; Takasaki, Jun; Kamohara, Masazumi; Soga, Takatoshi; Hiyama, Hideki; Ishii, Hiroyuki; Matsuo, Ayako; Nishimura, Shintaro; Matsuoka, Nobuya; Kobori, Masato; Matsushime, Hitoshi; Katoh, Masao; Furuichi, Kiyoshi; Weinberger, Daniel R

2008-04-22

The G protein-coupled receptor (GPCR) family is highly diversified and involved in many forms of information processing. SREB2 (GPR85) is the most conserved GPCR throughout vertebrate evolution and is expressed abundantly in brain structures exhibiting high levels of plasticity, e.g., the hippocampal dentate gyrus. Here, we show that SREB2 is involved in determining brain size, modulating diverse behaviors, and potentially in vulnerability to schizophrenia. Mild overexpression of SREB2 caused significant brain weight reduction and ventricular enlargement in transgenic (Tg) mice as well as behavioral abnormalities mirroring psychiatric disorders, e.g., decreased social interaction, abnormal sensorimotor gating, and impaired memory. SREB2 KO mice showed a reciprocal phenotype, a significant increase in brain weight accompanying a trend toward enhanced memory without apparent other behavioral abnormalities. In both Tg and KO mice, no gross malformation of brain structures was observed. Because of phenotypic overlap between SREB2 Tg mice and schizophrenia, we sought a possible link between the two. Minor alleles of two SREB2 SNPs, located in intron 2 and in the 3' UTR, were overtransmitted to schizophrenia patients in a family-based sample and showed an allele load association with reduced hippocampal gray matter volume in patients. Our data implicate SREB2 as a potential risk factor for psychiatric disorders and its pathway as a target for psychiatric therapy.

Evolutionary conservation of regulated longevity assurance mechanisms

PubMed Central

McElwee, Joshua J; Schuster, Eugene; Blanc, Eric; Piper, Matthew D; Thomas, James H; Patel, Dhaval S; Selman, Colin; Withers, Dominic J; Thornton, Janet M; Partridge, Linda; Gems, David

2007-01-01

Background To what extent are the determinants of aging in animal species universal? Insulin/insulin-like growth factor (IGF)-1 signaling (IIS) is an evolutionarily conserved (public) regulator of longevity; yet it remains unclear whether the genes and biochemical processes through which IIS acts on aging are public or private (that is, lineage specific). To address this, we have applied a novel, multi-level cross-species comparative analysis to compare gene expression changes accompanying increased longevity in mutant nematodes, fruitflies and mice with reduced IIS. Results Surprisingly, there is little evolutionary conservation at the level of individual, orthologous genes or paralogous genes under IIS regulation. However, a number of gene categories are significantly enriched for genes whose expression changes in long-lived animals of all three species. Down-regulated categories include protein biosynthesis-associated genes. Up-regulated categories include sugar catabolism, energy generation, glutathione-S-transferases (GSTs) and several other categories linked to cellular detoxification (that is, phase 1 and phase 2 metabolism of xenobiotic and endobiotic toxins). Protein biosynthesis and GST activity have recently been linked to aging and longevity assurance, respectively. Conclusion These processes represent candidate, regulated mechanisms of longevity-control that are conserved across animal species. The longevity assurance mechanisms via which IIS acts appear to be lineage-specific at the gene level (private), but conserved at the process level (or semi-public). In the case of GSTs, and cellular detoxification generally, this suggests that the mechanisms of aging against which longevity assurance mechanisms act are, to some extent, lineage specific. PMID:17612391

76 FR 50448 - Endangered and Threatened Species; 5-Year Reviews for 17 Evolutionarily Significant Units and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-15

... 11 evolutionarily significant units (ESUs) of Pacific salmon (Oncorhynchus sp.) and 6 distinct... and 6 DPSs of steelhead in Oregon, Washington, and Idaho shall remain listed as determined in 2005... Sound Chinook salmon; (4) Lower Columbia River Chinook salmon; (5) Upper Willamette Chinook salmon; (6...

Seed storage protein gene promoters contain conserved DNA motifs in Brassicaceae, Fabaceae and Poaceae

PubMed Central

Fauteux, François; Strömvik, Martina V

2009-01-01

Background Accurate computational identification of cis-regulatory motifs is difficult, particularly in eukaryotic promoters, which typically contain multiple short and degenerate DNA sequences bound by several interacting factors. Enrichment in combinations of rare motifs in the promoter sequence of functionally or evolutionarily related genes among several species is an indicator of conserved transcriptional regulatory mechanisms. This provides a basis for the computational identification of cis-regulatory motifs. Results We have used a discriminative seeding DNA motif discovery algorithm for an in-depth analysis of 54 seed storage protein (SSP) gene promoters from three plant families, namely Brassicaceae (mustards), Fabaceae (legumes) and Poaceae (grasses) using backgrounds based on complete sets of promoters from a representative species in each family, namely Arabidopsis (Arabidopsis thaliana (L.) Heynh.), soybean (Glycine max (L.) Merr.) and rice (Oryza sativa L.) respectively. We have identified three conserved motifs (two RY-like and one ACGT-like) in Brassicaceae and Fabaceae SSP gene promoters that are similar to experimentally characterized seed-specific cis-regulatory elements. Fabaceae SSP gene promoter sequences are also enriched in a novel, seed-specific E2Fb-like motif. Conserved motifs identified in Poaceae SSP gene promoters include a GCN4-like motif, two prolamin-box-like motifs and an Skn-1-like motif. Evidence of the presence of a variant of the TATA-box is found in the SSP gene promoters from the three plant families. Motifs discovered in SSP gene promoters were used to score whole-genome sets of promoters from Arabidopsis, soybean and rice. The highest-scoring promoters are associated with genes coding for different subunits or precursors of seed storage proteins. Conclusion Seed storage protein gene promoter motifs are conserved in diverse species, and different plant families are characterized by a distinct combination of conserved motifs

Topology-function conservation in protein-protein interaction networks.

PubMed

Davis, Darren; Yaveroğlu, Ömer Nebil; Malod-Dognin, Noël; Stojmirovic, Aleksandar; Pržulj, Nataša

2015-05-15

Proteins underlay the functioning of a cell and the wiring of proteins in protein-protein interaction network (PIN) relates to their biological functions. Proteins with similar wiring in the PIN (topology around them) have been shown to have similar functions. This property has been successfully exploited for predicting protein functions. Topological similarity is also used to guide network alignment algorithms that find similarly wired proteins between PINs of different species; these similarities are used to transfer annotation across PINs, e.g. from model organisms to human. To refine these functional predictions and annotation transfers, we need to gain insight into the variability of the topology-function relationships. For example, a function may be significantly associated with specific topologies, while another function may be weakly associated with several different topologies. Also, the topology-function relationships may differ between different species. To improve our understanding of topology-function relationships and of their conservation among species, we develop a statistical framework that is built upon canonical correlation analysis. Using the graphlet degrees to represent the wiring around proteins in PINs and gene ontology (GO) annotations to describe their functions, our framework: (i) characterizes statistically significant topology-function relationships in a given species, and (ii) uncovers the functions that have conserved topology in PINs of different species, which we term topologically orthologous functions. We apply our framework to PINs of yeast and human, identifying seven biological process and two cellular component GO terms to be topologically orthologous for the two organisms. © The Author 2015. Published by Oxford University Press.

RNA processing: pocket guides to ribosomal RNA.

PubMed

Peculis, B

1997-08-01

The functional role of a recently identified class of small nucleolar (sno) RNAs has been elucidated: the 'box H/ACA' snoRNAs act as guide RNAs, specifying the position of evolutionarily conserved pseudouridines in ribosomal (r)RNA via an rRNA-snoRNA base-pairing interaction that forms a 'pseudouridine pocket'.

A conserved interaction that is essential for the biogenesis of histone locus bodies.

PubMed

Yang, Xiao-cui; Sabath, Ivan; Kunduru, Lalitha; van Wijnen, Andre J; Marzluff, William F; Dominski, Zbigniew

2014-12-05

Nuclear protein, ataxia-telangiectasia locus (NPAT) and FLICE-associated huge protein (FLASH) are two major components of discrete nuclear structures called histone locus bodies (HLBs). NPAT is a key co-activator of histone gene transcription, whereas FLASH through its N-terminal region functions in 3' end processing of histone primary transcripts. The C-terminal region of FLASH contains a highly conserved domain that is also present at the end of Yin Yang 1-associated protein-related protein (YARP) and its Drosophila homologue, Mute, previously shown to localize to HLBs in Drosophila cells. Here, we show that the C-terminal domain of human FLASH and YARP interacts with the C-terminal region of NPAT and that this interaction is essential and sufficient to drive FLASH and YARP to HLBs in HeLa cells. Strikingly, only the last 16 amino acids of NPAT are sufficient for the interaction. We also show that the C-terminal domain of Mute interacts with a short region at the end of the Drosophila NPAT orthologue, multi sex combs (Mxc). Altogether, our data indicate that the conserved C-terminal domain shared by FLASH, YARP, and Mute recognizes the C-terminal sequence of NPAT orthologues, thus acting as a signal targeting proteins to HLBs. Finally, we demonstrate that the C-terminal domain of human FLASH can be directly joined with its N-terminal region through alternative splicing. The resulting 190-amino acid MiniFLASH, despite lacking 90% of full-length FLASH, contains all regions necessary for 3' end processing of histone pre-mRNA in vitro and accumulates in HLBs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

The nature of species interactions shifts profoundly between time periods

USDA-ARS?s Scientific Manuscript database

Species interactions change through time, for example ontogenetically, successionally, and evolutionarily. They also change as environmental conditions change, both within years (seasonally) and between years (year effects). The former are relatively well-studied, but the latter have received less a...

The Caenorhabditis elegans LET-418/Mi2 plays a conserved role in lifespan regulation.

PubMed

De Vaux, Véronique; Pfefferli, Catherine; Passannante, Myriam; Belhaj, Khaoula; von Essen, Alina; Sprecher, Simon G; Müller, Fritz; Wicky, Chantal

2013-12-01

The evolutionarily conserved nucleosome-remodeling protein Mi2 is involved in transcriptional repression during development in various model systems, plays a role in embryonic patterning and germ line development, and participates in DNA repair and cell cycle progression. It is the catalytic subunit of the nucleosome remodeling and histone deacetylase (NuRD) complex, a key determinant of differentiation in mammalian embryonic stem cells. In addition, the Drosophila and C. elegans Mi2 homologs participate in another complex, the MEC complex, which also plays an important developmental role in these organisms. Here we show a new and unexpected feature of the C. elegans Mi2 homolog, LET-418/Mi2. Lack of LET-418/Mi2 results in longevity and enhanced stress resistance, a feature that we found to be conserved in Drosophila and in Arabidopsis. The fact that depletion of other components of the NuRD and the MEC complexes did not result in longevity suggests that LET-418 may regulate lifespan in a different molecular context. Genetic interaction studies suggest that let-418 could act in the germ-cell-loss pathway, downstream of kri-1 and tcer-1. On the basis of our data and on previous findings showing a role for let-418 during development, we propose that LET-418/Mi2 could be part of a system that drives development and reproduction with concomitant life-reducing effects later in life. © 2013 the Anatomical Society and John Wiley & Sons Ltd.

A conservation law, entropy principle and quantization of fractal dimensions in hadron interactions

NASA Astrophysics Data System (ADS)

Zborovský, I.

2018-04-01

Fractal self-similarity of hadron interactions demonstrated by the z-scaling of inclusive spectra is studied. The scaling regularity reflects fractal structure of the colliding hadrons (or nuclei) and takes into account general features of fragmentation processes expressed by fractal dimensions. The self-similarity variable z is a function of the momentum fractions x1 and x2 of the colliding objects carried by the interacting hadron constituents and depends on the momentum fractions ya and yb of the scattered and recoil constituents carried by the inclusive particle and its recoil counterpart, respectively. Based on entropy principle, new properties of the z-scaling concept are found. They are conservation of fractal cumulativity in hadron interactions and quantization of fractal dimensions characterizing hadron structure and fragmentation processes at a constituent level.

Conservation Laws in Weak Interactions

DOE R&D Accomplishments Database

Lee, T. D.

1957-03-01

Notes are presented on four lectures given at Harvard University in March 1957 on elementary particle physics, the theta-tau problem, validity of parity conservation, tests for invariance under P, C, and T, and the two-component theory of the neutrino. (W.D.M.)

Improving homology modeling of G-protein coupled receptors through multiple-template derived conserved inter-residue interactions

NASA Astrophysics Data System (ADS)

Chaudhari, Rajan; Heim, Andrew J.; Li, Zhijun

2015-05-01

Evidenced by the three-rounds of G-protein coupled receptors (GPCR) Dock competitions, improving homology modeling methods of helical transmembrane proteins including the GPCRs, based on templates of low sequence identity, remains an eminent challenge. Current approaches addressing this challenge adopt the philosophy of "modeling first, refinement next". In the present work, we developed an alternative modeling approach through the novel application of available multiple templates. First, conserved inter-residue interactions are derived from each additional template through conservation analysis of each template-target pairwise alignment. Then, these interactions are converted into distance restraints and incorporated in the homology modeling process. This approach was applied to modeling of the human β2 adrenergic receptor using the bovin rhodopsin and the human protease-activated receptor 1 as templates and improved model quality was demonstrated compared to the homology model generated by standard single-template and multiple-template methods. This method of "refined restraints first, modeling next", provides a fast and complementary way to the current modeling approaches. It allows rational identification and implementation of additional conserved distance restraints extracted from multiple templates and/or experimental data, and has the potential to be applicable to modeling of all helical transmembrane proteins.

Rational Design of Evolutionarily Stable Microbial Kill Switches.

PubMed

Stirling, Finn; Bitzan, Lisa; O'Keefe, Samuel; Redfield, Elizabeth; Oliver, John W K; Way, Jeffrey; Silver, Pamela A

2017-11-16

The evolutionary stability of synthetic genetic circuits is key to both the understanding and application of genetic control elements. One useful but challenging situation is a switch between life and death depending on environment. Here are presented "essentializer" and "cryodeath" circuits, which act as kill switches in Escherichia coli. The essentializer element induces cell death upon the loss of a bi-stable cI/Cro memory switch. Cryodeath makes use of a cold-inducible promoter to express a toxin. We employ rational design and a toxin/antitoxin titering approach to produce and screen a small library of potential constructs, in order to select for constructs that are evolutionarily stable. Both kill switches were shown to maintain functionality in vitro for at least 140 generations. Additionally, cryodeath was shown to control the growth environment of a population, with an escape frequency of less than 1 in 10 5 after 10 days of growth in the mammalian gut. Copyright © 2017 Elsevier Inc. All rights reserved.

ROCC, a conserved region in cohesin's Mcd1 subunit, is essential for the proper regulation of the maintenance of cohesion and establishment of condensation

PubMed Central

Eng, Thomas; Guacci, Vincent; Koshland, Doug

2014-01-01

Cohesin helps orchestrate higher-order chromosome structure, thereby promoting sister chromatid cohesion, chromosome condensation, DNA repair, and transcriptional regulation. To elucidate how cohesin facilitates these diverse processes, we mutagenized Mcd1p, the kleisin regulatory subunit of budding yeast cohesin. In the linker region of Mcd1p, we identified a novel evolutionarily conserved 10–amino acid cluster, termed the regulation of cohesion and condensation (ROCC) box. We show that ROCC promotes cohesion maintenance by protecting a second activity of cohesin that is distinct from its stable binding to chromosomes. The existence of this second activity is incompatible with the simple embrace mechanism of cohesion. In addition, we show that the ROCC box is required for the establishment of condensation. We provide evidence that ROCC controls cohesion maintenance and condensation establishment through differential functional interactions with Pds5p and Wpl1p. PMID:24966169

Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells

PubMed Central

Camp, J. Gray; Weiser, Matthew; Cocchiaro, Jordan L.; Kingsley, David M.; Furey, Terrence S.; Sheikh, Shehzad Z.; Rawls, John F.

2017-01-01

The intestinal epithelium serves critical physiologic functions that are shared among all vertebrates. However, it is unknown how the transcriptional regulatory mechanisms underlying these functions have changed over the course of vertebrate evolution. We generated genome-wide mRNA and accessible chromatin data from adult intestinal epithelial cells (IECs) in zebrafish, stickleback, mouse, and human species to determine if conserved IEC functions are achieved through common transcriptional regulation. We found evidence for substantial common regulation and conservation of gene expression regionally along the length of the intestine from fish to mammals and identified a core set of genes comprising a vertebrate IEC signature. We also identified transcriptional start sites and other putative regulatory regions that are differentially accessible in IECs in all 4 species. Although these sites rarely showed sequence conservation from fish to mammals, surprisingly, they drove highly conserved IEC expression in a zebrafish reporter assay. Common putative transcription factor binding sites (TFBS) found at these sites in multiple species indicate that sequence conservation alone is insufficient to identify much of the functionally conserved IEC regulatory information. Among the rare, highly sequence-conserved, IEC-specific regulatory regions, we discovered an ancient enhancer upstream from her6/HES1 that is active in a distinct population of Notch-positive cells in the intestinal epithelium. Together, these results show how combining accessible chromatin and mRNA datasets with TFBS prediction and in vivo reporter assays can reveal tissue-specific regulatory information conserved across 420 million years of vertebrate evolution. We define an IEC transcriptional regulatory network that is shared between fish and mammals and establish an experimental platform for studying how evolutionarily distilled regulatory information commonly controls IEC development and physiology. PMID

Thioredoxins in evolutionarily primitive organisms

NASA Technical Reports Server (NTRS)

Buchanan, B. B.

1986-01-01

Thioredoxins are low molecular weight redox proteins, alternating between the S-S (oxidized) and SH (reduced) states, that function in a number of biochemical processes, including DNA synthesis, DNA replication, and enzyme regulation. Until recently, reduced ferredoxin was known to serve as the source of reducing power for the reduction of thioredoxins only in oxygenic photosynthetic cells. In all other organisms, the source of hydrogen (electrons) for thioredoxin reduction was considered to be NADPH. It was found that Clostridium pasteurianum, an anaerobic organism normally living in the soil unexposed to light, resembles photosynthetic cells in using ferredoxin for the reduction of thioredoxin. The results reveal the existence of a pathway in which ferredoxin, provides the reducing power for the reduction of thioredoxin via the flavoprotein enzyme, ferredoxinthioredoxin reductase. In related studies, it was found that Chromatium vinosum, an anaerobic photosynthetic purple sulfur bacterium, resembles evolutionarily more advanced micro-organisms in having an NADP-thioredoxin system composed of a single thioredoxin which is reduced by NADPH via NADP-thioredoxin reductase. The adoption of the NADP-thioredoxin system by Chromatium seems appropriate in view of evidence tha the organi sm utilizes ATP-driven reverse electron transport. Finally, results of research directed towards the identification of target enzymes of the ferredoxin/thioredoxin system in a cyanobacterium (Nostoc muscorum), show that thioredoxin-linked photosynthetic enzymes of cyanobateria are similar to those of chloroplasts. It now seems that the ferredoxin/thioredoxin system functions in regulating CO2 assimilation via the reductive pentose phosphate cycle in oxygenic but not anoxygenic photosynthetic cells.

Climate-Driven Reshuffling of Species and Genes: Potential Conservation Roles for Species Translocations and Recombinant Hybrid Genotypes

PubMed Central

Scriber, Jon Mark

2013-01-01

Comprising 50%–75% of the world’s fauna, insects are a prominent part of biodiversity in communities and ecosystems globally. Biodiversity across all levels of biological classifications is fundamentally based on genetic diversity. However, the integration of genomics and phylogenetics into conservation management may not be as rapid as climate change. The genetics of hybrid introgression as a source of novel variation for ecological divergence and evolutionary speciation (and resilience) may generate adaptive potential and diversity fast enough to respond to locally-altered environmental conditions. Major plant and herbivore hybrid zones with associated communities deserve conservation consideration. This review addresses functional genetics across multi-trophic-level interactions including “invasive species” in various ecosystems as they may become disrupted in different ways by rapid climate change. “Invasive genes” (into new species and populations) need to be recognized for their positive creative potential and addressed in conservation programs. “Genetic rescue” via hybrid translocations may provide needed adaptive flexibility for rapid adaptation to environmental change. While concerns persist for some conservationists, this review emphasizes the positive aspects of hybrids and hybridization. Specific implications of natural genetic introgression are addressed with a few examples from butterflies, including transgressive phenotypes and climate-driven homoploid recombinant hybrid speciation. Some specific examples illustrate these points using the swallowtail butterflies (Papilionidae) with their long-term historical data base (phylogeographical diversity changes) and recent (3-decade) climate-driven temporal and genetic divergence in recombinant homoploid hybrids and relatively recent hybrid speciation of Papilio appalachiensis in North America. Climate-induced “reshuffling” (recombinations) of species composition, genotypes, and genomes

Climate-Driven Reshuffling of Species and Genes: Potential Conservation Roles for Species Translocations and Recombinant Hybrid Genotypes.

PubMed

Scriber, Jon Mark

2013-12-24

Comprising 50%-75% of the world's fauna, insects are a prominent part of biodiversity in communities and ecosystems globally. Biodiversity across all levels of biological classifications is fundamentally based on genetic diversity. However, the integration of genomics and phylogenetics into conservation management may not be as rapid as climate change. The genetics of hybrid introgression as a source of novel variation for ecological divergence and evolutionary speciation (and resilience) may generate adaptive potential and diversity fast enough to respond to locally-altered environmental conditions. Major plant and herbivore hybrid zones with associated communities deserve conservation consideration. This review addresses functional genetics across multi-trophic-level interactions including "invasive species" in various ecosystems as they may become disrupted in different ways by rapid climate change. "Invasive genes" (into new species and populations) need to be recognized for their positive creative potential and addressed in conservation programs. "Genetic rescue" via hybrid translocations may provide needed adaptive flexibility for rapid adaptation to environmental change. While concerns persist for some conservationists, this review emphasizes the positive aspects of hybrids and hybridization. Specific implications of natural genetic introgression are addressed with a few examples from butterflies, including transgressive phenotypes and climate-driven homoploid recombinant hybrid speciation. Some specific examples illustrate these points using the swallowtail butterflies (Papilionidae) with their long-term historical data base (phylogeographical diversity changes) and recent (3-decade) climate-driven temporal and genetic divergence in recombinant homoploid hybrids and relatively recent hybrid speciation of Papilio appalachiensis in North America. Climate-induced "reshuffling" (recombinations) of species composition, genotypes, and genomes may become

The Mediator complex of Caenorhabditis elegans: insights into the developmental and physiological roles of a conserved transcriptional coregulator.

PubMed

Grants, Jennifer M; Goh, Grace Y S; Taubert, Stefan

2015-02-27

The Mediator multiprotein complex ('Mediator') is an important transcriptional coregulator that is evolutionarily conserved throughout eukaryotes. Although some Mediator subunits are essential for the transcription of all protein-coding genes, others influence the expression of only subsets of genes and participate selectively in cellular signaling pathways. Here, we review the current knowledge of Mediator subunit function in the nematode Caenorhabditis elegans, a metazoan in which established and emerging genetic technologies facilitate the study of developmental and physiological regulation in vivo. In this nematode, unbiased genetic screens have revealed critical roles for Mediator components in core developmental pathways such as epidermal growth factor (EGF) and Wnt/β-catenin signaling. More recently, important roles for C. elegans Mediator subunits have emerged in the regulation of lipid metabolism and of systemic stress responses, engaging conserved transcription factors such as nuclear hormone receptors (NHRs). We emphasize instances where similar functions for individual Mediator subunits exist in mammals, highlighting parallels between Mediator subunit action in nematode development and in human cancer biology. We also discuss a parallel between the association of the Mediator subunit MED12 with several human disorders and the role of its C. elegans ortholog mdt-12 as a regulatory hub that interacts with numerous signaling pathways. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Is it Possible to Conserve Electric Charge Without Separately Conserving Baryonic Number and Leptonic Number?

NASA Astrophysics Data System (ADS)

Tsan, Ung Chan

Charges that are sources of fields must be universally conserved. Any quantity which is proved to be violated in certain circumstance cannot be a source of field. To account for the asymmetry of our Universe baryon number A has to be violated; thus A cannot be a charge. We postulate a new interaction, matter creation, with (A-L) as charge and Z* as messenger. Conservation of (A-L) instead of (3A-L) suggested by Sakharov is deduced on the one hand from observational facts (our Universe is both material and neutral) and on the other hand from the generalized Gell-Mann and Nishijima formula. Conservation of (A-L) forbids neutrinoless double beta decay and neutron antineutron oscillations. The union of four interactions — electromagnetism, the MC interaction, the weak interaction and the strong interaction — considered as the product U(1) × U(1) × SU(2) × SU(3) would account for available experimental and observational data. Observation of processes violating baryon number conservation would be of great interest in falsifying this suggestion.

Neotropical fish-fruit interactions: eco-evolutionary dynamics and conservation.

PubMed

Correa, Sandra Bibiana; Costa-Pereira, Raul; Fleming, Theodore; Goulding, Michael; Anderson, Jill T

2015-11-01

Frugivorous fish play a prominent role in seed dispersal and reproductive dynamics of plant communities in riparian and floodplain habitats of tropical regions worldwide. In Neotropical wetlands, many plant species have fleshy fruits and synchronize their fruiting with the flood season, when fruit-eating fish forage in forest and savannahs for periods of up to 7 months. We conducted a comprehensive analysis to examine the evolutionary origin of fish-fruit interactions, describe fruit traits associated with seed dispersal and seed predation, and assess the influence of fish size on the effectiveness of seed dispersal by fish (ichthyochory). To date, 62 studies have documented 566 species of fruits and seeds from 82 plant families in the diets of 69 Neotropical fish species. Fish interactions with flowering plants are likely to be as old as 70 million years in the Neotropics, pre-dating most modern bird-fruit and mammal-fruit interactions, and contributing to long-distance seed dispersal and possibly the radiation of early angiosperms. Ichthyochory occurs across the angiosperm phylogeny, and is more frequent among advanced eudicots. Numerous fish species are capable of dispersing small seeds, but only a limited number of species can disperse large seeds. The size of dispersed seeds and the probability of seed dispersal both increase with fish size. Large-bodied species are the most effective seed dispersal agents and remain the primary target of fishing activities in the Neotropics. Thus, conservation efforts should focus on these species to ensure continuity of plant recruitment dynamics and maintenance of plant diversity in riparian and floodplain ecosystems. © 2015 Cambridge Philosophical Society.

Drosophila KCNQ Channel Displays Evolutionarily Conserved Electrophysiology and Pharmacology with Mammalian KCNQ Channels

PubMed Central

Cavaliere, Sonia; Hodge, James J. L.

2011-01-01

Of the five human KCNQ (Kv7) channels, KCNQ1 with auxiliary subunit KCNE1 mediates the native cardiac IKs current with mutations causing short and long QT cardiac arrhythmias. KCNQ4 mutations cause deafness. KCNQ2/3 channels form the native M-current controlling excitability of most neurons, with mutations causing benign neonatal febrile convulsions. Drosophila contains a single KCNQ (dKCNQ) that appears to serve alone the functions of all the duplicated mammalian neuronal and cardiac KCNQ channels sharing roughly 50–60% amino acid identity therefore offering a route to investigate these channels. Current information about the functional properties of dKCNQ is lacking therefore we have investigated these properties here. Using whole cell patch clamp electrophysiology we compare the biophysical and pharmacological properties of dKCNQ with the mammalian neuronal and cardiac KCNQ channels expressed in HEK cells. We show that Drosophila KCNQ (dKCNQ) is a slowly activating and slowly-deactivating K+ current open at sub-threshold potentials that has similar properties to neuronal KCNQ2/3 with some features of the cardiac KCNQ1/KCNE1 accompanied by conserved sensitivity to a number of clinically relevant KCNQ blockers (chromanol 293B, XE991, linopirdine) and opener (zinc pyrithione). We also investigate the molecular basis of the differential selectivity of KCNQ channels to the opener retigabine and show a single amino acid substitution (M217W) can confer sensitivity to dKCNQ. We show dKCNQ has similar electrophysiological and pharmacological properties as the mammalian KCNQ channels, allowing future study of physiological and pathological roles of KCNQ in Drosophila and whole organism screening for new modulators of KCNQ channelopathies. PMID:21915266

Orchid conservation: further links.

PubMed

Fay, Michael F

2016-07-01

Due in great part to their often complex interactions with mycorrhizal fungi, pollinators and host trees, Orchidaceae present particular challenges for conservation. Furthermore, orchids, as potentially the largest family of angiosperms with >26000 species, species complexes and frequent hybrid formation, are complex to catalogue. Following a highlight in 2015, a further seven papers focusing on orchids, their interactions with beneficial organisms, pollinators and mycorrhiza, and other factors relating to their conservation, including threats from human utilization and changing land use, are presented here. The production of an online flora of all known plants and an assessment of the conservation status of all known plant species as far as possible, to guide conservation action are the first two targets of the Global Strategy for Plant Conservation Without knowing how many species there are and how they should be circumscribed, neither of these targets is achievable. Orchids are a fascinating subject for fundamental research with rapid species evolution, specific organ structure and development, but they also suffer from high levels of threat. Effective orchid conservation must take account of the beneficial interactions with fungi and pollinators and the potentially detrimental effects of over-collection and changes in land use. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Usb1 controls U6 snRNP assembly through evolutionarily divergent cyclic phosphodiesterase activities.

PubMed

Didychuk, Allison L; Montemayor, Eric J; Carrocci, Tucker J; DeLaitsch, Andrew T; Lucarelli, Stefani E; Westler, William M; Brow, David A; Hoskins, Aaron A; Butcher, Samuel E

2017-09-08

U6 small nuclear ribonucleoprotein (snRNP) biogenesis is essential for spliceosome assembly, but not well understood. Here, we report structures of the U6 RNA processing enzyme Usb1 from yeast and a substrate analog bound complex from humans. Unlike the human ortholog, we show that yeast Usb1 has cyclic phosphodiesterase activity that leaves a terminal 3' phosphate which prevents overprocessing. Usb1 processing of U6 RNA dramatically alters its affinity for cognate RNA-binding proteins. We reconstitute the post-transcriptional assembly of yeast U6 snRNP in vitro, which occurs through a complex series of handoffs involving 10 proteins (Lhp1, Prp24, Usb1 and Lsm2-8) and anti-cooperative interactions between Prp24 and Lhp1. We propose a model for U6 snRNP assembly that explains how evolutionarily divergent and seemingly antagonistic proteins cooperate to protect and chaperone the nascent snRNA during its journey to the spliceosome.The mechanism of U6 small nuclear ribonucleoprotein (snRNP) biogenesis is not well understood. Here the authors characterize the enzymatic activities and structures of yeast and human U6 RNA processing enzyme Usb1, reconstitute post-transcriptional assembly of yeast U6 snRNP in vitro, and propose a model for U6 snRNP assembly.

Identification of an evolutionarily conserved regulatory element of the zebrafish col2a1a gene.

PubMed

Dale, Rodney M; Topczewski, Jacek

2011-09-15

Zebrafish (Danio rerio) is an excellent model organism for the study of vertebrate development including skeletogenesis. Studies of mammalian cartilage formation were greatly advanced through the use of a cartilage specific regulatory element of the Collagen type II alpha 1 (Col2a1) gene. In an effort to isolate such an element in zebrafish, we compared the expression of two col2a1 homologues and found that expression of col2a1b, a previously uncharacterized zebrafish homologue, only partially overlaps with col2a1a. We focused our analysis on col2a1a, as it is expressed in both the stacked chondrocytes and the perichondrium. By comparing the genomic sequence surrounding the predicted transcriptional start site of col2a1a among several species of teleosts we identified a small highly conserved sequence (R2) located 1.7 kb upstream of the presumptive transcriptional initiation site. Interestingly, neither the sequence nor location of this element is conserved between teleost and mammalian Col2a1. We generated transient and stable transgenic lines with just the R2 element or the entire 1.7 kb fragment 5' of the transcriptional initiation site. The identified regulatory elements enable the tracking of cellular development in various tissues by driving robust reporter expression in craniofacial cartilage, ear, notochord, floor plate, hypochord and fins in a pattern similar to the expression of endogenous col2a1a. Using a reporter gene driven by the R2 regulatory element, we analyzed the morphogenesis of the notochord sheath cells as they withdraw from the stack of initially uniform cells and encase the inflating vacuolated notochord cells. Finally, we show that like endogenous col2a1a, craniofacial expression of these reporter constructs depends on Sox9a transcription factor activity. At the same time, notochord expression is maintained after Sox9a knockdown, suggesting that other factors can activate expression through the identified regulatory element in this tissue

Identification of an evolutionarily conserved regulatory element of the zebrafish col2a1a gene

PubMed Central

Dale, Rodney M.; Topczewski, Jacek

2011-01-01

Zebrafish (Danio rerio) is an excellent model organism for the study of vertebrate development including skeletogenesis. Studies of mammalian cartilage formation were greatly advanced through the use of a cartilage specific regulatory element of the Collagen type II alpha 1 (Col2a1) gene. In an effort to isolate such an element in zebrafish, we compared the expression of two col2a1 homologues and found that expression of col2a1b, a previously uncharacterized zebrafish homologue, only partially overlaps with col2a1a. We focused our analysis on col2a1a, as it is expressed in both the stacked chondrocytes and the perichondrium. By comparing the genomic sequence surrounding the predicted transcriptional start site of col2a1a among several species of teleosts we identified a small highly conserved sequence (R2) located 1.7 kb upstream of the presumptive transcriptional initiation site. Interestingly, neither the sequence nor location of this element is conserved between teleost and mammalian Col2a1. We generated transient and stable transgenic lines with just the R2 element or the entire 1.7 kb fragment 5’ of the transcriptional initiation site. The identified regulatory elements enable the tracking of cellular development in various tissues by driving robust reporter expression in craniofacial cartilage, ear, notochord, floor plate, hypochord and fins in a pattern similar to the expression of endogenous col2a1a. Using a reporter gene driven by the R2 regulatory element, we analyzed the morphogenesis of the notochord sheath cells as they withdraw from the stack of initially uniform cells and encase the inflating vacuolated notochord cells. Finally, we show that like endogenous col2a1a, craniofacial expression of these reporter constructs depends on Sox9a transcription factor activity. At the same time, notochord expression is maintained after Sox9a knockdown, suggesting that other factors can activate expression through the identified regulatory element in this tissue

Biosocial Conservation: Integrating Biological and Ethnographic Methods to Study Human-Primate Interactions.

PubMed

Setchell, Joanna M; Fairet, Emilie; Shutt, Kathryn; Waters, Siân; Bell, Sandra

2017-01-01

Biodiversity conservation is one of the grand challenges facing society. Many people interested in biodiversity conservation have a background in wildlife biology. However, the diverse social, cultural, political, and historical factors that influence the lives of people and wildlife can be investigated fully only by incorporating social science methods, ideally within an interdisciplinary framework. Cultural hierarchies of knowledge and the hegemony of the natural sciences create a barrier to interdisciplinary understandings. Here, we review three different projects that confront this difficulty, integrating biological and ethnographic methods to study conservation problems. The first project involved wildlife foraging on crops around a newly established national park in Gabon. Biological methods revealed the extent of crop loss, the species responsible, and an effect of field isolation, while ethnography revealed institutional and social vulnerability to foraging wildlife. The second project concerned great ape tourism in the Central African Republic. Biological methods revealed that gorilla tourism poses risks to gorillas, while ethnography revealed why people seek close proximity to gorillas. The third project focused on humans and other primates living alongside one another in Morocco. Incorporating shepherds in the coproduction of ecological knowledge about primates built trust and altered attitudes to the primates. These three case studies demonstrate how the integration of biological and social methods can help us to understand the sustainability of human-wildlife interactions, and thus promote coexistence. In each case, an integrated biosocial approach incorporating ethnographic data produced results that would not otherwise have come to light. Research that transcends conventional academic boundaries requires the openness and flexibility to move beyond one's comfort zone to understand and acknowledge the legitimacy of "other" kinds of knowledge. It is

Limitations of outsourcing on-the-ground biodiversity conservation.

PubMed

Iacona, Gwenllian D; Bode, Michael; Armsworth, Paul R

2016-12-01

To counteract global species decline, modern biodiversity conservation engages in large projects, spends billions of dollars, and includes many organizations working simultaneously within regions. To add to this complexity, the conservation sector has hierarchical structure, where conservation actions are often outsourced by funders (foundations, government, etc.) to local organizations that work on-the-ground. In contrast, conservation science usually assumes that a single organization makes resource allocation decisions. This discrepancy calls for theory to understand how the expected biodiversity outcomes change when interactions between organizations are accounted for. Here, we used a game theoretic model to explore how biodiversity outcomes are affected by vertical and horizontal interactions between 3 conservation organizations: a funder that outsourced its actions and 2 local conservation organizations that work on-the-ground. Interactions between the organizations changed the spending decisions made by individual organizations, and thereby the magnitude and direction of the conservation benefits. We showed that funders would struggle to incentivize recipient organizations with set priorities to perform desired actions, even when they control substantial amounts of the funding and employ common contracting approaches to enhance outcomes. Instead, biodiversity outcomes depended on priority alignment across the organizations. Conservation outcomes for the funder were improved by strategic interactions when organizational priorities were well aligned, but decreased when priorities were misaligned. Meanwhile, local organizations had improved outcomes regardless of alignment due to additional funding in the system. Given that conservation often involves the aggregate actions of multiple organizations with different objectives, strategic interactions between organizations need to be considered if we are to predict possible outcomes of conservation programs or

Conservation of NLR-triggered immunity across plant lineages.

PubMed

Maekawa, Takaki; Kracher, Barbara; Vernaldi, Saskia; Ver Loren van Themaat, Emiel; Schulze-Lefert, Paul

2012-12-04

The nucleotide-binding domain and leucine-rich repeat (NLR) family of plant receptors detects pathogen-derived molecules, designated effectors, inside host cells and mediates innate immune responses to pathogenic invaders. Genetic evidence revealed species-specific coevolution of many NLRs with effectors from host-adapted pathogens, suggesting that the specificity of these NLRs is restricted to the host or closely related plant species. However, we report that an NLR immune receptor (MLA1) from monocotyledonous barley is fully functional in partially immunocompromised dicotyledonous Arabidopsis thaliana against the barley powdery mildew fungus, Blumeria graminis f. sp. hordei. This implies ~200 million years of evolutionary conservation of the underlying immune mechanism. A time-course RNA-seq analysis in transgenic Arabidopsis lines detected sustained expression of a large MLA1-dependent gene cluster. This cluster is greatly enriched in genes known to respond to the fungal cell wall-derived microbe-associated molecular pattern chitin. The MLA1-dependent sustained transcript accumulation could define a conserved function of the nuclear pool of MLA1 detected in barley and Arabidopsis. We also found that MLA1-triggered immunity was fully retained in mutant plants that are simultaneously depleted of ethylene, jasmonic acid, and salicylic acid signaling. This points to the existence of an evolutionarily conserved and phytohormone-independent MLA1-mediated resistance mechanism. This also suggests a conserved mechanism for internalization of B. graminis f. sp. hordei effectors into host cells of flowering plants. Furthermore, the deduced connectivity of the NLR to multiple branches of immune signaling pathways likely confers increased robustness against pathogen effector-mediated interception of host immune signaling and could have contributed to the evolutionary preservation of the immune mechanism.

Identification of a Conserved Interface of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Vifs with Cullin 5.

PubMed

Gu, Qinyong; Zhang, Zeli; Gertzen, Christoph G W; Häussinger, Dieter; Gohlke, Holger; Münk, Carsten

2018-03-15

Members of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC3 [A3]) family of DNA cytidine deaminases are intrinsic restriction factors against retroviruses. In felids such as the domestic cat ( Felis catus ), the A3 genes encode the A3Z2, A3Z3, and A3Z2Z3 antiviral cytidine deaminases. Only A3Z3 and A3Z2Z3 inhibit viral infectivity factor (Vif)-deficient feline immunodeficiency virus (FIV). The FIV Vif protein interacts with Cullin (CUL), Elongin B (ELOB), and Elongin C (ELOC) to form an E3 ubiquitination complex to induce the degradation of feline A3s. However, the functional domains in FIV Vif for the interaction with Cullin are poorly understood. Here, we found that the expression of dominant negative CUL5 prevented the degradation of feline A3s by FIV Vif, while dominant negative CUL2 had no influence on the degradation of A3. In coimmunoprecipitation assays, FIV Vif bound to CUL5 but not CUL2. To identify the CUL5 interaction site in FIV Vif, the conserved amino acids from positions 47 to 160 of FIV Vif were mutated, but these mutations did not impair the binding of Vif to CUL5. By focusing on a potential zinc-binding motif (K175-C161-C184-C187) of FIV Vif, we found a conserved hydrophobic region (174IR175) that is important for the CUL5 interaction. Mutation of this region also impaired the FIV Vif-induced degradation of feline A3s. Based on a structural model of the FIV Vif-CUL5 interaction, the 52LW53 region in CUL5 was identified as mediating binding to FIV Vif. By comparing our results to the human immunodeficiency virus type 1 (HIV-1) Vif-CUL5 interaction surface (120IR121, a hydrophobic region that is localized in the zinc-binding motif), we suggest that the CUL5 interaction surface in the diverse HIV-1 and FIV Vifs is evolutionarily conserved, indicating a strong structural constraint. However, the FIV Vif-CUL5 interaction is zinc independent, which contrasts with the zinc dependence of HIV-1 Vif. IMPORTANCE Feline

Structural analysis of the human U3 ribonucleoprotein particle reveal a conserved sequence available for base pairing with pre-rRNA.

PubMed Central

Parker, K A; Steitz, J A

1987-01-01

The human U3 ribonucleoprotein (RNP) has been analyzed to determine its protein constituents, sites of protein-RNA interaction, and RNA secondary structure. By using anti-U3 RNP antibodies and extracts prepared from HeLa cells labeled in vivo, the RNP was found to contain four nonphosphorylated proteins of 36, 30, 13, and 12.5 kilodaltons and two phosphorylated proteins of 74 and 59 kilodaltons. U3 nucleotides 72-90, 106-121, 154-166, and 190-217 must contain sites that interact with proteins since these regions are immunoprecipitated after treatment of the RNP with RNase A or T1. The secondary structure was probed with specific nucleases and by chemical modification with single-strand-specific reagents that block subsequent reverse transcription. Regions that are single stranded (and therefore potentially able to interact with a substrate RNA) include an evolutionarily conserved sequence at nucleotides 104-112 and nonconserved sequences at nucleotides 65-74, 80-84, and 88-93. Nucleotides 159-168 do not appear to be highly accessible, thus making it unlikely that this U3 sequence base pairs with sequences near the 5.8S rRNA-internal transcribed spacer II junction, as previously proposed. Alternative functions of the U3 RNP are discussed, including the possibility that U3 may participate in a processing event near the 3' end of 28S rRNA. Images PMID:2959855

A conserved function for pericentromeric satellite DNA

PubMed Central

Jagannathan, Madhav; Cummings, Ryan

2018-01-01

A universal and unquestioned characteristic of eukaryotic cells is that the genome is divided into multiple chromosomes and encapsulated in a single nucleus. However, the underlying mechanism to ensure such a configuration is unknown. Here, we provide evidence that pericentromeric satellite DNA, which is often regarded as junk, is a critical constituent of the chromosome, allowing the packaging of all chromosomes into a single nucleus. We show that the multi-AT-hook satellite DNA-binding proteins, Drosophila melanogaster D1 and mouse HMGA1, play an evolutionarily conserved role in bundling pericentromeric satellite DNA from heterologous chromosomes into ‘chromocenters’, a cytological association of pericentromeric heterochromatin. Defective chromocenter formation leads to micronuclei formation due to budding from the interphase nucleus, DNA damage and cell death. We propose that chromocenter and satellite DNA serve a fundamental role in encapsulating the full complement of the genome within a single nucleus, the universal characteristic of eukaryotic cells. PMID:29578410

Selective integrin endocytosis is driven by interactions between the integrin α-chain and AP2

PubMed Central

De Franceschi, Nicola; Arjonen, Antti; Elkhatib, Nadia; Denessiouk, Konstantin; Wrobel, Antoni G; Wilson, Thomas A; Pouwels, Jeroen; Montagnac, Guillaume; Owen, David J; Ivaska, Johanna

2016-01-01

Integrins are heterodimeric cell-surface adhesion molecules comprising one of possible 18 α-chains and one of possible 8 β-chains. They control a range of cell functions in a matrix- and ligand-specific manner. Integrins can be internalised by clathrin-mediated endocytosis (CME) through β subunit-based motifs found in all integrin heterodimers. However, whether specific integrin heterodimers can be selectively endocytosed was unknown. Here, we found that a subset of α subunits contain an evolutionarily conserved and functional YxxΦ motif directing integrins to selective internalisation by the most abundant endocytic clathrin adaptor, AP2. We determined the structure of the human integrin α4-tail motif in complex with AP2 C-µ2 subunit and confirmed the interaction by isothermal titration calorimetry. Mutagenesis of the motif impaired selective heterodimer endocytosis and attenuated integrin-mediated cell migration. We propose that integrins evolved to enable selective integrin-receptor turnover in response to changing matrix conditions. PMID:26779610

Selective integrin endocytosis is driven by interactions between the integrin α-chain and AP2.

PubMed

De Franceschi, Nicola; Arjonen, Antti; Elkhatib, Nadia; Denessiouk, Konstantin; Wrobel, Antoni G; Wilson, Thomas A; Pouwels, Jeroen; Montagnac, Guillaume; Owen, David J; Ivaska, Johanna

2016-02-01

Integrins are heterodimeric cell-surface adhesion molecules comprising one of 18 possible α-chains and one of eight possible β-chains. They control a range of cell functions in a matrix- and ligand-specific manner. Integrins can be internalized by clathrin-mediated endocytosis (CME) through β subunit-based motifs found in all integrin heterodimers. However, whether specific integrin heterodimers can be selectively endocytosed was unknown. Here, we found that a subset of α subunits contain an evolutionarily conserved and functional YxxΦ motif directing integrins to selective internalization by the most abundant endocytic clathrin adaptor, AP2. We determined the structure of the human integrin α4-tail motif in complex with the AP2 C-μ2 subunit and confirmed the interaction by isothermal titration calorimetry. Mutagenesis of the motif impaired selective heterodimer endocytosis and attenuated integrin-mediated cell migration. We propose that integrins evolved to enable selective integrin-receptor turnover in response to changing matrix conditions.

The conserved clag multigene family of malaria parasites: essential roles in host-pathogen interaction.

PubMed

Gupta, Ankit; Thiruvengadam, Girija; Desai, Sanjay A

2015-01-01

The clag multigene family is strictly conserved in malaria parasites, but absent from neighboring genera of protozoan parasites. Early research pointed to roles in merozoite invasion and infected cell cytoadherence, but more recent studies have implicated channel-mediated uptake of ions and nutrients from host plasma. Here, we review the current understanding of this gene family, which appears to be central to host-parasite interactions and an important therapeutic target. Published by Elsevier Ltd.

Matrix metalloproteinase-10/TIMP-2 structure and analyses define conserved core interactions and diverse exosite interactions in MMP/TIMP complexes.

PubMed

Batra, Jyotica; Soares, Alexei S; Mehner, Christine; Radisky, Evette S

2013-01-01

Matrix metalloproteinases (MMPs) play central roles in vertebrate tissue development, remodeling, and repair. The endogenous tissue inhibitors of metalloproteinases (TIMPs) regulate proteolytic activity by binding tightly to the MMP active site. While each of the four TIMPs can inhibit most MMPs, binding data reveal tremendous heterogeneity in affinities of different TIMP/MMP pairs, and the structural features that differentiate stronger from weaker complexes are poorly understood. Here we report the crystal structure of the comparatively weakly bound human MMP-10/TIMP-2 complex at 2.1 Å resolution. Comparison with previously reported structures of MMP-3/TIMP-1, MT1-MMP/TIMP-2, MMP-13/TIMP-2, and MMP-10/TIMP-1 complexes offers insights into the structural basis of binding selectivity. Our analyses identify a group of highly conserved contacts at the heart of MMP/TIMP complexes that define the conserved mechanism of inhibition, as well as a second category of diverse adventitious contacts at the periphery of the interfaces. The AB loop of the TIMP N-terminal domain and the contact loops of the TIMP C-terminal domain form highly variable peripheral contacts that can be considered as separate exosite interactions. In some complexes these exosite contacts are extensive, while in other complexes the AB loop or C-terminal domain contacts are greatly reduced and appear to contribute little to complex stability. Our data suggest that exosite interactions can enhance MMP/TIMP binding, although in the relatively weakly bound MMP-10/TIMP-2 complex they are not well optimized to do so. Formation of highly variable exosite interactions may provide a general mechanism by which TIMPs are fine-tuned for distinct regulatory roles in biology.

Evolutionary growth process of highly conserved sequences in vertebrate genomes.

PubMed

Ishibashi, Minaka; Noda, Akiko Ogura; Sakate, Ryuichi; Imanishi, Tadashi

2012-08-01

Genome sequence comparison between evolutionarily distant species revealed ultraconserved elements (UCEs) among mammals under strong purifying selection. Most of them were also conserved among vertebrates. Because they tend to be located in the flanking regions of developmental genes, they would have fundamental roles in creating vertebrate body plans. However, the evolutionary origin and selection mechanism of these UCEs remain unclear. Here we report that UCEs arose in primitive vertebrates, and gradually grew in vertebrate evolution. We searched for UCEs in two teleost fishes, Tetraodon nigroviridis and Oryzias latipes, and found 554 UCEs with 100% identity over 100 bps. Comparison of teleost and mammalian UCEs revealed 43 pairs of common, jawed-vertebrate UCEs (jUCE) with high sequence identities, ranging from 83.1% to 99.2%. Ten of them retain lower similarities to the Petromyzon marinus genome, and the substitution rates of four non-exonic jUCEs were reduced after the teleost-mammal divergence, suggesting that robust conservation had been acquired in the jawed vertebrate lineage. Our results indicate that prototypical UCEs originated before the divergence of jawed and jawless vertebrates and have been frozen as perfect conserved sequences in the jawed vertebrate lineage. In addition, our comparative sequence analyses of UCEs and neighboring regions resulted in a discovery of lineage-specific conserved sequences. They were added progressively to prototypical UCEs, suggesting step-wise acquisition of novel regulatory roles. Our results indicate that conserved non-coding elements (CNEs) consist of blocks with distinct evolutionary history, each having been frozen since different evolutionary era along the vertebrate lineage. Copyright © 2012 Elsevier B.V. All rights reserved.

Conserved sequence-specific lincRNA-steroid receptor interactions drive transcriptional repression and direct cell fate

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

Hudson, William H.; Pickard, Mark R.; de Vera, Ian Mitchelle S.

2014-12-23

The majority of the eukaryotic genome is transcribed, generating a significant number of long intergenic noncoding RNAs (lincRNAs). Although lincRNAs represent the most poorly understood product of transcription, recent work has shown lincRNAs fulfill important cellular functions. In addition to low sequence conservation, poor understanding of structural mechanisms driving lincRNA biology hinders systematic prediction of their function. Here we report the molecular requirements for the recognition of steroid receptors (SRs) by the lincRNA growth arrest-specific 5 (Gas5), which regulates steroid-mediated transcriptional regulation, growth arrest and apoptosis. We identify the functional Gas5-SR interface and generate point mutations that ablate the SR-Gas5more » lincRNA interaction, altering Gas5-driven apoptosis in cancer cell lines. Further, we find that the Gas5 SR-recognition sequence is conserved among haplorhines, with its evolutionary origin as a splice acceptor site. This study demonstrates that lincRNAs can recognize protein targets in a conserved, sequence-specific manner in order to affect critical cell functions.« less

BAG3 promotes stem cell-like phenotype in breast cancer by upregulation of CXCR4 via interaction with its transcript.

PubMed

Liu, Bao-Qin; Zhang, Song; Li, Si; An, Ming-Xin; Li, Chao; Yan, Jing; Wang, Jia-Mei; Wang, Hua-Qin

2017-07-13

BAG3 is an evolutionarily conserved co-chaperone expressed at high levels and has a prosurvival role in many tumor types. The current study reported that BAG3 was induced under specific floating culture conditions that enrich breast cancer stem cell (BCSC)-like cells in spheres. Ectopic BAG3 overexpression increased CD44 + /CD24 - CSC subpopulations, first-generation and second-generation mammosphere formation, indicating that BAG3 promotes CSC self-renewal and maintenance in breast cancer. We further demonstrated that mechanically, BAG3 upregulated CXCR4 expression at the post-transcriptional level. Further studies showed that BAG3 interacted with CXCR4 mRNA and promoted its expression via its coding and 3'-untranslational regions. BAG3 was also found to be positively correlated with CXCR4 expression and unfavorable prognosis in patients with breast cancer. Taken together, our data demonstrate that BAG3 promotes BCSC-like phenotype through CXCR4 via interaction with its transcript. Therefore, this study establishes BAG3 as a potential adverse prognostic factor and a therapeutic target of breast cancer.

BAG3 promotes stem cell-like phenotype in breast cancer by upregulation of CXCR4 via interaction with its transcript

PubMed Central

Liu, Bao-Qin; Zhang, Song; Li, Si; An, Ming-Xin; Li, Chao; Yan, Jing; Wang, Jia-Mei; Wang, Hua-Qin

2017-01-01

BAG3 is an evolutionarily conserved co-chaperone expressed at high levels and has a prosurvival role in many tumor types. The current study reported that BAG3 was induced under specific floating culture conditions that enrich breast cancer stem cell (BCSC)-like cells in spheres. Ectopic BAG3 overexpression increased CD44+/CD24− CSC subpopulations, first-generation and second-generation mammosphere formation, indicating that BAG3 promotes CSC self-renewal and maintenance in breast cancer. We further demonstrated that mechanically, BAG3 upregulated CXCR4 expression at the post-transcriptional level. Further studies showed that BAG3 interacted with CXCR4 mRNA and promoted its expression via its coding and 3′-untranslational regions. BAG3 was also found to be positively correlated with CXCR4 expression and unfavorable prognosis in patients with breast cancer. Taken together, our data demonstrate that BAG3 promotes BCSC-like phenotype through CXCR4 via interaction with its transcript. Therefore, this study establishes BAG3 as a potential adverse prognostic factor and a therapeutic target of breast cancer. PMID:28703799

A conserved Mediator–CDK8 kinase module association regulates Mediator–RNA polymerase II interaction

PubMed Central

Tsai, Kuang-Lei; Sato, Shigeo; Tomomori-Sato, Chieri; Conaway, Ronald C.; Conaway, Joan W.; Asturias, Francisco J.

2013-01-01

The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) carboxy-terminal domain (CTD) and individually recognized as transcriptional repressors before Mediator was identified as a preeminent complex in eukaryotic transcription regulation. We used macromolecular electron microscopy and biochemistry to investigate the subunit organization, structure, and Mediator interaction of the Saccharomyces cerevisiae CKM. We found that interaction of the CKM with Mediator’s Middle module interferes with CTD-dependent RNAPII binding to a previously unknown Middle module CTD-binding site targeted early on in a multi-step holoenzyme formation process. Taken together, our results reveal the basis for CKM repression, clarify the origin of the connection between CKM subunits and the CTD, and suggest that a combination of competitive interactions and conformational changes that facilitate holoenzyme formation underlie the Mediator mechanism. PMID:23563140

Distribution of caspase-14 in epidermis and hair follicles is evolutionarily conserved among mammals.

PubMed

Alibardi, Lorenzo; Tschachler, Erwin; Eckhart, Leopold

2005-10-01

Caspase-14, a member of the caspase family of cysteine proteases, is almost exclusively expressed in the epidermis. Studies on human and mouse cells and tissues have implicated caspase-14 in terminal differentiation of epidermal keratinocytes and in the formation of the stratum corneum. Here we investigated evolutionary aspects of the role of caspase-14 by analyzing its distribution in the epidermis and hair follicles of representative species of placental mammals, marsupials, and monotremes. Immunocytochemical staining showed that caspase-14 is consistently expressed in the granular and corneous layer of the epidermis of all mammalian species investigated. Ultrastructural analysis using gold-labeled anticaspase-14 antibodies revealed that caspase-14 is associated preferentially with keratin bundles and amorphous material of keratohyalin granules, but is also present in nuclei of transitional cells of the granular layer and in corneocytes. In hair follicles, caspase-14 was diffusely present in cornifying cells of the outer root sheath, in the companion layer, and, most abundantly, in the inner root sheath of all mammalian species here analyzed. In Henle and Huxley layers of the inner root sheath, labeling was seen in nuclei and, more diffusely, among trichohyalin granules of cornifying cells. In summary, the tissue expression pattern and the intracellular localization of caspase-14 are highly conserved among diverse mammalian species, suggesting that this enzyme is involved in a molecular process that appeared early in the evolution of mammalian skin. The association of caspase-14 with keratohyalin and trichohyalin granules may indicate a specific role of caspase-14 in the maturation of these keratinocyte-specific structures.

Chromatin Protein HP1α Interacts with the Mitotic Regulator Borealin Protein and Specifies the Centromere Localization of the Chromosomal Passenger Complex*

PubMed Central

Liu, Xing; Song, Zhenwei; Huo, Yuda; Zhang, Jiahai; Zhu, Tongge; Wang, Jianyu; Zhao, Xuannv; Aikhionbare, Felix; Zhang, Jiancun; Duan, Hequan; Wu, Jihui; Dou, Zhen; Shi, Yunyu; Yao, Xuebiao

2014-01-01

Accurate mitosis requires the chromosomal passenger protein complex (CPC) containing Aurora B kinase, borealin, INCENP, and survivin, which orchestrates chromosome dynamics. However, the chromatin factors that specify the CPC to the centromere remain elusive. Here we show that borealin interacts directly with heterochromatin protein 1α (HP1α) and that this interaction is mediated by an evolutionarily conserved PXVXL motif in the C-terminal borealin with the chromo shadow domain of HP1α. This borealin-HP1α interaction recruits the CPC to the centromere and governs an activation of Aurora B kinase judged by phosphorylation of Ser-7 in CENP-A, a substrate of Aurora B. Consistently, modulation of the motif PXVXL leads to defects in CPC centromere targeting and aberrant Aurora B activity. On the other hand, the localization of the CPC in the midzone is independent of the borealin-HP1α interaction, demonstrating the spatial requirement of HP1α in CPC localization to the centromere. These findings reveal a previously unrecognized but direct link between HP1α and CPC localization in the centromere and illustrate the critical role of borealin-HP1α interaction in orchestrating an accurate cell division. PMID:24917673

Echinococcus-Host Interactions at Cellular and Molecular Levels.

PubMed

Brehm, K; Koziol, U

2017-01-01

The potentially lethal zoonotic diseases alveolar and cystic echinococcosis are caused by the metacestode larval stages of the tapeworms Echinococcus multilocularis and Echinococcus granulosus, respectively. In both cases, metacestode growth and proliferation occurs within the inner organs of mammalian hosts, which is associated with complex molecular host-parasite interactions that regulate nutrient uptake by the parasite as well as metacestode persistence and development. Using in vitro cultivation systems for parasite larvae, and informed by recently released, comprehensive genome and transcriptome data for both parasites, these molecular host-parasite interactions have been subject to significant research during recent years. In this review, we discuss progress in this field, with emphasis on parasite development and proliferation. We review host-parasite interaction mechanisms that occur early during an infection, when the invading oncosphere stage undergoes a metamorphosis towards the metacestode, and outline the decisive role of parasite stem cells during this process. We also discuss special features of metacestode morphology, and how this parasite stage takes up nutrients from the host, utilizing newly evolved or expanded gene families. We comprehensively review mechanisms of host-parasite cross-communication via evolutionarily conserved signalling systems and how the parasite signalling systems might be exploited for the development of novel chemotherapeutics. Finally, we point to an urgent need for the development of functional genomic techniques in this parasite, which will be imperative for hypothesis-driven analyses into Echinococcus stem cell biology, developmental mechanisms and immunomodulatory activities, which are all highly relevant for the development of anti-infective measures. Copyright © 2017 Elsevier Ltd. All rights reserved.

Variation in conserved non-coding sequences on chromosome 5q andsusceptibility to asthma and atopy

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

Donfack, Joseph; Schneider, Daniel H.; Tan, Zheng

2005-09-10

Background: Evolutionarily conserved sequences likely havebiological function. Methods: To determine whether variation in conservedsequences in non-coding DNA contributes to risk for human disease, westudied six conserved non-coding elements in the Th2 cytokine cluster onhuman chromosome 5q31 in a large Hutterite pedigree and in samples ofoutbred European American and African American asthma cases and controls.Results: Among six conserved non-coding elements (>100 bp,>70percent identity; human-mouse comparison), we identified one singlenucleotide polymorphism (SNP) in each of two conserved elements and sixSNPs in the flanking regions of three conserved elements. We genotypedour samples for four of these SNPs and an additional three SNPs eachmore » inthe IL13 and IL4 genes. While there was only modest evidence forassociation with single SNPs in the Hutterite and European Americansamples (P<0.05), there were highly significant associations inEuropean Americans between asthma and haplotypes comprised of SNPs in theIL4 gene (P<0.001), including a SNP in a conserved non-codingelement. Furthermore, variation in the IL13 gene was strongly associatedwith total IgE (P = 0.00022) and allergic sensitization to mold allergens(P = 0.00076) in the Hutterites, and more modestly associated withsensitization to molds in the European Americans and African Americans (P<0.01). Conclusion: These results indicate that there is overalllittle variation in the conserved non-coding elements on 5q31, butvariation in IL4 and IL13, including possibly one SNP in a conservedelement, influence asthma and atopic phenotypes in diversepopulations.« less

Genome-wide identification of conserved intronic non-coding sequences using a Bayesian segmentation approach.

PubMed

Algama, Manjula; Tasker, Edward; Williams, Caitlin; Parslow, Adam C; Bryson-Richardson, Robert J; Keith, Jonathan M

2017-03-27

Computational identification of non-coding RNAs (ncRNAs) is a challenging problem. We describe a genome-wide analysis using Bayesian segmentation to identify intronic elements highly conserved between three evolutionarily distant vertebrate species: human, mouse and zebrafish. We investigate the extent to which these elements include ncRNAs (or conserved domains of ncRNAs) and regulatory sequences. We identified 655 deeply conserved intronic sequences in a genome-wide analysis. We also performed a pathway-focussed analysis on genes involved in muscle development, detecting 27 intronic elements, of which 22 were not detected in the genome-wide analysis. At least 87% of the genome-wide and 70% of the pathway-focussed elements have existing annotations indicative of conserved RNA secondary structure. The expression of 26 of the pathway-focused elements was examined using RT-PCR, providing confirmation that they include expressed ncRNAs. Consistent with previous studies, these elements are significantly over-represented in the introns of transcription factors. This study demonstrates a novel, highly effective, Bayesian approach to identifying conserved non-coding sequences. Our results complement previous findings that these sequences are enriched in transcription factors. However, in contrast to previous studies which suggest the majority of conserved sequences are regulatory factor binding sites, the majority of conserved sequences identified using our approach contain evidence of conserved RNA secondary structures, and our laboratory results suggest most are expressed. Functional roles at DNA and RNA levels are not mutually exclusive, and many of our elements possess evidence of both. Moreover, ncRNAs play roles in transcriptional and post-transcriptional regulation, and this may contribute to the over-representation of these elements in introns of transcription factors. We attribute the higher sensitivity of the pathway-focussed analysis compared to the genome

XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs

PubMed Central

Scott, Fiona L; Denault, Jean-Bernard; Riedl, Stefan J; Shin, Hwain; Renatus, Martin; Salvesen, Guy S

2005-01-01

The X-linked inhibitor of apoptosis protein (XIAP) uses its second baculovirus IAP repeat domain (BIR2) to inhibit the apoptotic executioner caspase-3 and -7. Structural studies have demonstrated that it is not the BIR2 domain itself but a segment N-terminal to it that directly targets the activity of these caspases. These studies failed to demonstrate a role of the BIR2 domain in inhibition. We used site-directed mutagenesis of BIR2 and its linker to determine the mechanism of executioner caspase inhibition by XIAP. We show that the BIR2 domain contributes substantially to inhibition of executioner caspases. A surface groove on BIR2, which also binds to Smac/DIABLO, interacts with a neoepitope generated at the N-terminus of the caspase small subunit following activation. Therefore, BIR2 uses a two-site interaction mechanism to achieve high specificity and potency for inhibition. Moreover, for caspase-7, the precise location of the activating cleavage is critical for subsequent inhibition. Since apical caspases utilize this cleavage site differently, we predict that the origin of the death stimulus should dictate the efficiency of inhibition by XIAP. PMID:15650747

Highly conserved type 1 pili promote enterotoxigenic E. coli pathogen-host interactions

PubMed Central

Rashu, Rasheduzzaman; Begum, Yasmin Ara; Ciorba, Matthew A.; Hultgren, Scott J.; Qadri, Firdausi

2017-01-01

Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as plasmid encoded colonization factors. Some of these adhesins undergo significant transcriptional modulation as ETEC encounter intestinal epithelia, perhaps suggesting that they cooperatively facilitate interaction with the host. Among genes significantly upregulated on cell contact are those encoding type 1 pili. We therefore investigated the role played by these pili in facilitating ETEC adhesion, and toxin delivery to model intestinal epithelia. We demonstrate that type 1 pili, encoded in the E. coli core genome, play an essential role in ETEC virulence, acting in concert with plasmid-encoded pathovar specific colonization factor (CF) fimbriae to promote optimal bacterial adhesion to cultured intestinal epithelium (CIE) and to epithelial monolayers differentiated from human small intestinal stem cells. Type 1 pili are tipped with the FimH adhesin which recognizes mannose with stereochemical specificity. Thus, enhanced production of highly mannosylated proteins on intestinal epithelia promoted FimH-mediated ETEC adhesion, while conversely, interruption of FimH lectin-epithelial interactions with soluble mannose, anti-FimH antibodies or mutagenesis of fimH effectively blocked ETEC adhesion. Moreover, fimH mutants were significantly impaired in delivery of both heat-stable and heat-labile toxins to the target epithelial cells in vitro, and these mutants were substantially less virulent in rabbit ileal loop assays, a classical model of ETEC pathogenesis. Collectively, our data suggest that these highly conserved pili play an essential role in virulence of these diverse

Mammalian splicing factor SF1 interacts with SURP domains of U2 snRNP-associated proteins

PubMed Central

Crisci, Angela; Raleff, Flore; Bagdiul, Ivona; Raabe, Monika; Urlaub, Henning; Rain, Jean-Christophe; Krämer, Angela

2015-01-01

Splicing factor 1 (SF1) recognizes the branch point sequence (BPS) at the 3′ splice site during the formation of early complex E, thereby pre-bulging the BPS adenosine, thought to facilitate subsequent base-pairing of the U2 snRNA with the BPS. The 65-kDa subunit of U2 snRNP auxiliary factor (U2AF65) interacts with SF1 and was shown to recruit the U2 snRNP to the spliceosome. Co-immunoprecipitation experiments of SF1-interacting proteins from HeLa cell extracts shown here are consistent with the presence of SF1 in early splicing complexes. Surprisingly almost all U2 snRNP proteins were found associated with SF1. Yeast two-hybrid screens identified two SURP domain-containing U2 snRNP proteins as partners of SF1. A short, evolutionarily conserved region of SF1 interacts with the SURP domains, stressing their role in protein–protein interactions. A reduction of A complex formation in SF1-depleted extracts could be rescued with recombinant SF1 containing the SURP-interaction domain, but only partial rescue was observed with SF1 lacking this sequence. Thus, SF1 can initially recruit the U2 snRNP to the spliceosome during E complex formation, whereas U2AF65 may stabilize the association of the U2 snRNP with the spliceosome at later times. In addition, these findings may have implications for alternative splicing decisions. PMID:26420826

Conserved properties of Drosophila Insomniac link sleep regulation and synaptic function.

PubMed

Li, Qiuling; Kellner, David A; Hatch, Hayden A M; Yumita, Tomohiro; Sanchez, Sandrine; Machold, Robert P; Frank, C Andrew; Stavropoulos, Nicholas

2017-05-01

Sleep is an ancient animal behavior that is regulated similarly in species ranging from flies to humans. Various genes that regulate sleep have been identified in invertebrates, but whether the functions of these genes are conserved in mammals remains poorly explored. Drosophila insomniac (inc) mutants exhibit severely shortened and fragmented sleep. Inc protein physically associates with the Cullin-3 (Cul3) ubiquitin ligase, and neuronal depletion of Inc or Cul3 strongly curtails sleep, suggesting that Inc is a Cul3 adaptor that directs the ubiquitination of neuronal substrates that impact sleep. Three proteins similar to Inc exist in vertebrates-KCTD2, KCTD5, and KCTD17-but are uncharacterized within the nervous system and their functional conservation with Inc has not been addressed. Here we show that Inc and its mouse orthologs exhibit striking biochemical and functional interchangeability within Cul3 complexes. Remarkably, KCTD2 and KCTD5 restore sleep to inc mutants, indicating that they can substitute for Inc in vivo and engage its neuronal targets relevant to sleep. Inc and its orthologs localize similarly within fly and mammalian neurons and can traffic to synapses, suggesting that their substrates may include synaptic proteins. Consistent with such a mechanism, inc mutants exhibit defects in synaptic structure and physiology, indicating that Inc is essential for both sleep and synaptic function. Our findings reveal that molecular functions of Inc are conserved through ~600 million years of evolution and support the hypothesis that Inc and its orthologs participate in an evolutionarily conserved ubiquitination pathway that links synaptic function and sleep regulation.

Structural and functional determinants of conserved lipid interaction domains of inward rectifying Kir6.2 channels.

PubMed

Cukras, Catherine A; Jeliazkova, Iana; Nichols, Colin G

2002-06-01

All members of the inward rectifiier K(+) (Kir) channel family are activated by phosphoinositides and other amphiphilic lipids. To further elucidate the mechanistic basis, we examined the membrane association of Kir6.2 fragments of K(ATP) channels, and the effects of site-directed mutations of these fragments and full-length Kir6.2 on membrane association and K(ATP) channel activity, respectively. GFP-tagged Kir6.2 COOH terminus and GFP-tagged pleckstrin homology domain from phospholipase C delta1 both associate with isolated membranes, and association of each is specifically reduced by muscarinic m1 receptor-mediated phospholipid depletion. Kir COOH termini are predicted to contain multiple beta-strands and a conserved alpha-helix (residues approximately 306-311 in Kir6.2). Systematic mutagenesis of D307-F315 reveals a critical role of E308, I309, W311 and F315, consistent with residues lying on one side of a alpha-helix. Together with systematic mutation of conserved charges, the results define critical determinants of a conserved domain that underlies phospholipid interaction in Kir channels.

Formal education, previous interaction and perception influence the attitudes of people toward the conservation of snakes in a large urban center of northeastern Brazil.

PubMed

Pinheiro, Luan Tavares; Rodrigues, João Fabrício Mota; Borges-Nojosa, Diva Maria

2016-06-20

The attitudes and perceptions of people toward animals are influenced by sociodemographic factors, such as formal education and gender, and by personal experience. Understanding these interactions is critical for the establishment of conservation strategies for animals that have conflictual relationships with humans, such as snakes. Our study aims to explain how perceptions and the human fear of snakes vary and are influenced by formal education and gender. In addition, it aims to show how prior interaction with these animals influence these perceptions and the human fear toward snakes and how these perceptions and fear influence the importance of conservation of these animals. We collected data from June 2010 to December 2013 using questionnaires given to 1142 visitors of a scientific serpentarium (Núcleo Regional de Ofiologia da Universidade Federal do Ceará) in the municipality of Fortaleza, northeastern Brazil. Negative perceptions toward snakes were less frequent according to an increase in levels of schooling. Women had more negative perceptions and were more afraid of snakes than were men. Prior interaction with snakes decreased the occurrence of negative perceptions and reduced the level of human fear of these animals. People with negative perceptions classified the conservation of snakes as not important and were more afraid of these animals. Understanding the relationship between sociodemographic factors, prior experiences, perceptions, fear, and the importance given to conservation can help to better understand human attitudes toward snakes. Environmental education activities considering gender differences, involving preliminary interaction with snakes and focusing on priority targets identified in our study, such as people with low formal education, can increase the efficiency of measures for the conservation of these animals.

Anomalous temperature-dependent heat transport in one-dimensional momentum-conserving systems with soft-type interparticle interaction

NASA Astrophysics Data System (ADS)

Xiong, Daxing

2017-04-01

We numerically investigate the heat transport problem in a one-dimensional momentum-conserving lattice with a soft-type (ST) anharmonic interparticle interaction. It is found that with the increase of the system's temperature, while the introduction of ST anharmonicity softens phonons and decreases their velocities, this type of nonlinearity like its hard type (HT) counterpart, can still not be able to fully damp the longest wavelength phonons. Therefore, a usual anomalous temperature dependence of heat transport with certain scaling properties similarly to those shown in the Fermi-Pasta-Ulam-β -like systems with HT interactions can be seen. Our detailed examination from simulations verifies this temperature-dependent behavior well.

Mechanosensation is evolutionarily tuned to locomotor mechanics

PubMed Central

Aiello, Brett R.; Westneat, Mark W.; Hale, Melina E.

2017-01-01

The biomechanics of animal limbs has evolved to meet the functional demands for movement associated with different behaviors and environments. Effective movement relies not only on limb mechanics but also on appropriate mechanosensory feedback. By comparing sensory ability and mechanics within a phylogenetic framework, we show that peripheral mechanosensation has evolved with limb biomechanics, evolutionarily tuning the neuromechanical system to its functional demands. We examined sensory physiology and mechanics of the pectoral fins, forelimb homologs, in the fish family Labridae. Labrid fishes exhibit extraordinary morphological and behavioral diversity and use pectoral fin-based propulsion with fins ranging in shape from high aspect ratio (AR) wing-like fins to low AR paddle-like fins. Phylogenetic character analysis demonstrates that high AR fins evolved independently multiple times in this group. Four pairs of species were examined; each included a plesiomorphic low AR and a high AR species. Within each species pair, the high AR species demonstrated significantly stiffer fin rays in comparison with the low AR species. Afferent sensory nerve activity was recorded during fin ray bending. In all cases, afferents of stiffer fins were more sensitive at lower displacement amplitudes, demonstrating mechanosensory tuning to fin mechanics and a consistent pattern of correlated evolution. We suggest that these data provide a clear example of parallel evolution in a complex neuromechanical system, with a strong link between multiple phenotypic characters: pectoral fin shape, swimming behavior, fin ray stiffness, and mechanosensory sensitivity. PMID:28396411

The dual role of autophagy under hypoxia-involvement of interaction between autophagy and apoptosis.

PubMed

Li, Mengmeng; Tan, Jin; Miao, Yuyang; Lei, Ping; Zhang, Qiang

2015-06-01

Hypoxia is one of severe cellular stress and it is well known to be associated with a worse outcome since a lack of oxygen accelerates the induction of apoptosis. Autophagy, an important and evolutionarily conserved mechanism for maintaining cellular homeostasis, is closely related to the apoptosis caused by hypoxia. Generally autophagy blocks the induction of apoptosis and inhibits the activation of apoptosis-associated caspase which could reduce cellular injury. However, in special cases, autophagy or autophagy-relevant proteins may help to induce apoptosis, which could aggravate cell damage under hypoxia condition. In addition, the activation of apoptosis-related proteins-caspase can also degrade autophagy-related proteins, such as Atg3, Atg4, Beclin1 protein, inhibiting autophagy. Although the relationship between autophagy and apoptosis has been known for rather complex for more than a decade, the underlying regulatory mechanisms have not been clearly understood. This short review discusses and summarizes the dual role of autophagy and the interaction and molecular regulatory mechanisms between autophagy and apoptosis under hypoxia.

Viruses are a dominant driver of protein adaptation in mammals.

PubMed

Enard, David; Cai, Le; Gwennap, Carina; Petrov, Dmitri A

2016-05-17

Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is unknown. Here, we analyze adaptation in ~1300 virus-interacting proteins manually curated from a set of 9900 proteins conserved in all sequenced mammalian genomes. We show that viruses (i) use the more evolutionarily constrained proteins within the cellular functions they interact with and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. We conservatively estimate that viruses have driven close to 30% of all adaptive amino acid changes in the part of the human proteome conserved within mammals. Our results suggest that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes.

Inositol hexakisphosphate (IP6) generated by IP5K mediates cullin-COP9 signalosome interactions and CRL function.

PubMed

Scherer, Paul C; Ding, Yan; Liu, Zhiqing; Xu, Jing; Mao, Haibin; Barrow, James C; Wei, Ning; Zheng, Ning; Snyder, Solomon H; Rao, Feng

2016-03-29

The family of cullin-RING E3 Ligases (CRLs) and the constitutive photomorphogenesis 9 (COP9) signalosome (CSN) form dynamic complexes that mediate ubiquitylation of 20% of the proteome, yet regulation of their assembly/disassembly remains poorly understood. Inositol polyphosphates are highly conserved signaling molecules implicated in diverse cellular processes. We now report that inositol hexakisphosphate (IP6) is a major physiologic determinant of the CRL-CSN interface, which includes a hitherto unidentified electrostatic interaction between the N-terminal acidic tail of CSN subunit 2 (CSN2) and a conserved basic canyon on cullins. IP6, with an EC50 of 20 nM, acts as an intermolecular "glue," increasing cullin-CSN2 binding affinity by 30-fold, thereby promoting assembly of the inactive CRL-CSN complexes. The IP6 synthase, Ins(1,3,4,5,6)P5 2-kinase (IPPK/IP5K) binds to cullins. Depleting IP5K increases the percentage of neddylated, active Cul1 and Cul4A, and decreases levels of the Cul1/4A substrates p27 and p21. Besides dysregulating CRL-mediated cell proliferation and UV-induced apoptosis, IP5K depletion potentiates by 28-fold the cytotoxic effect of the neddylation inhibitor MLN4924. Thus, IP5K and IP6 are evolutionarily conserved components of the CRL-CSN system and are potential targets for cancer therapy in conjunction with MLN4924.

The C-X-C signalling system in the rodent vs primate testis: impact on germ cell niche interaction.

PubMed

Heckmann, Laura; Pock, Tim; Tröndle, Ina; Neuhaus, Nina

2018-05-01

In zebrafish, action of the chemokine Cxcl12 is mediated through its G-protein-coupled seven-transmembrane domain receptor Cxcr4 and the atypical receptor Cxcr7. Employing this animal model, it was revealed that this Cxcl12 signalling system plays a crucial role for directed migration of primordial germ cells (PGC) during early testicular development. Importantly, subsequent studies indicated that this regulatory mechanism is evolutionarily conserved also in mice. What is more, the functional role of the CXCL12 system does not seem to be limited to early phases of testicular development. Data from mouse studies rather demonstrate that CXCL12 and its receptors are also involved in the homing process of gonocytes into their niches at the basal membrane of the seminiferous tubules. Intriguingly, even the spermatogonial stem cells (SSCs) present in the adult mouse testis appear to maintain the ability to migrate towards a CXCL12 gradient as demonstrated by functional in vitro migration assays and in vivo germ cell transplantation assays. These findings not only indicate a role of the CXCL12 system throughout male germ cell development in mice but also suggest that this system may be evolutionarily conserved. In this review, we take into account the available literature focusing on the localization patterns of the CXCL12 system not only in rodents but also in primates, including the human. Based on these data, we discuss whether the CXCL12 system is also conserved between rodents and primates and discuss the known and potential functional consequences. © 2018 Society for Reproduction and Fertility.

Sedimentation equilibrium analysis of protein interactions with global implicit mass conservation constraints and systematic noise decomposition.

PubMed

Vistica, Jennifer; Dam, Julie; Balbo, Andrea; Yikilmaz, Emine; Mariuzza, Roy A; Rouault, Tracey A; Schuck, Peter

2004-03-15

Sedimentation equilibrium is a powerful tool for the characterization of protein self-association and heterogeneous protein interactions. Frequently, it is applied in a configuration with relatively long solution columns and with equilibrium profiles being acquired sequentially at several rotor speeds. The present study proposes computational tools, implemented in the software SEDPHAT, for the global analysis of equilibrium data at multiple rotor speeds with multiple concentrations and multiple optical detection methods. The detailed global modeling of such equilibrium data can be a nontrivial computational problem. It was shown previously that mass conservation constraints can significantly improve and extend the analysis of heterogeneous protein interactions. Here, a method for using conservation of mass constraints for the macromolecular redistribution is proposed in which the effective loading concentrations are calculated from the sedimentation equilibrium profiles. The approach is similar to that described by Roark (Biophys. Chem. 5 (1976) 185-196), but its utility is extended by determining the bottom position of the solution columns from the macromolecular redistribution. For analyzing heterogeneous associations at multiple protein concentrations, additional constraints that relate the effective loading concentrations of the different components or their molar ratio in the global analysis are introduced. Equilibrium profiles at multiple rotor speeds also permit the algebraic determination of radial-dependent baseline profiles, which can govern interference optical ultracentrifugation data, but usually also occur, to a smaller extent, in absorbance optical data. Finally, the global analysis of equilibrium profiles at multiple rotor speeds with implicit mass conservation and computation of the bottom of the solution column provides an unbiased scale for determining molar mass distributions of noninteracting species. The properties of these tools are studied

Role of a highly conserved electrostatic interaction on the surface of cytochrome C in control of the redox function.

PubMed

Tai, Hulin; Mikami, Shin-ichi; Irie, Kiyofumi; Watanabe, Naoki; Shinohara, Naoya; Yamamoto, Yasuhiko

2010-01-12

In Hydrogenobacter thermophilus cytochrome c(552), an electrostatic interaction between Lys8 and Glu68 in the N- and C-terminal helices, respectively, stabilizes its protein structure [Travaglini-Allocatelli, C., Gianni, S., Dubey, V. K., Borgia, A., Di Matteo, A., Bonivento, D., Cutruzzola, F., Bren, K. L., and Brunori, M. (2005) J. Biol. Chem. 280, 25729-25734], this electrostatic interaction being a highly conserved structural feature of the cytochrome c family. In the present study, the functional consequences of removal of the interaction through replacement of Lys8 by Ala have been investigated in order to elucidate the molecular mechanisms responsible for functional control of the protein. The mutation resulted in a decrease in protein stability, as reflected in lowering of the denaturation temperature by approximately 2-9 degrees C, and a negative shift by approximately 8 mV of the redox potential (E(m)) of the protein. The decrease in the protein stability was attributed to the enthalpic loss due to the removal of the intramolecular interaction. The negative shift of the E(m) value was shown to be due to the effect of the mutation on the entropic contribution to the E(m) value. The small, but subtle, effects of removal of the conserved electrostatic interaction, occurring at approximately 1.4 nm away from heme iron, on the thermodynamic properties of the protein demonstrated not only that the interaction is important for maintaining the functional properties of the protein but also that amino acid residues relatively remote from the heme active site play sizable roles in functional control of the protein.

An Evolutionarily Conserved Role for the Aryl Hydrocarbon Receptor in the Regulation of Movement

PubMed Central

Williams, Evan G.; Mouchiroud, Laurent; Frochaux, Michael; Pandey, Ashutosh; Andreux, Pénélope A.; Deplancke, Bart; Auwerx, Johan

2014-01-01

The BXD genetic reference population is a recombinant inbred panel descended from crosses between the C57BL/6 (B6) and DBA/2 (D2) strains of mice, which segregate for about 5 million sequence variants. Recently, some of these variants have been established with effects on general metabolic phenotypes such as glucose response and bone strength. Here we phenotype 43 BXD strains and observe they have large variation (∼5-fold) in their spontaneous activity during waking hours. QTL analyses indicate that ∼40% of this variance is attributable to a narrow locus containing the aryl hydrocarbon receptor (Ahr), a basic helix-loop-helix transcription factor with well-established roles in development and xenobiotic metabolism. Strains with the D2 allele of Ahr have reduced gene expression compared to those with the B6 allele, and have significantly higher spontaneous activity. This effect was also observed in B6 mice with a congenic D2 Ahr interval, and in B6 mice with a humanized AHR allele which, like the D2 allele, is expressed much less and has less enzymatic activity than the B6 allele. Ahr is highly conserved in invertebrates, and strikingly inhibition of its orthologs in D. melanogaster and C. elegans (spineless and ahr-1) leads to marked increases in basal activity. In mammals, Ahr has numerous ligands, but most are either non-selective (e.g. resveratrol) or highly toxic (e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)). Thus, we chose to examine a major environmental influence—long term feeding with high fat diet (HFD)—to see if the effects of Ahr are dependent on major metabolic differences. Interestingly, while HFD robustly halved movement across all strains, the QTL position and effects of Ahr remained unchanged, indicating that the effects are independent. The highly consistent effects of Ahr on movement indicate that changes in its constitutive activity have a role on spontaneous movement and may influence human behavior. PMID:25255223

Sponge non-metastatic Group I Nme gene/protein - structure and function is conserved from sponges to humans

PubMed Central

2011-01-01

Background Nucleoside diphosphate kinases NDPK are evolutionarily conserved enzymes present in Bacteria, Archaea and Eukarya, with human Nme1 the most studied representative of the family and the first identified metastasis suppressor. Sponges (Porifera) are simple metazoans without tissues, closest to the common ancestor of all animals. They changed little during evolution and probably provide the best insight into the metazoan ancestor's genomic features. Recent studies show that sponges have a wide repertoire of genes many of which are involved in diseases in more complex metazoans. The original function of those genes and the way it has evolved in the animal lineage is largely unknown. Here we report new results on the metastasis suppressor gene/protein homolog from the marine sponge Suberites domuncula, NmeGp1Sd. The purpose of this study was to investigate the properties of the sponge Group I Nme gene and protein, and compare it to its human homolog in order to elucidate the evolution of the structure and function of Nme. Results We found that sponge genes coding for Group I Nme protein are intron-rich. Furthermore, we discovered that the sponge NmeGp1Sd protein has a similar level of kinase activity as its human homolog Nme1, does not cleave negatively supercoiled DNA and shows nonspecific DNA-binding activity. The sponge NmeGp1Sd forms a hexamer, like human Nme1, and all other eukaryotic Nme proteins. NmeGp1Sd interacts with human Nme1 in human cells and exhibits the same subcellular localization. Stable clones expressing sponge NmeGp1Sd inhibited the migratory potential of CAL 27 cells, as already reported for human Nme1, which suggests that Nme's function in migratory processes was engaged long before the composition of true tissues. Conclusions This study suggests that the ancestor of all animals possessed a NmeGp1 protein with properties and functions similar to evolutionarily recent versions of the protein, even before the appearance of true tissues

Crumbs regulates rhodopsin transport by interacting with and stabilizing myosin V

PubMed Central

Shevchenko, Anna

2011-01-01

The evolutionarily conserved Crumbs (Crb) complex is crucial for photoreceptor morphogenesis and homeostasis. Loss of Crb results in light-dependent retinal degeneration, which is prevented by feeding mutant flies carotenoid-deficient medium. This suggests a defect in rhodopsin 1 (Rh1) processing, transport, and/or signaling, causing degeneration; however, the molecular mechanism of this remained elusive. In this paper, we show that myosin V (MyoV) coimmunoprecipitated with the Crb complex and that loss of crb led to severe reduction in MyoV levels, which could be rescued by proteasomal inhibition. Loss of MyoV in crb mutant photoreceptors was accompanied by defective transport of the MyoV cargo Rh1 to the light-sensing organelle, the rhabdomere. This resulted in an age-dependent accumulation of Rh1 in the photoreceptor cell (PRC) body, a well-documented trigger of degeneration. We conclude that Crb protects against degeneration by interacting with and stabilizing MyoV, thereby ensuring correct Rh1 trafficking. Our data provide, for the first time, a molecular mechanism for the light-dependent degeneration of PRCs observed in crb mutant retinas. PMID:22105348

Systematic Differences in Signal Emitting and Receiving Revealed by PageRank Analysis of a Human Protein Interactome

PubMed Central

Li, Xiu-Qing

2012-01-01

Most protein PageRank studies do not use signal flow direction information in protein interactions because this information was not readily available in large protein databases until recently. Therefore, four questions have yet to be answered: A) What is the general difference between signal emitting and receiving in a protein interactome? B) Which proteins are among the top ranked in directional ranking? C) Are high ranked proteins more evolutionarily conserved than low ranked ones? D) Do proteins with similar ranking tend to have similar subcellular locations? In this study, we address these questions using the forward, reverse, and non-directional PageRank approaches to rank an information-directional network of human proteins and study their evolutionary conservation. The forward ranking gives credit to information receivers, reverse ranking to information emitters, and non-directional ranking mainly to the number of interactions. The protein lists generated by the forward and non-directional rankings are highly correlated, but those by the reverse and non-directional rankings are not. The results suggest that the signal emitting/receiving system is characterized by key-emittings and relatively even receivings in the human protein interactome. Signaling pathway proteins are frequent in top ranked ones. Eight proteins are both informational top emitters and top receivers. Top ranked proteins, except a few species-related novel-function ones, are evolutionarily well conserved. Protein-subunit ranking position reflects subunit function. These results demonstrate the usefulness of different PageRank approaches in characterizing protein networks and provide insights to protein interaction in the cell. PMID:23028653

Calsyntenin-3 molecular architecture and interaction with neurexin 1α.

PubMed

Lu, Zhuoyang; Wang, Yun; Chen, Fang; Tong, Huimin; Reddy, M V V V Sekhar; Luo, Lin; Seshadrinathan, Suchithra; Zhang, Lei; Holthauzen, Luis Marcelo F; Craig, Ann Marie; Ren, Gang; Rudenko, Gabby

2014-12-12

Calsyntenin 3 (Cstn3 or Clstn3), a recently identified synaptic organizer, promotes the development of synapses. Cstn3 localizes to the postsynaptic membrane and triggers presynaptic differentiation. Calsyntenin members play an evolutionarily conserved role in memory and learning. Cstn3 was recently shown in cell-based assays to interact with neurexin 1α (n1α), a synaptic organizer that is implicated in neuropsychiatric disease. Interaction would permit Cstn3 and n1α to form a trans-synaptic complex and promote synaptic differentiation. However, it is contentious whether Cstn3 binds n1α directly. To understand the structure and function of Cstn3, we determined its architecture by electron microscopy and delineated the interaction between Cstn3 and n1α biochemically and biophysically. We show that Cstn3 ectodomains form monomers as well as tetramers that are stabilized by disulfide bonds and Ca(2+), and both are probably flexible in solution. We show further that the extracellular domains of Cstn3 and n1α interact directly and that both Cstn3 monomers and tetramers bind n1α with nanomolar affinity. The interaction is promoted by Ca(2+) and requires minimally the LNS domain of Cstn3. Furthermore, Cstn3 uses a fundamentally different mechanism to bind n1α compared with other neurexin partners, such as the synaptic organizer neuroligin 2, because Cstn3 does not strictly require the sixth LNS domain of n1α. Our structural data suggest how Cstn3 as a synaptic organizer on the postsynaptic membrane, particularly in tetrameric form, may assemble radially symmetric trans-synaptic bridges with the presynaptic synaptic organizer n1α to recruit and spatially organize proteins into networks essential for synaptic function. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Inhibition of homologous phosphorolytic ribonucleases by citrate may represent an evolutionarily conserved communicative link between RNA degradation and central metabolism

PubMed Central

Stone, Carlanne M.; Butt, Louise E.; Bufton, Joshua C.; Lourenco, Daniel C.; Gowers, Darren M.; Pickford, Andrew R.; Cox, Paul A.

2017-01-01

Abstract Ribonucleases play essential roles in all aspects of RNA metabolism, including the coordination of post-transcriptional gene regulation that allows organisms to respond to internal changes and environmental stimuli. However, as inherently destructive enzymes, their activity must be carefully controlled. Recent research exemplifies the repertoire of regulatory strategies employed by ribonucleases. The activity of the phosphorolytic exoribonuclease, polynucleotide phosphorylase (PNPase), has previously been shown to be modulated by the Krebs cycle metabolite citrate in Escherichia coli. Here, we provide evidence for the existence of citrate-mediated inhibition of ribonucleases in all three domains of life. In silico molecular docking studies predict that citrate will bind not only to bacterial PNPases from E. coli and Streptomyces antibioticus, but also PNPase from human mitochondria and the structurally and functionally related archaeal exosome complex from Sulfolobus solfataricus. Critically, we show experimentally that citrate also inhibits the exoribonuclease activity of bacterial, eukaryotic and archaeal PNPase homologues in vitro. Furthermore, bioinformatics data, showing key citrate-binding motifs conserved across a broad range of PNPase homologues, suggests that this regulatory mechanism may be widespread. Overall, our data highlight a communicative link between ribonuclease activity and central metabolism that may have been conserved through the course of evolution. PMID:28334892

A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression.

PubMed

Mir, Riyaz A; Bele, Aditya; Mirza, Sameer; Srivastava, Shashank; Olou, Appolinaire A; Ammons, Shalis A; Kim, Jun Hyun; Gurumurthy, Channabasavaiah B; Qiu, Fang; Band, Hamid; Band, Vimla

2015-12-28

Ecdysoneless (ECD) is an evolutionarily conserved protein whose germ line deletion is embryonic lethal. Deletion of Ecd in cells causes cell cycle arrest, which is rescued by exogenous ECD, demonstrating a requirement of ECD for normal mammalian cell cycle progression. However, the exact mechanism by which ECD regulates cell cycle is unknown. Here, we demonstrate that ECD protein levels and subcellular localization are invariant during cell cycle progression, suggesting a potential role of posttranslational modifications or protein-protein interactions. Since phosphorylated ECD was recently shown to interact with the PIH1D1 adaptor component of the R2TP cochaperone complex, we examined the requirement of ECD phosphorylation in cell cycle progression. Notably, phosphorylation-deficient ECD mutants that failed to bind to PIH1D1 in vitro fully retained the ability to interact with the R2TP complex and yet exhibited a reduced ability to rescue Ecd-deficient cells from cell cycle arrest. Biochemical analyses demonstrated an additional phosphorylation-independent interaction of ECD with the RUVBL1 component of the R2TP complex, and this interaction is essential for ECD's cell cycle progression function. These studies demonstrate that interaction of ECD with RUVBL1, and its CK2-mediated phosphorylation, independent of its interaction with PIH1D1, are important for its cell cycle regulatory function. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression

PubMed Central

Mir, Riyaz A.; Bele, Aditya; Mirza, Sameer; Srivastava, Shashank; Olou, Appolinaire A.; Ammons, Shalis A.; Kim, Jun Hyun; Gurumurthy, Channabasavaiah B.; Qiu, Fang; Band, Hamid

2015-01-01

Ecdysoneless (ECD) is an evolutionarily conserved protein whose germ line deletion is embryonic lethal. Deletion of Ecd in cells causes cell cycle arrest, which is rescued by exogenous ECD, demonstrating a requirement of ECD for normal mammalian cell cycle progression. However, the exact mechanism by which ECD regulates cell cycle is unknown. Here, we demonstrate that ECD protein levels and subcellular localization are invariant during cell cycle progression, suggesting a potential role of posttranslational modifications or protein-protein interactions. Since phosphorylated ECD was recently shown to interact with the PIH1D1 adaptor component of the R2TP cochaperone complex, we examined the requirement of ECD phosphorylation in cell cycle progression. Notably, phosphorylation-deficient ECD mutants that failed to bind to PIH1D1 in vitro fully retained the ability to interact with the R2TP complex and yet exhibited a reduced ability to rescue Ecd-deficient cells from cell cycle arrest. Biochemical analyses demonstrated an additional phosphorylation-independent interaction of ECD with the RUVBL1 component of the R2TP complex, and this interaction is essential for ECD's cell cycle progression function. These studies demonstrate that interaction of ECD with RUVBL1, and its CK2-mediated phosphorylation, independent of its interaction with PIH1D1, are important for its cell cycle regulatory function. PMID:26711270

Evolutionary conservation and changes in insect TRP channels.

PubMed

Matsuura, Hironori; Sokabe, Takaaki; Kohno, Keigo; Tominaga, Makoto; Kadowaki, Tatsuhiko

2009-09-10

TRP (Transient Receptor Potential) channels respond to diverse stimuli and thus function as the primary integrators of varied sensory information. They are also activated by various compounds and secondary messengers to mediate cell-cell interactions as well as to detect changes in the local environment. Their physiological roles have been primarily characterized only in mice and fruit flies, and evolutionary studies are limited. To understand the evolution of insect TRP channels and the mechanisms of integrating sensory inputs in insects, we have identified and compared TRP channel genes in Drosophila melanogaster, Bombyx mori, Tribolium castaneum, Apis mellifera, Nasonia vitripennis, and Pediculus humanus genomes as part of genome sequencing efforts. All the insects examined have 2 TRPV, 1 TRPN, 1 TRPM, 3 TRPC, and 1 TRPML subfamily members, demonstrating that these channels have the ancient origins in insects. The common pattern also suggests that the mechanisms for detecting mechanical and visual stimuli and maintaining lysosomal functions may be evolutionarily well conserved in insects. However, a TRPP channel, the most ancient TRP channel, is missing in B. mori, A. mellifera, and N. vitripennis. Although P. humanus and D. melanogaster contain 4 TRPA subfamily members, the other insects have 5 TRPA subfamily members. T. castaneum, A. mellifera, and N. vitripennis contain TRPA5 channels, which have been specifically retained or gained in Coleoptera and Hymenoptera. Furthermore, TRPA1, which functions for thermotaxis in Drosophila, is missing in A. mellifera and N. vitripennis; however, they have other Hymenoptera-specific TRPA channels (AmHsTRPA and NvHsTRPA). NvHsTRPA expressed in HEK293 cells is activated by temperature increase, demonstrating that HsTRPAs function as novel thermal sensors in Hymenoptera. The total number of insect TRP family members is 13-14, approximately half that of mammalian TRP family members. As shown for mammalian TRP channels, this

Feline Immunodeficiency Virus Evolutionarily Acquires Two Proteins, Vif and Protease, Capable of Antagonizing Feline APOBEC3.

PubMed

Yoshikawa, Rokusuke; Takeuchi, Junko S; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Kimura, Yuichi; Ren, Fengrong; Miyazawa, Takayuki; Koyanagi, Yoshio; Sato, Kei

2017-06-01

The interplay between viral and host proteins has been well studied to elucidate virus-host interactions and their relevance to virulence. Mammalian genes encode apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins, which act as intrinsic restriction factors against lentiviruses. To overcome APOBEC3-mediated antiviral actions, lentiviruses have evolutionarily acquired an accessory protein, viral infectivity factor (Vif), and Vif degrades host APOBEC3 proteins via a ubiquitin/proteasome-dependent pathway. Although the Vif-APOBEC3 interaction and its evolutionary significance, particularly those of primate lentiviruses (including HIV) and primates (including humans), have been well investigated, those of nonprimate lentiviruses and nonprimates are poorly understood. Moreover, the factors that determine lentiviral pathogenicity remain unclear. Here, we focus on feline immunodeficiency virus (FIV), a pathogenic lentivirus in domestic cats, and the interaction between FIV Vif and feline APOBEC3 in terms of viral virulence and evolution. We reveal the significantly reduced diversity of FIV subtype B compared to that of other subtypes, which may associate with the low pathogenicity of this subtype. We also demonstrate that FIV subtype B Vif is less active with regard to feline APOBEC3 degradation. More intriguingly, we further reveal that FIV protease cleaves feline APOBEC3 in released virions. Taken together, our findings provide evidence that a lentivirus encodes two types of anti-APOBEC3 factors, Vif and viral protease. IMPORTANCE During the history of mammalian evolution, mammals coevolved with retroviruses, including lentiviruses. All pathogenic lentiviruses, excluding equine infectious anemia virus, have acquired the vif gene via evolution to combat APOBEC3 proteins, which are intrinsic restriction factors against exogenous lentiviruses. Here we demonstrate that FIV, a pathogenic lentivirus in domestic cats, antagonizes feline APOBEC3

Feline Immunodeficiency Virus Evolutionarily Acquires Two Proteins, Vif and Protease, Capable of Antagonizing Feline APOBEC3

PubMed Central

Yoshikawa, Rokusuke; Takeuchi, Junko S.; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Kimura, Yuichi; Ren, Fengrong; Miyazawa, Takayuki; Koyanagi, Yoshio

2017-01-01

ABSTRACT The interplay between viral and host proteins has been well studied to elucidate virus-host interactions and their relevance to virulence. Mammalian genes encode apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins, which act as intrinsic restriction factors against lentiviruses. To overcome APOBEC3-mediated antiviral actions, lentiviruses have evolutionarily acquired an accessory protein, viral infectivity factor (Vif), and Vif degrades host APOBEC3 proteins via a ubiquitin/proteasome-dependent pathway. Although the Vif-APOBEC3 interaction and its evolutionary significance, particularly those of primate lentiviruses (including HIV) and primates (including humans), have been well investigated, those of nonprimate lentiviruses and nonprimates are poorly understood. Moreover, the factors that determine lentiviral pathogenicity remain unclear. Here, we focus on feline immunodeficiency virus (FIV), a pathogenic lentivirus in domestic cats, and the interaction between FIV Vif and feline APOBEC3 in terms of viral virulence and evolution. We reveal the significantly reduced diversity of FIV subtype B compared to that of other subtypes, which may associate with the low pathogenicity of this subtype. We also demonstrate that FIV subtype B Vif is less active with regard to feline APOBEC3 degradation. More intriguingly, we further reveal that FIV protease cleaves feline APOBEC3 in released virions. Taken together, our findings provide evidence that a lentivirus encodes two types of anti-APOBEC3 factors, Vif and viral protease. IMPORTANCE During the history of mammalian evolution, mammals coevolved with retroviruses, including lentiviruses. All pathogenic lentiviruses, excluding equine infectious anemia virus, have acquired the vif gene via evolution to combat APOBEC3 proteins, which are intrinsic restriction factors against exogenous lentiviruses. Here we demonstrate that FIV, a pathogenic lentivirus in domestic cats, antagonizes

The Histone Chaperone NRP1 Interacts with WEREWOLF to Activate GLABRA2 in Arabidopsis Root Hair Development

PubMed Central

Rong, Liang; Luo, Qiang; Wang, Baihui; Zhou, Nana; Zhang, Chi; Feng, Haiyang

2017-01-01

NUCLEOSOME ASSEMBLY PROTEIN1 (NAP1) defines an evolutionarily conserved family of histone chaperones and loss of function of the Arabidopsis thaliana NAP1 family genes NAP1-RELATED PROTEIN1 (NRP1) and NRP2 causes abnormal root hair formation. Yet, the underlying molecular mechanisms remain unclear. Here, we show that NRP1 interacts with the transcription factor WEREWOLF (WER) in vitro and in vivo and enriches at the GLABRA2 (GL2) promoter in a WER-dependent manner. Crystallographic analysis indicates that NRP1 forms a dimer via its N-terminal α-helix. Mutants of NRP1 that either disrupt the α-helix dimerization or remove the C-terminal acidic tail, impair its binding to histones and WER and concomitantly lead to failure to activate GL2 transcription and to rescue the nrp1-1 nrp2-1 mutant phenotype. Our results further demonstrate that WER-dependent enrichment of NRP1 at the GL2 promoter is involved in local histone eviction and nucleosome loss in vivo. Biochemical competition assays imply that the association between NRP1 and histones may counteract the inhibitory effect of histones on the WER-DNA interaction. Collectively, our study provides important insight into the molecular mechanisms by which histone chaperones are recruited to target chromatin via interaction with a gene-specific transcription factor to moderate chromatin structure for proper root hair development. PMID:28138017

Conserved hypothetical protein Rv1977 in Mycobacterium tuberculosis strains contains sequence polymorphisms and might be involved in ongoing immune evasion.

PubMed

Jiang, Yi; Liu, Haican; Wang, Xuezhi; Li, Guilian; Qiu, Yan; Dou, Xiangfeng; Wan, Kanglin

2015-01-01

Host immune pressure and associated parasite immune evasion are key features of host-pathogen co-evolution. A previous study showed that human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved and thus it was deduced that M. tuberculosis lacks antigenic variation and immune evasion. Here, we selected 151 clinical Mycobacterium tuberculosis isolates from China, amplified gene encoding Rv1977 and compared the sequences. The results showed that Rv1977, a conserved hypothetical protein, is not conserved in M. tuberculosis strains and there are polymorphisms existed in the protein. Some mutations, especially one frameshift mutation, occurred in the antigen Rv1977, which is uncommon in M.tb strains and may lead to the protein function altering. Mutations and deletion in the gene all affect one of three T cell epitopes and the changed T cell epitope contained more than one variable position, which may suggest ongoing immune evasion.

Intraspecific phylogeography of Lasmigona subviridis (Bivalvia: Unionidae): Conservation implications of range discontinuity

USGS Publications Warehouse

King, T.L.; Eackles, M.S.; Gjetvaj, B.; Hoeh, W.R.

1999-01-01

A nucleotide sequence analysis of the first internal transcribed spacer region (ITS-1) between the 5.8S and 18S ribosomal DNA genes (640 bp) and cytochrome c oxidase subunit I (COI) of mitochondrial DNA (mtDNA) (576 bp) was conducted for the freshwater bivalve Lasmigona subviridis and three congeners to determine the utility of these regions in identifying phylogeographic and phylogenetic structure. Sequence analysis of the ITS-1 region indicated a zone of discontinuity in the genetic population structure between a group of L. subviridis populations inhabiting the Susquehanna and Potomac Rivers and more southern populations. Moreover, haplotype patterns resulting from variation in the COI region suggested an absence of gene exchange between tributaries within two different river drainages, as well as between adjacent rivers systems. The authors recommend that the northern and southern populations, which are reproductively isolated and constitute evolutionarily significant lineages, be managed as separate conservation units. Results from the COI region suggest that, in some cases, unionid relocations should be avoided between tributaries of the same drainage because these populations may have been reproductively isolated for thousands of generations. Therefore, unionid bivalves distributed among discontinuous habitats (e.g. Atlantic slope drainages) potentially should be considered evolutionarily distinct. The DNA sequence divergences observed in the nuclear and mtDNA regions among the Lasmigona species were congruent, although the level of divergence in the COI region was up to three times greater. The genus Lasmigona, as represented by the four species surveyed in this study, may not be monophyletic.

Co-chaperone Hsp70/Hsp90-organizing protein (Hop) is required for transposon silencing and Piwi-interacting RNA (piRNA) biogenesis.

PubMed

Karam, Joseph A; Parikh, Rasesh Y; Nayak, Dhananjaya; Rosenkranz, David; Gangaraju, Vamsi K

2017-04-14

Piwi-interacting RNAs (piRNAs) are 26-30-nucleotide germ line-specific small non-coding RNAs that have evolutionarily conserved function in mobile genetic element (transposons) silencing and maintenance of genome integrity. Drosophila Hsp70/90-organizing protein homolog (Hop), a co-chaperone, interacts with piRNA-binding protein Piwi and mediates silencing of phenotypic variations. However, it is not known whether Hop has a direct role in piRNA biogenesis and transposon silencing. Here, we show that knockdown of Hop in the germ line nurse cells (GLKD) of Drosophila ovaries leads to activation of transposons. Hop GLKD females can lay eggs at the same rate as wild-type counterparts, but the eggs do not hatch into larvae. Hop GLKD leads to the accumulation of γ-H2Av foci in the germ line, indicating increased DNA damage in the ovary. We also show that Hop GLKD-induced transposon up-regulation is due to inefficient piRNA biogenesis. Based on these results, we conclude that Hop is a critical component of the piRNA pathway and that it maintains genome integrity by silencing transposons. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence.

PubMed

Meuleman, Wouter; Peric-Hupkes, Daan; Kind, Jop; Beaudry, Jean-Bernard; Pagie, Ludo; Kellis, Manolis; Reinders, Marcel; Wessels, Lodewyk; van Steensel, Bas

2013-02-01

In metazoans, the nuclear lamina is thought to play an important role in the spatial organization of interphase chromosomes, by providing anchoring sites for large genomic segments named lamina-associated domains (LADs). Some of these LADs are cell-type specific, while many others appear constitutively associated with the lamina. Constitutive LADs (cLADs) may contribute to a basal chromosome architecture. By comparison of mouse and human lamina interaction maps, we find that the sizes and genomic positions of cLADs are strongly conserved. Moreover, cLADs are depleted of synteny breakpoints, pointing to evolutionary selective pressure to keep cLADs intact. Paradoxically, the overall sequence conservation is low for cLADs. Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this "A/T rule" in embryonic stem cells, but not in differentiated cells. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level. Taken together, these results reveal that the spatial organization of mammalian genomes is highly conserved and tightly linked to local nucleotide composition.

Hydrology and Conservation Ecology

NASA Astrophysics Data System (ADS)

Narayanan, M.

2006-12-01

Responses to change in the behavior of ecological systems are largely governed by interactions at different levels. Research is essential and is to be necessarily designed to gain insights into various interactions at the community level. Sustainable resource management is only possible if conservation of biodiversity can be accomplished by properly using the knowledge discovered. It is well known that the United States Department of Agriculture provides technical information, resources, and data necessary to assist the researchers in addressing their conservation needs. Conservation aims to protect, preserve and conserve the earth's natural resources. These include, but not limited to the conservation of soil, water, minerals, air, plants and all living beings. The United States Department of Agriculture also encourages farmers and ranchers to voluntarily address threats to soil and water. Protection of wetlands and wildlife habitat has been on the radar screen of conservation experts for a very long time. The main objective has always been to help farmers and landowners conform and comply with federal and state environmental laws. During the implementation phase, farmers should be encouraged to make beneficial, cost-effective changes to methods of irrigation systems. In some cases, the hydrologic regime of the project area can be thought of as principally an issue of river flow regimes for floodplain forests. In this presentation, the author tries to focus on the impact of hydrology and conservation ecology on global warming. He also discusses the impact of hydrology and conservation ecology global air concerns such as greenhouse gas concentrations in the atmosphere. References: Chow, V. T, D. R. Maidment, and L. W. Mays. 1988. Applied Hydrology. McGraw-Hill, Inc. U.S. Soil Conservation Service. Technical Release 55: Urban Hydrology for Small Watersheds. USDA (U.S. Department of Agriculture). June 1986. Lehner, B. and P. Döll (2004). Development and validation

Functional analysis of the MAPK pathways in fungi.

PubMed

Martínez-Soto, Domingo; Ruiz-Herrera, José

The Mitogen-Activated Protein Kinase (MAPK) signaling pathways constitute one of the most important and evolutionarily conserved mechanisms for the perception of extracellular information in all the eukaryotic organisms. The MAPK pathways are involved in the transfer to the cell of the information perceived from extracellular stimuli, with the final outcome of activation of different transcription factors that regulate gene expression in response to them. In all species of fungi, the MAPK pathways have important roles in their physiology and development; e.g. cell cycle control, mating, morphogenesis, response to different stresses, resistance to UV radiation and to temperature changes, cell wall assembly and integrity, degradation of cellular organelles, virulence, cell-cell signaling, fungus-plant interaction, and response to damage-associated molecular patterns (DAMPs). Considering the importance of the phylogenetically conserved MAPK pathways in fungi, an updated review of the knowledge on them is discussed in this article. This information reveals their importance, their distribution in fungal species evolutionarily distant and with different lifestyles, their organization and function, and the interactions occurring between different MAPK pathways, and with other signaling pathways, for the regulation of the most complex cellular processes. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

Impaired mitotic progression and preimplantation lethality in mice lacking OMCG1, a new evolutionarily conserved nuclear protein.

PubMed

Artus, Jérôme; Vandormael-Pournin, Sandrine; Frödin, Morten; Nacerddine, Karim; Babinet, Charles; Cohen-Tannoudji, Michel

2005-07-01

While highly conserved through evolution, the cell cycle has been extensively modified to adapt to new developmental programs. Recently, analyses of mouse mutants revealed that several important cell cycle regulators are either dispensable for development or have a tissue- or cell-type-specific function, indicating that many aspects of cell cycle regulation during mammalian embryo development remain to be elucidated. Here, we report on the characterization of a new gene, Omcg1, which codes for a nuclear zinc finger protein. Embryos lacking Omcg1 die by the end of preimplantation development. In vitro cultured Omcg1-null blastocysts exhibit a dramatic reduction in the total cell number, a high mitotic index, and the presence of abnormal mitotic figures. Importantly, we found that Omcg1 disruption results in the lengthening of M phase rather than in a mitotic block. We show that the mitotic delay in Omcg1-/- embryos is associated with neither a dysfunction of the spindle checkpoint nor abnormal global histone modifications. Taken together, these results suggest that Omcg1 is an important regulator of the cell cycle in the preimplantation embryo.

Tripeptidyl peptidase II promotes fat formation in a conserved fashion.

PubMed

McKay, Renée M; McKay, James P; Suh, Jae Myoung; Avery, Leon; Graff, Jonathan M

2007-12-01

Tripeptidyl peptidase II (TPPII) is a multifunctional and evolutionarily conserved protease. In the mammalian hypothalamus, TPPII has a proposed anti-satiety role affected by degradation of the satiety hormone cholecystokinin 8. Here, we show that TPPII also regulates the metabolic homoeostasis of Caenorhabditis elegans; TPPII RNA interference (RNAi) decreases worm fat stores. However, this occurs independently of feeding behaviour and seems to be a function within fat-storing tissues. In mammalian cell culture, TPPII stimulates adipogenesis and TPPII RNAi blocks adipogenesis. The pro-adipogenic action of TPPII seems to be independent of protease function, as catalytically inactive TPPII also increases adipogenesis. Mice that were homozygous for an insertion in the Tpp2 locus were embryonic lethal. However, Tpp2 heterozygous mutants were lean compared with wild-type littermates, although food intake was normal. These findings indicate that TPPII has central and peripheral roles in regulating metabolism and that TPPII actions in fat-storing tissues might be an ancient function carried out in a protease-independent manner.

Genetic interactions between Drosophila melanogaster Atg1 and paxillin reveal a role for paxillin in autophagosome formation.

PubMed

Chen, Guang-Chao; Lee, Janice Y; Tang, Hong-Wen; Debnath, Jayanta; Thomas, Sheila M; Settleman, Jeffrey

2008-01-01

Autophagy is a conserved cellular process of macromolecule recycling that involves vesicle-mediated degradation of cytoplasmic components. Autophagy plays essential roles in normal cell homeostasis and development, the response to stresses such as nutrient starvation, and contributes to disease processes including cancer and neurodegeneration. Although many of the autophagy components identified from genetic screens in yeast are well conserved in higher organisms, the mechanisms by which this process is regulated in any species are just beginning to be elucidated. In a genetic screen in Drosophila melanogaster, we have identified a link between the focal adhesion protein paxillin and the Atg1 kinase, which has been previously implicated in autophagy. In mammalian cells, we find that paxillin is redistributed from focal adhesions during nutrient deprivation, and paxillin-deficient cells exhibit defects in autophagosome formation. Together, these findings reveal a novel evolutionarily conserved role for paxillin in autophagy.

Blue Light–Dependent Interaction between Cryptochrome2 and CIB1 Regulates Transcription and Leaf Senescence in Soybean[W

PubMed Central

Meng, Yingying; Li, Hongyu; Wang, Qin; Liu, Bin; Lin, Chentao

2013-01-01

Cryptochromes are blue light receptors that regulate light responses in plants, including various crops. The molecular mechanism of plant cryptochromes has been extensively investigated in Arabidopsis thaliana, but it has not been reported in any crop species. Here, we report a study of the mechanism of soybean (Glycine max) cryptochrome2 (CRY2a). We found that CRY2a regulates leaf senescence, which is a life history trait regulated by light and photoperiods via previously unknown mechanisms. We show that CRY2a undergoes blue light–dependent interaction with the soybean basic helix-loop-helix transcription activator CIB1 (for cryptochrome-interacting bHLH1) that specifically interacts with the E-box (CANNTG) DNA sequences. Analyses of transgenic soybean plants expressing an elevated or reduced level of the CRY2a or CIB1 demonstrate that CIB1 promotes leaf senescence, whereas CRY2a suppresses leaf senescence. Results of the gene expression and molecular interaction analyses support the hypothesis that CIB1 activates transcription of senescence-associated genes, such as WRKY DNA BINDING PROTEIN53b (WRKY53b), and leaf senescence. CIB1 interacts with the E-box–containing promoter sequences of the WRKY53b chromatin, whereas photoexcited CRY2a interacts with CIB1 to inhibit its DNA binding activity. These findings argue that CIB-dependent transcriptional regulation is an evolutionarily conserved CRY-signaling mechanism in plants, and this mechanism is opted in evolution to mediate light regulation of different aspects of plant development in different plant species. PMID:24272488

Structure/Function Analysis of Recurrent Mutations in SETD2 Protein Reveals a Critical and Conserved Role for a SET Domain Residue in Maintaining Protein Stability and Histone H3 Lys-36 Trimethylation*

PubMed Central

Hacker, Kathryn E.; Fahey, Catherine C.; Shinsky, Stephen A.; Chiang, Yun-Chen J.; DiFiore, Julia V.; Jha, Deepak Kumar; Vo, Andy H.; Shavit, Jordan A.; Davis, Ian J.; Strahl, Brian D.; Rathmell, W. Kimryn

2016-01-01

The yeast Set2 histone methyltransferase is a critical enzyme that plays a number of key roles in gene transcription and DNA repair. Recently, the human homologue, SETD2, was found to be recurrently mutated in a significant percentage of renal cell carcinomas, raising the possibility that the activity of SETD2 is tumor-suppressive. Using budding yeast and human cell line model systems, we examined the functional significance of two evolutionarily conserved residues in SETD2 that are recurrently mutated in human cancers. Whereas one of these mutations (R2510H), located in the Set2 Rpb1 interaction domain, did not result in an observable defect in SETD2 enzymatic function, a second mutation in the catalytic domain of this enzyme (R1625C) resulted in a complete loss of histone H3 Lys-36 trimethylation (H3K36me3). This mutant showed unchanged thermal stability as compared with the wild type protein but diminished binding to the histone H3 tail. Surprisingly, mutation of the conserved residue in Set2 (R195C) similarly resulted in a complete loss of H3K36me3 but did not affect dimethylated histone H3 Lys-36 (H3K36me2) or functions associated with H3K36me2 in yeast. Collectively, these data imply a critical role for Arg-1625 in maintaining the protein interaction with H3 and specific H3K36me3 function of this enzyme, which is conserved from yeast to humans. They also may provide a refined biochemical explanation for how H3K36me3 loss leads to genomic instability and cancer. PMID:27528607

Global Alignment of Pairwise Protein Interaction Networks for Maximal Common Conserved Patterns

DOE PAGES

Tian, Wenhong; Samatova, Nagiza F.

2013-01-01

A number of tools for the alignment of protein-protein interaction (PPI) networks have laid the foundation for PPI network analysis. Most of alignment tools focus on finding conserved interaction regions across the PPI networks through either local or global mapping of similar sequences. Researchers are still trying to improve the speed, scalability, and accuracy of network alignment. In view of this, we introduce a connected-components based fast algorithm, HopeMap, for network alignment. Observing that the size of true orthologs across species is small comparing to the total number of proteins in all species, we take a different approach based onmore » a precompiled list of homologs identified by KO terms. Applying this approach to S. cerevisiae (yeast) and D. melanogaster (fly), E. coli K12 and S. typhimurium , E. coli K12 and C. crescenttus , we analyze all clusters identified in the alignment. The results are evaluated through up-to-date known gene annotations, gene ontology (GO), and KEGG ortholog groups (KO). Comparing to existing tools, our approach is fast with linear computational cost, highly accurate in terms of KO and GO terms specificity and sensitivity, and can be extended to multiple alignments easily.« less

Lysosomal Interaction of Akt with Phafin2: A Critical Step in the Induction of Autophagy

PubMed Central

Matsuda-Lennikov, Mami; Suizu, Futoshi; Hirata, Noriyuki; Hashimoto, Manabu; Kimura, Kohki; Nagamine, Tadashi; Fujioka, Yoichiro; Ohba, Yusuke; Iwanaga, Toshihiko; Noguchi, Masayuki

2014-01-01

Autophagy is an evolutionarily conserved mechanism for the gross disposal of intracellular proteins in mammalian cells and dysfunction in this pathway has been associated with human disease. Although the serine threonine kinase Akt is suggested to play a role in this process, little is known about the molecular mechanisms by which Akt induces autophagy. Using a yeast two-hybrid screen, Phafin2 (EAPF or PLEKHF2), a lysosomal protein with a unique structure of N-terminal PH (pleckstrin homology) domain and C-terminal FYVE (Fab 1, YOTB, Vac 1, and EEA1) domain was found to interact with Akt. A sucrose gradient fractionation experiment revealed that both Akt and Phafin2 co-existed in the same lysosome enriched fraction after autophagy induction. Confocal microscopic analysis and BiFC analysis demonstrated that both Akt and Phafin2 accumulate in the lysosome after induction of autophagy. BiFC analysis using PtdIns (3)P interaction defective mutant of Phafin2 demonstrated that lysosomal accumulation of the Akt-Phafin2 complex and subsequent induction of autophagy were lysosomal PtdIns (3)P dependent events. Furthermore, in murine macrophages, both Akt and Phafin2 were required for digestion of fluorescent bacteria and/or LPS-induced autophagy. Taken together, these findings establish that lysosomal accumulation of Akt and Phafin2 is a critical step in the induction of autophagy via an interaction with PtdIns (3)P. PMID:24416124

The Prp19 WD40 Domain Contains a Conserved Protein Interaction Region Essential for its Function

PubMed Central

Vander Kooi, Craig W.; Ren, Liping; Xu, Ping; Ohi, Melanie D.; Gould, Kathleen L.; Chazin, Walter J.

2010-01-01

Summary Prp19 is a member of the WD40-repeat family of E3 ubiquitin ligases and a conserved eukaryotic RNA splicing factor essential for activation and stabilization of the spliceosome. To understand the role of the WD40 repeat domain of Prp19 we have determined its structure using X-ray crystallography. The domain has a distorted seven bladed WD40 architecture with significant asymmetry due to irregular packing of blades one and seven into the core of the WD40 domain. Structure-based mutagenesis identified a highly conserved surface centered around blade five that is required for the physical interaction between Prp19 and Cwc2, another essential splicing factor. This region is found to be required for Prp19 function and yeast viability. Experiments in vitro and in vivo demonstrate that two molecules of Cwc2 bind to the Prp19 tetramer. These coupled structural and functional studies provide a model for the functional architecture of Prp19. PMID:20462492

RNA expression in a cartilaginous fish cell line reveals ancient 3′ noncoding regions highly conserved in vertebrates

PubMed Central

Forest, David; Nishikawa, Ryuhei; Kobayashi, Hiroshi; Parton, Angela; Bayne, Christopher J.; Barnes, David W.

2007-01-01

We have established a cartilaginous fish cell line [Squalus acanthias embryo cell line (SAE)], a mesenchymal stem cell line derived from the embryo of an elasmobranch, the spiny dogfish shark S. acanthias. Elasmobranchs (sharks and rays) first appeared >400 million years ago, and existing species provide useful models for comparative vertebrate cell biology, physiology, and genomics. Comparative vertebrate genomics among evolutionarily distant organisms can provide sequence conservation information that facilitates identification of critical coding and noncoding regions. Although these genomic analyses are informative, experimental verification of functions of genomic sequences depends heavily on cell culture approaches. Using ESTs defining mRNAs derived from the SAE cell line, we identified lengthy and highly conserved gene-specific nucleotide sequences in the noncoding 3′ UTRs of eight genes involved in the regulation of cell growth and proliferation. Conserved noncoding 3′ mRNA regions detected by using the shark nucleotide sequences as a starting point were found in a range of other vertebrate orders, including bony fish, birds, amphibians, and mammals. Nucleotide identity of shark and human in these regions was remarkably well conserved. Our results indicate that highly conserved gene sequences dating from the appearance of jawed vertebrates and representing potential cis-regulatory elements can be identified through the use of cartilaginous fish as a baseline. Because the expression of genes in the SAE cell line was prerequisite for their identification, this cartilaginous fish culture system also provides a physiologically valid tool to test functional hypotheses on the role of these ancient conserved sequences in comparative cell biology. PMID:17227856

Focusing ecological research for conservation.

PubMed

Cristescu, Bogdan; Boyce, Mark S

2013-11-01

Ecologists are increasingly actively involved in conservation. We identify five key topics from a broad sweep of ecology that merit research attention to meet conservation needs. We examine questions from landscape ecology, behavioral ecology, ecosystem dynamics, community ecology, and nutrient cycling related to key topics. Based on literature review and publication trend assessment, consultation with colleagues, and roundtable discussions at the 24th International Congress for Conservation Biology, focused research on the following topics could benefit conservation while advancing ecological understanding: 1. Carbon sequestration, requiring increased linkages to biodiversity conservation; 2. Ecological invasiveness, challenging our ability to find solutions to ecological aliens; 3. Individual variation, having applications in the conservation of rare species; 4. Movement of organisms, integrating ecological processes across landscapes and scales and addressing habitat fragmentation; and 5. Trophic-level interactions, driving ecological dynamics at the ecosystem-level. Addressing these will require cross-disciplinary research under the overarching framework of conservation ecology.

Indole: An evolutionarily conserved influencer of behavior across kingdoms.

PubMed

Tomberlin, Jeffery K; Crippen, Tawni L; Wu, Guoyao; Griffin, Ashleigh S; Wood, Thomas K; Kilner, Rebecca M

2017-02-01

Indole is a key environmental cue that is used by many organisms. Based on its biochemistry, we suggest indole is used so universally, and by such different organisms, because it derives from the metabolism of tryptophan, a resource essential for many species yet rare in nature. These properties make it a valuable, environmental cue for resources almost universally important for promoting fitness. We then describe how indole is used to coordinate actions within organisms, to influence the behavior of conspecifics and can even be used to change the behavior of species that belong to other kingdoms. Drawing on the evolutionary framework that has been developed for understanding animal communication, we show how this is diversely achieved by indole acting as a cue, a manipulative signal, and an honest signal, as well as how indole can be used synergistically to amplify information conveyed by other molecules. Clarifying these distinct functions of indole identifies patterns that transcend different kingdoms of organisms. © 2016 WILEY Periodicals, Inc.

Impaired Mitotic Progression and Preimplantation Lethality in Mice Lacking OMCG1, a New Evolutionarily Conserved Nuclear Protein†

PubMed Central

Artus, Jérôme; Vandormael-Pournin, Sandrine; Frödin, Morten; Nacerddine, Karim; Babinet, Charles; Cohen-Tannoudji, Michel

2005-01-01

While highly conserved through evolution, the cell cycle has been extensively modified to adapt to new developmental programs. Recently, analyses of mouse mutants revealed that several important cell cycle regulators are either dispensable for development or have a tissue- or cell-type-specific function, indicating that many aspects of cell cycle regulation during mammalian embryo development remain to be elucidated. Here, we report on the characterization of a new gene, Omcg1, which codes for a nuclear zinc finger protein. Embryos lacking Omcg1 die by the end of preimplantation development. In vitro cultured Omcg1-null blastocysts exhibit a dramatic reduction in the total cell number, a high mitotic index, and the presence of abnormal mitotic figures. Importantly, we found that Omcg1 disruption results in the lengthening of M phase rather than in a mitotic block. We show that the mitotic delay in Omcg1−/− embryos is associated with neither a dysfunction of the spindle checkpoint nor abnormal global histone modifications. Taken together, these results suggest that Omcg1 is an important regulator of the cell cycle in the preimplantation embryo. PMID:15988037

Physical and Functional Interaction between the Eukaryotic Orthologs of Prokaryotic Translation Initiation Factors IF1 and IF2

PubMed Central

Choi, Sang Ki; Olsen, DeAnne S.; Roll-Mecak, Antonina; Martung, Agnes; Remo, Keith L.; Burley, Stephen K.; Hinnebusch, Alan G.; Dever, Thomas E.

2000-01-01

To initiate protein synthesis, a ribosome with bound initiator methionyl-tRNA must be assembled at the start codon of an mRNA. This process requires the coordinated activities of three translation initiation factors (IF) in prokaryotes and at least 12 translation initiation factors in eukaryotes (eIF). The factors eIF1A and eIF5B from eukaryotes show extensive amino acid sequence similarity to the factors IF1 and IF2 from prokaryotes. By a combination of two-hybrid, coimmunoprecipitation, and in vitro binding assays eIF1A and eIF5B were found to interact directly, and the eIF1A binding site was mapped to the C-terminal region of eIF5B. This portion of eIF5B was found to be critical for growth in vivo and for translation in vitro. Overexpression of eIF1A exacerbated the slow-growth phenotype of yeast strains expressing C-terminally truncated eIF5B. These findings indicate that the physical interaction between the evolutionarily conserved factors eIF1A and eIF5B plays an important role in translation initiation, perhaps to direct or stabilize the binding of methionyl-tRNA to the ribosomal P site. PMID:10982835

Evolutionarily stable and convergent stable strategies in reaction-diffusion models for conditional dispersal.

PubMed

Lam, King-Yeung; Lou, Yuan

2014-02-01

We consider a mathematical model of two competing species for the evolution of conditional dispersal in a spatially varying, but temporally constant environment. Two species are different only in their dispersal strategies, which are a combination of random dispersal and biased movement upward along the resource gradient. In the absence of biased movement or advection, Hastings showed that the mutant can invade when rare if and only if it has smaller random dispersal rate than the resident. When there is a small amount of biased movement or advection, we show that there is a positive random dispersal rate that is both locally evolutionarily stable and convergent stable. Our analysis of the model suggests that a balanced combination of random and biased movement might be a better habitat selection strategy for populations.

Viruses are a dominant driver of protein adaptation in mammals

PubMed Central

Enard, David; Cai, Le; Gwennap, Carina; Petrov, Dmitri A

2016-01-01

Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is unknown. Here, we analyze adaptation in ~1300 virus-interacting proteins manually curated from a set of 9900 proteins conserved in all sequenced mammalian genomes. We show that viruses (i) use the more evolutionarily constrained proteins within the cellular functions they interact with and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. We conservatively estimate that viruses have driven close to 30% of all adaptive amino acid changes in the part of the human proteome conserved within mammals. Our results suggest that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes. DOI: http://dx.doi.org/10.7554/eLife.12469.001 PMID:27187613

Hydra meiosis reveals unexpected conservation of structural synaptonemal complex proteins across metazoans.

PubMed

Fraune, Johanna; Alsheimer, Manfred; Volff, Jean-Nicolas; Busch, Karoline; Fraune, Sebastian; Bosch, Thomas C G; Benavente, Ricardo

2012-10-09

The synaptonemal complex (SC) is a key structure of meiosis, mediating the stable pairing (synapsis) of homologous chromosomes during prophase I. Its remarkable tripartite structure is evolutionarily well conserved and can be found in almost all sexually reproducing organisms. However, comparison of the different SC protein components in the common meiosis model organisms Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealed no sequence homology. This discrepancy challenged the hypothesis that the SC arose only once in evolution. To pursue this matter we focused on the evolution of SYCP1 and SYCP3, the two major structural SC proteins of mammals. Remarkably, our comparative bioinformatic and expression studies revealed that SYCP1 and SYCP3 are also components of the SC in the basal metazoan Hydra. In contrast to previous assumptions, we therefore conclude that SYCP1 and SYCP3 form monophyletic groups of orthologous proteins across metazoans.

Functional base-pairing interaction between highly conserved elements of U3 small nucleolar RNA and the small ribosomal subunit RNA.

PubMed

Hughes, J M

1996-06-21

The U3 nucleolar RNA has a remarkably wide phyletic distribution extending from the Eukarya to the Archaea. It functions in maturation of the small subunit (SSU) rRNA through a mechanism which is as yet unknown but which involves base-pairing with pre-rRNA. The most conserved part of U3 is within 30 nucleotides of the 5' end, but as yet no function for this domain has been proposed. Elements within this domain are complementary to highly conserved sequences in the SSU rRNA which, in the mature form, fold into a universally conserved pseudoknot. The nature of the complementarity suggests a novel mechanism for U3 function whereby U3 facilitates correct folding of the pseudoknot. Wide phylogenetic comparison provides compelling evidence in support of the interaction in that significant complementary changes have taken place, particularly in the archaeon Sulfolobus, which maintain the base-pairing. Base-substitution mutations in yeast U3 designed to disrupt the base-pairing indicate that the interaction is probably essential. These include cold-sensitivity mutations which exhibit phenotypes similar to U3-depletion, but without impairment of the AO processing step, which occurs within the 5' ETS. These phenotypes are consistent with the destabilization of SSU precursors and partial impairment of the processing steps A1, at the 5' ETS/18 S boundary, and A2, within the ITS1.

Mutations in the evolutionarily highly conserved KEOPS complex genes cause nephrotic syndrome with microcephaly

PubMed Central

Braun, Daniela A.; Rao, Jia; Mollet, Geraldine; Schapiro, David; Daugeron, Marie-Claire; Tan, Weizhen; Gribouval, Olivier; Boyer, Olivia; Revy, Patrick; Jobst-Schwan, Tilman; Schmidt, Johanna Magdalena; Lawson, Jennifer A.; Schanze, Denny; Ashraf, Shazia; Boddaert, Nathalie; Collinet, Bruno; Martin, Gaëlle; Liger, Dominique; Lovric, Svjetlana; Furlano, Monica; Guerrera, I. Chiara; Sanchez-Ferras, Oraly; Menten, Björn; Vergult, Sarah; De Rocker, Nina; Airik, Merlin; Hermle, Tobias; Shril, Shirlee; Widmeier, Eugen; Gee, Heon Yung; Choi, Won-Il; Sadowski, Carolin E.; Pabst, Werner L.; Warejko, Jillian; Daga, Ankana; LeBerre, Tamara Basta; Matejas, Verena; Behnam, Babak; Beeson, Brendan; Begtrup, Amber; Bruce, Malcolm; Ch'ng, Gaik-Siew; Lin, Shuan-Pei; Chang, Jui-Hsing; Chen, Chao-Huei; Cho, Megan T.; Gipson, Patrick E.; Hsu, Chyong-Hsin; Kari, Jameela A.; Ke, Yu-Yuan; Kiraly-Borri, Cathy; Lai, Wai-ming; Lemyre, Emmanuelle; Littlejohn, Rebecca Okasha; Masri, Amira; Moghtaderi, Mastaneh; Nakamura, Kazuyuki; Praet, Marleen; Prasad, Chitra; Prytula, Agnieszka; Roeder, Elizabeth; Rump, Patrick; Schnur, Rhonda E.; Shiihara, Takashi; Sinha, Manish; Soliman, Neveen A; Soulami, Kenza; Sweetser, David A.; Tsai, Wen-Hui; Tsai, Jeng-Daw; Vester, Udo; Viskochil, David H.; Vatanavicharn, Nithiwat; Waxler, Jessica L.; Wolf, Matthias T.F.; Wong, Sik-Nin; Poduri, Annapurna; Truglio, Gessica; Mane, Shrikant; Lifton, Richard P.; Bouchard, Maxime; Kannu, Peter; Chitayat, David; Magen, Daniella; Calleweart, Bert; van Tilbeurgh, Herman; Zenker, Martin; Antignac, Corinne; Hildebrandt, Friedhelm

2018-01-01

Galloway-Mowat syndrome (GAMOS) is a severe autosomal-recessive disease characterized by the combination of early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies. To date, mutations of WDR73 are the only known monogenic cause of GAMOS and in most affected individuals the molecular diagnosis remains elusive. We here identify recessive mutations of OSGEP, TP53RK, TPRKB, or LAGE3, encoding the 4 subunits of the KEOPS complex in 33 individuals of 30 families with GAMOS. CRISPR/Cas9 knockout in zebrafish and mice recapitulates the human phenotype of microcephaly and results in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibits cell proliferation, which human mutations fail to rescue, and knockdown of either gene activates DNA damage response signaling and induces apoptosis. OSGEP and TP53RK molecularly interact and co-localize with the actin-regulating ARP2/3 complex. Furthermore, knockdown of OSGEP and TP53RK induces defects of the actin cytoskeleton and reduces migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identify 4 novel monogenic causes of GAMOS, describe the first link between KEOPS function and human disease, and delineate potential pathogenic mechanisms. PMID:28805828

Genes with stable DNA methylation levels show higher evolutionary conservation than genes with fluctuant DNA methylation levels.

PubMed

Zhang, Ruijie; Lv, Wenhua; Luan, Meiwei; Zheng, Jiajia; Shi, Miao; Zhu, Hongjie; Li, Jin; Lv, Hongchao; Zhang, Mingming; Shang, Zhenwei; Duan, Lian; Jiang, Yongshuai

2015-11-24

Different human genes often exhibit different degrees of stability in their DNA methylation levels between tissues, samples or cell types. This may be related to the evolution of human genome. Thus, we compared the evolutionary conservation between two types of genes: genes with stable DNA methylation levels (SM genes) and genes with fluctuant DNA methylation levels (FM genes). For long-term evolutionary characteristics between species, we compared the percentage of the orthologous genes, evolutionary rate dn/ds and protein sequence identity. We found that the SM genes had greater percentages of the orthologous genes, lower dn/ds, and higher protein sequence identities in all the 21 species. These results indicated that the SM genes were more evolutionarily conserved than the FM genes. For short-term evolutionary characteristics among human populations, we compared the single nucleotide polymorphism (SNP) density, and the linkage disequilibrium (LD) degree in HapMap populations and 1000 genomes project populations. We observed that the SM genes had lower SNP densities, and higher degrees of LD in all the 11 HapMap populations and 13 1000 genomes project populations. These results mean that the SM genes had more stable chromosome genetic structures, and were more conserved than the FM genes.

The dinoflagellates Durinskia baltica and Kryptoperidinium foliaceum retain functionally overlapping mitochondria from two evolutionarily distinct lineages

PubMed Central

Imanian, Behzad; Keeling, Patrick J

2007-01-01

Background The dinoflagellates Durinskia baltica and Kryptoperidinium foliaceum are distinguished by the presence of a tertiary plastid derived from a diatom endosymbiont. The diatom is fully integrated with the host cell cycle and is so altered in structure as to be difficult to recognize it as a diatom, and yet it retains a number of features normally lost in tertiary and secondary endosymbionts, most notably mitochondria. The dinoflagellate host is also reported to retain mitochondrion-like structures, making these cells unique in retaining two evolutionarily distinct mitochondria. This redundancy raises the question of whether the organelles share any functions in common or have distributed functions between them. Results We show that both host and endosymbiont mitochondrial genomes encode genes for electron transport proteins. We have characterized cytochrome c oxidase 1 (cox1), cytochrome oxidase 2 (cox2), cytochrome oxidase 3 (cox3), cytochrome b (cob), and large subunit of ribosomal RNA (LSUrRNA) of endosymbiont mitochondrial ancestry, and cox1 and cob of host mitochondrial ancestry. We show that all genes are transcribed and that those ascribed to the host mitochondrial genome are extensively edited at the RNA level, as expected for a dinoflagellate mitochondrion-encoded gene. We also found evidence for extensive recombination in the host mitochondrial genes and that recombination products are also transcribed, as expected for a dinoflagellate. Conclusion Durinskia baltica and K. foliaceum retain two mitochondria from evolutionarily distinct lineages, and the functions of these organelles are at least partially overlapping, since both express genes for proteins in electron transport. PMID:17892581

Using publicly available data to quantify plant–pollinator interactions and evaluate conservation seeding mixes in the Northern Great Plains

USGS Publications Warehouse

Otto, Clint R.; O'Dell, Samuel; Bryant, R. B.; Euliss, Ned H. Jr.; Bush, Rachel; Smart, Matthew

2017-01-01

Concern over declining pollinators has led to multiple conservation initiatives for improving forage for bees in agroecosystems. Using data available through the Pollinator Library (npwrc.usgs.gov/pollinator/), we summarize plant–pollinator interaction data collected from 2012–2015 on lands managed by the U.S. Fish and Wildlife Service and private lands enrolled in U.S. Department of Agriculture conservation programs in eastern North Dakota (ND). Furthermore, we demonstrate how plant–pollinator interaction data from the Pollinator Library and seed cost information can be used to evaluate hypothetical seeding mixes for pollinator habitat enhancements. We summarize records of 314 wild bee and 849 honey bee (Apis mellifera L.) interactions detected on 63 different plant species. The wild bee observations consisted of 46 species, 15 genera, and 5 families. Over 54% of all wild bee observations were represented by three genera―Bombus, Lassioglossum, and Melissodes. The most commonly visited forbs by wild bees were Monarda fistulosa, Sonchus arvensis, and Zizia aurea. The most commonly visited forbs by A. mellifera were Cirsium arvense, Melilotus officinalis, and Medicago sativa. Among all interactions, 13% of A. mellifera and 77% of wild bee observations were made on plants native to ND. Our seed mix evaluation shows that mixes may often need to be tailored to meet the unique needs of wild bees and managed honey bees in agricultural landscapes. Our evaluation also demonstrates the importance of incorporating both biologic and economic information when attempting to design cost-effective seeding mixes for supporting pollinators in a critically important part of the United States.

Novel Insights into the Role of Neurospora crassa NDUFAF2, an Evolutionarily Conserved Mitochondrial Complex I Assembly Factor

PubMed Central

Pereira, Bruno; Videira, Arnaldo

2013-01-01

Complex I deficiency is commonly associated with mitochondrial oxidative phosphorylation diseases. Mutations in nuclear genes encoding structural subunits or assembly factors of complex I have been increasingly identified as the cause of the diseases. One such factor, NDUFAF2, is a paralog of the NDUFA12 structural subunit of the enzyme, but the mechanism by which it exerts its function remains unknown. Herein, we demonstrate that the Neurospora crassa NDUFAF2 homologue, the 13.4L protein, is a late assembly factor that associates with complex I assembly intermediates containing the membrane arm and the connecting part but lacking the N module of the enzyme. Furthermore, we provide evidence that dissociation of the assembly factor is dependent on the incorporation of the putative regulatory module composed of the subunits of 13.4 (NDUFA12), 18.4 (NDUFS6), and 21 (NDUFS4) kDa. Our results demonstrate that the 13.4L protein is a complex I assembly factor functionally conserved from fungi to mammals. PMID:23648483

A Conserved Circular Network of Coregulated Lipids Modulates Innate Immune Responses

PubMed Central

Köberlin, Marielle S.; Snijder, Berend; Heinz, Leonhard X.; Baumann, Christoph L.; Fauster, Astrid; Vladimer, Gregory I.; Gavin, Anne-Claude; Superti-Furga, Giulio

2015-01-01

Summary Lipid composition affects the biophysical properties of membranes that provide a platform for receptor-mediated cellular signaling. To study the regulatory role of membrane lipid composition, we combined genetic perturbations of sphingolipid metabolism with the quantification of diverse steps in Toll-like receptor (TLR) signaling and mass spectrometry-based lipidomics. Membrane lipid composition was broadly affected by these perturbations, revealing a circular network of coregulated sphingolipids and glycerophospholipids. This evolutionarily conserved network architecture simultaneously reflected membrane lipid metabolism, subcellular localization, and adaptation mechanisms. Integration of the diverse TLR-induced inflammatory phenotypes with changes in lipid abundance assigned distinct functional roles to individual lipid species organized across the network. This functional annotation accurately predicted the inflammatory response of cells derived from patients suffering from lipid storage disorders, based solely on their altered membrane lipid composition. The analytical strategy described here empowers the understanding of higher-level organization of membrane lipid function in diverse biological systems. PMID:26095250

[Three regions of Rpb10 mini-subunit of nuclear RNA polymerases are strictly conserved in all eukaryotes].

PubMed

Shpakovskiĭ, G V; Lebedenko, E N

1996-12-01

The rpb10+ cDNA from the fission yeast Schizosaccharomyces pombe was cloned using two independent approaches (PCR and genetic suppression). The cloned cDNA encoded the Rpb10 subunit common for all three RNA polymerases. Comparison of the deduced amino acid sequence of the Sz. pombe Rbp10 subunit (71 amino acid residues) with those of the homologous subunits of RNA polymerases I, II, and III from Saccharomyces cerevisiae and Home sapiens revealed that heptapeptides RCFT/SCGK (residues 6-12), RYCCRRM (residues 43-49), and HVDLIEK (residues 53-59) were evolutionarily the most conserved structural motifs of these subunits. It is shown that the Rbp10 subunit from Sz. pombe can substitute its homolog (ABC10 beta) in the baker's yeast S. cerevisiae.

A disturbance-based ecosystem approach to maintaining and restoring freshwater habitats of evolutionarily significant units of anadromous salmonids in the Pacific Northwest.

Treesearch

G.H. Reeves; L.E. Benda; K.M. Burnett; P.A. Bisson; J.R. Sedell

1995-01-01

To preserve and recover evolutionarily significant units (ESUs) of anadromous salmonids Oncorhynchus spp. in the Pacific Northwest, long-term and short-term ecological processes that create and maintain freshwater habitats must be restored and protected. Aquatic ecosystems through- out the region are dynamic in space and time, and lack of...

Conservation of connectivity of model-space effective interactions under a class of similarity transformation.

PubMed

Duan, Chang-Kui; Gong, Yungui; Dong, Hui-Ning; Reid, Michael F

2004-09-15

Effective interaction operators usually act on a restricted model space and give the same energies (for Hamiltonian) and matrix elements (for transition operators, etc.) as those of the original operators between the corresponding true eigenstates. Various types of effective operators are possible. Those well defined effective operators have been shown to be related to each other by similarity transformation. Some of the effective operators have been shown to have connected-diagram expansions. It is shown in this paper that under a class of very general similarity transformations, the connectivity is conserved. The similarity transformation between Hermitian and non-Hermitian Rayleigh-Schrodinger perturbative effective operators is one of such transformations and hence the connectivity can be deducted from each other.

Cloning and characterization of carboxyl terminus of heat shock cognate 70-interacting protein gene from the silkworm, Bombyx mori.

PubMed

Ohsawa, Takeshi; Fujimoto, Shota; Tsunakawa, Akane; Shibano, Yuka; Kawasaki, Hideki; Iwanaga, Masashi

2016-11-01

Carboxyl terminus of heat shock cognate 70-interacting protein (CHIP) is an evolutionarily conserved E3 ubiquitin ligase across different eukaryotic species and is known to play a key role in protein quality control. CHIP has two distinct functional domains, an N-terminal tetratricopeptide repeat (TPR) and a C-terminal U-box domain, which are required for the ubiquitination of numerous labile client proteins that are chaperoned by heat shock proteins (HSPs) and heat shock cognate proteins (HSCs). During our screen for CHIP-like proteins in the Bombyx mori databases, we found a novel silkworm gene, Bombyx mori CHIP. Phylogenetic analysis showed that BmCHIP belongs to Lepidopteran lineages. Quantitative reverse transcription-PCR analysis indicated that BmCHIP was relatively highly expressed in the gonad and fat body. A pull-down experiment and auto-ubiquitination assay showed that BmCHIP interacted with BmHSC70 and had E3 ligase activity. Additionally, immunohistochemical analysis revealed that BmCHIP was partially co-localized with ubiquitin in BmN4 cells. These data support that BmCHIP plays an important role in the ubiquitin proteasome system as an E3 ubiquitin ligase in B. mori. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative Analysis of Four Calypogeia Species Revealed Unexpected Change in Evolutionarily-Stable Liverwort Mitogenomes

PubMed Central

Ślipiko, Monika; Buczkowska-Chmielewska, Katarzyna; Bączkiewicz, Alina; Szczecińska, Monika; Sawicki, Jakub

2017-01-01

Liverwort mitogenomes are considered to be evolutionarily stable. A comparative analysis of four Calypogeia species revealed differences compared to previously sequenced liverwort mitogenomes. Such differences involve unexpected structural changes in the two genes, cox1 and atp1, which have lost three and two introns, respectively. The group I introns in the cox1 gene are proposed to have been lost by two-step localized retroprocessing, whereas one-step retroprocessing could be responsible for the disappearance of the group II introns in the atp1 gene. These cases represent the first identified losses of introns in mitogenomes of leafy liverworts (Jungermanniopsida) contrasting the stability of mitochondrial gene order with certain changes in the gene content and intron set in liverworts. PMID:29257096

Herpes Simplex Virus 1 UL37 Protein Tyrosine Residues Conserved among All Alphaherpesviruses Are Required for Interactions with Glycoprotein K, Cytoplasmic Virion Envelopment, and Infectious Virus Production

PubMed Central

Chouljenko, Dmitry V.; Jambunathan, Nithya; Chouljenko, Vladimir N.; Naderi, Misagh; Brylinski, Michal; Caskey, John R.

2016-01-01

ABSTRACT The herpes simplex virus 1 (HSV-1) UL37 protein functions in virion envelopment at trans-Golgi membranes, as well as in retrograde and anterograde transport of virion capsids. Recently, we reported that UL37 interacts with glycoprotein K (gK) and its interacting partner protein UL20 (N. Jambunathan, D. Chouljenko, P. Desai, A. S. Charles, R. Subramanian, V. N. Chouljenko, and K. G. Kousoulas, J Virol 88:5927–5935, 2014, http://dx.doi.org/10.1128/JVI.00278-14), facilitating cytoplasmic virion envelopment. Alignment of UL37 homologs encoded by alphaherpesviruses revealed the presence of highly conserved residues in the central portion of the UL37 protein. A cadre of nine UL37 site-specific mutations were produced and tested for their ability to inhibit virion envelopment and infectious virus production. Complementation analysis revealed that replacement of tyrosines 474 and 480 with alanine failed to complement the UL37-null virus, while all other mutated UL37 genes complemented the virus efficiently. The recombinant virus DC474-480 constructed with tyrosines 474, 476, 477, and 480 mutated to alanine residues produced a gK-null-like phenotype characterized by the production of very small plaques and accumulation of capsids in the cytoplasm of infected cells. Recombinant viruses having either tyrosine 476 or 477 replaced with alanine produced a wild-type phenotype. Immunoprecipitation assays revealed that replacement of all four tyrosines with alanines substantially reduced the ability of gK to interact with UL37. Alignment of HSV UL37 with the human cytomegalovirus and Epstein-Barr virus UL37 homologs revealed that Y480 was conserved only for alphaherpesviruses. Collectively, these results suggest that the UL37 conserved tyrosine 480 residue plays a crucial role in interactions with gK to facilitate cytoplasmic virion envelopment and infectious virus production. IMPORTANCE The HSV-1 UL37 protein is conserved among all herpesviruses, functions in both

3D model for Cancerous Inhibitor of Protein Phosphatase 2A armadillo domain unveils highly conserved protein-protein interaction characteristics.

PubMed

Dahlström, Käthe M; Salminen, Tiina A

2015-12-07

Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) is a human oncoprotein, which exerts its cancer-promoting function through interaction with other proteins, for example Protein Phosphatase 2A (PP2A) and MYC. The lack of structural information for CIP2A significantly prevents the design of anti-cancer therapeutics targeting this protein. In an attempt to counteract this fact, we modeled the three-dimensional structure of the N-terminal domain (CIP2A-ArmRP), analyzed key areas and amino acids, and coupled the results to the existing literature. The model reliably shows a stable armadillo repeat fold with a positively charged groove. The fact that this conserved groove highly likely binds peptides is corroborated by the presence of a conserved polar ladder, which is essential for the proper peptide-binding mode of armadillo repeat proteins and, according to our results, several known CIP2A interaction partners appropriately possess an ArmRP-binding consensus motif. Moreover, we show that Arg229Gln, which has been linked to the development of cancer, causes a significant change in charge and surface properties of CIP2A-ArmRP. In conclusion, our results reveal that CIP2A-ArmRP shares the typical fold, protein-protein interaction site and interaction patterns with other natural armadillo proteins and that, presumably, several interaction partners bind into the central groove of the modeled CIP2A-ArmRP. By providing essential structural characteristics of CIP2A, the present study significantly increases our knowledge on how CIP2A interacts with other proteins in cancer progression and how to develop new therapeutics targeting CIP2A. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Local Geometry and Evolutionary Conservation of Protein Surfaces Reveal the Multiple Recognition Patches in Protein-Protein Interactions

PubMed Central

Laine, Elodie; Carbone, Alessandra

2015-01-01

Protein-protein interactions (PPIs) are essential to all biological processes and they represent increasingly important therapeutic targets. Here, we present a new method for accurately predicting protein-protein interfaces, understanding their properties, origins and binding to multiple partners. Contrary to machine learning approaches, our method combines in a rational and very straightforward way three sequence- and structure-based descriptors of protein residues: evolutionary conservation, physico-chemical properties and local geometry. The implemented strategy yields very precise predictions for a wide range of protein-protein interfaces and discriminates them from small-molecule binding sites. Beyond its predictive power, the approach permits to dissect interaction surfaces and unravel their complexity. We show how the analysis of the predicted patches can foster new strategies for PPIs modulation and interaction surface redesign. The approach is implemented in JET2, an automated tool based on the Joint Evolutionary Trees (JET) method for sequence-based protein interface prediction. JET2 is freely available at www.lcqb.upmc.fr/JET2. PMID:26690684

Genomic diversity guides conservation strategies among rare terrestrial orchid species when taxonomy remains uncertain.

PubMed

Ahrens, Collin W; Supple, Megan A; Aitken, Nicola C; Cantrill, David J; Borevitz, Justin O; James, Elizabeth A

2017-06-01

Species are often used as the unit for conservation, but may not be suitable for species complexes where taxa are difficult to distinguish. Under such circumstances, it may be more appropriate to consider species groups or populations as evolutionarily significant units (ESUs). A population genomic approach was employed to investigate the diversity within and among closely related species to create a more robust, lineage-specific conservation strategy for a nationally endangered terrestrial orchid and its relatives from south-eastern Australia. Four putative species were sampled from a total of 16 populations in the Victorian Volcanic Plain (VVP) bioregion and one population of a sub-alpine outgroup in south-eastern Australia. Morphological measurements were taken in situ along with leaf material for genotyping by sequencing (GBS) and microsatellite analyses. Species could not be differentiated using morphological measurements. Microsatellite and GBS markers confirmed the outgroup as distinct, but only GBS markers provided resolution of population genetic structure. The nationally endangered Diuris basaltica was indistinguishable from two related species ( D. chryseopsis and D. behrii ), while the state-protected D. gregaria showed genomic differentiation. Genomic diversity identified among the four Diuris species suggests that conservation of this taxonomically complex group will be best served by considering them as one ESU rather than separately aligned with species as currently recognized. This approach will maximize evolutionary potential among all species during increased isolation and environmental change. The methods used here can be applied generally to conserve evolutionary processes for groups where taxonomic uncertainty hinders the use of species as conservation units. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

The Histone Chaperone NRP1 Interacts with WEREWOLF to Activate GLABRA2 in Arabidopsis Root Hair Development.

PubMed

Zhu, Yan; Rong, Liang; Luo, Qiang; Wang, Baihui; Zhou, Nana; Yang, Yue; Zhang, Chi; Feng, Haiyang; Zheng, Lina; Shen, Wen-Hui; Ma, Jinbiao; Dong, Aiwu

2017-02-01

NUCLEOSOME ASSEMBLY PROTEIN1 (NAP1) defines an evolutionarily conserved family of histone chaperones and loss of function of the Arabidopsis thaliana NAP1 family genes NAP1-RELATED PROTEIN1 ( NRP1 ) and NRP2 causes abnormal root hair formation. Yet, the underlying molecular mechanisms remain unclear. Here, we show that NRP1 interacts with the transcription factor WEREWOLF (WER) in vitro and in vivo and enriches at the GLABRA2 ( GL2 ) promoter in a WER-dependent manner. Crystallographic analysis indicates that NRP1 forms a dimer via its N-terminal α-helix. Mutants of NRP1 that either disrupt the α-helix dimerization or remove the C-terminal acidic tail, impair its binding to histones and WER and concomitantly lead to failure to activate GL2 transcription and to rescue the nrp1-1 nrp2-1 mutant phenotype. Our results further demonstrate that WER-dependent enrichment of NRP1 at the GL2 promoter is involved in local histone eviction and nucleosome loss in vivo. Biochemical competition assays imply that the association between NRP1 and histones may counteract the inhibitory effect of histones on the WER-DNA interaction. Collectively, our study provides important insight into the molecular mechanisms by which histone chaperones are recruited to target chromatin via interaction with a gene-specific transcription factor to moderate chromatin structure for proper root hair development. © 2017 American Society of Plant Biologists. All rights reserved.

Interactions between subunits of Saccharomyces cerevisiae RNase MRP support a conserved eukaryotic RNase P/MRP architecture.

PubMed

Aspinall, Tanya V; Gordon, James M B; Bennett, Hayley J; Karahalios, Panagiotis; Bukowski, John-Paul; Walker, Scott C; Engelke, David R; Avis, Johanna M

2007-01-01

Ribonuclease MRP is an endonuclease, related to RNase P, which functions in eukaryotic pre-rRNA processing. In Saccharomyces cerevisiae, RNase MRP comprises an RNA subunit and ten proteins. To improve our understanding of subunit roles and enzyme architecture, we have examined protein-protein and protein-RNA interactions in vitro, complementing existing yeast two-hybrid data. In total, 31 direct protein-protein interactions were identified, each protein interacting with at least three others. Furthermore, seven proteins self-interact, four strongly, pointing to subunit multiplicity in the holoenzyme. Six protein subunits interact directly with MRP RNA and four with pre-rRNA. A comparative analysis with existing data for the yeast and human RNase P/MRP systems enables confident identification of Pop1p, Pop4p and Rpp1p as subunits that lie at the enzyme core, with probable addition of Pop5p and Pop3p. Rmp1p is confirmed as an integral subunit, presumably associating preferentially with RNase MRP, rather than RNase P, via interactions with Snm1p and MRP RNA. Snm1p and Rmp1p may act together to assist enzyme specificity, though roles in substrate binding are also indicated for Pop4p and Pop6p. The results provide further evidence of a conserved eukaryotic RNase P/MRP architecture and provide a strong basis for studies of enzyme assembly and subunit function.

Coiled-coil destabilizing residues in the group A Streptococcus M1 protein are required for functional interaction.

PubMed

Stewart, Chelsea M; Buffalo, Cosmo Z; Valderrama, J Andrés; Henningham, Anna; Cole, Jason N; Nizet, Victor; Ghosh, Partho

2016-08-23

The sequences of M proteins, the major surface-associated virulence factors of the widespread bacterial pathogen group A Streptococcus, are antigenically variable but have in common a strong propensity to form coiled coils. Paradoxically, these sequences are also replete with coiled-coil destabilizing residues. These features are evident in the irregular coiled-coil structure and thermal instability of M proteins. We present an explanation for this paradox through studies of the B repeats of the medically important M1 protein. The B repeats are required for interaction of M1 with fibrinogen (Fg) and consequent proinflammatory activation. The B repeats sample multiple conformations, including intrinsically disordered, dissociated, as well as two alternate coiled-coil conformations: a Fg-nonbinding register 1 and a Fg-binding register 2. Stabilization of M1 in the Fg-nonbinding register 1 resulted in attenuation of Fg binding as expected, but counterintuitively, so did stabilization in the Fg-binding register 2. Strikingly, these register-stabilized M1 proteins gained the ability to bind Fg when they were destabilized by a chaotrope. These results indicate that M1 stability is antithetical to Fg interaction and that M1 conformational dynamics, as specified by destabilizing residues, are essential for interaction. A "capture-and-collapse" model of association accounts for these observations, in which M1 captures Fg through a dynamic conformation and then collapses into a register 2-coiled coil as a result of stabilization provided by binding energy. Our results support the general conclusion that destabilizing residues are evolutionarily conserved in M proteins to enable functional interactions necessary for pathogenesis.

Analysis of sDMA modifications of PIWI proteins

PubMed Central

Honda, Shozo; Kirino, Yoriko; Kirino, Yohei

2015-01-01

Summary Arginine methylation is an important post-translational protein modification that modulates protein function for a wide range of biological processes. PIWI proteins, a subclade of the Argonaute family proteins, contain evolutionarily conserved symmetrical dimethylarginines (sDMAs). It has become increasingly apparent that the sDMAs of PIWI proteins serve as binding elements for TUDOR-domain containing proteins and that sDMA-dependent protein interactions play crucial roles in the biogenesis and function of PIWI-interacting RNAs (piRNAs). We describe a method for detecting PIWI sDMAs and purifying PIWI/piRNA complexes using anti-sDMA antibodies. PMID:24178562

Packaging signals in two single-stranded RNA viruses imply a conserved assembly mechanism and geometry of the packaged genome.

PubMed

Dykeman, Eric C; Stockley, Peter G; Twarock, Reidun

2013-09-09

The current paradigm for assembly of single-stranded RNA viruses is based on a mechanism involving non-sequence-specific packaging of genomic RNA driven by electrostatic interactions. Recent experiments, however, provide compelling evidence for sequence specificity in this process both in vitro and in vivo. The existence of multiple RNA packaging signals (PSs) within viral genomes has been proposed, which facilitates assembly by binding coat proteins in such a way that they promote the protein-protein contacts needed to build the capsid. The binding energy from these interactions enables the confinement or compaction of the genomic RNAs. Identifying the nature of such PSs is crucial for a full understanding of assembly, which is an as yet untapped potential drug target for this important class of pathogens. Here, for two related bacterial viruses, we determine the sequences and locations of their PSs using Hamiltonian paths, a concept from graph theory, in combination with bioinformatics and structural studies. Their PSs have a common secondary structure motif but distinct consensus sequences and positions within the respective genomes. Despite these differences, the distributions of PSs in both viruses imply defined conformations for the packaged RNA genomes in contact with the protein shell in the capsid, consistent with a recent asymmetric structure determination of the MS2 virion. The PS distributions identified moreover imply a preferred, evolutionarily conserved assembly pathway with respect to the RNA sequence with potentially profound implications for other single-stranded RNA viruses known to have RNA PSs, including many animal and human pathogens. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optimal packaging of FIV genomic RNA depends upon a conserved long-range interaction and a palindromic sequence within gag.

PubMed

Rizvi, Tahir A; Kenyon, Julia C; Ali, Jahabar; Aktar, Suriya J; Phillip, Pretty S; Ghazawi, Akela; Mustafa, Farah; Lever, Andrew M L

2010-10-15

The feline immunodeficiency virus (FIV) is a lentivirus that is related to human immunodeficiency virus (HIV), causing a similar pathology in cats. It is a potential small animal model for AIDS and the FIV-based vectors are also being pursued for human gene therapy. Previous studies have mapped the FIV packaging signal (ψ) to two or more discontinuous regions within the 5' 511 nt of the genomic RNA and structural analyses have determined its secondary structure. The 5' and 3' sequences within ψ region interact through extensive long-range interactions (LRIs), including a conserved heptanucleotide interaction between R/U5 and gag. Other secondary structural elements identified include a conserved 150 nt stem-loop (SL2) and a small palindromic stem-loop within gag open reading frame that might act as a viral dimerization initiation site. We have performed extensive mutational analysis of these sequences and structures and ascertained their importance in FIV packaging using a trans-complementation assay. Disrupting the conserved heptanucleotide LRI to prevent base pairing between R/U5 and gag reduced packaging by 2.8-5.5 fold. Restoration of pairing using an alternative, non-wild type (wt) LRI sequence restored RNA packaging and propagation to wt levels, suggesting that it is the structure of the LRI, rather than its sequence, that is important for FIV packaging. Disrupting the palindrome within gag reduced packaging by 1.5-3-fold, but substitution with a different palindromic sequence did not restore packaging completely, suggesting that the sequence of this region as well as its palindromic nature is important. Mutation of individual regions of SL2 did not have a pronounced effect on FIV packaging, suggesting that either it is the structure of SL2 as a whole that is necessary for optimal packaging, or that there is redundancy within this structure. The mutational analysis presented here has further validated the previously predicted RNA secondary structure of FIV

Hydra meiosis reveals unexpected conservation of structural synaptonemal complex proteins across metazoans

PubMed Central

Fraune, Johanna; Alsheimer, Manfred; Volff, Jean-Nicolas; Busch, Karoline; Fraune, Sebastian; Bosch, Thomas C. G.; Benavente, Ricardo

2012-01-01

The synaptonemal complex (SC) is a key structure of meiosis, mediating the stable pairing (synapsis) of homologous chromosomes during prophase I. Its remarkable tripartite structure is evolutionarily well conserved and can be found in almost all sexually reproducing organisms. However, comparison of the different SC protein components in the common meiosis model organisms Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealed no sequence homology. This discrepancy challenged the hypothesis that the SC arose only once in evolution. To pursue this matter we focused on the evolution of SYCP1 and SYCP3, the two major structural SC proteins of mammals. Remarkably, our comparative bioinformatic and expression studies revealed that SYCP1 and SYCP3 are also components of the SC in the basal metazoan Hydra. In contrast to previous assumptions, we therefore conclude that SYCP1 and SYCP3 form monophyletic groups of orthologous proteins across metazoans. PMID:23012415

A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs.

PubMed

Lu, Mingjian; Kinchen, Jason M; Rossman, Kent L; Grimsley, Cynthia; Hall, Matthew; Sondek, John; Hengartner, Michael O; Yajnik, Vijay; Ravichandran, Kodi S

2005-02-22

CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex. Additional genetic rescue studies in C. elegans suggested that the regulation of the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining region is evolutionarily conserved. This steric-inhibition model may be a general mechanism for regulating multiple SH3-domain-containing Dock180 family members and may have implications for a variety of biological processes.

A Conserved Non-Canonical Docking Mechanism Regulates the Binding of Dual Specificity Phosphatases to Cell Integrity Mitogen-Activated Protein Kinases (MAPKs) in Budding and Fission Yeasts

PubMed Central

Sacristán-Reviriego, Almudena; Madrid, Marisa; Cansado, José; Martín, Humberto; Molina, María

2014-01-01

Dual-specificity MAPK phosphatases (MKPs) are essential for the negative regulation of MAPK pathways. Similar to other MAPK-interacting proteins, most MKPs bind MAPKs through specific docking domains known as D-motifs. However, we found that the Saccharomyces cerevisiae MKP Msg5 binds the MAPK Slt2 within the cell wall integrity (CWI) pathway through a distinct motif (IYT). Here, we demonstrate that the IYT motif mediates binding of the Msg5 paralogue Sdp1 to Slt2 as well as of the MKP Pmp1 to its CWI MAPK counterpart Pmk1 in the evolutionarily distant yeast Schizosaccharomyces pombe. As a consequence, removal of the IYT site in Msg5, Sdp1 and Pmp1 reduces MAPK trapping caused by the overexpression of catalytically inactive versions of these phosphatases. Accordingly, an intact IYT site is necessary for inactive Sdp1 to prevent nuclear accumulation of Slt2. We also show that both Ile and Tyr but not Thr are essential for the functionality of the IYT motif. These results provide mechanistic insight into MKP-MAPK interplay and stress the relevance of this conserved non-canonical docking site in the regulation of the CWI pathway in fungi. PMID:24465549

Tripeptidyl peptidase II promotes fat formation in a conserved fashion

PubMed Central

McKay, Renée M; McKay, James P; Suh, Jae Myoung; Avery, Leon; Graff, Jonathan M

2007-01-01

Tripeptidyl peptidase II (TPPII) is a multifunctional and evolutionarily conserved protease. In the mammalian hypothalamus, TPPII has a proposed anti-satiety role affected by degradation of the satiety hormone cholecystokinin 8. Here, we show that TPPII also regulates the metabolic homoeostasis of Caenorhabditis elegans; TPPII RNA interference (RNAi) decreases worm fat stores. However, this occurs independently of feeding behaviour and seems to be a function within fat-storing tissues. In mammalian cell culture, TPPII stimulates adipogenesis and TPPII RNAi blocks adipogenesis. The pro-adipogenic action of TPPII seems to be independent of protease function, as catalytically inactive TPPII also increases adipogenesis. Mice that were homozygous for an insertion in the Tpp2 locus were embryonic lethal. However, Tpp2 heterozygous mutants were lean compared with wild-type littermates, although food intake was normal. These findings indicate that TPPII has central and peripheral roles in regulating metabolism and that TPPII actions in fat-storing tissues might be an ancient function carried out in a protease-independent manner. PMID:17932511

Weak Interactions

DOE R&D Accomplishments Database

Lee, T. D.

1957-06-01

Experimental results on the non-conservation of parity and charge conservation in weak interactions are reviewed. The two-component theory of the neutrino is discussed. Lepton reactions are examined under the assumption of the law of conservation of leptons and that the neutrino is described by a two- component theory. From the results of this examination, the universal Fermi interactions are analyzed. Although reactions involving the neutrino can be described, the same is not true of reactions which do not involve the lepton, as the discussion of the decay of K mesons and hyperons shows. The question of the invariance of time reversal is next examined. (J.S.R.)

Calcium Pumps and Interacting BON1 Protein Modulate Calcium Signature, Stomatal Closure, and Plant Immunity1[OPEN

PubMed Central

Bao, Yongmei; Yang, Ziyuan; Yu, Huiyun; Li, Yun; Wang, Shu; Zou, Baohong; Xu, Dachao; Ma, Zhiqi

2017-01-01

Calcium signaling is essential for environmental responses including immune responses. Here, we provide evidence that the evolutionarily conserved protein BONZAI1 (BON1) functions together with autoinhibited calcium ATPase10 (ACA10) and ACA8 to regulate calcium signals in Arabidopsis. BON1 is a plasma membrane localized protein that negatively regulates the expression of immune receptor genes and positively regulates stomatal closure. We found that BON1 interacts with the autoinhibitory domains of ACA10 and ACA8, and the aca10 loss-of-function (LOF) mutants have an autoimmune phenotype similar to that of the bon1 LOF mutants. Genetic evidences indicate that BON1 positively regulates the activities of ACA10 and ACA8. Consistent with this idea, the steady level of calcium concentration is increased in both aca10 and bon1 mutants. Most strikingly, cytosolic calcium oscillation imposed by external calcium treatment was altered in aca10, aca8, and bon1 mutants in guard cells. In addition, calcium- and pathogen-induced stomatal closure was compromised in the aca10 and bon1 mutants. Taken together, this study indicates that ACA10/8 and BON1 physically interact on plasma membrane and function in the generation of cytosol calcium signatures that are critical for stomatal movement and impact plant immunity. PMID:28701352

Evolutionary Diversification of Prey and Predator Species Facilitated by Asymmetric Interactions.

PubMed

Zu, Jian; Wang, Jinliang; Huang, Gang

We investigate the influence of asymmetric interactions on coevolutionary dynamics of a predator-prey system by using the theory of adaptive dynamics. We assume that the defense ability of prey and the attack ability of predators all can adaptively evolve, either caused by phenotypic plasticity or by behavioral choice, but there are certain costs in terms of their growth rate or death rate. The coevolutionary model is constructed from a deterministic approximation of random mutation-selection process. To sum up, if prey's trade-off curve is globally weakly concave, then five outcomes of coevolution are demonstrated, which depend on the intensity and shape of asymmetric predator-prey interactions and predator's trade-off shape. Firstly, we find that if there is a weakly decelerating cost and a weakly accelerating benefit for predator species, then evolutionary branching in the predator species may occur, but after branching further coevolution may lead to extinction of the predator species with a larger trait value. However, if there is a weakly accelerating cost and a weakly accelerating benefit for predator species, then evolutionary branching in the predator species is also possible and after branching the dimorphic predator can evolutionarily stably coexist with a monomorphic prey species. Secondly, if the asymmetric interactions become a little strong, then prey and predators will evolve to an evolutionarily stable equilibrium, at which they can stably coexist on a long-term timescale of evolution. Thirdly, if there is a weakly accelerating cost and a relatively strongly accelerating benefit for prey species, then evolutionary branching in the prey species is possible and the finally coevolutionary outcome contains a dimorphic prey and a monomorphic predator species. Fourthly, if the asymmetric interactions become more stronger, then predator-prey coevolution may lead to cycles in both traits and equilibrium population densities. The Red Queen dynamic is a

Credibility and advocacy in conservation science

PubMed Central

Horton, Cristi C.; Peterson, Tarla Rai; Banerjee, Paulami

2015-01-01

Abstract Conservation policy sits at the nexus of natural science and politics. On the one hand, conservation scientists strive to maintain scientific credibility by emphasizing that their research findings are the result of disinterested observations of reality. On the other hand, conservation scientists are committed to conservation even if they do not advocate a particular policy. The professional conservation literature offers guidance on negotiating the relationship between scientific objectivity and political advocacy without damaging conservation science's credibility. The value of this guidance, however, may be restricted by limited recognition of credibility's multidimensionality and emergent nature: it emerges through perceptions of expertise, goodwill, and trustworthiness. We used content analysis of the literature to determine how credibility is framed in conservation science as it relates to apparent contradictions between science and advocacy. Credibility typically was framed as a static entity lacking dimensionality. Authors identified expertise or trustworthiness as important, but rarely mentioned goodwill. They usually did not identify expertise, goodwill, or trustworthiness as dimensions of credibility or recognize interactions among these 3 dimensions of credibility. This oversimplification may limit the ability of conservation scientists to contribute to biodiversity conservation. Accounting for the emergent quality and multidimensionality of credibility should enable conservation scientists to advance biodiversity conservation more effectively. PMID:26041036

Credibility and advocacy in conservation science.

PubMed

Horton, Cristi C; Peterson, Tarla Rai; Banerjee, Paulami; Peterson, Markus J

2016-02-01

Conservation policy sits at the nexus of natural science and politics. On the one hand, conservation scientists strive to maintain scientific credibility by emphasizing that their research findings are the result of disinterested observations of reality. On the other hand, conservation scientists are committed to conservation even if they do not advocate a particular policy. The professional conservation literature offers guidance on negotiating the relationship between scientific objectivity and political advocacy without damaging conservation science's credibility. The value of this guidance, however, may be restricted by limited recognition of credibility's multidimensionality and emergent nature: it emerges through perceptions of expertise, goodwill, and trustworthiness. We used content analysis of the literature to determine how credibility is framed in conservation science as it relates to apparent contradictions between science and advocacy. Credibility typically was framed as a static entity lacking dimensionality. Authors identified expertise or trustworthiness as important, but rarely mentioned goodwill. They usually did not identify expertise, goodwill, or trustworthiness as dimensions of credibility or recognize interactions among these 3 dimensions of credibility. This oversimplification may limit the ability of conservation scientists to contribute to biodiversity conservation. Accounting for the emergent quality and multidimensionality of credibility should enable conservation scientists to advance biodiversity conservation more effectively. © 2015 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism.

PubMed

Loboda, Agnieszka; Damulewicz, Milena; Pyza, Elzbieta; Jozkowicz, Alicja; Dulak, Jozef

2016-09-01

The multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) is considered not only as a cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory and detoxifying proteins, but it is also a powerful modulator of species longevity. The vertebrate Nrf2 belongs to Cap 'n' Collar (Cnc) bZIP family of transcription factors and shares a high homology with SKN-1 from Caenorhabditis elegans or CncC found in Drosophila melanogaster. The major characteristics of Nrf2 are to some extent mimicked by Nrf2-dependent genes and their proteins including heme oxygenase-1 (HO-1), which besides removing toxic heme, produces biliverdin, iron ions and carbon monoxide. HO-1 and their products exert beneficial effects through the protection against oxidative injury, regulation of apoptosis, modulation of inflammation as well as contribution to angiogenesis. On the other hand, the disturbances in the proper HO-1 level are associated with the pathogenesis of some age-dependent disorders, including neurodegeneration, cancer or macular degeneration. This review summarizes our knowledge about Nrf2 and HO-1 across different phyla suggesting their conservative role as stress-protective and anti-aging factors.

Interactions between spatially explicit conservation and management measures: implications for the governance of marine protected areas.

PubMed

Cárcamo, P Francisco; Gaymer, Carlos F

2013-12-01

Marine protected areas are not established in an institutional and governance vacuum and managers should pay attention to the wider social-ecological system in which they are immersed. This article examines Islas Choros-Damas Marine Reserve, a small marine protected area located in a highly productive and biologically diverse coastal marine ecosystem in northern Chile, and the interactions between human, institutional, and ecological dimensions beyond those existing within its boundaries. Through documents analysis, surveys, and interviews, we described marine reserve implementation (governing system) and the social and natural ecosystem-to-be-governed. We analyzed the interactions and the connections between the marine reserve and other spatially explicit conservation and/or management measures existing in the area and influencing management outcomes and governance. A top-down approach with poor stakeholder involvement characterized the implementation process. The marine reserve is highly connected with other spatially explicit measures and with a wider social-ecological system through various ecological processes and socio-economic interactions. Current institutional interactions with positive effects on the management and governance are scarce, although several potential interactions may be developed. For the study area, any management action must recognize interferences from outside conditions and consider some of them (e.g., ecotourism management) as cross-cutting actions for the entire social-ecological system. We consider that institutional interactions and the development of social networks are opportunities to any collective effort aiming to improve governance of Islas Choros-Damas marine reserve. Communication of connections and interactions between marine protected areas and the wider social-ecological system (as described in this study) is proposed as a strategy to improve stakeholder participation in Chilean marine protected areas.

Interactions Between Spatially Explicit Conservation and Management Measures: Implications for the Governance of Marine Protected Areas

NASA Astrophysics Data System (ADS)

Cárcamo, P. Francisco; Gaymer, Carlos F.

2013-12-01

Marine protected areas are not established in an institutional and governance vacuum and managers should pay attention to the wider social-ecological system in which they are immersed. This article examines Islas Choros-Damas Marine Reserve, a small marine protected area located in a highly productive and biologically diverse coastal marine ecosystem in northern Chile, and the interactions between human, institutional, and ecological dimensions beyond those existing within its boundaries. Through documents analysis, surveys, and interviews, we described marine reserve implementation (governing system) and the social and natural ecosystem-to-be-governed. We analyzed the interactions and the connections between the marine reserve and other spatially explicit conservation and/or management measures existing in the area and influencing management outcomes and governance. A top-down approach with poor stakeholder involvement characterized the implementation process. The marine reserve is highly connected with other spatially explicit measures and with a wider social-ecological system through various ecological processes and socio-economic interactions. Current institutional interactions with positive effects on the management and governance are scarce, although several potential interactions may be developed. For the study area, any management action must recognize interferences from outside conditions and consider some of them (e.g., ecotourism management) as cross-cutting actions for the entire social-ecological system. We consider that institutional interactions and the development of social networks are opportunities to any collective effort aiming to improve governance of Islas Choros-Damas marine reserve. Communication of connections and interactions between marine protected areas and the wider social-ecological system (as described in this study) is proposed as a strategy to improve stakeholder participation in Chilean marine protected areas.

Illustrating some implications of the conservation laws in relativistic mechanics

NASA Astrophysics Data System (ADS)

Boyer, Timothy H.

2009-06-01

The conservation laws of nonrelativistic and relativistic systems are reviewed and some simple illustrations are provided for the restrictive nature of the relativistic conservation law involving the center of energy compared to the nonrelativistic conservation law for the center of mass. Extension of the nonrelativistic interaction of particles through a potential to a system that is Lorentz-invariant through order v2/c2 is found to require new velocity- and acceleration-dependent forces that are suggestive of a field theory where the no-interaction theorem of Currie, Jordan, and Sudershan does not hold.

The evolution of CpG density and lifespan in conserved primate and mammalian promoters

PubMed Central

McLain, Adam T.

2018-01-01

Gene promoters are evolutionarily conserved across holozoans and enriched in CpG sites, the target for DNA methylation. As animals age, the epigenetic pattern of DNA methylation degrades, with highly methylated CpG sites gradually becoming demethylated while CpG islands increase in methylation. Across vertebrates, aging is a trait that varies among species. We used this variation to determine whether promoter CpG density correlates with species’ maximum lifespan. Human promoter sequences were used to identify conserved regions in 131 mammals and a subset of 28 primate genomes. We identified approximately 1000 gene promoters (5% of the total), that significantly correlated CpG density with lifespan. The correlations were performed via the phylogenetic least squares method to account for trait similarity by common descent using phylogenetic branch lengths. Gene set enrichment analysis revealed no significantly enriched pathways or processes, consistent with the hypothesis that aging is not under positive selection. However, within both mammals and primates, 95% of the promoters showed a positive correlation between increasing CpG density and species lifespan, and two thirds were shared between the primate subset and mammalian datasets. Thus, these genes may require greater buffering capacity against age-related dysregulation of DNA methylation in longer-lived species. PMID:29661983

Decentralizing conservation and diversifying livelihoods within Kanchenjunga Conservation Area, Nepal.

PubMed

Parker, Pete; Thapa, Brijesh; Jacob, Aerin

2015-12-01

To alleviate poverty and enhance conservation in resource dependent communities, managers must identify existing livelihood strategies and the associated factors that impede household access to livelihood assets. Researchers increasingly advocate reallocating management power from exclusionary central institutions to a decentralized system of management based on local and inclusive participation. However, it is yet to be shown if decentralizing conservation leads to diversified livelihoods within a protected area. The purpose of this study was to identify and assess factors affecting household livelihood diversification within Nepal's Kanchenjunga Conservation Area Project, the first protected area in Asia to decentralize conservation. We randomly surveyed 25% of Kanchenjunga households to assess household socioeconomic and demographic characteristics and access to livelihood assets. We used a cluster analysis with the ten most common income generating activities (both on- and off-farm) to group the strategies households use to diversify livelihoods, and a multinomial logistic regression to identify predictors of livelihood diversification. We found four distinct groups of household livelihood strategies with a range of diversification that directly corresponded to household income. The predictors of livelihood diversification were more related to pre-existing socioeconomic and demographic factors (e.g., more landholdings and livestock, fewer dependents, receiving remittances) than activities sponsored by decentralizing conservation (e.g., microcredit, training, education, interaction with project staff). Taken together, our findings indicate that without direct policies to target marginalized groups, decentralized conservation in Kanchenjunga will continue to exclude marginalized groups, limiting a household's ability to diversify their livelihood and perpetuating their dependence on natural resources. Copyright © 2015 Elsevier Ltd. All rights reserved.

Using Publicly Available Data to Quantify Plant-Pollinator Interactions and Evaluate Conservation Seeding Mixes in the Northern Great Plains.

PubMed

Otto, C R V; O'Dell, S; Bryant, R B; Euliss, N H; Bush, R M; Smart, M D

2017-06-01

Concern over declining pollinators has led to multiple conservation initiatives for improving forage for bees in agroecosystems. Using data available through the Pollinator Library (npwrc.usgs.gov/pollinator/), we summarize plant-pollinator interaction data collected from 2012-2015 on lands managed by the U.S. Fish and Wildlife Service and private lands enrolled in U.S. Department of Agriculture conservation programs in eastern North Dakota (ND). Furthermore, we demonstrate how plant-pollinator interaction data from the Pollinator Library and seed cost information can be used to evaluate hypothetical seeding mixes for pollinator habitat enhancements. We summarize records of 314 wild bee and 849 honey bee (Apis mellifera L.) interactions detected on 63 different plant species. The wild bee observations consisted of 46 species, 15 genera, and 5 families. Over 54% of all wild bee observations were represented by three genera-Bombus, Lassioglossum, and Melissodes. The most commonly visited forbs by wild bees were Monarda fistulosa, Sonchus arvensis, and Zizia aurea. The most commonly visited forbs by A. mellifera were Cirsium arvense, Melilotus officinalis, and Medicago sativa. Among all interactions, 13% of A. mellifera and 77% of wild bee observations were made on plants native to ND. Our seed mix evaluation shows that mixes may often need to be tailored to meet the unique needs of wild bees and managed honey bees in agricultural landscapes. Our evaluation also demonstrates the importance of incorporating both biologic and economic information when attempting to design cost-effective seeding mixes for supporting pollinators in a critically important part of the United States. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.

3D RNA and functional interactions from evolutionary couplings

PubMed Central

Weinreb, Caleb; Riesselman, Adam; Ingraham, John B.; Gross, Torsten; Sander, Chris; Marks, Debora S.

2016-01-01

Summary Non-coding RNAs are ubiquitous, but the discovery of new RNA gene sequences far outpaces research on their structure and functional interactions. We mine the evolutionary sequence record to derive precise information about function and structure of RNAs and RNA-protein complexes. As in protein structure prediction, we use maximum entropy global probability models of sequence co-variation to infer evolutionarily constrained nucleotide-nucleotide interactions within RNA molecules, and nucleotide-amino acid interactions in RNA-protein complexes. The predicted contacts allow all-atom blinded 3D structure prediction at good accuracy for several known RNA structures and RNA-protein complexes. For unknown structures, we predict contacts in 160 non-coding RNA families. Beyond 3D structure prediction, evolutionary couplings help identify important functional interactions, e.g., at switch points in riboswitches and at a complex nucleation site in HIV. Aided by accelerating sequence accumulation, evolutionary coupling analysis can accelerate the discovery of functional interactions and 3D structures involving RNA. PMID:27087444

Multiple conserved cell adhesion protein interactions mediate neural wiring of a sensory circuit in C. elegans.

PubMed

Kim, Byunghyuk; Emmons, Scott W

2017-09-13

Nervous system function relies on precise synaptic connections. A number of widely-conserved cell adhesion proteins are implicated in cell recognition between synaptic partners, but how these proteins act as a group to specify a complex neural network is poorly understood. Taking advantage of known connectivity in C. elegans , we identified and studied cell adhesion genes expressed in three interacting neurons in the mating circuits of the adult male. Two interacting pairs of cell surface proteins independently promote fasciculation between sensory neuron HOA and its postsynaptic target interneuron AVG: BAM-2/neurexin-related in HOA binds to CASY-1/calsyntenin in AVG; SAX-7/L1CAM in sensory neuron PHC binds to RIG-6/contactin in AVG. A third, basal pathway results in considerable HOA-AVG fasciculation and synapse formation in the absence of the other two. The features of this multiplexed mechanism help to explain how complex connectivity is encoded and robustly established during nervous system development.

Wound-Induced Polyploidization: Regulation by Hippo and JNK Signaling and Conservation in Mammals

PubMed Central

Losick, Vicki P.; Jun, Albert S.; Spradling, Allan C.

2016-01-01

Tissue integrity and homeostasis often rely on the proliferation of stem cells or differentiated cells to replace lost, aged, or damaged cells. Recently, we described an alternative source of cell replacement- the expansion of resident, non-dividing diploid cells by wound-induced polyploidization (WIP). Here we show that the magnitude of WIP is proportional to the extent of cell loss using a new semi-automated assay with single cell resolution. Hippo and JNK signaling regulate WIP; unexpectedly however, JNK signaling through AP-1 limits rather than stimulates the level of Yki activation and polyploidization in the Drosophila epidermis. We found that polyploidization also quantitatively compensates for cell loss in a mammalian tissue, mouse corneal endothelium, where increased cell death occurs with age in a mouse model of Fuchs Endothelial Corneal Dystrophy (FECD). Our results suggest that WIP is an evolutionarily conserved homeostatic mechanism that maintains the size and synthetic capacity of adult tissues. PMID:26958853

Wound-Induced Polyploidization: Regulation by Hippo and JNK Signaling and Conservation in Mammals.

PubMed

Losick, Vicki P; Jun, Albert S; Spradling, Allan C

2016-01-01

Tissue integrity and homeostasis often rely on the proliferation of stem cells or differentiated cells to replace lost, aged, or damaged cells. Recently, we described an alternative source of cell replacement- the expansion of resident, non-dividing diploid cells by wound-induced polyploidization (WIP). Here we show that the magnitude of WIP is proportional to the extent of cell loss using a new semi-automated assay with single cell resolution. Hippo and JNK signaling regulate WIP; unexpectedly however, JNK signaling through AP-1 limits rather than stimulates the level of Yki activation and polyploidization in the Drosophila epidermis. We found that polyploidization also quantitatively compensates for cell loss in a mammalian tissue, mouse corneal endothelium, where increased cell death occurs with age in a mouse model of Fuchs Endothelial Corneal Dystrophy (FECD). Our results suggest that WIP is an evolutionarily conserved homeostatic mechanism that maintains the size and synthetic capacity of adult tissues.

The Fourth World Conservation Lecture: The Evolution of Conservation and Contemporary Issues.

ERIC Educational Resources Information Center

Kassas, Mohammed

1985-01-01

Traces the international movements that focused on the conservation and protection of nature within the past five decades. Explains how man-nature relationships are influenced by the interaction of the three systems of the biosphere, technosphere, and sociosphere. Issues involved with deforestation and desertification are also described. (ML)

The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation.

PubMed

Malik, Sohail; Roeder, Robert G

2010-11-01

The Mediator is an evolutionarily conserved, multiprotein complex that is a key regulator of protein-coding genes. In metazoan cells, multiple pathways that are responsible for homeostasis, cell growth and differentiation converge on the Mediator through transcriptional activators and repressors that target one or more of the almost 30 subunits of this complex. Besides interacting directly with RNA polymerase II, Mediator has multiple functions and can interact with and coordinate the action of numerous other co-activators and co-repressors, including those acting at the level of chromatin. These interactions ultimately allow the Mediator to deliver outputs that range from maximal activation of genes to modulation of basal transcription to long-term epigenetic silencing.

Growth and patterning are evolutionarily dissociated in the vestigial wing discs of workers of the red imported fire ant, Solenopsis invicta.

PubMed

Bowsher, Julia H; Wray, Gregory A; Abouheif, Ehab

2007-12-15

Over the last decade, it has become clear that organismal form is largely determined by developmental and evolutionary changes in the growth and pattern formation of tissues. Yet, there is little known about how these two integrated processes respond to environmental cues or how they evolve relative to one another. Here, we present the discovery of vestigial wing imaginal discs in worker larvae of the red imported fire ant, Solenopsis invicta. These vestigial wing discs are present in all worker larvae, which is uncommon for a species with a large worker size distribution. Furthermore, the growth trajectory of these vestigial discs is distinct from all of the ant species examined to date because they grow at a rate slower than the leg discs. We predicted that the growth trajectory of the vestigial wing discs would be mirrored by evolutionary changes in their patterning. We tested this prediction by examining the expression of three patterning genes, extradenticle, ultrabithorax, and engrailed, known to underlie the wing polyphenism in ants. Surprisingly, the expression patterns of these three genes in the vestigial wing discs was the same as those found in ant species with different worker size distributions and wing disc growth than fire ants. We conclude that growth and patterning are evolutionarily dissociated in the vestigial wing discs of S. invicta because patterning in these discs is conserved, whereas their growth trajectories are not. The evolutionary dissociation of growth and patterning may be an important feature of gene networks that underlie polyphenic traits. 2007 Wiley-Liss, Inc

Test of Von Baer's law of the conservation of early development.

PubMed

Poe, Steven

2006-11-01

One of the oldest and most pervasive ideas in comparative embryology is the perceived evolutionary conservation of early ontogeny relative to late ontogeny. Karl Von Baer first noted the similarity of early ontogeny across taxa, and Ernst Haeckel and Charles Darwin gave evolutionary interpretation to this phenomenon. In spite of a resurgence of interest in comparative embryology and the development of mechanistic explanations for Von Baer's law, the pattern itself has been largely untested. Here, I use statistical phylogenetic approaches to show that Von Baer's law is an unnecessarily complex explanation of the patterns of ontogenetic timing in several clades of vertebrates. Von Baer's law suggests a positive correlation between ontogenetic time and amount of evolutionary change. I compare ranked position in ontogeny to frequency of evolutionary change in rank for developmental events and find that these measures are not correlated, thus failing to support Von Baer's model. An alternative model that postulates that small changes in ontogenetic rank are evolutionarily easier than large changes is tentatively supported.

Conserved queen pheromones in bumblebees: a reply to Amsalem et al.

PubMed

Holman, Luke; van Zweden, Jelle S; Oliveira, Ricardo C; van Oystaeyen, Annette; Wenseleers, Tom

2017-01-01

In a recent study, Amsalem, Orlova & Grozinger (2015) performed experiments with Bombus impatiens bumblebees to test the hypothesis that saturated cuticular hydrocarbons are evolutionarily conserved signals used to regulate reproductive division of labor in many Hymenopteran social insects. They concluded that the cuticular hydrocarbon pentacosane (C 25 ), previously identified as a queen pheromone in a congeneric bumblebee, does not affect worker reproduction in B. impatiens . Here we discuss some shortcomings of Amsalem et al.'s study that make its conclusions unreliable. In particular, several confounding effects may have affected the results of both experimental manipulations in the study. Additionally, the study's low sample sizes (mean n per treatment = 13.6, range: 4-23) give it low power, not 96-99% power as claimed, such that its conclusions may be false negatives. Inappropriate statistical tests were also used, and our reanalysis found that C 25 substantially reduced and delayed worker egg laying in B. impatiens . We review the evidence that cuticular hydrocarbons act as queen pheromones, and offer some recommendations for future queen pheromone experiments.

A Conserved Structural Motif Mediates Retrograde Trafficking of Shiga Toxin Types 1 and 2.

PubMed

Selyunin, Andrey S; Mukhopadhyay, Somshuvra

2015-12-01

Shiga toxin-producing Escherichia coli (STEC) produce two types of Shiga toxin (STx): STx1 and STx2. The toxin A-subunits block protein synthesis, while the B-subunits mediate retrograde trafficking. STEC infections do not have definitive treatments, and there is growing interest in generating toxin transport inhibitors for therapy. However, a comprehensive understanding of the mechanisms of toxin trafficking is essential for drug development. While STx2 is more toxic in vivo, prior studies focused on STx1 B-subunit (STx1B) trafficking. Here, we show that, compared with STx1B, trafficking of the B-subunit of STx2 (STx2B) to the Golgi occurs with slower kinetics. Despite this difference, similar to STx1B, endosome-to-Golgi transport of STx2B does not involve transit through degradative late endosomes and is dependent on dynamin II, epsinR, retromer and syntaxin5. Importantly, additional experiments show that a surface-exposed loop in STx2B (β4-β5 loop) is required for its endosome-to-Golgi trafficking. We previously demonstrated that residues in the corresponding β4-β5 loop of STx1B are required for interaction with GPP130, the STx1B-specific endosomal receptor, and for endosome-to-Golgi transport. Overall, STx1B and STx2B share a common pathway and use a similar structural motif to traffic to the Golgi, suggesting that the underlying mechanisms of endosomal sorting may be evolutionarily conserved. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparative developmental analysis of Drosophila and Tribolium reveals conserved and diverged roles of abrupt in insect wing evolution.

PubMed

Ravisankar, Padmapriyadarshini; Lai, Yi-Ting; Sambrani, Nagraj; Tomoyasu, Yoshinori

2016-01-15

Morphological innovation is a fundamental process in evolution, yet its molecular basis is still elusive. Acquisition of elytra, highly modified beetle forewings, is an important innovation that has driven the successful radiation of beetles. Our RNAi screening for candidate genes has identified abrupt (ab) as a potential key player in elytron evolution. In this study, we performed a series of RNA interference (RNAi) experiments in both Tribolium and Drosophila to understand the contributions of ab to the evolution of beetle elytra. We found that (i) ab is essential for proper wing vein patterning both in Tribolium and Drosophila, (ii) ab has gained a novel function in determining the unique elytron shape in the beetle lineage, (iii) unlike Hippo and Insulin, other shape determining pathways, the shape determining function of ab is specific to the elytron and not required in the hindwing, (iv) ab has a previously undescribed role in the Notch signal-associated wing formation processes, which appears to be conserved between beetles and flies. These data suggest that ab has gained a new function during elytron evolution in beetles without compromising the conserved wing-related functions. Gaining a new function without losing evolutionarily conserved functions may be a key theme in the evolution of morphologically novel structures. Copyright © 2015 Elsevier Inc. All rights reserved.

Conserving Earth's Biodiversity. [CD-ROM and] Instructor's Manual.

ERIC Educational Resources Information Center

2000

This CD-ROM is designed as an interactive learning tool to support teaching in highly interdisciplinary fields such as conservation of biodiversity. Topics introduced in the software include the impact of humans on natural landscapes, threats to biodiversity, methods and theories of conservation biology, environmental laws, and relevant economic…

Fmrp Interacts with Adar and Regulates RNA Editing, Synaptic Density and Locomotor Activity in Zebrafish

PubMed Central

Porath, Hagit T.; Barak, Michal; Pinto, Yishay; Wachtel, Chaim; Zilberberg, Alona; Lerer-Goldshtein, Tali; Efroni, Sol; Levanon, Erez Y.; Appelbaum, Lior

2015-01-01

Fragile X syndrome (FXS) is the most frequent inherited form of mental retardation. The cause for this X-linked disorder is the silencing of the fragile X mental retardation 1 (fmr1) gene and the absence of the fragile X mental retardation protein (Fmrp). The RNA-binding protein Fmrp represses protein translation, particularly in synapses. In Drosophila, Fmrp interacts with the adenosine deaminase acting on RNA (Adar) enzymes. Adar enzymes convert adenosine to inosine (A-to-I) and modify the sequence of RNA transcripts. Utilizing the fmr1 zebrafish mutant (fmr1-/-), we studied Fmrp-dependent neuronal circuit formation, behavior, and Adar-mediated RNA editing. By combining behavior analyses and live imaging of single axons and synapses, we showed hyperlocomotor activity, as well as increased axonal branching and synaptic density, in fmr1-/- larvae. We identified thousands of clustered RNA editing sites in the zebrafish transcriptome and showed that Fmrp biochemically interacts with the Adar2a protein. The expression levels of the adar genes and Adar2 protein increased in fmr1-/- zebrafish. Microfluidic-based multiplex PCR coupled with deep sequencing showed a mild increase in A-to-I RNA editing levels in evolutionarily conserved neuronal and synaptic Adar-targets in fmr1-/- larvae. These findings suggest that loss of Fmrp results in increased Adar-mediated RNA editing activity on target-specific RNAs, which, in turn, might alter neuronal circuit formation and behavior in FXS. PMID:26637167

Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

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

Kanginakudru, Sriramana, E-mail: skangina@iu.edu; DeSmet, Marsha, E-mail: mdesmet@iupui.edu; Thomas, Yanique, E-mail: ysthomas@umail.iu.edu

2015-04-15

The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reducedmore » viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication.« less

Mechanisms of stable lipid loss in a social insect

PubMed Central

Ament, Seth A.; Chan, Queenie W.; Wheeler, Marsha M.; Nixon, Scott E.; Johnson, S. Peir; Rodriguez-Zas, Sandra L.; Foster, Leonard J.; Robinson, Gene E.

2011-01-01

SUMMARY Worker honey bees undergo a socially regulated, highly stable lipid loss as part of their behavioral maturation. We used large-scale transcriptomic and proteomic experiments, physiological experiments and RNA interference to explore the mechanistic basis for this lipid loss. Lipid loss was associated with thousands of gene expression changes in abdominal fat bodies. Many of these genes were also regulated in young bees by nutrition during an initial period of lipid gain. Surprisingly, in older bees, which is when maximum lipid loss occurs, diet played less of a role in regulating fat body gene expression for components of evolutionarily conserved nutrition-related endocrine systems involving insulin and juvenile hormone signaling. By contrast, fat body gene expression in older bees was regulated more strongly by evolutionarily novel regulatory factors, queen mandibular pheromone (a honey bee-specific social signal) and vitellogenin (a conserved yolk protein that has evolved novel, maturation-related functions in the bee), independent of nutrition. These results demonstrate that conserved molecular pathways can be manipulated to achieve stable lipid loss through evolutionarily novel regulatory processes. PMID:22031746

Mechanisms of stable lipid loss in a social insect.

PubMed

Ament, Seth A; Chan, Queenie W; Wheeler, Marsha M; Nixon, Scott E; Johnson, S Peir; Rodriguez-Zas, Sandra L; Foster, Leonard J; Robinson, Gene E

2011-11-15

Worker honey bees undergo a socially regulated, highly stable lipid loss as part of their behavioral maturation. We used large-scale transcriptomic and proteomic experiments, physiological experiments and RNA interference to explore the mechanistic basis for this lipid loss. Lipid loss was associated with thousands of gene expression changes in abdominal fat bodies. Many of these genes were also regulated in young bees by nutrition during an initial period of lipid gain. Surprisingly, in older bees, which is when maximum lipid loss occurs, diet played less of a role in regulating fat body gene expression for components of evolutionarily conserved nutrition-related endocrine systems involving insulin and juvenile hormone signaling. By contrast, fat body gene expression in older bees was regulated more strongly by evolutionarily novel regulatory factors, queen mandibular pheromone (a honey bee-specific social signal) and vitellogenin (a conserved yolk protein that has evolved novel, maturation-related functions in the bee), independent of nutrition. These results demonstrate that conserved molecular pathways can be manipulated to achieve stable lipid loss through evolutionarily novel regulatory processes.

Virulence Factors of Geminivirus Interact with MYC2 to Subvert Plant Resistance and Promote Vector Performance[C][W

PubMed Central

Li, Ran; Weldegergis, Berhane T.; Li, Jie; Jung, Choonkyun; Qu, Jing; Sun, Yanwei; Qian, Hongmei; Tee, ChuanSia; van Loon, Joop J.A.; Dicke, Marcel; Chua, Nam-Hai; Liu, Shu-Sheng

2014-01-01

A pathogen may cause infected plants to promote the performance of its transmitting vector, which accelerates the spread of the pathogen. This positive effect of a pathogen on its vector via their shared host plant is termed indirect mutualism. For example, terpene biosynthesis is suppressed in begomovirus-infected plants, leading to reduced plant resistance and enhanced performance of the whiteflies (Bemisia tabaci) that transmit these viruses. Although begomovirus-whitefly mutualism has been known, the underlying mechanism is still elusive. Here, we identified βC1 of Tomato yellow leaf curl China virus, a monopartite begomovirus, as the viral genetic factor that suppresses plant terpene biosynthesis. βC1 directly interacts with the basic helix-loop-helix transcription factor MYC2 to compromise the activation of MYC2-regulated terpene synthase genes, thereby reducing whitefly resistance. MYC2 associates with the bipartite begomoviral protein BV1, suggesting that MYC2 is an evolutionarily conserved target of begomoviruses for the suppression of terpene-based resistance and the promotion of vector performance. Our findings describe how this viral pathogen regulates host plant metabolism to establish mutualism with its insect vector. PMID:25490915

A periodic pattern of evolutionarily conserved basic and acidic residues constitutes the binding interface of actin-tropomyosin.

PubMed

Barua, Bipasha; Fagnant, Patricia M; Winkelmann, Donald A; Trybus, Kathleen M; Hitchcock-DeGregori, Sarah E

2013-04-05

Actin filament cytoskeletal and muscle functions are regulated by actin binding proteins using a variety of mechanisms. A universal actin filament regulator is the protein tropomyosin, which binds end-to-end along the length of the filament. The actin-tropomyosin filament structure is unknown, but there are atomic models in different regulatory states based on electron microscopy reconstructions, computational modeling of actin-tropomyosin, and docking of atomic resolution structures of tropomyosin to actin filament models. Here, we have tested models of the actin-tropomyosin interface in the "closed state" where tropomyosin binds to actin in the absence of myosin or troponin. Using mutagenesis coupled with functional analyses, we determined residues of actin and tropomyosin required for complex formation. The sites of mutations in tropomyosin were based on an evolutionary analysis and revealed a pattern of basic and acidic residues in the first halves of the periodic repeats (periods) in tropomyosin. In periods P1, P4, and P6, basic residues are most important for actin affinity, in contrast to periods P2, P3, P5, and P7, where both basic and acidic residues or predominantly acidic residues contribute to actin affinity. Hydrophobic interactions were found to be relatively less important for actin binding. We mutated actin residues in subdomains 1 and 3 (Asp(25)-Glu(334)-Lys(326)-Lys(328)) that are poised to make electrostatic interactions with the residues in the repeating motif on tropomyosin in the models. Tropomyosin failed to bind mutant actin filaments. Our mutagenesis studies provide the first experimental support for the atomic models of the actin-tropomyosin interface.

Spectraplakins promote microtubule-mediated axonal growth by functioning as structural microtubule-associated proteins and EB1-dependent +TIPs (tip interacting proteins).

PubMed

Alves-Silva, Juliana; Sánchez-Soriano, Natalia; Beaven, Robin; Klein, Melanie; Parkin, Jill; Millard, Thomas H; Bellen, Hugo J; Venken, Koen J T; Ballestrem, Christoph; Kammerer, Richard A; Prokop, Andreas

2012-07-04

The correct outgrowth of axons is essential for the development and regeneration of nervous systems. Axon growth is primarily driven by microtubules. Key regulators of microtubules in this context are the spectraplakins, a family of evolutionarily conserved actin-microtubule linkers. Loss of function of the mouse spectraplakin ACF7 or of its close Drosophila homolog Short stop/Shot similarly cause severe axon shortening and microtubule disorganization. How spectraplakins perform these functions is not known. Here we show that axonal growth-promoting roles of Shot require interaction with EB1 (End binding protein) at polymerizing plus ends of microtubules. We show that binding of Shot to EB1 requires SxIP motifs in Shot's C-terminal tail (Ctail), mutations of these motifs abolish Shot functions in axonal growth, loss of EB1 function phenocopies Shot loss, and genetic interaction studies reveal strong functional links between Shot and EB1 in axonal growth and microtubule organization. In addition, we report that Shot localizes along microtubule shafts and stabilizes them against pharmacologically induced depolymerization. This function is EB1-independent but requires net positive charges within Ctail which essentially contribute to the microtubule shaft association of Shot. Therefore, spectraplakins are true members of two important classes of neuronal microtubule regulating proteins: +TIPs (tip interacting proteins; plus end regulators) and structural MAPs (microtubule-associated proteins). From our data we deduce a model that relates the different features of the spectraplakin C terminus to the two functions of Shot during axonal growth.

Embryonic lethality is not sufficient to explain hourglass-like conservation of vertebrate embryos.

PubMed

Uchida, Yui; Uesaka, Masahiro; Yamamoto, Takayoshi; Takeda, Hiroyuki; Irie, Naoki

2018-01-01

Understanding the general trends in developmental changes during animal evolution, which are often associated with morphological diversification, has long been a central issue in evolutionary developmental biology. Recent comparative transcriptomic studies revealed that gene expression profiles of mid-embryonic period tend to be more evolutionarily conserved than those in earlier or later periods. While the hourglass-like divergence of developmental processes has been demonstrated in a variety of animal groups such as vertebrates, arthropods, and nematodes, the exact mechanism leading to this mid-embryonic conservation remains to be clarified. One possibility is that the mid-embryonic period (pharyngula period in vertebrates) is highly prone to embryonic lethality, and the resulting negative selections lead to evolutionary conservation of this phase. Here, we tested this "mid-embryonic lethality hypothesis" by measuring the rate of lethal phenotypes of three different species of vertebrate embryos subjected to two kinds of perturbations: transient perturbations and genetic mutations. By subjecting zebrafish ( Danio rerio ), African clawed frog ( Xenopus laevis ), and chicken ( Gallus gallus ) embryos to transient perturbations, namely heat shock and inhibitor treatments during three developmental periods [early (represented by blastula and gastrula), pharyngula, and late], we found that the early stages showed the highest rate of lethal phenotypes in all three species. This result was corroborated by perturbation with genetic mutations. By tracking the survival rate of wild-type embryos and embryos with genetic mutations induced by UV irradiation in zebrafish and African clawed frogs, we found that the highest decrease in survival rate was at the early stages particularly around gastrulation in both these species. In opposition to the "mid-embryonic lethality hypothesis," our results consistently showed that the stage with the highest lethality was not around the

Biochemical Conservation and Evolution of Germacrene A Oxidase in Asteraceae*

PubMed Central

Nguyen, Don Trinh; Göpfert, Jens Christian; Ikezawa, Nobuhiro; MacNevin, Gillian; Kathiresan, Meena; Conrad, Jürgen; Spring, Otmar; Ro, Dae-Kyun

2010-01-01

Sesquiterpene lactones are characteristic natural products in Asteraceae, which constitutes ∼8% of all plant species. Despite their physiological and pharmaceutical importance, the biochemistry and evolution of sesquiterpene lactones remain unexplored. Here we show that germacrene A oxidase (GAO), evolutionarily conserved in all major subfamilies of Asteraceae, catalyzes three consecutive oxidations of germacrene A to yield germacrene A acid. Furthermore, it is also capable of oxidizing non-natural substrate amorphadiene. Co-expression of lettuce GAO with germacrene synthase in engineered yeast synthesized aberrant products, costic acids and ilicic acid, in an acidic condition. However, cultivation in a neutral condition allowed the de novo synthesis of a single novel compound that was identified as germacrene A acid by gas and liquid chromatography and NMR analyses. To trace the evolutionary lineage of GAO in Asteraceae, homologous genes were further isolated from the representative species of three major subfamilies of Asteraceae (sunflower, chicory, and costus from Asteroideae, Cichorioideae, and Carduoideae, respectively) and also from the phylogenetically basal species, Barnadesia spinosa, from Barnadesioideae. The recombinant GAOs from these genes clearly showed germacrene A oxidase activities, suggesting that GAO activity is widely conserved in Asteraceae including the basal lineage. All GAOs could catalyze the three-step oxidation of non-natural substrate amorphadiene to artemisinic acid, whereas amorphadiene oxidase diverged from GAO displayed negligible activity for germacrene A oxidation. The observed amorphadiene oxidase activity in GAOs suggests that the catalytic plasticity is embedded in ancestral GAO enzymes that may contribute to the chemical and catalytic diversity in nature. PMID:20351109

Functional analysis of the Arabidopsis PLDZ2 promoter reveals an evolutionarily conserved low-Pi-responsive transcriptional enhancer element

PubMed Central

Oropeza-Aburto, Araceli; Cruz-Ramírez, Alfredo; Acevedo-Hernández, Gustavo J.; Pérez-Torres, Claudia-Anahí; Caballero-Pérez, Juan; Herrera-Estrella, Luis

2012-01-01

Plants have evolved a plethora of responses to cope with phosphate (Pi) deficiency, including the transcriptional activation of a large set of genes. Among Pi-responsive genes, the expression of the Arabidopsis phospholipase DZ2 (PLDZ2) is activated to participate in the degradation of phospholipids in roots in order to release Pi to support other cellular activities. A deletion analysis was performed to identify the regions determining the strength, tissue-specific expression, and Pi responsiveness of this regulatory region. This study also reports the identification and characterization of a transcriptional enhancer element that is present in the PLDZ2 promoter and able to confer Pi responsiveness to a minimal, inactive 35S promoter. This enhancer also shares the cytokinin and sucrose responsive properties observed for the intact PLDZ2 promoter. The EZ2 element contains two P1BS motifs, each of which is the DNA binding site of transcription factor PHR1. Mutation analysis showed that the P1BS motifs present in EZ2 are necessary but not sufficient for the enhancer function, revealing the importance of adjacent sequences. The structural organization of EZ2 is conserved in the orthologous genes of at least eight families of rosids, suggesting that architectural features such as the distance between the two P1BS motifs are also important for the regulatory properties of this enhancer element. PMID:22210906

Integrating network ecology with applied conservation: a synthesis and guide to implementation.

PubMed

Kaiser-Bunbury, Christopher N; Blüthgen, Nico

2015-07-10

Ecological networks are a useful tool to study the complexity of biotic interactions at a community level. Advances in the understanding of network patterns encourage the application of a network approach in other disciplines than theoretical ecology, such as biodiversity conservation. So far, however, practical applications have been meagre. Here we present a framework for network analysis to be harnessed to advance conservation management by using plant-pollinator networks and islands as model systems. Conservation practitioners require indicators to monitor and assess management effectiveness and validate overall conservation goals. By distinguishing between two network attributes, the 'diversity' and 'distribution' of interactions, on three hierarchical levels (species, guild/group and network) we identify seven quantitative metrics to describe changes in network patterns that have implications for conservation. Diversity metrics are partner diversity, vulnerability/generality, interaction diversity and interaction evenness, and distribution metrics are the specialization indices d' and [Formula: see text] and modularity. Distribution metrics account for sampling bias and may therefore be suitable indicators to detect human-induced changes to plant-pollinator communities, thus indirectly assessing the structural and functional robustness and integrity of ecosystems. We propose an implementation pathway that outlines the stages that are required to successfully embed a network approach in biodiversity conservation. Most importantly, only if conservation action and study design are aligned by practitioners and ecologists through joint experiments, are the findings of a conservation network approach equally beneficial for advancing adaptive management and ecological network theory. We list potential obstacles to the framework, highlight the shortfall in empirical, mostly experimental, network data and discuss possible solutions. Published by Oxford University

Scale and the evolutionarily based approximate number system: an exploratory study

NASA Astrophysics Data System (ADS)

Delgado, Cesar; Jones, M. Gail; You, Hye Sun; Robertson, Laura; Chesnutt, Katherine; Halberda, Justin

2017-05-01

Crosscutting concepts such as scale, proportion, and quantity are recognised by U.S. science standards as a potential vehicle for students to integrate their scientific and mathematical knowledge; yet, U.S. students and adults trail their international peers in scale and measurement estimation. Culturally based knowledge of scale such as measurement units may be built on evolutionarily-based systems of number such as the approximate number system (ANS), which processes approximate representations of numerical magnitude. ANS is related to mathematical achievement in pre-school and early elementary students, but there is little research on ANS among older students or in science-related areas such as scale. Here, we investigate the relationship between ANS precision in public school U.S. seventh graders and their accuracy estimating the length of standard units of measurement in SI and U.S. customary units. We also explored the relationship between ANS and science and mathematics achievement. Accuracy estimating the metre was positively and significantly related to ANS precision. Mathematics achievement, science achievement, and accuracy estimating other units were not significantly related to ANS. We thus suggest that ANS precision may be related to mathematics understanding beyond arithmetic, beyond the early school years, and to the crosscutting concepts of scale, proportion, and quantity.

Transcriptional regulation of human eosinophil RNases by an evolutionary- conserved sequence motif in primate genome

PubMed Central

Wang, Hsiu-Yu; Chang, Hao-Teng; Pai, Tun-Wen; Wu, Chung-I; Lee, Yuan-Hung; Chang, Yen-Hsin; Tai, Hsiu-Ling; Tang, Chuan-Yi; Chou, Wei-Yao; Chang, Margaret Dah-Tsyr

2007-01-01

Background Human eosinophil-derived neurotoxin (edn) and eosinophil cationic protein (ecp) are members of a subfamily of primate ribonuclease (rnase) genes. Although they are generated by gene duplication event, distinct edn and ecp expression profile in various tissues have been reported. Results In this study, we obtained the upstream promoter sequences of several representative primate eosinophil rnases. Bioinformatic analysis revealed the presence of a shared 34-nucleotide (nt) sequence stretch located at -81 to -48 in all edn promoters and macaque ecp promoter. Such a unique sequence motif constituted a region essential for transactivation of human edn in hepatocellular carcinoma cells. Gel electrophoretic mobility shift assay, transient transfection and scanning mutagenesis experiments allowed us to identify binding sites for two transcription factors, Myc-associated zinc finger protein (MAZ) and SV-40 protein-1 (Sp1), within the 34-nt segment. Subsequent in vitro and in vivo binding assays demonstrated a direct molecular interaction between this 34-nt region and MAZ and Sp1. Interestingly, overexpression of MAZ and Sp1 respectively repressed and enhanced edn promoter activity. The regulatory transactivation motif was mapped to the evolutionarily conserved -74/-65 region of the edn promoter, which was guanidine-rich and critical for recognition by both transcription factors. Conclusion Our results provide the first direct evidence that MAZ and Sp1 play important roles on the transcriptional activation of the human edn promoter through specific binding to a 34-nt segment present in representative primate eosinophil rnase promoters. PMID:17927842

Cross-species transcriptional network analysis reveals conservation and variation in response to metal stress in cyanobacteria

PubMed Central

2013-01-01

Background As one of the most dominant bacterial groups on Earth, cyanobacteria play a pivotal role in the global carbon cycling and the Earth atmosphere composition. Understanding their molecular responses to environmental perturbations has important scientific and environmental values. Since important biological processes or networks are often evolutionarily conserved, the cross-species transcriptional network analysis offers a useful strategy to decipher conserved and species-specific transcriptional mechanisms that cells utilize to deal with various biotic and abiotic disturbances, and it will eventually lead to a better understanding of associated adaptation and regulatory networks. Results In this study, the Weighted Gene Co-expression Network Analysis (WGCNA) approach was used to establish transcriptional networks for four important cyanobacteria species under metal stress, including iron depletion and high copper conditions. Cross-species network comparison led to discovery of several core response modules and genes possibly essential to metal stress, as well as species-specific hub genes for metal stresses in different cyanobacteria species, shedding light on survival strategies of cyanobacteria responding to different environmental perturbations. Conclusions The WGCNA analysis demonstrated that the application of cross-species transcriptional network analysis will lead to novel insights to molecular response to environmental changes which will otherwise not be achieved by analyzing data from a single species. PMID:23421563

Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis

DOE PAGES

Zhang, Chunhua; Brown, Michelle Q.; van de Ven, Wilhelmina; ...

2015-11-25

The exocyst complex regulates the last steps of exocytosis, which is essential to organisms across kingdoms. In humans, its dysfunction is correlated with several significant diseases, such as diabetes and cancer progression. Investigation of the dynamic regulation of the evolutionarily conserved exocyst-related processes using mutants in genetically tractable organisms such as Arabidopsis thaliana is limited by the lethality or the severity of phenotypes. We discovered that the small molecule Endosidin2 (ES2) binds to the EXO70 (exocyst component of 70 kDa) subunit of the exocyst complex, resulting in inhibition of exocytosis and endosomal recycling in both plant and human cells andmore » enhancement of plant vacuolar trafficking. An EXO70 protein with a C-terminal truncation results in dominant ES2 resistance, uncovering possible distinct regulatory roles for the N terminus of the protein. Ultimately, this study not only provides a valuable tool in studying exocytosis regulation but also offers a potentially new target for drugs aimed at addressing human disease.« less

Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis

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

Zhang, Chunhua; Brown, Michelle Q.; van de Ven, Wilhelmina

The exocyst complex regulates the last steps of exocytosis, which is essential to organisms across kingdoms. In humans, its dysfunction is correlated with several significant diseases, such as diabetes and cancer progression. Investigation of the dynamic regulation of the evolutionarily conserved exocyst-related processes using mutants in genetically tractable organisms such as Arabidopsis thaliana is limited by the lethality or the severity of phenotypes. We discovered that the small molecule Endosidin2 (ES2) binds to the EXO70 (exocyst component of 70 kDa) subunit of the exocyst complex, resulting in inhibition of exocytosis and endosomal recycling in both plant and human cells andmore » enhancement of plant vacuolar trafficking. An EXO70 protein with a C-terminal truncation results in dominant ES2 resistance, uncovering possible distinct regulatory roles for the N terminus of the protein. Ultimately, this study not only provides a valuable tool in studying exocytosis regulation but also offers a potentially new target for drugs aimed at addressing human disease.« less

Patterns of amino acid conservation in human and animal immunodeficiency viruses.

PubMed

Voitenko, Olga S; Dhroso, Andi; Feldmann, Anna; Korkin, Dmitry; Kalinina, Olga V

2016-09-01

Due to their high genomic variability, RNA viruses and retroviruses present a unique opportunity for detailed study of molecular evolution. Lentiviruses, with HIV being a notable example, are one of the best studied viral groups: hundreds of thousands of sequences are available together with experimentally resolved three-dimensional structures for most viral proteins. In this work, we use these data to study specific patterns of evolution of the viral proteins, and their relationship to protein interactions and immunogenicity. We propose a method for identification of two types of surface residues clusters with abnormal conservation: extremely conserved and extremely variable clusters. We identify them on the surface of proteins from HIV and other animal immunodeficiency viruses. Both types of clusters are overrepresented on the interaction interfaces of viral proteins with other proteins, nucleic acids or low molecular-weight ligands, both in the viral particle and between the virus and its host. In the immunodeficiency viruses, the interaction interfaces are not more conserved than the corresponding proteins on an average, and we show that extremely conserved clusters coincide with protein-protein interaction hotspots, predicted as the residues with the largest energetic contribution to the interaction. Extremely variable clusters have been identified here for the first time. In the HIV-1 envelope protein gp120, they overlap with known antigenic sites. These antigenic sites also contain many residues from extremely conserved clusters, hence representing a unique interacting interface enriched both in extremely conserved and in extremely variable clusters of residues. This observation may have important implication for antiretroviral vaccine development. A Python package is available at https://bioinf.mpi-inf.mpg.de/publications/viral-ppi-pred/ voitenko@mpi-inf.mpg.de or kalinina@mpi-inf.mpg.de Supplementary data are available at Bioinformatics online. © The

Competitive inhibition can linearize dose-response and generate a linear rectifier.

PubMed

Savir, Yonatan; Tu, Benjamin P; Springer, Michael

2015-09-23

Many biological responses require a dynamic range that is larger than standard bi-molecular interactions allow, yet the also ability to remain off at low input. Here we mathematically show that an enzyme reaction system involving a combination of competitive inhibition, conservation of the total level of substrate and inhibitor, and positive feedback can behave like a linear rectifier-that is, a network motif with an input-output relationship that is linearly sensitive to substrate above a threshold but unresponsive below the threshold. We propose that the evolutionarily conserved yeast SAGA histone acetylation complex may possess the proper physiological response characteristics and molecular interactions needed to perform as a linear rectifier, and we suggest potential experiments to test this hypothesis. One implication of this work is that linear responses and linear rectifiers might be easier to evolve or synthetically construct than is currently appreciated.

Competitive inhibition can linearize dose-response and generate a linear rectifier

PubMed Central

Savir, Yonatan; Tu, Benjamin P.; Springer, Michael

2015-01-01

Summary Many biological responses require a dynamic range that is larger than standard bi-molecular interactions allow, yet the also ability to remain off at low input. Here we mathematically show that an enzyme reaction system involving a combination of competitive inhibition, conservation of the total level of substrate and inhibitor, and positive feedback can behave like a linear rectifier—that is, a network motif with an input-output relationship that is linearly sensitive to substrate above a threshold but unresponsive below the threshold. We propose that the evolutionarily conserved yeast SAGA histone acetylation complex may possess the proper physiological response characteristics and molecular interactions needed to perform as a linear rectifier, and we suggest potential experiments to test this hypothesis. One implication of this work is that linear responses and linear rectifiers might be easier to evolve or synthetically construct than is currently appreciated. PMID:26495436

Genetic interactions between the chromosome axis-associated protein Hop1 and homologous recombination determinants in Schizosaccharomyces pombe.

PubMed

Brown, Simon David; Jarosinska, Olga Dorota; Lorenz, Alexander

2018-03-17

Hop1 is a component of the meiosis-specific chromosome axis and belongs to the evolutionarily conserved family of HORMA domain proteins. Hop1 and its orthologs in higher eukaryotes are a major factor in promoting double-strand DNA break formation and inter-homolog recombination. In budding yeast and mammals, they are also involved in a meiotic checkpoint kinase cascade monitoring the completion of double-strand DNA break repair. We used the fission yeast, Schizosaccharomyces pombe, which lacks a canonical synaptonemal complex to test whether Hop1 has a role beyond supporting the generation of double-strand DNA breaks and facilitating inter-homolog recombination events. We determined how mutants of homologous recombination factors genetically interact with hop1, studied the role(s) of the HORMA domain of Hop1, and characterized a bio-informatically predicted interactor of Hop1, Aho1 (SPAC688.03c). Our observations indicate that in fission yeast, Hop1 does require its HORMA domain to support wild-type levels of meiotic recombination and localization to meiotic chromatin. Furthermore, we show that hop1∆ only weakly interacts genetically with mutants of homologous recombination factors, and in fission yeast likely has no major role beyond break formation and promoting inter-homolog events. We speculate that after the evolutionary loss of the synaptonemal complex, Hop1 likely has become less important for modulating recombination outcome during meiosis in fission yeast, and that this led to a concurrent rewiring of genetic pathways controlling meiotic recombination.

Neurotransmitter release mechanisms studied in Caenorhabditis elegans.

PubMed

Barclay, Jeff W; Morgan, Alan; Burgoyne, Robert D

2012-01-01

The process of regulated exocytosis has received considerable interest as a key component of synaptic transmission. Fusion of presynaptic vesicles and the subsequent release of their neurotransmitter contents is driven by a series of interactions between evolutionarily conserved proteins. Key insights into the molecular mechanisms of vesicle fusion have come from research using genetic model systems such as the nematode worm Caenorhabditis elegans. We review here the current knowledge regarding regulated exocytosis at the C. elegans synapse and future research directions involving this model organism. Copyright © 2012 Elsevier Ltd. All rights reserved.

Temperature Induced Syllable Breaking Unveils Nonlinearly Interacting Timescales in Birdsong Motor Pathway

PubMed Central

Goldin, Matías A.; Alonso, Leandro M.; Alliende, Jorge A.; Goller, Franz; Mindlin, Gabriel B.

2013-01-01

The nature of telencephalic control over premotor and motor circuits is debated. Hypotheses range from complete usurping of downstream circuitry to highly interactive mechanisms of control. We show theoretically and experimentally, that telencephalic song motor control in canaries is consistent with a highly interactive strategy. As predicted from a theoretical model of respiratory control, mild cooling of a forebrain nucleus (HVC) led to song stretching, but further cooling caused progressive restructuring of song, consistent with the hypothesis that respiratory gestures are subharmonic responses to a timescale present in the output of HVC. This interaction between a life-sustaining motor function (respiration) and telencephalic song motor control suggests a more general mechanism of how nonlinear integration of evolutionarily new brain structures into existing circuitry gives rise to diverse, new behavior. PMID:23818988

Temperature induced syllable breaking unveils nonlinearly interacting timescales in birdsong motor pathway.

PubMed

Goldin, Matías A; Alonso, Leandro M; Alliende, Jorge A; Goller, Franz; Mindlin, Gabriel B

2013-01-01

The nature of telencephalic control over premotor and motor circuits is debated. Hypotheses range from complete usurping of downstream circuitry to highly interactive mechanisms of control. We show theoretically and experimentally, that telencephalic song motor control in canaries is consistent with a highly interactive strategy. As predicted from a theoretical model of respiratory control, mild cooling of a forebrain nucleus (HVC) led to song stretching, but further cooling caused progressive restructuring of song, consistent with the hypothesis that respiratory gestures are subharmonic responses to a timescale present in the output of HVC. This interaction between a life-sustaining motor function (respiration) and telencephalic song motor control suggests a more general mechanism of how nonlinear integration of evolutionarily new brain structures into existing circuitry gives rise to diverse, new behavior.

Evolutionary Diversification of Prey and Predator Species Facilitated by Asymmetric Interactions

PubMed Central

Zu, Jian; Wang, Jinliang; Huang, Gang

2016-01-01

We investigate the influence of asymmetric interactions on coevolutionary dynamics of a predator-prey system by using the theory of adaptive dynamics. We assume that the defense ability of prey and the attack ability of predators all can adaptively evolve, either caused by phenotypic plasticity or by behavioral choice, but there are certain costs in terms of their growth rate or death rate. The coevolutionary model is constructed from a deterministic approximation of random mutation-selection process. To sum up, if prey’s trade-off curve is globally weakly concave, then five outcomes of coevolution are demonstrated, which depend on the intensity and shape of asymmetric predator-prey interactions and predator’s trade-off shape. Firstly, we find that if there is a weakly decelerating cost and a weakly accelerating benefit for predator species, then evolutionary branching in the predator species may occur, but after branching further coevolution may lead to extinction of the predator species with a larger trait value. However, if there is a weakly accelerating cost and a weakly accelerating benefit for predator species, then evolutionary branching in the predator species is also possible and after branching the dimorphic predator can evolutionarily stably coexist with a monomorphic prey species. Secondly, if the asymmetric interactions become a little strong, then prey and predators will evolve to an evolutionarily stable equilibrium, at which they can stably coexist on a long-term timescale of evolution. Thirdly, if there is a weakly accelerating cost and a relatively strongly accelerating benefit for prey species, then evolutionary branching in the prey species is possible and the finally coevolutionary outcome contains a dimorphic prey and a monomorphic predator species. Fourthly, if the asymmetric interactions become more stronger, then predator-prey coevolution may lead to cycles in both traits and equilibrium population densities. The Red Queen dynamic is a

Effectiveness of conservation easements in agricultural regions.

PubMed

Braza, Mark

2017-08-01

Conservation easements are a standard technique for preventing habitat loss, particularly in agricultural regions with extensive cropland cultivation, yet little is known about their effectiveness. I developed a spatial econometric approach to propensity-score matching and used the approach to estimate the amount of habitat loss prevented by a grassland conservation easement program of the U.S. federal government. I used a spatial autoregressive probit model to predict tract enrollment in the easement program as of 2001 based on tract agricultural suitability, habitat quality, and spatial interactions among neighboring tracts. Using the predicted values from the model, I matched enrolled tracts with similar unenrolled tracts to form a treatment group and a control group. To measure the program's impact on subsequent grassland loss, I estimated cropland cultivation rates for both groups in 2014 with a second spatial probit model. Between 2001 and 2014, approximately 14.9% of control tracts were cultivated and 0.3% of treated tracts were cultivated. Therefore, approximately 14.6% of the protected land would have been cultivated in the absence of the program. My results demonstrate that conservation easements can significantly reduce habitat loss in agricultural regions; however, the enrollment of tracts with low cropland suitability may constrain the amount of habitat loss they prevent. My results also show that spatial econometric models can improve the validity of control groups and thereby strengthen causal inferences about program effectiveness in situations when spatial interactions influence conservation decisions. © 2017 Society for Conservation Biology.

Social-psychological principles of community-based conservation and conservancy motivation: attaining goals within an autonomy-supportive environment.

PubMed

Decaro, Daniel; Stokes, Michael

2008-12-01

Community-based natural resource conservation programs in developing nations face many implementation challenges underpinned by social-psychological mechanisms. One challenge is garnering local support in an economically and socially sustainable fashion despite economic hardship and historical alienation from local resources. Unfortunately, conservationists' limited understanding of the social-psychological mechanisms underlying participatory conservation impedes the search for appropriate solutions. We address this issue by revealing key underlying social-psychological mechanisms of participatory conservation. Different administrative designs create social atmospheres that differentially affect endorsement of conservation goals. Certain forms of endorsement may be less effective motivators and less economically and socially sustainable than others. From a literature review we found that conservation initiatives endorsed primarily for nonautonomous instrumental reasons, such as to avoid economic fines or to secure economic rewards, are less motivating than those endorsed for autonomous reasons, such as for the opportunity for personal expression and growth. We suggest that successful participatory programs promote autonomous endorsement of conservation through an administrative framework of autonomy support-free and open democratic participation in management, substantive recognition and inclusion of local stakeholder identity, and respectful, noncoercive social interaction. This framework of the autonomy-supportive environment (self-determination theory) has important implications for future research into program design and incentive-based conservation and identifies a testable social-psychological theory of conservancy motivation.

Turning Minds On and Faucets Off: Water Conservation Education in Jordanian Schools.

ERIC Educational Resources Information Center

Middlestadt, Susan; Grieser, Mona; Hernandez, Orlando; Tubaishat, Khulood; Sanchack, Julie; Southwell, Brian; Schwartz, Reva

2001-01-01

An evaluation was conducted to measure the impact of a curriculum implemented through the Jordan Water Conservation Education Project. Examines the effect of recommending water conservation at the household level and the impact of using interactive teaching methods to promote conservation behaviors among students and their families. (Author/SAH)

The phospholipase PNPLA7 functions as a lysophosphatidylcholine hydrolase and interacts with lipid droplets through its catalytic domain.

PubMed

Heier, Christoph; Kien, Benedikt; Huang, Feifei; Eichmann, Thomas O; Xie, Hao; Zechner, Rudolf; Chang, Ping-An

2017-11-17

Mammalian patatin-like phospholipase domain-containing proteins (PNPLAs) are lipid-metabolizing enzymes with essential roles in energy metabolism, skin barrier development, and brain function. A detailed annotation of enzymatic activities and structure-function relationships remains an important prerequisite to understand PNPLA functions in (patho-)physiology, for example, in disorders such as neutral lipid storage disease, non-alcoholic fatty liver disease, and neurodegenerative syndromes. In this study, we characterized the structural features controlling the subcellular localization and enzymatic activity of PNPLA7, a poorly annotated phospholipase linked to insulin signaling and energy metabolism. We show that PNPLA7 is an endoplasmic reticulum (ER) transmembrane protein that specifically promotes hydrolysis of lysophosphatidylcholine in mammalian cells. We found that transmembrane and regulatory domains in the PNPLA7 N-terminal region cooperate to regulate ER targeting but are dispensable for substrate hydrolysis. Enzymatic activity is instead mediated by the C-terminal domain, which maintains full catalytic competence even in the absence of N-terminal regions. Upon elevated fatty acid flux, the catalytic domain targets cellular lipid droplets and promotes interactions of PNPLA7 with these organelles in response to increased cAMP levels. We conclude that PNPLA7 acts as an ER-anchored lysophosphatidylcholine hydrolase that is composed of specific functional domains mediating catalytic activity, subcellular positioning, and interactions with cellular organelles. Our study provides critical structural insights into an evolutionarily conserved class of phospholipid-metabolizing enzymes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Genetic differentiation and selection against migrants in evolutionarily replicated extreme environments.

PubMed

Plath, Martin; Pfenninger, Markus; Lerp, Hannes; Riesch, Rüdiger; Eschenbrenner, Christoph; Slattery, Patrick A; Bierbach, David; Herrmann, Nina; Schulte, Matthias; Arias-Rodriguez, Lenin; Rimber Indy, Jeane; Passow, Courtney; Tobler, Michael

2013-09-01

We investigated mechanisms of reproductive isolation in livebearing fishes (genus Poecilia) inhabiting sulfidic and nonsulfidic habitats in three replicate river drainages. Although sulfide spring fish convergently evolved divergent phenotypes, it was unclear if mechanisms of reproductive isolation also evolved convergently. Using microsatellites, we found strongly reduced gene flow between adjacent populations from different habitat types, suggesting that local adaptation to sulfidic habitats repeatedly caused the emergence of reproductive isolation. Reciprocal translocation experiments indicate strong selection against immigrants into sulfidic waters, but also variation among drainages in the strength of selection against immigrants into nonsulfidic waters. Mate choice experiments revealed the evolution of assortative mating preferences in females from nonsulfidic but not from sulfidic habitats. The inferred strength of sexual selection against immigrants (RI(s)) was negatively correlated with the strength of natural selection (RI(m)), a pattern that could be attributed to reinforcement, whereby natural selection strengthens behavioral isolation due to reduced hybrid fitness. Overall, reproductive isolation and genetic differentiation appear to be replicated and direct consequences of local adaptation to sulfide spring environments, but the relative contributions of different mechanisms of reproductive isolation vary across these evolutionarily independent replicates, highlighting both convergent and nonconvergent evolutionary trajectories of populations in each drainage. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Remote sensing for the sustainable management and conservation of forest environments biodiversity: the conservation managers perspective.

NASA Astrophysics Data System (ADS)

Aguilar-Amuchas, N.; Henebry, G. M.; Blanchard, J.; Sutter, R.

2008-12-01

The potential use of remote sensing for the design and implementation of sustainable management, conservation, and monitoring of forest biodiversity has been well documented in the scientific literature. However, when we look into how often remote sensing is actually being used in the decision making processes affecting biodiversity conservation and sustainable management, we find that, apart from specific study cases, its use is not as widespread as we know it should. There is an enormous gap between our scientific achievements and their use in the real world towards the preservation of a rapidly vanishing biodiversity. Conservation managers understand the potential remote sensing has. However, logistical constraints and high technical skills requirements render the use of remote sensing data difficult. Sound and easy approaches need to be developed and implemented. We present two study cases that illustrate 1st. How the interaction between tropical forest managers and remote sensing specialist allowed developing a simple method for the identification of priority areas for field surveys of tropical forests management ecological sustainability indicators and, 2nd. How remote sensing is being used by The Nature Conservancy as a first level approach towards the assessment of forest conservation strategies effectiveness in for areas located in 11 states, covering different forest types and a variety of conservation objectives.

Heart structure-specific transcriptomic atlas reveals conserved microRNA-mRNA interactions.

PubMed

Vacchi-Suzzi, Caterina; Hahne, Florian; Scheubel, Philippe; Marcellin, Magali; Dubost, Valerie; Westphal, Magdalena; Boeglen, Catherine; Büchmann-Møller, Stine; Cheung, Ming Sin; Cordier, André; De Benedetto, Christopher; Deurinck, Mark; Frei, Moritz; Moulin, Pierre; Oakeley, Edward; Grenet, Olivier; Grevot, Armelle; Stull, Robert; Theil, Diethilde; Moggs, Jonathan G; Marrer, Estelle; Couttet, Philippe

2013-01-01

MicroRNAs are short non-coding RNAs that regulate gene expression at the post-transcriptional level and play key roles in heart development and cardiovascular diseases. Here, we have characterized the expression and distribution of microRNAs across eight cardiac structures (left and right ventricles, apex, papillary muscle, septum, left and right atrium and valves) in rat, Beagle dog and cynomolgus monkey using microRNA sequencing. Conserved microRNA signatures enriched in specific heart structures across these species were identified for cardiac valve (miR-let-7c, miR-125b, miR-127, miR-199a-3p, miR-204, miR-320, miR-99b, miR-328 and miR-744) and myocardium (miR-1, miR-133b, miR-133a, miR-208b, miR-30e, miR-499-5p, miR-30e*). The relative abundance of myocardium-enriched (miR-1) and valve-enriched (miR-125b-5p and miR-204) microRNAs was confirmed using in situ hybridization. MicroRNA-mRNA interactions potentially relevant for cardiac functions were explored using anti-correlation expression analysis and microRNA target prediction algorithms. Interactions between miR-1/Timp3, miR-125b/Rbm24, miR-204/Tgfbr2 and miR-208b/Csnk2a2 were identified and experimentally investigated in human pulmonary smooth muscle cells and luciferase reporter assays. In conclusion, we have generated a high-resolution heart structure-specific mRNA/microRNA expression atlas for three mammalian species that provides a novel resource for investigating novel microRNA regulatory circuits involved in cardiac molecular physiopathology.

Evolutionary conservation of vertebrate notochord genes in the ascidian Ciona intestinalis.

PubMed

Kugler, Jamie E; Passamaneck, Yale J; Feldman, Taya G; Beh, Jeni; Regnier, Todd W; Di Gregorio, Anna

2008-11-01

To reconstruct a minimum complement of notochord genes evolutionarily conserved across chordates, we scanned the Ciona intestinalis genome using the sequences of 182 genes reported to be expressed in the notochord of different vertebrates and identified 139 candidate notochord genes. For 66 of these Ciona genes expression data were already available, hence we analyzed the expression of the remaining 73 genes and found notochord expression for 20. The predicted products of the newly identified notochord genes range from the transcription factors Ci-XBPa and Ci-miER1 to extracellular matrix proteins. We examined the expression of the newly identified notochord genes in embryos ectopically expressing Ciona Brachyury (Ci-Bra) and in embryos expressing a repressor form of this transcription factor in the notochord, and we found that while a subset of the genes examined are clearly responsive to Ci-Bra, other genes are not affected by alterations in its levels. We provide a first description of notochord genes that are not evidently influenced by the ectopic expression of Ci-Bra and we propose alternative regulatory mechanisms that might control their transcription. Copyright 2008 Wiley-Liss, Inc.

Adaptability of Protein Structures to Enable Functional Interactions and Evolutionary Implications

PubMed Central

Haliloglu, Turkan; Bahar, Ivet

2015-01-01

Several studies in recent years have drawn attention to the ability of proteins to adapt to intermolecular interactions by conformational changes along structure-encoded collective modes of motions. These so-called soft modes, primarily driven by entropic effects, facilitate, if not enable, functional interactions. They represent excursions on the conformational space along principal low-ascent directions/paths away from the original free energy minimum, and they are accessible to the protein even prior to protein-protein/ligand interactions. An emerging concept from these studies is the evolution of structures or modular domains to favor such modes of motion that will be recruited or integrated for enabling functional interactions. Structural dynamics, including the allosteric switches in conformation that are often stabilized upon formation of complexes and multimeric assemblies, emerge as key properties that are evolutionarily maintained to accomplish biological activities, consistent with the paradigm sequence → structure → dynamics → function where ‘dynamics’ bridges structure and function. PMID:26254902

Hydration in drug design. 3. Conserved water molecules at the ligand-binding sites of homologous proteins

NASA Astrophysics Data System (ADS)

Poornima, C. S.; Dean, P. M.

1995-12-01

Water molecules are known to play an important rôle in mediating protein-ligand interactions. If water molecules are conserved at the ligand-binding sites of homologous proteins, such a finding may suggest the structural importance of water molecules in ligand binding. Structurally conserved water molecules change the conventional definition of `binding sites' by changing the shape and complementarity of these sites. Such conserved water molecules can be important for site-directed ligand/drug design. Therefore, five different sets of homologous protein/protein-ligand complexes have been examined to identify the conserved water molecules at the ligand-binding sites. Our analysis reveals that there are as many as 16 conserved water molecules at the FAD binding site of glutathione reductase between the crystal structures obtained from human and E. coli. In the remaining four sets of high-resolution crystal structures, 2-4 water molecules have been found to be conserved at the ligand-binding sites. The majority of these conserved water molecules are either bound in deep grooves at the protein-ligand interface or completely buried in cavities between the protein and the ligand. All these water molecules, conserved between the protein/protein-ligand complexes from different species, have identical or similar apolar and polar interactions in a given set. The site residues interacting with the conserved water molecules at the ligand-binding sites have been found to be highly conserved among proteins from different species; they are more conserved compared to the other site residues interacting with the ligand. These water molecules, in general, make multiple polar contacts with protein-site residues.

The potential for species conservation in tropical secondary forests

Treesearch

Robin L. Chazdon; Carlos A. Peres; Daisy Dent; Douglas Sheil; Ariel E. Lugo; David Lamb; Nigel E. Stork; Scott E. Miller

2009-01-01

In the wake of widespread loss of old-growth forests throughout the tropics, secondary forests will likely play a growing role in the conservation of forest biodiversity. We considered a complex hierarchy of factors that interact in space and time to determine the conservation potential of tropical secondary forests. Beyond the characteristics of local forest patches,...

A spotlight on snow leopard conservation in China.

PubMed

Alexander, Justine S; Zhang, Chengcheng; Shi, Kun; Riordan, Philip

2016-07-01

China holds the greatest proportion of the snow leopard's (Panthera uncia) global range and is central to their conservation. The country is also undergoing unprecedented economic growth, which increases both the threats to the snow leopard and the opportunities for its conservation. In this paper we aim to review published literature (from 1950 to 2014) in English and Mandarin on snow leopard ecology and conservation in China in order to identify thematic and geographic research gaps and propose research priorities. We first retrieved all published items that considered snow leopards in China (n = 106). We extracted from these papers 274 reports of snow leopard presence in China. We then reviewed a subset of papers (n = 33) of this literature, which specifically focused on snow leopard ecology and conservation within China. We introduced a thematic framework that allows a structured and comprehensive assessment of findings. This framework recognizes 4 critical and interrelated topics underpinning snow leopard ecology and conservation: habitat (distribution and protected area coverage); prey (distribution and abundance, predator-prey relationships); human interactions (hunting and trade, livestock interactions and conflicts); and the underlying policy context. Significant gains in knowledge as well as research gaps and priorities are discussed with reference to our framework. The modest quantity and limited scope of published research on the snow leopard in China calls for a continued and intensified effort to inform and support national conservation policies. © 2016 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

A polymorphism in a conserved posttranscriptional regulatory motif alters bone morphogenetic protein 2 (BMP2) RNA:protein interactions.

PubMed

Fritz, David T; Jiang, Shan; Xu, Junwang; Rogers, Melissa B

2006-07-01

The bone morphogenetic protein (BMP)2 gene has been genetically linked to osteoporosis and osteoarthritis. We have shown that the 3'-untranslated regions (UTR) of BMP2 genes from mammals to fishes are extraordinarily conserved. This indicates that the BMP2 3'-UTR is under stringent selective pressure. We present evidence that the conserved region is a strong posttranscriptional regulator of BMP2 expression. Polymorphisms in cis-regulatory elements have been proven to influence susceptibility to a growing number of diseases. A common single nucleotide polymorphism (SNP) disrupts a putative posttranscriptional regulatory motif, an AU-rich element, within the BMP2 3'-UTR. The affinity of specific proteins for the rs15705 SNP sequence differs from their affinity for the normal human sequence. More importantly, the in vitro decay rate of RNAs with the SNP is higher than that of RNAs with the normal sequence. Such changes in mRNA:protein interactions may influence the posttranscriptional mechanisms that control BMP2 gene expression. The consequent alterations in BMP2 protein levels may influence the development or physiology of bone or other BMP2-influenced tissues.

Shape-shifting corals: Molecular markers show morphology is evolutionarily plastic in Porites

PubMed Central

Forsman, Zac H; Barshis, Daniel J; Hunter, Cynthia L; Toonen, Robert J

2009-01-01

Background Corals are notoriously difficult to identify at the species-level due to few diagnostic characters and variable skeletal morphology. This 'coral species problem' is an impediment to understanding the evolution and biodiversity of this important and threatened group of organisms. We examined the evolution of the nuclear ribosomal internal transcribed spacer (ITS) and mitochondrial markers (COI, putative control region) in Porites, one of the most taxonomically challenging and ecologically important genera of reef-building corals. Results Nuclear and mitochondrial markers were congruent, clearly resolving many traditionally recognized species; however, branching and mounding varieties were genetically indistinguishable within at least two clades, and specimens matching the description of 'Porites lutea' sorted into three genetically divergent groups. Corallite-level features were generally concordant with genetic groups, although hyper-variability in one group (Clade I) overlapped and obscured several others, and Synarea (previously thought to be a separate subgenus) was closely related to congeners despite its unique morphology. Scanning electron microscopy revealed subtle differences between genetic groups that may have been overlooked previously as taxonomic characters. Conclusion This study demonstrates that the coral skeleton can be remarkably evolutionarily plastic, which may explain some taxonomic difficulties, and obscure underlying patterns of endemism and diversity. PMID:19239678

Molecular and biochemical analysis of rainbow trout LCK suggests a conserved mechanism for T-cell signaling in gnathostomes

USGS Publications Warehouse

Laing, K.J.; Dutton, S.; Hansen, J.D.

2007-01-01

Two genes were identified in rainbow trout that display high sequence identity to vertebrate Lck. Both of the trout Lck transcripts are associated with lymphoid tissues and were found to be highly expressed in IgM-negative lymphocytes. In vitro analysis of trout lymphocytes indicates that trout Lck mRNA is up-regulated by T-cell mitogens, supporting an evolutionarily conserved function for Lck in the signaling pathways of T-lymphocytes. Here, we describe the generation and characterization of a specific monoclonal antibody raised against the N-terminal domains of recombinant trout Lck that can recognize Lck protein(s) from trout thymocyte lysates that are similar in size (???57 kDa) to mammalian Lck. This antibody also reacted with permeabilized lymphocytes during FACS analysis, indicating its potential usage for cellular analyses of trout lymphocytes, thus representing an important tool for investigations of salmonid T-cell function.

Distinct Contributions of Conserved Modules to Runt Transcription Factor Activity

PubMed Central

Walrad, Pegine B.; Hang, Saiyu; Joseph, Genevieve S.; Salas, Julia

2010-01-01

Runx proteins play vital roles in regulating transcription in numerous developmental pathways throughout the animal kingdom. Two Runx protein hallmarks are the DNA-binding Runt domain and a C-terminal VWRPY motif that mediates interaction with TLE/Gro corepressor proteins. A phylogenetic analysis of Runt, the founding Runx family member, identifies four distinct regions C-terminal to the Runt domain that are conserved in Drosophila and other insects. We used a series of previously described ectopic expression assays to investigate the functions of these different conserved regions in regulating gene expression during embryogenesis and in controlling axonal projections in the developing eye. The results indicate each conserved region is required for a different subset of activities and identify distinct regions that participate in the transcriptional activation and repression of the segmentation gene sloppy-paired-1 (slp1). Interestingly, the C-terminal VWRPY-containing region is not required for repression but instead plays a role in slp1 activation. Genetic experiments indicating that Groucho (Gro) does not participate in slp1 regulation further suggest that Runt's conserved C-terminus interacts with other factors to promote transcriptional activation. These results provide a foundation for further studies on the molecular interactions that contribute to the context-dependent properties of Runx proteins as developmental regulators. PMID:20462957

Improving interactions between animal rights groups and conservation biologists.

PubMed

Perry, Dan; Perry, Gad

2008-02-01

Invasive species are often considered to be a major threat to biodiversity, leading conservation biologists to often recommend their complete eradication. Animal rights groups typically categorically oppose killing animals, and their opposition has brought eradication attempts of gray squirrels in northern Italy (Europe) and mute swans in Vermont to a halt. As a result native red squirrels may disappear from Europe and ecosystem-wide impacts are expected to be caused by the swan. In contrast, cooperation between managers and animal rights groups has resulted in a successful control program for feral pigs in Fort Worth, Texas (U.S.A.). The philosophical differences between animal rights and conservation biologists' views make cooperation seem unlikely, yet documented cases of cooperation have been beneficial for both groups. We recommend that managers dealing with invasive species should consult with social scientists and ethicists to gain a better understanding of the implications of some of their policy decisions. In addition, we recommend that animal rights groups do more to support alternatives to lethal control, which are often excluded by economic limitations. Prevention of arrival of invasive species via application of the precautionary principle may be an especially productive avenue for such collaboration because it fits the goals and values of both groups.

Conservation Action Planning: Lessons learned from the St. Marys River watershed biodiversity conservation planning process

USGS Publications Warehouse

Patterson, Tamatha A.; Grundel, Ralph

2014-01-01

Conservation Action Planning (CAP) is an adaptive management planning process refined by The Nature Conservancy (TNC) and embraced worldwide as the Open Standards for the Practice of Conservation. The CAP process facilitates open, multi-institutional collaboration on a common conservation agenda through organized actions and quantified results. While specifically designed for conservation efforts, the framework is adaptable and flexible to multiple scales and can be used for any collaborative planning effort. The CAP framework addresses inception; design and development of goals, measures, and strategies; and plan implementation and evaluation. The specific components of the CAP include defining the project scope and conservation targets; assessing the ecological viability; ascertaining threats and surrounding situation; identifying opportunities and designing strategies for action; and implementing actions and monitoring results. In 2007, TNC and a multidisciplinary graduate student team from the University of Michigan's School of Natural Resources and Environment initiated a CAP for the St. Marys River, the connecting channel between Lake Superior and Lake Huron, and its local watershed. The students not only gained experience in conservation planning, but also learned lessons that notably benefited the CAP process and were valuable for any successful collaborative effort—a dedicated core team improved product quality, accelerated the timeline, and provided necessary support for ongoing efforts; an academic approach in preparation for engagement in the planning process brought applicable scientific research to the forefront, enhanced workshop facilitation, and improved stakeholder participation; and early and continuous interactions with regional stakeholders improved cooperation and built a supportive network for collaboration.

Arizona Conserve Water Educators Guide

ERIC Educational Resources Information Center

Project WET Foundation, 2007

2007-01-01

This award-winning, 350-page, full-color book provides a thorough study of Arizona water resources from a water conservation perspective. Its background section contains maps, graphs, diagrams and photos that facilitate the teaching of 15 interactive, multi-disciplinary lessons to K-12 students. In addition, 10 Arizona case studies are highlighted…

Huntingtin-interacting protein 1 (Hip1) and Hip1-related protein (Hip1R) bind the conserved sequence of clathrin light chains and thereby influence clathrin assembly in vitro and actin distribution in vivo.

PubMed

Chen, Chih-Ying; Brodsky, Frances M

2005-02-18

Clathrin heavy and light chains form triskelia, which assemble into polyhedral coats of membrane vesicles that mediate transport for endocytosis and organelle biogenesis. Light chain subunits regulate clathrin assembly in vitro by suppressing spontaneous self-assembly of the heavy chains. The residues that play this regulatory role are at the N terminus of a conserved 22-amino acid sequence that is shared by all vertebrate light chains. Here we show that these regulatory residues and others in the conserved sequence mediate light chain interaction with Hip1 and Hip1R. These related proteins were previously found to be enriched in clathrin-coated vesicles and to promote clathrin assembly in vitro. We demonstrate Hip1R binding preference for light chains associated with clathrin heavy chain and show that Hip1R stimulation of clathrin assembly in vitro is blocked by mutations in the conserved sequence of light chains that abolish interaction with Hip1 and Hip1R. In vivo overexpression of a fragment of clathrin light chain comprising the Hip1R-binding region affected cellular actin distribution. Together these results suggest that the roles of Hip1 and Hip1R in affecting clathrin assembly and actin distribution are mediated by their interaction with the conserved sequence of clathrin light chains.

The PRC2-binding long non-coding RNAs in human and mouse genomes are associated with predictive sequence features

NASA Astrophysics Data System (ADS)

Tu, Shiqi; Yuan, Guo-Cheng; Shao, Zhen

2017-01-01

Recently, long non-coding RNAs (lncRNAs) have emerged as an important class of molecules involved in many cellular processes. One of their primary functions is to shape epigenetic landscape through interactions with chromatin modifying proteins. However, mechanisms contributing to the specificity of such interactions remain poorly understood. Here we took the human and mouse lncRNAs that were experimentally determined to have physical interactions with Polycomb repressive complex 2 (PRC2), and systematically investigated the sequence features of these lncRNAs by developing a new computational pipeline for sequences composition analysis, in which each sequence is considered as a series of transitions between adjacent nucleotides. Through that, PRC2-binding lncRNAs were found to be associated with a set of distinctive and evolutionarily conserved sequence features, which can be utilized to distinguish them from the others with considerable accuracy. We further identified fragments of PRC2-binding lncRNAs that are enriched with these sequence features, and found they show strong PRC2-binding signals and are more highly conserved across species than the other parts, implying their functional importance.

High-Throughput Sequencing Reveals Diverse Sets of Conserved, Nonconserved, and Species-Specific miRNAs in Jute

PubMed Central

Islam, Md. Tariqul; Ferdous, Ahlan Sabah; Najnin, Rifat Ara; Sarker, Suprovath Kumar; Khan, Haseena

2015-01-01

MicroRNAs play a pivotal role in regulating a broad range of biological processes, acting by cleaving mRNAs or by translational repression. A group of plant microRNAs are evolutionarily conserved; however, others are expressed in a species-specific manner. Jute is an agroeconomically important fibre crop; nonetheless, no practical information is available for microRNAs in jute to date. In this study, Illumina sequencing revealed a total of 227 known microRNAs and 17 potential novel microRNA candidates in jute, of which 164 belong to 23 conserved families and the remaining 63 belong to 58 nonconserved families. Among a total of 81 identified microRNA families, 116 potential target genes were predicted for 39 families and 11 targets were predicted for 4 among the 17 identified novel microRNAs. For understanding better the functions of microRNAs, target genes were analyzed by Gene Ontology and their pathways illustrated by KEGG pathway analyses. The presence of microRNAs identified in jute was validated by stem-loop RT-PCR followed by end point PCR and qPCR for randomly selected 20 known and novel microRNAs. This study exhaustively identifies microRNAs and their target genes in jute which will ultimately pave the way for understanding their role in this crop and other crops. PMID:25861616

Weak conservation of structural features in the interfaces of homologous transient protein–protein complexes

PubMed Central

Sudha, Govindarajan; Singh, Prashant; Swapna, Lakshmipuram S; Srinivasan, Narayanaswamy

2015-01-01

Residue types at the interface of protein–protein complexes (PPCs) are known to be reasonably well conserved. However, we show, using a dataset of known 3-D structures of homologous transient PPCs, that the 3-D location of interfacial residues and their interaction patterns are only moderately and poorly conserved, respectively. Another surprising observation is that a residue at the interface that is conserved is not necessarily in the interface in the homolog. Such differences in homologous complexes are manifested by substitution of the residues that are spatially proximal to the conserved residue and structural differences at the interfaces as well as differences in spatial orientations of the interacting proteins. Conservation of interface location and the interaction pattern at the core of the interfaces is higher than at the periphery of the interface patch. Extents of variability of various structural features reported here for homologous transient PPCs are higher than the variation in homologous permanent homomers. Our findings suggest that straightforward extrapolation of interfacial nature and inter-residue interaction patterns from template to target could lead to serious errors in the modeled complex structure. Understanding the evolution of interfaces provides insights to improve comparative modeling of PPC structures. PMID:26311309

Lymphatic filarial species differentiation using evolutionarily modified tandem repeats: generation of new genetic markers.

PubMed

Sakthidevi, Moorthy; Murugan, Vadivel; Hoti, Sugeerappa Laxmanappa; Kaliraj, Perumal

2010-05-01

Polymerase chain reaction based methods are promising tools for the monitoring and evaluation of the Global Program for the Elimination of Lymphatic Filariasis. The currently available PCR methods do not differentiate the DNA of Wuchereria bancrofti or Brugia malayi by a single PCR and hence are cumbersome. Therefore, we designed a single step PCR strategy for differentiating Bancroftian infection from Brugian infection based on a newly identified gene from the W. bancrofti genome, abundant larval transcript-2 (alt-2), which is abundantly expressed. The difference in PCR product sizes generated from the presence or absence of evolutionarily altered tandem repeats in alt-2 intron-3 differentiated W. bancrofti from B. malayi. The analysis was performed on the genomic DNA of microfilariae from a number of patient blood samples or microfilariae positive slides from different Indian geographical regions. The assay gave consistent results, differentiating the two filarial parasite species accurately. This alt-2 intron-3 based PCR assay can be a potential tool for the diagnosis and differentiation of co-infections by lymphatic filarial parasites. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Pub1p C-Terminal RRM Domain Interacts with Tif4631p through a Conserved Region Neighbouring the Pab1p Binding Site

PubMed Central

Rico-Lastres, Palma; Pérez-Cañadillas, José Manuel

2011-01-01

Pub1p, a highly abundant poly(A)+ mRNA binding protein in Saccharomyces cerevisiae, influences the stability and translational control of many cellular transcripts, particularly under some types of environmental stresses. We have studied the structure, RNA and protein recognition modes of different Pub1p constructs by NMR spectroscopy. The structure of the C-terminal RRM domain (RRM3) shows a non-canonical N-terminal helix that packs against the canonical RRM fold in an original fashion. This structural trait is conserved in Pub1p metazoan homologues, the TIA-1 family, defining a new class of RRM-type domains that we propose to name TRRM (TIA-1 C-terminal domain-like RRM). Pub1p TRRM and the N-terminal RRM1-RRM2 tandem bind RNA with high selectivity for U-rich sequences, with TRRM showing additional preference for UA-rich ones. RNA-mediated chemical shift changes map to β-sheet and protein loops in the three RRMs. Additionally, NMR titration and biochemical in vitro cross-linking experiments determined that Pub1p TRRM interacts specifically with the N-terminal region (1–402) of yeast eIF4G1 (Tif4631p), very likely through the conserved Box1, a short sequence motif neighbouring the Pab1p binding site in Tif4631p. The interaction involves conserved residues of Pub1p TRRM, which define a protein interface that mirrors the Pab1p-Tif4631p binding mode. Neither protein nor RNA recognition involves the novel N-terminal helix, whose functional role remains unclear. By integrating these new results with the current knowledge about Pub1p, we proposed different mechanisms of Pub1p recruitment to the mRNPs and Pub1p-mediated mRNA stabilization in which the Pub1p/Tif4631p interaction would play an important role. PMID:21931728

Current conserving theory at the operator level

NASA Astrophysics Data System (ADS)

Yuan, Jiangtao; Wang, Yin; Wang, Jian

The basic assumption of quantum transport in mesoscopic systems is that the total charge inside the scattering region is zero. This means that the potential deep inside reservoirs is effectively screened and therefore the electric field at interface of scattering region is zero. Thus the current conservation condition can be satisfied automatically which is an important condition in mesoscopic transport. So far the current conserving ac theory is well developed by considering the displacement current which is due to Coulomb interaction if we just focus on the average current. However, the frequency dependent shot noise does not satisfy the conservation condition since we do not consider the current conservation at the operator level. In this work, we formulate a generalized current conserving theory at the operator level using non-equilibrium Green's function theory which could be applied to both average current and frequency dependent shot noise. A displacement operator is derived for the first time so that the frequency dependent correlation of displacement currents could be investigated. Moreover, the equilibrium shot noise is investigated and a generalized fluctuation-dissipation relationship is presented.

A Dominant Mutation in Nuclear Receptor Interacting Protein 1 Causes Urinary Tract Malformations via Dysregulation of Retinoic Acid Signaling.

PubMed

Vivante, Asaf; Mann, Nina; Yonath, Hagith; Weiss, Anna-Carina; Getwan, Maike; Kaminski, Michael M; Bohnenpoll, Tobias; Teyssier, Catherine; Chen, Jing; Shril, Shirlee; van der Ven, Amelie T; Ityel, Hadas; Schmidt, Johanna Magdalena; Widmeier, Eugen; Bauer, Stuart B; Sanna-Cherchi, Simone; Gharavi, Ali G; Lu, Weining; Magen, Daniella; Shukrun, Rachel; Lifton, Richard P; Tasic, Velibor; Stanescu, Horia C; Cavaillès, Vincent; Kleta, Robert; Anikster, Yair; Dekel, Benjamin; Kispert, Andreas; Lienkamp, Soeren S; Hildebrandt, Friedhelm

2017-08-01

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of CKD in the first three decades of life. However, for most patients with CAKUT, the causative mutation remains unknown. We identified a kindred with an autosomal dominant form of CAKUT. By whole-exome sequencing, we identified a heterozygous truncating mutation (c.279delG, p.Trp93fs*) of the nuclear receptor interacting protein 1 gene ( NRIP1 ) in all seven affected members. NRIP1 encodes a nuclear receptor transcriptional cofactor that directly interacts with the retinoic acid receptors (RARs) to modulate retinoic acid transcriptional activity. Unlike wild-type NRIP1, the altered NRIP1 protein did not translocate to the nucleus, did not interact with RAR α , and failed to inhibit retinoic acid-dependent transcriptional activity upon expression in HEK293 cells. Notably, we also showed that treatment with retinoic acid enhanced NRIP1 binding to RAR α RNA in situ hybridization confirmed Nrip1 expression in the developing urogenital system of the mouse. In explant cultures of embryonic kidney rudiments, retinoic acid stimulated Nrip1 expression, whereas a pan-RAR antagonist strongly reduced it. Furthermore, mice heterozygous for a null allele of Nrip1 showed a CAKUT-spectrum phenotype. Finally, expression and knockdown experiments in Xenopus laevis confirmed an evolutionarily conserved role for NRIP1 in renal development. These data indicate that dominant NRIP1 mutations can cause CAKUT by interference with retinoic acid transcriptional signaling, shedding light on the well documented association between abnormal vitamin A levels and renal malformations in humans, and suggest a possible gene-environment pathomechanism in this disease. Copyright © 2017 by the American Society of Nephrology.

Deep conservation of cis-regulatory elements in metazoans

PubMed Central

Maeso, Ignacio; Irimia, Manuel; Tena, Juan J.; Casares, Fernando; Gómez-Skarmeta, José Luis

2013-01-01

Despite the vast morphological variation observed across phyla, animals share multiple basic developmental processes orchestrated by a common ancestral gene toolkit. These genes interact with each other building complex gene regulatory networks (GRNs), which are encoded in the genome by cis-regulatory elements (CREs) that serve as computational units of the network. Although GRN subcircuits involved in ancient developmental processes are expected to be at least partially conserved, identification of CREs that are conserved across phyla has remained elusive. Here, we review recent studies that revealed such deeply conserved CREs do exist, discuss the difficulties associated with their identification and describe new approaches that will facilitate this search. PMID:24218633

African wildlife conservation and the evolution of hunting institutions

NASA Astrophysics Data System (ADS)

't Sas-Rolfes, Michael

2017-11-01

Hunting regulation presents a significant challenge for contemporary global conservation governance. Motivated by various incentives, hunters may act legally or illegally, for or against the interests of conservation. Hunter incentives are shaped by the interactions between unevenly evolving formal and informal institutions, embedded in socio-ecological systems. To work effectively for conservation, regulatory interventions must take these evolving institutional interactions into account. Drawing on analytical tools from evolutionary institutional economics, this article examines the trajectory of African hunting regulation and its consequences. Concepts of institutional dynamics, fit, scale, and interplay are applied to case studies of rhinoceros and lion hunting to highlight issues of significance to conservation outcomes. These include important links between different forms of hunting and dynamic interplay with institutions of trade. The case studies reveal that inappropriate formal regulatory approaches may be undermined by adaptive informal market responses. Poorly regulated hunting may lead to calls for stricter regulations or bans, but such legal restrictions may in turn perversely lead to more intensified and organised illegal hunting activity, further undermining conservation objectives. I conclude by offering insights and recommendations to guide more effective future regulatory interventions and priorities for further research. Specifically, I advocate approaches that move beyond simplistic regulatory interventions toward more complex, but supportive, institutional arrangements that align formal and informal institutions through inclusive stakeholder engagement.

Conserved herpesvirus protein kinases

PubMed Central

Gershburg, Edward; Pagano, Joseph S.

2008-01-01

Conserved herpesviral protein kinases (CHPKs) are a group of enzymes conserved throughout all subfamilies of Herpesviridae. Members of this group are serine/threonine protein kinases that are likely to play a conserved role in viral infection by interacting with common host cellular and viral factors; however along with a conserved role, individual kinases may have unique functions in the context of viral infection in such a way that they are only partially replaceable even by close homologues. Recent studies demonstrated that CHPKs are crucial for viral infection and suggested their involvement in regulation of numerous processes at various infection steps (primary infection, nuclear egress, tegumentation), although the mechanisms of this regulation remain unknown. Notwithstanding, recent advances in discovery of new CHPK targets, and studies of CHPK knockout phenotypes have raised their attractiveness as targets for antiviral therapy. A number of compounds have been shown to inhibit the activity of human cytomegalovirus (HCMV)-encoded UL97 protein kinase and exhibit a pronounced antiviral effect, although the same compounds are inactive against Epstein-Barr Virus (EBV)-encoded protein kinase BGLF4, illustrating the fact that low homology between the members of this group complicates development of compounds targeting the whole group, and suggesting that individualized, structure-based inhibitor design will be more effective. Determination of CHPK structures will greatly facilitate this task. PMID:17881303

Understanding the lessons and limitations of conservation and development.

PubMed

Oldekop, Johan A; Bebbington, Anthony J; Brockington, Dan; Preziosi, Richard F

2010-04-01

The lack of concrete instances in which conservation and development have been successfully merged has strengthened arguments for strict exclusionist conservation policies. Research has focused more on social cooperation and conflict of different management regimes and less on how these factors actually affect the natural environments they seek to conserve. Consequently, it is still unknown which strategies yield better conservation outcomes? We conducted a meta-analysis of 116 published case studies on common resource management regimes from Africa, south and central America, and southern and Southeast Asia. Using ranked sociodemographic, political, and ecological data, we analyzed the effect of land tenure, population size, social heterogeneity, as well as internally devised resource-management rules and regulations (institutions) on conservation outcome. Although land tenure, population size, and social heterogeneity did not significantly affect conservation outcome, institutions were positively associated with better conservation outcomes. There was also a significant interaction effect between population size and institutions, which implies complex relationships between population size and conservation outcome. Our results suggest that communities managing a common resource can play a significant role in conservation and that institutions lead to management regimes with lower environmental impacts.

Conservation of a vitellogenin gene cluster in oviparous vertebrates and identification of its traces in the platypus genome.

PubMed

Babin, Patrick J

2008-04-30

Vitellogenin (Vtg) derivatives are the main egg-yolk proteins in most oviparous animal species, and are, therefore, key players in reproduction and embryo development. Conserved synteny and phylogeny were used to identify a Vtg gene cluster (VGC) that had been evolutionarily conserved in most oviparous vertebrates, encompassing the three linked Vtgs on chicken (Gallus gallus) chromosome 8. Tandem arranged homologs to chicken VtgII and VtgIII were retrieved in similar locations in Xenopus (Xenopus tropicalis) and homologous transcribed inverted genes were found in medaka (Oryzias latipes), stickleback (Gasterosteus aculeatus), pufferfish (Takifugu rubripes), and Tetrahodon (Tetraodon nigroviridis), while zebrafish (Danio rerio) Vtg3 may represent a residual trace of VGC in this genome. Vtgs were not conserved in the paralogous chromosomal segment attributed to a whole-genome duplication event in the ancestor of teleosts, while tandem duplicated forms have survived the recent African clawed frog (Xenopus laevis) tetraploidization. Orthologs to chicken VtgI were found in similar locations in teleost fish, as well as in the platypus (Ornithorhynchus anatinus). Additional Vtg fragments found suggested that VGC had been conserved in this egg-laying mammal. A low ratio of nonsynonymous-to-synonymous substitution values and the paucity of pseudogene features suggest functional platypus Vtg products. Genomic identification of Vtgs, Apob, and Mtp in this genome, together with maximum likelihood and Bayesian inference phylogenetic analyses, support the existence of these three large lipid transfer protein superfamily members at the base of the mammalian lineage. In conclusion, the establishment of a VGC in the vertebrate lineage predates the divergence of ray-finned fish and tetrapods and the shift in reproductive and developmental strategy observed between prototherians and therians may be associated with its loss, as shown by its absence from the genomic resources currently

Novel Mechanisms of Herbal Therapies for Inhibiting HMGB1 Secretion or Action

PubMed Central

Wu, Andrew H.; He, Li; Long, Wei; Zhou, Qiuping; Zhu, Shu; Wang, Ping; Fan, Saijun; Wang, Haichao

2015-01-01

High mobility group box 1 (HMGB1) is an evolutionarily conserved protein and is constitutively expressed in virtually all types of cells. In response to microbial infections, HMGB1 is secreted from activated immune cells to orchestrate rigorous inflammatory responses. Here we review the distinct mechanisms by which several herbal components inhibit HMGB1 action or secretion, such as by modulating inflammasome activation, autophagic degradation, or endocytic uptake. In light of the reciprocal interactions between these cellular processes, it is possible to develop more effective combinational herbal therapies for the clinical management of inflammatory diseases. PMID:25821489

Conservative management of tendinopathies around hip

PubMed Central

Frizziero, Antonio; Vittadini, Filippo; Pignataro, Andrea; Gasparre, Giuseppe; Biz, Carlo; Ruggieri, Pietro; Masiero, Stefano

2016-01-01

Summary Background The anatomy of hip is widely complex and several anatomical structures interact and contribute to its functioning. For position and role, hip and the surrounding tendons, which have their insertion around, are overstressed and often overloaded, especially in athletes. This could lead to the developing of several tendinopathies, among which the differential diagnosis is often complicated. Many conservative treatments are used in clinical practice, while actually, no defined conservative protocol is recommended. Methods This is a review article. The aim of this manuscript is to evaluate the current evidences about the effectiveness of conservative management in hip tendinopathies. Conclusion Conservative treatment is effective in the management of hip tendinopathies and may be considered the first-line approach for patients affected. However, there is lack of evidences about which is the most effective treatment. Exercise therapy seems to provide long-term pain relief, but the literature is still lacking about the correct type, dose, posology, intensity of exercise prescribed. Further studies about different local approaches, as PRP or hyaluronic acid injections, may be encouraged. Level of evidence I. PMID:28066732

Creating Learning Experiences that Promote Informal Science Education: Designing Conservation-Focused Interactive Zoo Exhibits through Action Research

NASA Astrophysics Data System (ADS)

Kalenda, Peter

Research on exhibit design over the past twenty years has started to identify many different methods to increase the learning that occurs in informal education environments. This study utilized relevant research on exhibit design to create and study the effectiveness of a mobile interactive exhibit at the Seneca Park Zoo that promotes socialization, engagement in science, and conservation-related practices among guests. This study will serve as one component of a major redesign project at the Seneca Park Zoo for their Rocky Coasts exhibit. This action research study targeted the following question, "How can interactive exhibits be designed to promote socialization, engagement in science, and real-world conservation-related practices (RCPs) among zoo guests?" Specific research questions included: 1. In what ways did guests engage with the exhibit? 2. In what ways were guests impacted by the exhibit? a) What evidence exists, if any, of guests learning science content from the exhibit? b) What evidence exists, if any, of guests being emotionally affected by the exhibit? c) What evidence exists, if any, of guests changing their RCPs after visiting the exhibit? Data were collected through zoo guest surveys completed by zoo guests comparing multiple exhibits, interviews with guests before and after they used the prototype exhibit, observations and audio recordings of guests using the prototype exhibit, and follow-up phone interviews with guests who volunteered to participate. Data were analyzed collaboratively with members of the zoo's exhibit Redesign Team using grounded theory qualitative data analysis techniques to find patterns and trends among data. Initial findings from data analysis were used to develop shifts in the exhibit in order to increase visitor engagement and learning. This process continued for two full action research spirals, which resulted in three iterations of the prototype exhibit. The overall findings of this study highlight the ways in which

From conservative to reactive transport under diffusion-controlled conditions

NASA Astrophysics Data System (ADS)

Babey, Tristan; de Dreuzy, Jean-Raynald; Ginn, Timothy R.

2016-05-01

We assess the possibility to use conservative transport information, such as that contained in transit time distributions, breakthrough curves and tracer tests, to predict nonlinear fluid-rock interactions in fracture/matrix or mobile/immobile conditions. Reference simulated data are given by conservative and reactive transport simulations in several diffusive porosity structures differing by their topological organization. Reactions includes nonlinear kinetically controlled dissolution and desorption. Effective Multi-Rate Mass Transfer models (MRMT) are calibrated solely on conservative transport information without pore topology information and provide concentration distributions on which effective reaction rates are estimated. Reference simulated reaction rates and effective reaction rates evaluated by MRMT are compared, as well as characteristic desorption and dissolution times. Although not exactly equal, these indicators remain very close whatever the porous structure, differing at most by 0.6% and 10% for desorption and dissolution. At early times, this close agreement arises from the fine characterization of the diffusive porosity close to the mobile zone that controls fast mobile-diffusive exchanges. At intermediate to late times, concentration gradients are strongly reduced by diffusion, and reactivity can be captured by a very limited number of rates. We conclude that effective models calibrated solely on conservative transport information like MRMT can accurately estimate monocomponent kinetically controlled nonlinear fluid-rock interactions. Their relevance might extend to more advanced biogeochemical reactions because of the good characterization of conservative concentration distributions, even by parsimonious models (e.g., MRMT with 3-5 rates). We propose a methodology to estimate reactive transport from conservative transport in mobile-immobile conditions.

Activity budget and social interactions in semi-captive gray woolly monkeys (Lagothrix lagotricha cana) living in an ex situ conservation area in Central Amazonia.

PubMed

Cartagena-Matos, Bárbara; Gasnier, Thierry; Cravo-Mota, Mariana; Martins Bezerra, Bruna

2017-01-01

Areas holding primates in semi-captivity conditions represent an excellent opportunity for collecting data on rare, little known, and endangered taxa, contributing with insightful information to help in their conservation. Here, we present information on the activity budget and social interactions of the elusive gray woolly monkeys, Lagothrix lagotricha cana, in an ex situ conservation area in central Amazonia. We studied the behavior of 18 semi-captive individuals through instantaneous scan and focal animal samplings during 4 months in the wet season. The most frequent activity registered was resting (45%). The remaining time was dedicated to foraging (29%), travelling (23%), social interactions (3%), and self-grooming (1%). Resting and travelling time may be correlated to fruit availability in the area through different seasons. Huddling was the most frequent social interaction, being more common from young individuals toward adult females, which may be associated with breastfeeding. Playing was more common among young males. This activity prepares them to defend themselves from possible attacks and allows them to develop their role in the social group, as future adult males. Aggression was most frequent among adults, primarily from males toward females, likely to demonstrate their dominance over females. Social grooming occurred predominantly from mother to offspring. This interaction can reduce the risk of young predation, directly increasing the female reproductive success. Our data not only add to our understanding of the sociality and behaviors of the genus Lagothrix, but may also serve as a tool to identify environments that support an adequate activity budget for these monkeys. Zoo Biol. 36:21-29, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Tree phylogenetic diversity promotes host-parasitoid interactions.

PubMed

Staab, Michael; Bruelheide, Helge; Durka, Walter; Michalski, Stefan; Purschke, Oliver; Zhu, Chao-Dong; Klein, Alexandra-Maria

2016-07-13

Evidence from grassland experiments suggests that a plant community's phylogenetic diversity (PD) is a strong predictor of ecosystem processes, even stronger than species richness per se This has, however, never been extended to species-rich forests and host-parasitoid interactions. We used cavity-nesting Hymenoptera and their parasitoids collected in a subtropical forest as a model system to test whether hosts, parasitoids, and their interactions are influenced by tree PD and a comprehensive set of environmental variables, including tree species richness. Parasitism rate and parasitoid abundance were positively correlated with tree PD. All variables describing parasitoids decreased with elevation, and were, except parasitism rate, dependent on host abundance. Quantitative descriptors of host-parasitoid networks were independent of the environment. Our study indicates that host-parasitoid interactions in species-rich forests are related to the PD of the tree community, which influences parasitism rates through parasitoid abundance. We show that effects of tree community PD are much stronger than effects of tree species richness, can cascade to high trophic levels, and promote trophic interactions. As during habitat modification phylogenetic information is usually lost non-randomly, even species-rich habitats may not be able to continuously provide the ecosystem process parasitism if the evolutionarily most distinct plant lineages vanish. © 2016 The Author(s).

Genetic Dissection of Photoreceptor Subtype Specification by the Drosophila melanogaster Zinc Finger Proteins Elbow and No ocelli

PubMed Central

Wernet, Mathias F.; Meier, Kerstin M.; Baumann-Klausener, Franziska; Dorfman, Ruslan; Weihe, Ulrich; Labhart, Thomas; Desplan, Claude

2014-01-01

The elbow/no ocelli (elb/noc) complex of Drosophila melanogaster encodes two paralogs of the evolutionarily conserved NET family of zinc finger proteins. These transcriptional repressors share a conserved domain structure, including a single atypical C2H2 zinc finger. In flies, Elb and Noc are important for the development of legs, eyes and tracheae. Vertebrate NET proteins play an important role in the developing nervous system, and mutations in the homolog ZNF703 human promote luminal breast cancer. However, their interaction with transcriptional regulators is incompletely understood. Here we show that loss of both Elb and Noc causes mis-specification of polarization-sensitive photoreceptors in the ‘dorsal rim area’ (DRA) of the fly retina. This phenotype is identical to the loss of the homeodomain transcription factor Homothorax (Hth)/dMeis. Development of DRA ommatidia and expression of Hth are induced by the Wingless/Wnt pathway. Our data suggest that Elb/Noc genetically interact with Hth, and we identify two conserved domains crucial for this function. Furthermore, we show that Elb/Noc specifically interact with the transcription factor Orthodenticle (Otd)/Otx, a crucial regulator of rhodopsin gene transcription. Interestingly, different Elb/Noc domains are required to antagonize Otd functions in transcriptional activation, versus transcriptional repression. We propose that similar interactions between vertebrate NET proteins and Meis and Otx factors might play a role in development and disease. PMID:24625735

The candidate tumor suppressor SASH1 interacts with the actin cytoskeleton and stimulates cell-matrix adhesion.

PubMed

Martini, Melanie; Gnann, Alexandra; Scheikl, Daniela; Holzmann, Bernhard; Janssen, Klaus-Peter

2011-11-01

SASH1, a member of the SLY-family of signal adapter proteins, is a candidate tumor suppressor in breast and colon cancer. Reduced expression of SASH1 is correlated with aggressive tumor growth, metastasis formation, and inferior prognosis. However, the biological role of SASH1 remains largely unknown. To unravel the function of SASH1, we have analyzed the intracellular localization of endogenous SASH1, and have generated structural SASH1 mutants. SASH1 localized to the nucleus as well as to the cytoplasm in epithelial cells. In addition, SASH1 was enriched in lamellipodia and membrane ruffles, where it co-distributed with the actin cytoskeleton. Moreover, we demonstrate a novel interaction of SASH1 with the oncoprotein cortactin, a known regulator of actin polymerization in lamellipodia. Enhanced SASH1 expression significantly increased the content of filamentous actin, leading to the formation of cell protrusions and elongated cell shape. This activity was mapped to the central, evolutionarily conserved domain of SASH1. Furthermore, expression of SASH1 inhibited cell migration and lead to increased cell adhesion to fibronectin and laminin, whereas knock-down of endogenous SASH1 resulted in significantly reduced cell-matrix adhesion. Taken together, our findings unravel for the first time a mechanistic role for SASH1 in tumor formation by regulating the adhesive and migratory behaviour of cancer cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

Botanic gardens science for conservation and global change.

PubMed

Donaldson, John S

2009-11-01

The contributions of botanic gardens to conservation biology and global-change research need to be understood within the context of the traditional strengths of such gardens in herbarium collections, living collections and interactions with the public. Here, I propose that research in conservation planning, modelling species responses to climate change, conservation of threatened species and experimental tests of global change build on the core strengths of botanic gardens. However, there are limits to what can be achieved through traditional gardens-based programs, and some botanic gardens have adapted their research to include studies of threatening processes and to monitor and verify global-change impacts. There is an opportunity for botanic gardens to use their living collections more effectively in global-change research and for them to have a role in linking biodiversity conservation with benefits derived from ecosystem services.

Insights into eukaryotic DNA priming from the structure and functional interactions of the 4Fe-4S cluster domain of human DNA primase

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

Vaithiyalingam, Sivaraja; Warren, Eric M.; Eichman, Brandt F.

2010-10-19

DNA replication requires priming of DNA templates by enzymes known as primases. Although DNA primase structures are available from archaea and bacteria, the mechanism of DNA priming in higher eukaryotes remains poorly understood in large part due to the absence of the structure of the unique, highly conserved C-terminal regulatory domain of the large subunit (p58C). Here, we present the structure of this domain determined to 1.7-{angstrom} resolution by X-ray crystallography. The p58C structure reveals a novel arrangement of an evolutionarily conserved 4Fe-4S cluster buried deeply within the protein core and is not similar to any known protein structure. Analysismore » of the binding of DNA to p58C by fluorescence anisotropy measurements revealed a strong preference for ss/dsDNA junction substrates. This approach was combined with site-directed mutagenesis to confirm that the binding of DNA occurs to a distinctively basic surface on p58C. A specific interaction of p58C with the C-terminal domain of the intermediate subunit of replication protein A (RPA32C) was identified and characterized by isothermal titration calorimetry and NMR. Restraints from NMR experiments were used to drive computational docking of the two domains and generate a model of the p58C-RPA32C complex. Together, our results explain functional defects in human DNA primase mutants and provide insights into primosome loading on RPA-coated ssDNA and regulation of primase activity.« less

Interaction between forest biodiversity and people's use of forest resources in Roviana, Solomon Islands: implications for biocultural conservation under socioeconomic changes.

PubMed

Furusawa, Takuro; Sirikolo, Myknee Qusa; Sasaoka, Masatoshi; Ohtsuka, Ryutaro

2014-01-27

In Solomon Islands, forests have provided people with ecological services while being affected by human use and protection. This study used a quantitative ethnobotanical analysis to explore the society-forest interaction and its transformation in Roviana, Solomon Islands. We compared local plant and land uses between a rural village and urbanized village. Special attention was paid to how local people depend on biodiversity and how traditional human modifications of forest contribute to biodiversity conservation. After defining locally recognized land-use classes, vegetation surveys were conducted in seven forest classes. For detailed observations of daily plant uses, 15 and 17 households were randomly selected in the rural and urban villages, respectively. We quantitatively documented the plant species that were used as food, medicine, building materials, and tools. The vegetation survey revealed that each local forest class represented a different vegetative community with relatively low similarity between communities. Although commercial logging operations and agriculture were both prohibited in the customary nature reserve, local people were allowed to cut down trees for their personal use and to take several types of non-timber forest products. Useful trees were found at high frequencies in the barrier island's primary forest (68.4%) and the main island's reserve (68.3%). Various useful tree species were found only in the reserve forest and seldom available in the urban village. In the rural village, customary governance and control over the use of forest resources by the local people still functioned. Human modifications of the forest created unique vegetation communities, thus increasing biodiversity overall. Each type of forest had different species that varied in their levels of importance to the local subsistence lifestyle, and the villagers' behaviors, such as respect for forest reserves and the semidomestication of some species, contributed to

Inducible SUMO modification of TANK alleviates its repression of TLR7 signalling.

PubMed

Renner, Florian; Saul, Vera V; Pagenstecher, Axel; Wittwer, Tobias; Schmitz, Michael Lienhard

2011-02-01

Adaptor proteins allow temporal and spatial coordination of signalling. In this study, we show SUMOylation of the adaptor protein TANK and its interacting kinase TANK-binding kinase 1 (TBK1). Modification of TANK by the small ubiquitin-related modifier (SUMO) at the evolutionarily conserved Lys 282 is triggered by the kinase activities of IκB kinase ɛ (IKKɛ) and TBK1. Stimulation of TLR7 leads to inducible SUMOylation of TANK, which in turn weakens the interaction with IKKɛ and thus relieves the negative function of TANK on signal propagation. Reconstitution experiments show that an absence of TANK SUMOylation impairs inducible expression of distinct TLR7-dependent target genes, providing a molecular mechanism that allows the control of TANK function.

The effect of travel loss on evolutionarily stable distributions of populations in space

USGS Publications Warehouse

DeAngelis, D.L.; Wolkowicz, G.S.K.; Lou, Y.; Jiang, Y.; Novak, M.; Svanback, R.; Araujo, M.S.; Jo, Y.S.; Cleary, E.A.

2011-01-01

A key assumption of the ideal free distribution (IFD) is that there are no costs in moving between habitat patches. However, because many populations exhibit more or less continuous population movement between patches and traveling cost is a frequent factor, it is important to determine the effects of costs on expected population movement patterns and spatial distributions. We consider a food chain (tritrophic or bitrophic) in which one species moves between patches, with energy cost or mortality risk in movement. In the two-patch case, assuming forced movement in one direction, an evolutionarily stable strategy requires bidirectional movement, even if costs during movement are high. In the N-patch case, assuming that at least one patch is linked bidirectionally to all other patches, optimal movement rates can lead to source-sink dynamics where patches with negative growth rates are maintained by other patches with positive growth rates. As well, dispersal between patches is not balanced (even in the two-patch case), leading to a deviation from the IFD. Our results indicate that cost-associated forced movement can have important consequences for spatial metapopulation dynamics. Relevance to marine reserve design and the study of stream communities subject to drift is discussed. ?? 2011 by The University of Chicago.

Evolutionarily diverse determinants of meiotic DNA break and recombination landscapes across the genome

PubMed Central

Fowler, Kyle R.; Sasaki, Mariko; Milman, Neta

2014-01-01

Fission yeast Rec12 (Spo11 homolog) initiates meiotic recombination by forming developmentally programmed DNA double-strand breaks (DSBs). DSB distributions influence patterns of heredity and genome evolution, but the basis of the highly nonrandom choice of Rec12 cleavage sites is poorly understood, largely because available maps are of relatively low resolution and sensitivity. Here, we determined DSBs genome-wide at near-nucleotide resolution by sequencing the oligonucleotides attached to Rec12 following DNA cleavage. The single oligonucleotide size class allowed us to deeply sample all break events. We find strong evidence across the genome for differential DSB repair accounting for crossover invariance (constant cM/kb in spite of DSB hotspots). Surprisingly, about half of all crossovers occur in regions where DSBs occur at low frequency and are widely dispersed in location from cell to cell. These previously undetected, low-level DSBs thus play an outsized and crucial role in meiosis. We further find that the influence of underlying nucleotide sequence and chromosomal architecture differs in multiple ways from that in budding yeast. DSBs are not strongly restricted to nucleosome-depleted regions, as they are in budding yeast, but are nevertheless spatially influenced by chromatin structure. Our analyses demonstrate that evolutionarily fluid factors contribute to crossover initiation and regulation. PMID:25024163

The effect of travel loss on evolutionarily stable distributions of populations in space.

PubMed

Deangelis, Donald L; Wolkowicz, Gail S K; Lou, Yuan; Jiang, Yuexin; Novak, Mark; Svanbäck, Richard; Araújo, Márcio S; Jo, Youngseung; Cleary, Erin A

2011-07-01

A key assumption of the ideal free distribution (IFD) is that there are no costs in moving between habitat patches. However, because many populations exhibit more or less continuous population movement between patches and traveling cost is a frequent factor, it is important to determine the effects of costs on expected population movement patterns and spatial distributions. We consider a food chain (tritrophic or bitrophic) in which one species moves between patches, with energy cost or mortality risk in movement. In the two-patch case, assuming forced movement in one direction, an evolutionarily stable strategy requires bidirectional movement, even if costs during movement are high. In the N-patch case, assuming that at least one patch is linked bidirectionally to all other patches, optimal movement rates can lead to source-sink dynamics where patches with negative growth rates are maintained by other patches with positive growth rates. As well, dispersal between patches is not balanced (even in the two-patch case), leading to a deviation from the IFD. Our results indicate that cost-associated forced movement can have important consequences for spatial metapopulation dynamics. Relevance to marine reserve design and the study of stream communities subject to drift is discussed.

Assisted colonization is not a viable conservation strategy.

PubMed

Ricciardi, Anthony; Simberloff, Daniel

2009-05-01

A potential conservation strategy increasingly discussed by conservation biologists is the translocation of species to favorable habitat beyond their native range to protect them from human-induced threats, such as climate change. Even if preceded by careful risk assessment, such action is likely to produce myriad unintended and unpredictable consequences. Accurate risk assessment is impeded by contingency: the impacts of introduced species vary over time and space under the influence of local environmental variables, interspecific interactions and evolutionary change. Some impacts, such as native species extinctions, are large and irrevocable. Here we argue that conservation biologists have not yet developed a sufficient understanding of the impacts of introduced species to make informed decisions regarding species translocations.

The Modular Organization of Protein Interactions in Escherichia coli

PubMed Central

Peregrín-Alvarez, José M.; Xiong, Xuejian; Su, Chong; Parkinson, John

2009-01-01

Escherichia coli serves as an excellent model for the study of fundamental cellular processes such as metabolism, signalling and gene expression. Understanding the function and organization of proteins within these processes is an important step towards a ‘systems’ view of E. coli. Integrating experimental and computational interaction data, we present a reliable network of 3,989 functional interactions between 1,941 E. coli proteins (∼45% of its proteome). These were combined with a recently generated set of 3,888 high-quality physical interactions between 918 proteins and clustered to reveal 316 discrete modules. In addition to known protein complexes (e.g., RNA and DNA polymerases), we identified modules that represent biochemical pathways (e.g., nitrate regulation and cell wall biosynthesis) as well as batteries of functionally and evolutionarily related processes. To aid the interpretation of modular relationships, several case examples are presented, including both well characterized and novel biochemical systems. Together these data provide a global view of the modular organization of the E. coli proteome and yield unique insights into structural and evolutionary relationships in bacterial networks. PMID:19798435

Structural Basis for the Interaction of Mutasome Assembly Factor REV1 with Ubiquitin.

PubMed

Cui, Gaofeng; Botuyan, Maria Victoria; Mer, Georges

2018-05-18

REV1 is an evolutionarily conserved translesion synthesis (TLS) DNA polymerase and an assembly factor key for the recruitment of other TLS polymerases to DNA damage sites. REV1-mediated recognition of ubiquitin in the proliferative cell nuclear antigen is thought to be the trigger for TLS activation. Here we report the solution NMR structure of a 108-residue fragment of human REV1 encompassing the two putative ubiquitin-binding motifs UBM1 and UBM2 in complex with ubiquitin. While in mammals UBM1 and UBM2 are both required for optimal association of REV1 with replication factories after DNA damage, we show that only REV1 UBM2 binds ubiquitin. Structure-guided mutagenesis in Saccharomyces cerevisiae further highlights the importance of UBM2 for REV1-mediated mutagenesis and DNA damage tolerance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Conservative algorithms for non-Maxwellian plasma kinetics

DOE PAGES

Le, Hai P.; Cambier, Jean -Luc

2017-12-08

Here, we present a numerical model and a set of conservative algorithms for Non-Maxwellian plasma kinetics with inelastic collisions. These algorithms self-consistently solve for the time evolution of an isotropic electron energy distribution function interacting with an atomic state distribution function of an arbitrary number of levels through collisional excitation, deexcitation, as well as ionization and recombination. Electron-electron collisions, responsible for thermalization of the electron distribution, are also included in the model. The proposed algorithms guarantee mass/charge and energy conservation in a single step, and is applied to the case of non-uniform gridding of the energy axis in the phasemore » space of the electron distribution function. Numerical test cases are shown to demonstrate the accuracy of the method and its conservation properties.« less

Digital technology and human development: a charter for nature conservation.

PubMed

Maffey, Georgina; Homans, Hilary; Banks, Ken; Arts, Koen

2015-11-01

The application of digital technology in conservation holds much potential for advancing the understanding of, and facilitating interaction with, the natural world. In other sectors, digital technology has long been used to engage communities and share information. Human development-which holds parallels with the nature conservation sector-has seen a proliferation of innovation in technological development. Throughout this Perspective, we consider what nature conservation can learn from the introduction of digital technology in human development. From this, we derive a charter to be used before and throughout project development, in order to help reduce replication and failure of digital innovation in nature conservation projects. We argue that the proposed charter will promote collaboration with the development of digital tools and ensure that nature conservation projects progress appropriately with the development of new digital technologies.

Transforming conservation science and practice for a postnormal world.

PubMed

Colloff, Matthew J; Lavorel, Sandra; van Kerkhoff, Lorrae E; Wyborn, Carina A; Fazey, Ioan; Gorddard, Russell; Mace, Georgina M; Foden, Wendy B; Dunlop, Michael; Prentice, I Colin; Crowley, John; Leadley, Paul; Degeorges, Patrick

2017-10-01

We examine issues to consider when reframing conservation science and practice in the context of global change. New framings of the links between ecosystems and society are emerging that are changing peoples' values and expectations of nature, resulting in plural perspectives on conservation. Reframing conservation for global change can thus be regarded as a stage in the evolving relationship between people and nature rather than some recent trend. New models of how conservation links with transformative adaptation include how decision contexts for conservation can be reframed and integrated with an adaptation pathways approach to create new options for global-change-ready conservation. New relationships for conservation science and governance include coproduction of knowledge that supports social learning. New processes for implementing adaptation for conservation outcomes include deliberate practices used to develop new strategies, shift world views, work with conflict, address power and intergenerational equity in decisions, and build consciousness and creativity that empower agents to act. We argue that reframing conservation for global change requires scientists and practitioners to implement approaches unconstrained by discipline and sectoral boundaries, geopolitical polarities, or technical problematization. We consider a stronger focus on inclusive creation of knowledge and the interaction of this knowledge with societal values and rules is likely to result in conservation science and practice that meets the challenges of a postnormal world. © 2017 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

Tigers of Sundarbans in India: is the population a separate conservation unit?

PubMed

Singh, Sujeet Kumar; Mishra, Sudhanshu; Aspi, Jouni; Kvist, Laura; Nigam, Parag; Pandey, Puneet; Sharma, Reeta; Goyal, Surendra Prakash

2014-01-01

The Sundarbans tiger inhabits a unique mangrove habitat and are morphologically distinct from the recognized tiger subspecies in terms of skull morphometrics and body size. Thus, there is an urgent need to assess their ecological and genetic distinctiveness and determine if Sundarbans tigers should be defined and managed as separate conservation unit. We utilized nine microsatellites and 3 kb from four mitochondrial DNA (mtDNA) genes to estimate genetic variability, population structure, demographic parameters and visualize historic and contemporary connectivity among tiger populations from Sundarbans and mainland India. We also evaluated the traits that determine exchangeability or adaptive differences among tiger populations. Data from both markers suggest that Sundarbans tiger is not a separate tiger subspecies and should be regarded as Bengal tiger (P. t. tigris) subspecies. Maximum likelihood phylogenetic analyses of the mtDNA data revealed reciprocal monophyly. Genetic differentiation was found stronger for mtDNA than nuclear DNA. Microsatellite markers indicated low genetic variation in Sundarbans tigers (He= 0.58) as compared to other mainland populations, such as northern and Peninsular (Hebetween 0.67- 0.70). Molecular data supports migration between mainland and Sundarbans populations until very recent times. We attribute this reduction in gene flow to accelerated fragmentation and habitat alteration in the landscape over the past few centuries. Demographic analyses suggest that Sundarbans tigers have diverged recently from peninsular tiger population within last 2000 years. Sundarbans tigers are the most divergent group of Bengal tigers, and ecologically non-exchangeable with other tiger populations, and thus should be managed as a separate "evolutionarily significant unit" (ESU) following the adaptive evolutionary conservation (AEC) concept.

Tigers of Sundarbans in India: Is the Population a Separate Conservation Unit?

PubMed Central

Singh, Sujeet Kumar; Mishra, Sudhanshu; Aspi, Jouni; Kvist, Laura; Nigam, Parag; Pandey, Puneet; Sharma, Reeta; Goyal, Surendra Prakash

2015-01-01

The Sundarbans tiger inhabits a unique mangrove habitat and are morphologically distinct from the recognized tiger subspecies in terms of skull morphometrics and body size. Thus, there is an urgent need to assess their ecological and genetic distinctiveness and determine if Sundarbans tigers should be defined and managed as separate conservation unit. We utilized nine microsatellites and 3 kb from four mitochondrial DNA (mtDNA) genes to estimate genetic variability, population structure, demographic parameters and visualize historic and contemporary connectivity among tiger populations from Sundarbans and mainland India. We also evaluated the traits that determine exchangeability or adaptive differences among tiger populations. Data from both markers suggest that Sundarbans tiger is not a separate tiger subspecies and should be regarded as Bengal tiger (P. t. tigris) subspecies. Maximum likelihood phylogenetic analyses of the mtDNA data revealed reciprocal monophyly. Genetic differentiation was found stronger for mtDNA than nuclear DNA. Microsatellite markers indicated low genetic variation in Sundarbans tigers (He= 0.58) as compared to other mainland populations, such as northern and Peninsular (Hebetween 0.67- 0.70). Molecular data supports migration between mainland and Sundarbans populations until very recent times. We attribute this reduction in gene flow to accelerated fragmentation and habitat alteration in the landscape over the past few centuries. Demographic analyses suggest that Sundarbans tigers have diverged recently from peninsular tiger population within last 2000 years. Sundarbans tigers are the most divergent group of Bengal tigers, and ecologically non-exchangeable with other tiger populations, and thus should be managed as a separate “evolutionarily significant unit” (ESU) following the adaptive evolutionary conservation (AEC) concept. PMID:25919139

Are there really no evolutionarily stable strategies in the iterated prisoner's dilemma?

PubMed

Lorberbaum, Jeffrey P; Bohning, Daryl E; Shastri, Ananda; Sine, Lauren E

2002-01-21

The evolutionary form of the iterated prisoner's dilemma (IPD) is a repeated game where players strategically choose whether to cooperate with or exploit opponents and reproduce in proportion to game success. It has been widely used to study the evolution of cooperation among selfish agents. In the past 15 years, researchers proved over a series of papers that there is no evolutionarily stable strategy (ESS) in the IPD when players maintain long-term relationships. This makes it difficult to make predictions about what strategies can actually persist as prevalent in a population over time. Here, we show that this no ESS finding may be a mathematical technicality, relying on implausible players who are "too perfect" in that their probability of cooperating on any move is arbitrarily close to either 0 or 1. Specifically, in the no ESS proof, all strategies were allowed, meaning that after a strategy X experiences any history H, X cooperates with an unrestricted probability p (X, H) where 0< or =p (X, H)< or =1. Here, we restrict strategies to the set S in which X is a member of S [corrected] if after any H, X cooperates with a restricted probability p (X, H) where e< or =p (X, H)< or =1-e and 0interact with one another. This greatly simplifies the search for ESSs. Using these results, we finally show that when e is sufficiently small, exactly three one-move memory ESSs exist in S: [1] Pavlov-e which generally cooperates (i.e. cooperates with

Using a social-ecological framework to inform the implementation of conservation plans.

PubMed

Guerrero, Angela M; Wilson, Kerrie A

2017-04-01

One of the key determinants of success in biodiversity conservation is how well conservation planning decisions account for the social system in which actions are to be implemented. Understanding elements of how the social and ecological systems interact can help identify opportunities for implementation. Utilizing data from a large-scale conservation initiative in southwestern of Australia, we explored how a social-ecological system framework can be applied to identify how social and ecological factors interact to influence the opportunities for conservation. Using data from semistructured interviews, an online survey, and publicly available data, we developed a conceptual model of the social-ecological system associated with the conservation of the Fitz-Stirling region. We used this model to identify the relevant variables (remnants of vegetation, stakeholder presence, collaboration between stakeholders, and their scale of management) that affect the implementation of conservation actions in the region. We combined measures for these variables to ascertain how areas associated with different levels of ecological importance coincided with areas associated with different levels of stakeholder presence, stakeholder collaboration, and scales of management. We identified areas that could benefit from different implementation strategies, from those suitable for immediate conservation action to areas requiring implementation over the long term to increase on-the-ground capacity and identify mechanisms to incentivize implementation. The application of a social-ecological framework can help conservation planners and practitioners facilitate the integration of ecological and social data to inform the translation of priorities for action into implementation strategies that account for the complexities of conservation problems in a focused way. © 2016 Society for Conservation Biology.

Structure-Templated Predictions of Novel Protein Interactions from Sequence Information

PubMed Central

Betel, Doron; Breitkreuz, Kevin E; Isserlin, Ruth; Dewar-Darch, Danielle; Tyers, Mike; Hogue, Christopher W. V

2007-01-01

The multitude of functions performed in the cell are largely controlled by a set of carefully orchestrated protein interactions often facilitated by specific binding of conserved domains in the interacting proteins. Interacting domains commonly exhibit distinct binding specificity to short and conserved recognition peptides called binding profiles. Although many conserved domains are known in nature, only a few have well-characterized binding profiles. Here, we describe a novel predictive method known as domain–motif interactions from structural topology (D-MIST) for elucidating the binding profiles of interacting domains. A set of domains and their corresponding binding profiles were derived from extant protein structures and protein interaction data and then used to predict novel protein interactions in yeast. A number of the predicted interactions were verified experimentally, including new interactions of the mitotic exit network, RNA polymerases, nucleotide metabolism enzymes, and the chaperone complex. These results demonstrate that new protein interactions can be predicted exclusively from sequence information. PMID:17892321

Identification of conserved amino acids in the herpes simplex virus type 1 UL8 protein required for DNA synthesis and UL52 primase interaction in the virus replisome.

PubMed

Muylaert, Isabella; Zhao, Zhiyuan; Andersson, Torbjörn; Elias, Per

2012-09-28

We have used oriS-dependent transient replication assays to search for species-specific interactions within the herpes simplex virus replisome. Hybrid replisomes derived from herpes simplex virus type 1 (HSV-1) and equine herpesvirus type 1 (EHV-1) failed to support DNA replication in cells. Moreover, the replisomes showed a preference for their cognate origin of replication. The results demonstrate that the herpesvirus replisome behaves as a molecular machine relying on functionally important interactions. We then searched for functional interactions in the replisome context by subjecting HSV-1 UL8 protein to extensive mutagenesis. 52 mutants were made by replacing single or clustered charged amino acids with alanines. Four mutants showed severe replication defects. Mutant A23 exhibited a lethal phenotype, and mutants A49, A52 and A53 had temperature-sensitive phenotypes. Mutants A49 and A53 did not interact with UL52 primase as determined by co-immunoprecipitation experiments. Using GFP-tagged UL8, we demonstrate that all mutants were unable to support formation of ICP8-containing nuclear replication foci. Extended mutagenesis suggested that a highly conserved motif corresponding to mutant A49 serves an important role for establishing a physical contact between UL8 and UL52. The replication-defective mutations affected conserved amino acids, and similar phenotypes were observed when the corresponding mutations were introduced into EHV-1 UL8.

Conserved Cysteine Residues Provide a Protein-Protein Interaction Surface in Dual Oxidase (DUOX) Proteins*

PubMed Central

Meitzler, Jennifer L.; Hinde, Sara; Bánfi, Botond; Nauseef, William M.; Ortiz de Montellano, Paul R.

2013-01-01

Intramolecular disulfide bond formation is promoted in oxidizing extracellular and endoplasmic reticulum compartments and often contributes to protein stability and function. DUOX1 and DUOX2 are distinguished from other members of the NOX protein family by the presence of a unique extracellular N-terminal region. These peroxidase-like domains lack the conserved cysteines that confer structural stability to mammalian peroxidases. Sequence-based structure predictions suggest that the thiol groups present are solvent-exposed on a single protein surface and are too distant to support intramolecular disulfide bond formation. To investigate the role of these thiol residues, we introduced four individual cysteine to glycine mutations in the peroxidase-like domains of both human DUOXs and purified the recombinant proteins. The mutations caused little change in the stabilities of the monomeric proteins, supporting the hypothesis that the thiol residues are solvent-exposed and not involved in disulfide bonds that are critical for structural integrity. However, the ability of the isolated hDUOX1 peroxidase-like domain to dimerize was altered, suggesting a role for these cysteines in protein-protein interactions that could facilitate homodimerization of the peroxidase-like domain or, in the full-length protein, heterodimeric interactions with a maturation protein. When full-length hDUOX1 was expressed in HEK293 cells, the mutations resulted in decreased H2O2 production that correlated with a decreased amount of the enzyme localized to the membrane surface rather than with a loss of activity or with a failure to synthesize the mutant proteins. These results support a role for the cysteine residues in intermolecular disulfide bond formation with the DUOX maturation factor DUOXA1. PMID:23362256

B and T Cell Epitope-Based Peptides Predicted from Evolutionarily Conserved and Whole Protein Sequences of Ebola Virus as Vaccine Targets.

PubMed

Yasmin, T; Nabi, A H M Nurun

2016-05-01

Ebola virus (EBV) has become a serious threat to public health. Different approaches were applied to predict continuous and discontinuous B cell epitopes as well as T cell epitopes from the sequence-based and available three-dimensional structural analyses of each protein of EBV. Peptides '(79) VPSATKRWGFRSGVPP(94) ' from GP1 and '(515) LHYWTTQDEGAAIGLA(530) ' from GP2 of Ebola were found to be the consensus peptidic sequences predicted as linear B cell epitope of which the latter contains a region (519) TTQDEG(524) that fulfilled all the criteria of accessibility, hydrophilicity, flexibility and beta turn region for becoming an ideal B cell epitope. Different nonamers as T cell epitopes were obtained that interacted with different numbers of MHC class I and class II alleles with a binding affinity of <100 nm. Interestingly, these alleles also bound to the MHC class I alleles mostly prevalent in African and South Asian regions. Of these, 'LANETTQAL' and 'FLYDRLAST' nonamers were predicted to be the most potent T cell epitopes and they, respectively, interacted with eight and twelve class I alleles that covered 63.79% and 54.16% of world population, respectively. These nonamers were found to be the core sequences of 15mer peptides that interacted with the most common class II allele, HLA-DRB1*01:01. They were further validated for their binding to specific class I alleles using docking technique. Thus, these predicted epitopes may be used as vaccine targets against EBV and can be validated in model hosts to verify their efficacy as vaccine. © 2016 The Foundation for the Scandinavian Journal of Immunology.

Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence.

PubMed

Benko, Sabina; Fantes, Judy A; Amiel, Jeanne; Kleinjan, Dirk-Jan; Thomas, Sophie; Ramsay, Jacqueline; Jamshidi, Negar; Essafi, Abdelkader; Heaney, Simon; Gordon, Christopher T; McBride, David; Golzio, Christelle; Fisher, Malcolm; Perry, Paul; Abadie, Véronique; Ayuso, Carmen; Holder-Espinasse, Muriel; Kilpatrick, Nicky; Lees, Melissa M; Picard, Arnaud; Temple, I Karen; Thomas, Paul; Vazquez, Marie-Paule; Vekemans, Michel; Roest Crollius, Hugues; Hastie, Nicholas D; Munnich, Arnold; Etchevers, Heather C; Pelet, Anna; Farlie, Peter G; Fitzpatrick, David R; Lyonnet, Stanislas

2009-03-01

Pierre Robin sequence (PRS) is an important subgroup of cleft palate. We report several lines of evidence for the existence of a 17q24 locus underlying PRS, including linkage analysis results, a clustering of translocation breakpoints 1.06-1.23 Mb upstream of SOX9, and microdeletions both approximately 1.5 Mb centromeric and approximately 1.5 Mb telomeric of SOX9. We have also identified a heterozygous point mutation in an evolutionarily conserved region of DNA with in vitro and in vivo features of a developmental enhancer. This enhancer is centromeric to the breakpoint cluster and maps within one of the microdeletion regions. The mutation abrogates the in vitro enhancer function and alters binding of the transcription factor MSX1 as compared to the wild-type sequence. In the developing mouse mandible, the 3-Mb region bounded by the microdeletions shows a regionally specific chromatin decompaction in cells expressing Sox9. Some cases of PRS may thus result from developmental misexpression of SOX9 due to disruption of very-long-range cis-regulatory elements.

Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1.

PubMed

Garapaty, Shivani; Mahajan, Muktar A; Samuels, Herbert H

2008-03-14

CCR4-NOT is an evolutionarily conserved, multicomponent complex known to be involved in transcription as well as mRNA degradation. Various subunits (e.g. CNOT1 and CNOT7/CAF1) have been reported to be involved in influencing nuclear hormone receptor activities. Here, we show that CCR4/CNOT6 and RCD1/CNOT9, members of the CCR4-NOT complex, potentiate nuclear receptor activity. RCD1 interacts in vivo and in vitro with NIF-1 (NRC-interacting factor), a previously characterized nuclear receptor cotransducer that activates nuclear receptors via its interaction with NRC. As with NIF-1, RCD1 and CCR4 do not directly associate with nuclear receptors; however, they enhance ligand-dependent transcriptional activation by nuclear hormone receptors. CCR4 mediates its effect through the ligand binding domain of nuclear receptors and small interference RNA-mediated silencing of endogenous CCR4 results in a marked decrease in nuclear receptor activation. Furthermore, knockdown of CCR4 results in an attenuated stimulation of RARalpha target genes (e.g. Sox9 and HoxA1) as shown by quantitative PCR assays. The silencing of endogenous NIF-1 also resulted in a comparable decrease in the RAR-mediated induction of both Sox9 and HoxA1. Furthermore, CCR4 associates in vivo with NIF-1. In addition, the CCR4-enhanced transcriptional activation by nuclear receptors is dependent on NIF-1. The small interference RNA-mediated knockdown of NIF-1 blocks the ligand-dependent potentiating effect of CCR4. Our results suggest that CCR4 plays a role in the regulation of certain endogenous RARalpha target genes and that RCD1 and CCR4 might mediate their function through their interaction with NIF-1.

Coexistence and survival in conservative Lotka-Volterra networks.

PubMed

Knebel, Johannes; Krüger, Torben; Weber, Markus F; Frey, Erwin

2013-04-19

Analyzing coexistence and survival scenarios of Lotka-Volterra (LV) networks in which the total biomass is conserved is of vital importance for the characterization of long-term dynamics of ecological communities. Here, we introduce a classification scheme for coexistence scenarios in these conservative LV models and quantify the extinction process by employing the Pfaffian of the network's interaction matrix. We illustrate our findings on global stability properties for general systems of four and five species and find a generalized scaling law for the extinction time.

Coexistence and Survival in Conservative Lotka-Volterra Networks

NASA Astrophysics Data System (ADS)

Knebel, Johannes; Krüger, Torben; Weber, Markus F.; Frey, Erwin

2013-04-01

Analyzing coexistence and survival scenarios of Lotka-Volterra (LV) networks in which the total biomass is conserved is of vital importance for the characterization of long-term dynamics of ecological communities. Here, we introduce a classification scheme for coexistence scenarios in these conservative LV models and quantify the extinction process by employing the Pfaffian of the network’s interaction matrix. We illustrate our findings on global stability properties for general systems of four and five species and find a generalized scaling law for the extinction time.

A systems biology model of the regulatory network in Populus leaves reveals interacting regulators and conserved regulation

PubMed Central

2011-01-01

Background Green plant leaves have always fascinated biologists as hosts for photosynthesis and providers of basic energy to many food webs. Today, comprehensive databases of gene expression data enable us to apply increasingly more advanced computational methods for reverse-engineering the regulatory network of leaves, and to begin to understand the gene interactions underlying complex emergent properties related to stress-response and development. These new systems biology methods are now also being applied to organisms such as Populus, a woody perennial tree, in order to understand the specific characteristics of these species. Results We present a systems biology model of the regulatory network of Populus leaves. The network is reverse-engineered from promoter information and expression profiles of leaf-specific genes measured over a large set of conditions related to stress and developmental. The network model incorporates interactions between regulators, such as synergistic and competitive relationships, by evaluating increasingly more complex regulatory mechanisms, and is therefore able to identify new regulators of leaf development not found by traditional genomics methods based on pair-wise expression similarity. The approach is shown to explain available gene function information and to provide robust prediction of expression levels in new data. We also use the predictive capability of the model to identify condition-specific regulation as well as conserved regulation between Populus and Arabidopsis. Conclusions We outline a computationally inferred model of the regulatory network of Populus leaves, and show how treating genes as interacting, rather than individual, entities identifies new regulators compared to traditional genomics analysis. Although systems biology models should be used with care considering the complexity of regulatory programs and the limitations of current genomics data, methods describing interactions can provide hypotheses about

Conservation of tubulin-binding sequences in TRPV1 throughout evolution.

PubMed

Sardar, Puspendu; Kumar, Abhishek; Bhandari, Anita; Goswami, Chandan

2012-01-01

Transient Receptor Potential Vanilloid sub type 1 (TRPV1), commonly known as capsaicin receptor can detect multiple stimuli ranging from noxious compounds, low pH, temperature as well as electromagnetic wave at different ranges. In addition, this receptor is involved in multiple physiological and sensory processes. Therefore, functions of TRPV1 have direct influences on adaptation and further evolution also. Availability of various eukaryotic genomic sequences in public domain facilitates us in studying the molecular evolution of TRPV1 protein and the respective conservation of certain domains, motifs and interacting regions that are functionally important. Using statistical and bioinformatics tools, our analysis reveals that TRPV1 has evolved about ∼420 million years ago (MYA). Our analysis reveals that specific regions, domains and motifs of TRPV1 has gone through different selection pressure and thus have different levels of conservation. We found that among all, TRP box is the most conserved and thus have functional significance. Our results also indicate that the tubulin binding sequences (TBS) have evolutionary significance as these stretch sequences are more conserved than many other essential regions of TRPV1. The overall distribution of positively charged residues within the TBS motifs is conserved throughout evolution. In silico analysis reveals that the TBS-1 and TBS-2 of TRPV1 can form helical structures and may play important role in TRPV1 function. Our analysis identifies the regions of TRPV1, which are important for structure-function relationship. This analysis indicates that tubulin binding sequence-1 (TBS-1) near the TRP-box forms a potential helix and the tubulin interactions with TRPV1 via TBS-1 have evolutionary significance. This interaction may be required for the proper channel function and regulation and may also have significance in the context of Taxol®-induced neuropathy.

Collaboration and nested environmental governance: Scale dependency, scale framing, and cross-scale interactions in collaborative conservation.

PubMed

Wyborn, Carina; Bixler, R Patrick

2013-07-15

The problem of fit between social institutions and ecological systems is an enduring challenge in natural resource management and conservation. Developments in the science of conservation biology encourage the management of landscapes at increasingly larger scales. In contrast, sociological approaches to conservation emphasize the importance of ownership, collaboration and stewardship at scales relevant to the individual or local community. Despite the proliferation of initiatives seeking to work with local communities to undertake conservation across large landscapes, there is an inherent tension between these scales of operation. Consequently, questions about the changing nature of effective conservation across scales abound. Through an analysis of three nested cases working in a semiautonomous fashion in the Northern Rocky Mountains in North America, this paper makes an empirical contribution to the literature on nested governance, collaboration and communication across scales. Despite different scales of operation, constituencies and scale frames, we demonstrate a surprising similarity in organizational structure and an implicit dependency between these initiatives. This paper examines the different capacities and capabilities of collaborative conservation from the local to regional to supra regional. We draw on the underexplored concept of 'scale-dependent comparative advantage' (Cash and Moser, 2000), to gain insight into what activities take place at which scale and what those activities contribute to nested governance and collaborative conservation. The comparison of these semiautonomous cases provides fruitful territory to draw lessons for understanding the roles and relationships of organizations operating at different scales in more connected networks of nested governance. Copyright © 2013 Elsevier Ltd. All rights reserved.

An interactive database for setting conservation priorities for western neotropical migrants

Treesearch

Michael F. Carter; Keith Barker

1993-01-01

We develop and explain a species ranking system for the states and physiographic regions of the Neotropical Migratory Bird Conservation Program's West Working Group. The ranking criteria attempt to measure characteristics of species which make them vulnerable to extirpation, as well as assess the relative importance of different geographic and/or political areas...

Evolutionarily conserved TCR binding sites, identification of T cells in primary lymphoid tissues, and surprising trans-rearrangements in nurse shark.

PubMed

Criscitiello, Michael F; Ohta, Yuko; Saltis, Mark; McKinney, E Churchill; Flajnik, Martin F

2010-06-15

Cartilaginous fish are the oldest animals that generate RAG-based Ag receptor diversity. We have analyzed the genes and expressed transcripts of the four TCR chains for the first time in a cartilaginous fish, the nurse shark (Ginglymostoma cirratum). Northern blotting found TCR mRNA expression predominantly in lymphoid and mucosal tissues. Southern blotting suggested translocon-type loci encoding all four chains. Based on diversity of V and J segments, the expressed combinatorial diversity for gamma is similar to that of human, alpha and beta may be slightly lower, and delta diversity is the highest of any organism studied to date. Nurse shark TCRdelta have long CDR3 loops compared with the other three chains, creating binding site topologies comparable to those of mammalian TCR in basic paratope structure; additionally, nurse shark TCRdelta CDR3 are more similar to IgH CDR3 in length and heterogeneity than to other TCR chains. Most interestingly, several cDNAs were isolated that contained IgM or IgW V segments rearranged to other gene segments of TCRdelta and alpha. Finally, in situ hybridization experiments demonstrate a conservation of both alpha/beta and gamma/delta T cell localization in the thymus across 450 million years of vertebrate evolution, with gamma/delta TCR expression especially high in the subcapsular region. Collectively, these data make the first cellular identification of TCR-expressing lymphocytes in a cartilaginous fish.

Mechanisms of EHD/RME-1 Protein Function in Endocytic Transport

PubMed Central

Grant, Barth D.; Caplan, Steve

2009-01-01

The evolutionarily conserved Eps15 homology domain (EHD)/receptor-mediated endocytosis (RME)-1 family of C-terminal EH domain proteins has recently come under intense scrutiny because of its importance in intracellular membrane transport, especially with regard to the recycling of receptors from endosomes to the plasma membrane. Recent studies have shed new light on the mode by which these adenosine triphosphatases function on endosomal membranes in mammals and Caenorhabditis elegans. This review highlights our current understanding of the physiological roles of these proteins in vivo, discussing conserved features as well as emerging functional differences between individual mammalian paralogs. In addition, these findings are discussed in light of the identification of novel EHD/RME-1 protein and lipid interactions and new structural data for proteins in this family, indicating intriguing similarities to the Dynamin superfamily of large guanosine triphosphatases. PMID:18801062

Problems with Piagetian Conservation and Musical Objects.

ERIC Educational Resources Information Center

Bartholomew, Douglas

1987-01-01

Notes that Piaget's theory of cognitive development was based on the child's interaction with material objects and quantitative relationships. Examines the applicability of Piaget's concept of operational intelligence and conservation to music learning. Concludes that a theory of music learning must apply equally to the non-material and…

SARM1-specific motifs in the TIR domain enable NAD+ loss and regulate injury-induced SARM1 activation.

PubMed

Summers, Daniel W; Gibson, Daniel A; DiAntonio, Aaron; Milbrandt, Jeffrey

2016-10-11

Axon injury in response to trauma or disease stimulates a self-destruction program that promotes the localized clearance of damaged axon segments. Sterile alpha and Toll/interleukin receptor (TIR) motif-containing protein 1 (SARM1) is an evolutionarily conserved executioner of this degeneration cascade, also known as Wallerian degeneration; however, the mechanism of SARM1-dependent neuronal destruction is still obscure. SARM1 possesses a TIR domain that is necessary for SARM1 activity. In other proteins, dimerized TIR domains serve as scaffolds for innate immune signaling. In contrast, dimerization of the SARM1 TIR domain promotes consumption of the essential metabolite NAD + and induces neuronal destruction. This activity is unique to the SARM1 TIR domain, yet the structural elements that enable this activity are unknown. In this study, we identify fundamental properties of the SARM1 TIR domain that promote NAD + loss and axon degeneration. Dimerization of the TIR domain from the Caenorhabditis elegans SARM1 ortholog TIR-1 leads to NAD + loss and neuronal death, indicating these activities are an evolutionarily conserved feature of SARM1 function. Detailed analysis of sequence homology identifies canonical TIR motifs as well as a SARM1-specific (SS) loop that are required for NAD + loss and axon degeneration. Furthermore, we identify a residue in the SARM1 BB loop that is dispensable for TIR activity yet required for injury-induced activation of full-length SARM1, suggesting that SARM1 function requires multidomain interactions. Indeed, we identify a physical interaction between the autoinhibitory N terminus and the TIR domain of SARM1, revealing a previously unrecognized direct connection between these domains that we propose mediates autoinhibition and activation upon injury.

Ancient Regulatory Role of Lysine Acetylation in Central Metabolism

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

Nakayasu, Ernesto S.; Burnet, Meagan C.; Walukiewicz, Hanna E.

ABSTRACT Lysine acetylation is a common protein post-translational modification in bacteria and eukaryotes. Unlike phosphorylation, whose functional role in signaling has been established, it is unclear what regulatory mechanism acetylation plays and whether it is conserved across evolution. By performing a proteomic analysis of 48 phylogenetically distant bacteria, we discovered conserved acetylation sites on catalytically essential lysine residues that are invariant throughout evolution. Lysine acetylation removes the residue’s charge and changes the shape of the pocket required for substrate or cofactor binding. Two-thirds of glycolytic and tricarboxylic acid (TCA) cycle enzymes are acetylated at these critical sites. Our data suggestmore » that acetylation may play a direct role in metabolic regulation by switching off enzyme activity. We propose that protein acetylation is an ancient and widespread mechanism of protein activity regulation. IMPORTANCEPost-translational modifications can regulate the activity and localization of proteins inside the cell. Similar to phosphorylation, lysine acetylation is present in both eukaryotes and prokaryotes and modifies hundreds to thousands of proteins in cells. However, how lysine acetylation regulates protein function and whether such a mechanism is evolutionarily conserved is still poorly understood. Here, we investigated evolutionary and functional aspects of lysine acetylation by searching for acetylated lysines in a comprehensive proteomic data set from 48 phylogenetically distant bacteria. We found that lysine acetylation occurs in evolutionarily conserved lysine residues in catalytic sites of enzymes involved in central carbon metabolism. Moreover, this modification inhibits enzymatic activity. Our observations suggest that lysine acetylation is an evolutionarily conserved mechanism of controlling central metabolic activity by directly blocking enzyme active sites.« less

Ancient Regulatory Role of Lysine Acetylation in Central Metabolism

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

Nakayasu, Ernesto S.; Burnet, Meagan C.; Walukiewicz, Hanna E.

ABSTRACT Lysine acetylation is a common protein post-translational modification in bacteria and eukaryotes. Unlike phosphorylation, whose functional role in signaling has been established, it is unclear what regulatory mechanism acetylation plays and whether it is conserved across evolution. By performing a proteomic analysis of 48 phylogenetically distant bacteria, we discovered conserved acetylation sites on catalytically essential lysine residues that are invariant throughout evolution. Lysine acetylation removes the residue’s charge and changes the shape of the pocket required for substrate or cofactor binding. Two-thirds of glycolytic and tricarboxylic acid (TCA) cycle enzymes are acetylated at these critical sites. Our data suggestmore » that acetylation may play a direct role in metabolic regulation by switching off enzyme activity. We propose that protein acetylation is an ancient and widespread mechanism of protein activity regulation. IMPORTANCE Post-translational modifications can regulate the activity and localization of proteins inside the cell. Similar to phosphorylation, lysine acetylation is present in both eukaryotes and prokaryotes and modifies hundreds to thousands of proteins in cells. However, how lysine acetylation regulates protein function and whether such a mechanism is evolutionarily conserved is still poorly understood. Here, we investigated evolutionary and functional aspects of lysine acetylation by searching for acetylated lysines in a comprehensive proteomic data set from 48 phylogenetically distant bacteria. We found that lysine acetylation occurs in evolutionarily conserved lysine residues in catalytic sites of enzymes involved in central carbon metabolism. Moreover, this modification inhibits enzymatic activity. Our observations suggest that lysine acetylation is an evolutionarily conserved mechanism of controlling central metabolic activity by directly blocking enzyme active sites.« less

Ancient Regulatory Role of Lysine Acetylation in Central Metabolism

DOE PAGES

Nakayasu, Ernesto S.; Burnet, Meagan C.; Walukiewicz, Hanna E.; ...

2017-11-28

ABSTRACT Lysine acetylation is a common protein post-translational modification in bacteria and eukaryotes. Unlike phosphorylation, whose functional role in signaling has been established, it is unclear what regulatory mechanism acetylation plays and whether it is conserved across evolution. By performing a proteomic analysis of 48 phylogenetically distant bacteria, we discovered conserved acetylation sites on catalytically essential lysine residues that are invariant throughout evolution. Lysine acetylation removes the residue’s charge and changes the shape of the pocket required for substrate or cofactor binding. Two-thirds of glycolytic and tricarboxylic acid (TCA) cycle enzymes are acetylated at these critical sites. Our data suggestmore » that acetylation may play a direct role in metabolic regulation by switching off enzyme activity. We propose that protein acetylation is an ancient and widespread mechanism of protein activity regulation. IMPORTANCE Post-translational modifications can regulate the activity and localization of proteins inside the cell. Similar to phosphorylation, lysine acetylation is present in both eukaryotes and prokaryotes and modifies hundreds to thousands of proteins in cells. However, how lysine acetylation regulates protein function and whether such a mechanism is evolutionarily conserved is still poorly understood. Here, we investigated evolutionary and functional aspects of lysine acetylation by searching for acetylated lysines in a comprehensive proteomic data set from 48 phylogenetically distant bacteria. We found that lysine acetylation occurs in evolutionarily conserved lysine residues in catalytic sites of enzymes involved in central carbon metabolism. Moreover, this modification inhibits enzymatic activity. Our observations suggest that lysine acetylation is an evolutionarily conserved mechanism of controlling central metabolic activity by directly blocking enzyme active sites.« less

How research-prioritization exercises affect conservation policy.

PubMed

Rudd, Murray A

2011-10-01

Conservation scientists are concerned about the apparent lack of impact their research is having on policy. By better aligning research with policy needs, conservation science might become more relevant to policy and increase its real-world salience in the conservation of biological diversity. Consequently, some conservation scientists have embarked on a variety of exercises to identify research questions that, if answered, would provide the evidence base with which to develop and implement effective conservation policies. I synthesized two existing approaches to conceptualizing research impacts. One widely used approach classifies the impacts of research as conceptual, instrumental, and symbolic. Conceptual impacts occur when policy makers are sensitized to new issues and change their beliefs or thinking. Instrumental impacts arise when scientific research has a direct effect on policy decisions. The use of scientific research results to support established policy positions are symbolic impacts. The second approach classifies research issues according to whether scientific knowledge is developed fully and whether the policy issue has been articulated clearly. I believe exercises to identify important research questions have objectives of increasing the clarity of policy issues while strengthening science-policy interactions. This may facilitate the transmission of scientific knowledge to policy makers and, potentially, accelerate the development and implementation of effective conservation policy. Other, similar types of exercises might also be useful. For example, identification of visionary science questions independent of current policy needs, prioritization of best practices for transferring scientific knowledge to policy makers, and identification of questions about human values and their role in political processes could all help advance real-world conservation science. It is crucial for conservation scientists to understand the wide variety of ways in which

Learning to Cooperate: The Evolution of Social Rewards in Repeated Interactions.

PubMed

Dridi, Slimane; Akçay, Erol

2018-01-01

Understanding the behavioral and psychological mechanisms underlying social behaviors is one of the major goals of social evolutionary theory. In particular, a persistent question about animal cooperation is to what extent it is supported by other-regarding preferences-the motivation to increase the welfare of others. In many situations, animals adjust their behaviors through learning by responding to the rewards they experience as a consequence of their actions. Therefore, we may ask whether learning in social situations can be driven by evolved other-regarding rewards. Here we develop a mathematical model in order to ask whether the mere act of cooperating with a social partner will evolve to be inherently rewarding. Individuals interact repeatedly in pairs and adjust their behaviors through reinforcement learning. We assume that individuals associate with each game outcome an internal reward value. These perceived rewards are genetically evolving traits. We find that conditionally cooperative rewards that value mutual cooperation positively but the sucker's outcome negatively tend to be evolutionarily stable. Purely other-regarding rewards can evolve only under special parameter combinations. On the other hand, selfish rewards that always lead to pure defection are also evolutionarily successful. These findings are consistent with empirical observations showing that humans tend to display conditionally cooperative behavior and also exhibit a diversity of preferences. Our model also demonstrates the need to further integrate multiple levels of biological causation of behavior.

Development of a dedicated peptide tandem mass spectral library for conservation science.

PubMed

Fremout, Wim; Dhaenens, Maarten; Saverwyns, Steven; Sanyova, Jana; Vandenabeele, Peter; Deforce, Dieter; Moens, Luc

2012-05-30

In recent years, the use of liquid chromatography tandem mass spectrometry (LC-MS/MS) on tryptic digests of cultural heritage objects has attracted much attention. It allows for unambiguous identification of peptides and proteins, and even in complex mixtures species-specific identification becomes feasible with minimal sample consumption. Determination of the peptides is commonly based on theoretical cleavage of known protein sequences and on comparison of the expected peptide fragments with those found in the MS/MS spectra. In this approach, complex computer programs, such as Mascot, perform well identifying known proteins, but fail when protein sequences are unknown or incomplete. Often, when trying to distinguish evolutionarily well preserved collagens of different species, Mascot lacks the required specificity. Complementary and often more accurate information on the proteins can be obtained using a reference library of MS/MS spectra of species-specific peptides. Therefore, a library dedicated to various sources of proteins in works of art was set up, with an initial focus on collagen rich materials. This paper discusses the construction and the advantages of this spectral library for conservation science, and its application on a number of samples from historical works of art. Copyright © 2012 Elsevier B.V. All rights reserved.

Hundreds of conserved non-coding genomic regions are independently lost in mammals

PubMed Central

Hiller, Michael; Schaar, Bruce T.; Bejerano, Gill

2012-01-01

Conserved non-protein-coding DNA elements (CNEs) often encode cis-regulatory elements and are rarely lost during evolution. However, CNE losses that do occur can be associated with phenotypic changes, exemplified by pelvic spine loss in sticklebacks. Using a computational strategy to detect complete loss of CNEs in mammalian genomes while strictly controlling for artifacts, we find >600 CNEs that are independently lost in at least two mammalian lineages, including a spinal cord enhancer near GDF11. We observed several genomic regions where multiple independent CNE loss events happened; the most extreme is the DIAPH2 locus. We show that CNE losses often involve deletions and that CNE loss frequencies are non-uniform. Similar to less pleiotropic enhancers, we find that independently lost CNEs are shorter, slightly less constrained and evolutionarily younger than CNEs without detected losses. This suggests that independently lost CNEs are less pleiotropic and that pleiotropic constraints contribute to non-uniform CNE loss frequencies. We also detected 35 CNEs that are independently lost in the human lineage and in other mammals. Our study uncovers an interesting aspect of the evolution of functional DNA in mammalian genomes. Experiments are necessary to test if these independently lost CNEs are associated with parallel phenotype changes in mammals. PMID:23042682

Defining Mononuclear Phagocyte Subset Homology Across Several Distant Warm-Blooded Vertebrates Through Comparative Transcriptomics

PubMed Central

Vu Manh, Thien-Phong; Elhmouzi-Younes, Jamila; Urien, Céline; Ruscanu, Suzana; Jouneau, Luc; Bourge, Mickaël; Moroldo, Marco; Foucras, Gilles; Salmon, Henri; Marty, Hélène; Quéré, Pascale; Bertho, Nicolas; Boudinot, Pierre; Dalod, Marc; Schwartz-Cornil, Isabelle

2015-01-01

Mononuclear phagocytes are organized in a complex system of ontogenetically and functionally distinct subsets, that has been best described in mouse and to some extent in human. Identification of homologous mononuclear phagocyte subsets in other vertebrate species of biomedical, economic, and environmental interest is needed to improve our knowledge in physiologic and physio-pathologic processes, and to design intervention strategies against a variety of diseases, including zoonotic infections. We developed a streamlined approach combining refined cell sorting and integrated comparative transcriptomics analyses which revealed conservation of the mononuclear phagocyte organization across human, mouse, sheep, pigs and, in some respect, chicken. This strategy should help democratizing the use of omics analyses for the identification and study of cell types across tissues and species. Moreover, we identified conserved gene signatures that enable robust identification and universal definition of these cell types. We identified new evolutionarily conserved gene candidates and gene interaction networks for the molecular regulation of the development or functions of these cell types, as well as conserved surface candidates for refined subset phenotyping throughout species. A phylogenetic analysis revealed that orthologous genes of the conserved signatures exist in teleost fishes and apparently not in Lamprey. PMID:26150816

Hydrodynamic and kinetic models for spin-1/2 electron-positron quantum plasmas: Annihilation interaction, helicity conservation, and wave dispersion in magnetized plasmas

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

Andreev, Pavel A., E-mail: andreevpa@physics.msu.ru

2015-06-15

We discuss the complete theory of spin-1/2 electron-positron quantum plasmas, when electrons and positrons move with velocities mach smaller than the speed of light. We derive a set of two fluid quantum hydrodynamic equations consisting of the continuity, Euler, spin (magnetic moment) evolution equations for each species. We explicitly include the Coulomb, spin-spin, Darwin and annihilation interactions. The annihilation interaction is the main topic of the paper. We consider the contribution of the annihilation interaction in the quantum hydrodynamic equations and in the spectrum of waves in magnetized electron-positron plasmas. We consider the propagation of waves parallel and perpendicular tomore » an external magnetic field. We also consider the oblique propagation of longitudinal waves. We derive the set of quantum kinetic equations for electron-positron plasmas with the Darwin and annihilation interactions. We apply the kinetic theory to the linear wave behavior in absence of external fields. We calculate the contribution of the Darwin and annihilation interactions in the Landau damping of the Langmuir waves. We should mention that the annihilation interaction does not change number of particles in the system. It does not related to annihilation itself, but it exists as a result of interaction of an electron-positron pair via conversion of the pair into virtual photon. A pair of the non-linear Schrodinger equations for the electron-positron plasmas including the Darwin and annihilation interactions is derived. Existence of the conserving helicity in electron-positron quantum plasmas of spinning particles with the Darwin and annihilation interactions is demonstrated. We show that the annihilation interaction plays an important role in the quantum electron-positron plasmas giving the contribution of the same magnitude as the spin-spin interaction.« less

Identification of an evolutionarily conserved extracellular threonine residue critical for surface expression and its potential coupling of adjacent voltage-sensing and gating domains in voltage-gated potassium channels.

PubMed

Mckeown, Lynn; Burnham, Matthew P; Hodson, Charlotte; Jones, Owen T

2008-10-31

The dynamic expression of voltage-gated potassium channels (Kvs) at the cell surface is a fundamental factor controlling membrane excitability. In exploring possible mechanisms controlling Kv surface expression, we identified a region in the extracellular linker between the first and second of the six (S1-S6) transmembrane-spanning domains of the Kv1.4 channel, which we hypothesized to be critical for its biogenesis. Using immunofluorescence microscopy, flow cytometry, patch clamp electrophysiology, and mutagenesis, we identified a single threonine residue at position 330 within the Kv1.4 S1-S2 linker that is absolutely required for cell surface expression. Mutation of Thr-330 to an alanine, aspartate, or lysine prevented surface expression. However, surface expression occurred upon co-expression of mutant and wild type Kv1.4 subunits or mutation of Thr-330 to a serine. Mutation of the corresponding residue (Thr-211) in Kv3.1 to alanine also caused intracellular retention, suggesting that the conserved threonine plays a generalized role in surface expression. In support of this idea, sequence comparisons showed conservation of the critical threonine in all Kv families and in organisms across the evolutionary spectrum. Based upon the Kv1.2 crystal structure, further mutagenesis, and the partial restoration of surface expression in an electrostatic T330K bridging mutant, we suggest that Thr-330 hydrogen bonds to equally conserved outer pore residues, which may include a glutamate at position 502 that is also critical for surface expression. We propose that Thr-330 serves to interlock the voltage-sensing and gating domains of adjacent monomers, thereby yielding a structure competent for the surface expression of functional tetramers.

Conserved Arginines at the P-Protein Stalk Binding Site and the Active Site Are Critical for Ribosome Interactions of Shiga Toxins but Do Not Contribute to Differences in the Affinity of the A1 Subunits for the Ribosome.

PubMed

Basu, Debaleena; Kahn, Jennifer N; Li, Xiao-Ping; Tumer, Nilgun E

2016-12-01

The A1 subunits of Shiga toxin 1 (Stx1A1) and Shiga toxin 2 (Stx2A1) interact with the conserved C termini of ribosomal-stalk P-proteins to remove a specific adenine from the sarcin/ricin loop. We previously showed that Stx2A1 has higher affinity for the ribosome and higher catalytic activity than Stx1A1. To determine if conserved arginines at the distal face of the active site contribute to the higher affinity of Stx2A1 for the ribosome, we mutated Arg172, Arg176, and Arg179 in both toxins. We show that Arg172 and Arg176 are more important than Arg179 for the depurination activity and toxicity of Stx1A1 and Stx2A1. Mutation of a single arginine reduced the depurination activity of Stx1A1 more than that of Stx2A1. In contrast, mutation of at least two arginines was necessary to reduce depurination by Stx2A1 to a level similar to that of Stx1A1. R176A and R172A/R176A mutations eliminated interaction of Stx1A1 and Stx2A1 with ribosomes and with the stalk, while mutation of Arg170 at the active site reduced the binding affinity of Stx1A1 and Stx2A1 for the ribosome, but not for the stalk. These results demonstrate that conserved arginines at the distal face of the active site are critical for interactions of Stx1A1 and Stx2A1 with the stalk, while a conserved arginine at the active site is critical for non-stalk-specific interactions with the ribosome. Arginine mutations at either site reduced ribosome interactions of Stx1A1 and Stx2A1 similarly, indicating that conserved arginines are critical for ribosome interactions but do not contribute to the higher affinity of Stx2A1 for the ribosome. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Planar Cell Polarity Pathway – Coordinating morphogenetic cell behaviors with embryonic polarity

PubMed Central

Gray, Ryan S.; Roszko, Isabelle; Solnica-Krezel, Lilianna

2011-01-01

Planar cell polarization entails establishment of cellular asymmetries within the tissue plane. An evolutionarily conserved Planar Cell Polarity (PCP) signaling system employs intra- and intercellular feedback interactions between its core components, including Frizzled, Van Gogh, Flamingo, Prickle and Dishevelled, to establish their characteristic asymmetric intracellular distributions and coordinate planar polarity of cell populations. By translating global patterning information into asymmetries of cell membranes and intracellular organelles, PCP signaling coordinates morphogenetic behaviors of individual cells and cell populations with the embryonic polarity. In vertebrates, by polarizing cilia in the node/Kupffer’s vesicle, PCP signaling links the anteroposterior to left-right embryonic polarity. PMID:21763613

Staufen2 isoforms localize to the somatodendritic domain of neurons and interact with different organelles.

PubMed

Duchaîne, Thomas F; Hemraj, Indradeo; Furic, Luc; Deitinghoff, Anke; Kiebler, Michael A; DesGroseillers, Luc

2002-08-15

Mammalian Staufen2 (Stau2) is involved in mRNA transport in neurons. Here, we report that Stau2 is a double-stranded RNA-binding protein that is mainly expressed in the brain. We show that Stau2 is found in the somatodendritic compartment of neurons. In dendrites, Stau2 is aligned on individual tracts and colocalizes with microtubules. Stau2 is expressed as at least three splice isoforms, which can be observed in several subcellular complexes. Although a 62 kDa isoform (Stau2(62)) fractionates in ribosome-free fractions of light density, Stau2(59) and Stau2(52) are found in high-density complexes. These complexes are resistant to EDTA and to non-ionic detergent. For the first time, we also provide evidence for an interaction of some Stau2 isoforms with ribosomes, thus pointing to an interesting new role for Stau2 in translation. EDTA treatment, which dissociates ribosome subunits, does not release Stau2 from the subunits, suggesting that Stau2-ribosome associations are not mediated mainly by mRNA intermediates. Although Stau2 has many features in common with its paralogue Stau1, it does not colocalize with Stau1-containing particles, indicating that these proteins are components of different complexes in dendrites. Our findings suggest that members of the Staufen family share evolutionarily conserved properties and highlight the complexity of Staufen-mediated RNA transport in neurons.

Protected Areas' Impacts on Brazilian Amazon Deforestation: Examining Conservation-Development Interactions to Inform Planning.

PubMed

Pfaff, Alexander; Robalino, Juan; Herrera, Diego; Sandoval, Catalina

2015-01-01

Protected areas are the leading forest conservation policy for species and ecoservices goals and they may feature in climate policy if countries with tropical forest rely on familiar tools. For Brazil's Legal Amazon, we estimate the average impact of protection upon deforestation and show how protected areas' forest impacts vary significantly with development pressure. We use matching, i.e., comparisons that are apples-to-apples in observed land characteristics, to address the fact that protected areas (PAs) tend to be located on lands facing less pressure. Correcting for that location bias lowers our estimates of PAs' forest impacts by roughly half. Further, it reveals significant variation in PA impacts along development-related dimensions: for example, the PAs that are closer to roads and the PAs closer to cities have higher impact. Planners have multiple conservation and development goals, and are constrained by cost, yet still conservation planning should reflect what our results imply about future impacts of PAs.

Structure of H/ACA RNP protein Nhp2p reveals cis/trans isomerization of a conserved proline at the RNA and Nop10 binding interface

PubMed Central

Koo, Bon-Kyung; Park, Chin-Ju; Fernandez, Cesar F.; Chim, Nicholas; Ding, Yi; Chanfreau, Guillaume; Feigon, Juli

2011-01-01

H/ACA small nucleolar and Cajal body ribonucleoproteins (RNPs) function in site-specific pseudouridylation of eukaryotic rRNA and snRNA, rRNA processing, and vertebrate telomerase biogenesis. Nhp2, one of four essential protein components of eukaryotic H/ACA RNPs, forms a core trimer with the pseudouridylase Cbf5 and Nop10 that specifically binds to H/ACA RNAs. Crystal structures of archaeal H/ACA RNPs have revealed how the protein components interact with each other and with the H/ACA RNA. However, in place of Nhp2p, archaeal H/ACA RNPs contain L7Ae, which binds specifically to an RNA K-loop motif absent in eukaryotic H/ACA RNPs, while Nhp2 binds a broader range of RNA structures. We report solution NMR studies of S. cerevisiae Nhp2 (Nhp2p), which reveal that Nhp2p exhibits two major conformations in solution due to cis/trans isomerization of the evolutionarily conserved Pro83. The equivalent proline is in the cis conformation in all reported structures of L7Ae and other homologous proteins. Nhp2p has the expected α-β-α fold, but the solution structures of the major conformation of Nhp2p with trans Pro83 and of Nhp2p-S82W with cis Pro83 reveal that Pro83 cis/trans isomerization affects the positions of numerous residues at the Nop10- and RNA-binding interface. An S82W substitution, which stabilizes the cis conformation, also stabilizes the association of Nhp2p with H/ACA snoRNPs in vivo. We propose that Pro83 plays a key role in the assembly of the eukaryotic H/ACA RNP, with the cis conformation locking in a stable Cbf5-Nop10-Nhp2 ternary complex and positioning the protein backbone to interact with the H/ACA RNA. PMID:21708174

A Highly Conserved Leucine in Mammarenavirus Matrix Z Protein Is Required for Z Interaction with the Virus L Polymerase and Z Stability in Cells Harboring an Active Viral Ribonucleoprotein.

PubMed

Iwasaki, Masaharu; de la Torre, Juan C

2018-06-01

Mammarenaviruses cause chronic infections in their natural rodent hosts. Infected rodents shed infectious virus into excreta. Humans are infected through mucosal exposure to aerosols or direct contact of abraded skin with fomites, resulting in a wide range of manifestations from asymptomatic or mild febrile illness to severe life-threatening hemorrhagic fever. The mammarenavirus matrix Z protein has been shown to be a main driving force of virus budding and to act as a negative regulator of viral RNA synthesis. To gain a better understanding of how the Z protein exerts its several different functions, we investigated the interaction between Z and viral polymerase L protein using the prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV). We found that in the presence of an active viral ribonucleoprotein (vRNP), the Z protein translocated from nonionic detergent-resistant, membrane-rich structures to a subcellular compartment with a different membrane composition susceptible to disruption by nonionic detergents. Alanine (A) substitution of a highly conserved leucine (L) at position 72 in LCMV Z protein abrogated Z-L interaction. The L72A mutation did not affect the stability or budding activity of Z when expressed alone, but in the presence of an active vRNP, mutation L72A promoted rapid degradation of Z via a proteasome- and lysosome-independent pathway. Accordingly, L72A mutation in the Z protein resulted in nonviable LCMV. Our findings have uncovered novel aspects of the dynamics of the Z protein for which a highly conserved L residue was strictly required. IMPORTANCE Several mammarenaviruses, chiefly Lassa virus (LASV), cause hemorrhagic fever disease in humans and pose important public health concerns in their regions of endemicity. Moreover, mounting evidence indicates that the worldwide-distributed, prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. The mammarenavirus

[Interconnection between architecture of protein globule and disposition of conformational conservative oligopeptides in proteins from one protein family].

PubMed

Batianovskiĭ, A V; Filatov, I V; Namiot, V A; Esipova, N G; Volotovskiĭ, I D

2012-01-01

It was shown that selective interactions between helical segments of macromolecules can realize in globular proteins in the segments characterized by the same periodicities of charge distribution i.e. between conformationally conservative oligopeptides. It was found that in the macromolecules of alpha-helical proteins conformationally conservative oligopeptides are disposed at a distance being characteristic of direct interactions. For representatives of many structural families of alpha-type proteins specific disposition of conformationally conservative segments is observed. This disposition is inherent to a particular structural family. Disposition of conformationally conservative segments is not related to homology of the amino acid sequence but reflects peculiarities of native 3D-architectures of protein globules.

Summoning compassion to address the challenges of conservation.

PubMed

Wallach, Arian D; Bekoff, Marc; Batavia, Chelsea; Nelson, Michael P; Ramp, Daniel

2018-04-27

Conservation practice is informed by science, but also reflects ethical beliefs about how we ought to value and interact with the Earth's biota. As human activities continue to drive extinctions and diminish critical life-sustaining ecosystem processes, achieving conservation goals becomes increasingly urgent. In our determination to react decisively, conservation challenges can be handled without due deliberation, particularly when wildlife individuals are sacrificed "for the greater good" of wildlife collectives (populations, species, ecosystems). With growing recognition of the widespread sentience and sapience of many nonhuman animals, standard conservation practices that categorically prioritize collectives without due consideration for the wellbeing of individuals are ethically untenable. Here we highlight three overarching ethical orientations characterizing current and historical practices in conservation that suppress compassion: instrumentalism, collectivism, and nativism. We illustrate how establishing a commitment to compassion could re-orient conservation in more ethically expansive directions, which incorporate recognition of the intrinsic value of wildlife, the sentience of nonhuman animals, and the values of novel ecosystems, introduced species and their members. A compassionate conservation approach allays practices that intentionally and unnecessarily harm wildlife individuals, while aligning with critical conservation goals. Although the urgency of achieving effective outcomes for solving major conservation problems may enhance the appeal of quick and harsh measures, the costs are too high. Continuing to justify moral indifference when causing the suffering of wildlife individuals, particularly those who possess sophisticated capacities for emotion, consciousness, and sociality, risks estranging conservation practice from prevailing, and appropriate, social values. As conservationists and compassionate beings, we must demonstrate concern for both

Elementary Particles and Weak Interactions

DOE R&D Accomplishments Database

Lee, T. D.; Yang, C. N.

1957-01-01

Some general patterns of interactions between various elementary particles are reviewed and some general questions concerning the symmetry properties of these particles are studied. Topics are included on the theta-tau puzzle, experimental limits on the validity of parity conservation, some general discussions on the consequences due to possible non-invariance under P, C, and T, various possible experimental tests on invariance under P, C, and T, a two-component theory of the neutrino, a possible law of conservation of leptons and the universal Fermi interactions, and time reversal invariance and Mach's principle. (M.H.R.)

Conservation physiology of animal migration

PubMed Central

Lennox, Robert J.; Chapman, Jacqueline M.; Souliere, Christopher M.; Tudorache, Christian; Wikelski, Martin; Metcalfe, Julian D.; Cooke, Steven J.

2016-01-01

Migration is a widespread phenomenon among many taxa. This complex behaviour enables animals to exploit many temporally productive and spatially discrete habitats to accrue various fitness benefits (e.g. growth, reproduction, predator avoidance). Human activities and global environmental change represent potential threats to migrating animals (from individuals to species), and research is underway to understand mechanisms that control migration and how migration responds to modern challenges. Focusing on behavioural and physiological aspects of migration can help to provide better understanding, management and conservation of migratory populations. Here, we highlight different physiological, behavioural and biomechanical aspects of animal migration that will help us to understand how migratory animals interact with current and future anthropogenic threats. We are in the early stages of a changing planet, and our understanding of how physiology is linked to the persistence of migratory animals is still developing; therefore, we regard the following questions as being central to the conservation physiology of animal migrations. Will climate change influence the energetic costs of migration? Will shifting temperatures change the annual clocks of migrating animals? Will anthropogenic influences have an effect on orientation during migration? Will increased anthropogenic alteration of migration stopover sites/migration corridors affect the stress physiology of migrating animals? Can physiological knowledge be used to identify strategies for facilitating the movement of animals? Our synthesis reveals that given the inherent challenges of migration, additional stressors derived from altered environments (e.g. climate change, physical habitat alteration, light pollution) or interaction with human infrastructure (e.g. wind or hydrokinetic turbines, dams) or activities (e.g. fisheries) could lead to long-term changes to migratory phenotypes. However, uncertainty remains

Conservation physiology of animal migration.

PubMed

Lennox, Robert J; Chapman, Jacqueline M; Souliere, Christopher M; Tudorache, Christian; Wikelski, Martin; Metcalfe, Julian D; Cooke, Steven J

2016-01-01

Migration is a widespread phenomenon among many taxa. This complex behaviour enables animals to exploit many temporally productive and spatially discrete habitats to accrue various fitness benefits (e.g. growth, reproduction, predator avoidance). Human activities and global environmental change represent potential threats to migrating animals (from individuals to species), and research is underway to understand mechanisms that control migration and how migration responds to modern challenges. Focusing on behavioural and physiological aspects of migration can help to provide better understanding, management and conservation of migratory populations. Here, we highlight different physiological, behavioural and biomechanical aspects of animal migration that will help us to understand how migratory animals interact with current and future anthropogenic threats. We are in the early stages of a changing planet, and our understanding of how physiology is linked to the persistence of migratory animals is still developing; therefore, we regard the following questions as being central to the conservation physiology of animal migrations. Will climate change influence the energetic costs of migration? Will shifting temperatures change the annual clocks of migrating animals? Will anthropogenic influences have an effect on orientation during migration? Will increased anthropogenic alteration of migration stopover sites/migration corridors affect the stress physiology of migrating animals? Can physiological knowledge be used to identify strategies for facilitating the movement of animals? Our synthesis reveals that given the inherent challenges of migration, additional stressors derived from altered environments (e.g. climate change, physical habitat alteration, light pollution) or interaction with human infrastructure (e.g. wind or hydrokinetic turbines, dams) or activities (e.g. fisheries) could lead to long-term changes to migratory phenotypes. However, uncertainty remains

INTEGRATING ECOLOGY AND SOCIOECONOMICS FOR WILDLIFE MANAGEMENT AND CONSERVATION

EPA Science Inventory

Many researchers have studied impacts of human activity on wildlife or human attitudes toward wildlife, but not both simultaneously. Understanding these interactions is critical to better understand the intricacies of real world conservation issues. The goal of my presentation ...

An evolutionarily conserved RNase-based mechanism for repression of transcriptional positive autoregulation

PubMed Central

Wurtmann, Elisabeth J.; Ratushny, Alexander V.; Pan, Min; Beer, Karlyn D.; Aitchison, John D.; Baliga, Nitin S.

2014-01-01

Summary It is known that environmental context influences the degree of regulation at the transcriptional and post-transcriptional levels. However, the principles governing the differential usage and interplay of regulation at these two levels are not clear. Here, we show that the integration of transcriptional and post-transcriptional regulatory mechanisms in a characteristic network motif drives efficient environment-dependent state transitions. Through phenotypic screening, systems analysis, and rigorous experimental validation, we discovered an RNase (VNG2099C) in Halobacterium salinarum that is transcriptionally co-regulated with genes of the aerobic physiologic state but acts on transcripts of the anaerobic state. Through modeling and experimentation we show that this arrangement generates an efficient state-transition switch, within which RNase-repression of a transcriptional positive autoregulation (RPAR) loop is critical for shutting down ATP-consuming active potassium uptake to reserve energy required for salinity adaptation under aerobic, high potassium, or dark conditions. Subsequently, we discovered that many Escherichia coli operons with energy-associated functions are also putatively controlled by RPAR indicating that this network motif may have evolved independently in phylogenetically distant organisms. Thus, our data suggest that interplay of transcriptional and post-transcriptional regulation in the RPAR motifis a generalized principle for efficient environment-dependent state transitions across prokaryotes. PMID:24612392

Monoacylglycerol Lipases Act as Evolutionarily Conserved Regulators of Non-oxidative Ethanol Metabolism*

PubMed Central

Heier, Christoph; Taschler, Ulrike; Radulovic, Maja; Aschauer, Philip; Eichmann, Thomas O.; Grond, Susanne; Wolinski, Heimo; Oberer, Monika; Zechner, Rudolf; Kohlwein, Sepp D.; Zimmermann, Robert

2016-01-01

Fatty acid ethyl esters (FAEEs) are non-oxidative metabolites of ethanol that accumulate in human tissues upon ethanol intake. Although FAEEs are considered as toxic metabolites causing cellular dysfunction and tissue damage, the enzymology of FAEE metabolism remains poorly understood. In this study, we used a biochemical screen in Saccharomyces cerevisiae to identify and characterize putative hydrolases involved in FAEE catabolism. We found that Yju3p, the functional orthologue of mammalian monoacylglycerol lipase (MGL), contributes >90% of cellular FAEE hydrolase activity, and its loss leads to the accumulation of FAEE. Heterologous expression of mammalian MGL in yju3Δ mutants restored cellular FAEE hydrolase activity and FAEE catabolism. Moreover, overexpression or pharmacological inhibition of MGL in mouse AML-12 hepatocytes decreased or increased FAEE levels, respectively. FAEEs were transiently incorporated into lipid droplets (LDs) and both Yju3p and MGL co-localized with these organelles. We conclude that the storage of FAEE in inert LDs and their mobilization by LD-resident FAEE hydrolases facilitate a controlled metabolism of these potentially toxic lipid metabolites. PMID:27036938

WASP and SCAR are evolutionarily conserved in actin-filled pseudopod-based motility

PubMed Central

2017-01-01

Diverse eukaryotic cells crawl through complex environments using distinct modes of migration. To understand the underlying mechanisms and their evolutionary relationships, we must define each mode and identify its phenotypic and molecular markers. In this study, we focus on a widely dispersed migration mode characterized by dynamic actin-filled pseudopods that we call “α-motility.” Mining genomic data reveals a clear trend: only organisms with both WASP and SCAR/WAVE—activators of branched actin assembly—make actin-filled pseudopods. Although SCAR has been shown to drive pseudopod formation, WASP’s role in this process is controversial. We hypothesize that these genes collectively represent a genetic signature of α-motility because both are used for pseudopod formation. WASP depletion from human neutrophils confirms that both proteins are involved in explosive actin polymerization, pseudopod formation, and cell migration. WASP and WAVE also colocalize to dynamic signaling structures. Moreover, retention of WASP together with SCAR correctly predicts α-motility in disease-causing chytrid fungi, which we show crawl at >30 µm/min with actin-filled pseudopods. By focusing on one migration mode in many eukaryotes, we identify a genetic marker of pseudopod formation, the morphological feature of α-motility, providing evidence for a widely distributed mode of cell crawling with a single evolutionary origin. PMID:28473602

Evidence for an Evolutionarily Conserved Memory Coding Scheme in the Mammalian Hippocampus

PubMed Central

Thome, Alexander; Lisanby, Sarah H.; McNaughton, Bruce L.

2017-01-01

Decades of research identify the hippocampal formation as central to memory storage and recall. Events are stored via distributed population codes, the parameters of which (e.g., sparsity and overlap) determine both storage capacity and fidelity. However, it remains unclear whether the parameters governing information storage are similar between species. Because episodic memories are rooted in the space in which they are experienced, the hippocampal response to navigation is often used as a proxy to study memory. Critically, recent studies in rodents that mimic the conditions typical of navigation studies in humans and nonhuman primates (i.e., virtual reality) show that reduced sensory input alters hippocampal representations of space. The goal of this study was to quantify this effect and determine whether there are commonalities in information storage across species. Using functional molecular imaging, we observe that navigation in virtual environments elicits activity in fewer CA1 neurons relative to real-world conditions. Conversely, comparable neuronal activity is observed in hippocampus region CA3 and the dentate gyrus under both conditions. Surprisingly, we also find evidence that the absolute number of neurons used to represent an experience is relatively stable between nonhuman primates and rodents. We propose that this convergence reflects an optimal ensemble size for episodic memories. SIGNIFICANCE STATEMENT One primary factor constraining memory capacity is the sparsity of the engram, the proportion of neurons that encode a single experience. Investigating sparsity in humans is hampered by the lack of single-cell resolution and differences in behavioral protocols. Sparsity can be quantified in freely moving rodents, but extrapolating these data to humans assumes that information storage is comparable across species and is robust to restraint-induced reduction in sensory input. Here, we test these assumptions and show that species differences in brain size build memory capacity without altering the structure of the data being stored. Furthermore, sparsity in most of the hippocampus is resilient to reduced sensory information. This information is vital to integrating animal data with human imaging navigation studies. PMID:28174334

Human Populations and the World Conservation Strategy. Commission on Ecology Paper Number 11.

ERIC Educational Resources Information Center

Hanks, J.

This document serves as a supplement to the World Conservation Strategy (WCS) and outlines some of the critical aspects of the interaction between human populations, natural resources, and social and economic conditions. Particular emphasis is placed on the importance of planning with people, and on packaging conservation programs so they are more…

Right-handed neutrinos and T-violating, P-conserving interactions

NASA Astrophysics Data System (ADS)

El-Menoufi, Basem Kamal; Ramsey-Musolf, Michael J.; Seng, Chien-Yeah

2017-02-01

We show that experimental probes of the P-conserving, T-violating triple correlation in polarized neutron or nuclear β-decay provide a unique probe of possible T-violation at the TeV scale in the presence of right-handed neutrinos. In contrast to other possible sources of semileptonic T-violation involving only left-handed neutrinos, those involving right-handed neutrinos are relatively unconstrained by present limits on the permanent electric dipole moments of the electron, neutral atoms, and the neutron. On the other hand, LHC results for pp → e + missing transverse energy imply that an order of magnitude of improvement in D-coefficient sensitivity would be needed for discovery. Finally, we discuss the interplay with the scale of neutrino mass and naturalness considerations.

Interactive Mapping of Inundation Metrics Using Cloud Computing for Improved Floodplain Conservation and Management

NASA Astrophysics Data System (ADS)

Bulliner, E. A., IV; Lindner, G. A.; Bouska, K.; Paukert, C.; Jacobson, R. B.

2017-12-01

Within large-river ecosystems, floodplains serve a variety of important ecological functions. A recent survey of 80 managers of floodplain conservation lands along the Upper and Middle Mississippi and Lower Missouri Rivers in the central United States found that the most critical information needed to improve floodplain management centered on metrics for characterizing depth, extent, frequency, duration, and timing of inundation. These metrics can be delivered to managers efficiently through cloud-based interactive maps. To calculate these metrics, we interpolated an existing one-dimensional hydraulic model for the Lower Missouri River, which simulated water surface elevations at cross sections spaced (<1 km) to sufficiently characterize water surface profiles along an approximately 800 km stretch upstream from the confluence with the Mississippi River over an 80-year record at a daily time step. To translate these water surface elevations to inundation depths, we subtracted a merged terrain model consisting of floodplain LIDAR and bathymetric surveys of the river channel. This approach resulted in a 29000+ day time series of inundation depths across the floodplain using grid cells with 30 m spatial resolution. Initially, we used these data on a local workstation to calculate a suite of nine spatially distributed inundation metrics for the entire model domain. These metrics are calculated on a per pixel basis and encompass a variety of temporal criteria generally relevant to flora and fauna of interest to floodplain managers, including, for example, the average number of days inundated per year within a growing season. Using a local workstation, calculating these metrics for the entire model domain requires several hours. However, for the needs of individual floodplain managers working at site scales, these metrics may be too general and inflexible. Instead of creating a priori a suite of inundation metrics able to satisfy all user needs, we present the usage of

The need to respect nature and its limits challenges society and conservation science

PubMed Central

Martin, Jean-Louis; Maris, Virginie; Simberloff, Daniel S.

2016-01-01

Increasing human population interacts with local and global environments to deplete biodiversity and resources humans depend on, thus challenging societal values centered on growth and relying on technology to mitigate environmental stress. Although the need to address the environmental crisis, central to conservation science, generated greener versions of the growth paradigm, we need fundamental shifts in values that ensure transition from a growth-centered society to one acknowledging biophysical limits and centered on human well-being and biodiversity conservation. We discuss the role conservation science can play in this transformation, which poses ethical challenges and obstacles. We analyze how conservation and economics can achieve better consonance, the extent to which technology should be part of the solution, and difficulties the “new conservation science” has generated. An expanded ambition for conservation science should reconcile day-to-day action within the current context with uncompromising, explicit advocacy for radical transitions in core attitudes and processes that govern our interactions with the biosphere. A widening of its focus to understand better the interconnectedness between human well-being and acknowledgment of the limits of an ecologically functional and diverse planet will need to integrate ecological and social sciences better. Although ecology can highlight limits to growth and consequences of ignoring them, social sciences are necessary to diagnose societal mechanisms at work, how to correct them, and potential drivers of social change. PMID:27185943

The need to respect nature and its limits challenges society and conservation science.

PubMed

Martin, Jean-Louis; Maris, Virginie; Simberloff, Daniel S

2016-05-31

Increasing human population interacts with local and global environments to deplete biodiversity and resources humans depend on, thus challenging societal values centered on growth and relying on technology to mitigate environmental stress. Although the need to address the environmental crisis, central to conservation science, generated greener versions of the growth paradigm, we need fundamental shifts in values that ensure transition from a growth-centered society to one acknowledging biophysical limits and centered on human well-being and biodiversity conservation. We discuss the role conservation science can play in this transformation, which poses ethical challenges and obstacles. We analyze how conservation and economics can achieve better consonance, the extent to which technology should be part of the solution, and difficulties the "new conservation science" has generated. An expanded ambition for conservation science should reconcile day-to-day action within the current context with uncompromising, explicit advocacy for radical transitions in core attitudes and processes that govern our interactions with the biosphere. A widening of its focus to understand better the interconnectedness between human well-being and acknowledgment of the limits of an ecologically functional and diverse planet will need to integrate ecological and social sciences better. Although ecology can highlight limits to growth and consequences of ignoring them, social sciences are necessary to diagnose societal mechanisms at work, how to correct them, and potential drivers of social change.

GOLGI TRANSPORT 1B Regulates Protein Export from the Endoplasmic Reticulum in Rice Endosperm Cells[OPEN

PubMed Central

Liu, Feng; Wang, Yunlong; Liu, Xi; Wang, Di; Zhu, Xiaopin; Jing, Ruonan; Wu, Mingming; Hao, Yuanyuan; Jiang, Ling; Wang, Chunming

2016-01-01

Coat protein complex II (COPII) mediates the first step of anterograde transport of newly synthesized proteins from the endoplasmic reticulum (ER) to other endomembrane compartments in eukaryotes. A group of evolutionarily conserved proteins (Sar1, Sec23, Sec24, Sec13, and Sec31) constitutes the basic COPII coat machinery; however, the details of how the COPII coat assembly is regulated remain unclear. Here, we report a protein transport mutant of rice (Oryza sativa), named glutelin precursor accumulation4 (gpa4), which accumulates 57-kD glutelin precursors and forms two types of ER-derived abnormal structures. GPA4 encodes the evolutionarily conserved membrane protein GOT1B (also known as GLUP2), homologous to the Saccharomyces cerevisiae GOT1p. The rice GOT1B protein colocalizes with Arabidopsis thaliana Sar1b at Golgi-associated ER exit sites (ERESs) when they are coexpressed in Nicotiana benthamiana. Moreover, GOT1B physically interacts with rice Sec23, and both proteins are present in the same complex(es) with rice Sar1b. The distribution of rice Sar1 in the endomembrane system, its association with rice Sec23c, and the ERES organization pattern are significantly altered in the gpa4 mutant. Taken together, our results suggest that GOT1B plays an important role in mediating COPII vesicle formation at ERESs, thus facilitating anterograde transport of secretory proteins in plant cells. PMID:27803308

Integration of ecological-biological thresholds in conservation decision making.

PubMed

Mavrommati, Georgia; Bithas, Kostas; Borsuk, Mark E; Howarth, Richard B

2016-12-01

In the Anthropocene, coupled human and natural systems dominate and only a few natural systems remain relatively unaffected by human influence. On the one hand, conservation criteria based on areas of minimal human impact are not relevant to much of the biosphere. On the other hand, conservation criteria based on economic factors are problematic with respect to their ability to arrive at operational indicators of well-being that can be applied in practice over multiple generations. Coupled human and natural systems are subject to economic development which, under current management structures, tends to affect natural systems and cross planetary boundaries. Hence, designing and applying conservation criteria applicable in real-world systems where human and natural systems need to interact and sustainably coexist is essential. By recognizing the criticality of satisfying basic needs as well as the great uncertainty over the needs and preferences of future generations, we sought to incorporate conservation criteria based on minimal human impact into economic evaluation. These criteria require the conservation of environmental conditions such that the opportunity for intergenerational welfare optimization is maintained. Toward this end, we propose the integration of ecological-biological thresholds into decision making and use as an example the planetary-boundaries approach. Both conservation scientists and economists must be involved in defining operational ecological-biological thresholds that can be incorporated into economic thinking and reflect the objectives of conservation, sustainability, and intergenerational welfare optimization. © 2016 Society for Conservation Biology.

[Conserved motifs in voltage sensing proteins].

PubMed

Wang, Chang-He; Xie, Zhen-Li; Lv, Jian-Wei; Yu, Zhi-Dan; Shao, Shu-Li

2012-08-25

This paper was aimed to study conserved motifs of voltage sensing proteins (VSPs) and establish a voltage sensing model. All VSPs were collected from the Uniprot database using a comprehensive keyword search followed by manual curation, and the results indicated that there are only two types of known VSPs, voltage gated ion channels and voltage dependent phosphatases. All the VSPs have a common domain of four helical transmembrane segments (TMS, S1-S4), which constitute the voltage sensing module of the VSPs. The S1 segment was shown to be responsible for membrane targeting and insertion of these proteins, while S2-S4 segments, which can sense membrane potential, for protein properties. Conserved motifs/residues and their functional significance of each TMS were identified using profile-to-profile sequence alignments. Conserved motifs in these four segments are strikingly similar for all VSPs, especially, the conserved motif [RK]-X(2)-R-X(2)-R-X(2)-[RK] was presented in all the S4 segments, with positively charged arginine (R) alternating with two hydrophobic or uncharged residues. Movement of these arginines across the membrane electric field is the core mechanism by which the VSPs detect changes in membrane potential. The negatively charged aspartate (D) in the S3 segment is universally conserved in all the VSPs, suggesting that the aspartate residue may be involved in voltage sensing properties of VSPs as well as the electrostatic interactions with the positively charged residues in the S4 segment, which may enhance the thermodynamic stability of the S4 segments in plasma membrane.

Conservation of coevolving protein interfaces bridges prokaryote–eukaryote homologies in the twilight zone

PubMed Central

Rodriguez-Rivas, Juan; Marsili, Simone; Juan, David; Valencia, Alfonso

2016-01-01

Protein–protein interactions are fundamental for the proper functioning of the cell. As a result, protein interaction surfaces are subject to strong evolutionary constraints. Recent developments have shown that residue coevolution provides accurate predictions of heterodimeric protein interfaces from sequence information. So far these approaches have been limited to the analysis of families of prokaryotic complexes for which large multiple sequence alignments of homologous sequences can be compiled. We explore the hypothesis that coevolution points to structurally conserved contacts at protein–protein interfaces, which can be reliably projected to homologous complexes with distantly related sequences. We introduce a domain-centered protocol to study the interplay between residue coevolution and structural conservation of protein–protein interfaces. We show that sequence-based coevolutionary analysis systematically identifies residue contacts at prokaryotic interfaces that are structurally conserved at the interface of their eukaryotic counterparts. In turn, this allows the prediction of conserved contacts at eukaryotic protein–protein interfaces with high confidence using solely mutational patterns extracted from prokaryotic genomes. Even in the context of high divergence in sequence (the twilight zone), where standard homology modeling of protein complexes is unreliable, our approach provides sequence-based accurate information about specific details of protein interactions at the residue level. Selected examples of the application of prokaryotic coevolutionary analysis to the prediction of eukaryotic interfaces further illustrate the potential of this approach. PMID:27965389

Conservation of coevolving protein interfaces bridges prokaryote-eukaryote homologies in the twilight zone.

PubMed

Rodriguez-Rivas, Juan; Marsili, Simone; Juan, David; Valencia, Alfonso

2016-12-27

Protein-protein interactions are fundamental for the proper functioning of the cell. As a result, protein interaction surfaces are subject to strong evolutionary constraints. Recent developments have shown that residue coevolution provides accurate predictions of heterodimeric protein interfaces from sequence information. So far these approaches have been limited to the analysis of families of prokaryotic complexes for which large multiple sequence alignments of homologous sequences can be compiled. We explore the hypothesis that coevolution points to structurally conserved contacts at protein-protein interfaces, which can be reliably projected to homologous complexes with distantly related sequences. We introduce a domain-centered protocol to study the interplay between residue coevolution and structural conservation of protein-protein interfaces. We show that sequence-based coevolutionary analysis systematically identifies residue contacts at prokaryotic interfaces that are structurally conserved at the interface of their eukaryotic counterparts. In turn, this allows the prediction of conserved contacts at eukaryotic protein-protein interfaces with high confidence using solely mutational patterns extracted from prokaryotic genomes. Even in the context of high divergence in sequence (the twilight zone), where standard homology modeling of protein complexes is unreliable, our approach provides sequence-based accurate information about specific details of protein interactions at the residue level. Selected examples of the application of prokaryotic coevolutionary analysis to the prediction of eukaryotic interfaces further illustrate the potential of this approach.

Solving multi-objective optimization problems in conservation with the reference point method

PubMed Central

Dujardin, Yann; Chadès, Iadine

2018-01-01

Managing the biodiversity extinction crisis requires wise decision-making processes able to account for the limited resources available. In most decision problems in conservation biology, several conflicting objectives have to be taken into account. Most methods used in conservation either provide suboptimal solutions or use strong assumptions about the decision-maker’s preferences. Our paper reviews some of the existing approaches to solve multi-objective decision problems and presents new multi-objective linear programming formulations of two multi-objective optimization problems in conservation, allowing the use of a reference point approach. Reference point approaches solve multi-objective optimization problems by interactively representing the preferences of the decision-maker with a point in the criteria (objectives) space, called the reference point. We modelled and solved the following two problems in conservation: a dynamic multi-species management problem under uncertainty and a spatial allocation resource management problem. Results show that the reference point method outperforms classic methods while illustrating the use of an interactive methodology for solving combinatorial problems with multiple objectives. The method is general and can be adapted to a wide range of ecological combinatorial problems. PMID:29293650

Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination of endocytic clathrin-coated pits

PubMed Central

Messa, Mirko; Fernández-Busnadiego, Rubén; Sun, Elizabeth Wen; Chen, Hong; Czapla, Heather; Wrasman, Kristie; Wu, Yumei; Ko, Genevieve; Ross, Theodora; Wendland, Beverly; De Camilli, Pietro

2014-01-01

Epsin is an evolutionarily conserved endocytic clathrin adaptor whose most critical function(s) in clathrin coat dynamics remain(s) elusive. To elucidate such function(s), we generated embryonic fibroblasts from conditional epsin triple KO mice. Triple KO cells displayed a dramatic cell division defect. Additionally, a robust impairment in clathrin-mediated endocytosis was observed, with an accumulation of early and U-shaped pits. This defect correlated with a perturbation of the coupling between the clathrin coat and the actin cytoskeleton, which we confirmed in a cell-free assay of endocytosis. Our results indicate that a key evolutionary conserved function of epsin, in addition to other roles that include, as we show here, a low affinity interaction with SNAREs, is to help generate the force that leads to invagination and then fission of clathrin-coated pits. DOI: http://dx.doi.org/10.7554/eLife.03311.001 PMID:25122462

Interactions between a Trawl Fishery and Spatial Closures for Biodiversity Conservation in the Great Barrier Reef World Heritage Area, Australia

PubMed Central

Grech, Alana; Coles, Rob

2011-01-01

Background The Queensland East Coast Otter Trawl Fishery (ECOTF) for penaeid shrimp fishes within Australia's Great Barrier Reef World Heritage Area (GBRWHA). The past decade has seen the implementation of conservation and fisheries management strategies to reduce the impact of the ECOTF on the seabed and improve biodiversity conservation. New information from electronic vessel location monitoring systems (VMS) provides an opportunity to review the interactions between the ECOTF and spatial closures for biodiversity conservation. Methodology and Results We used fishing metrics and spatial information on the distribution of closures and modelled VMS data in a geographical information system (GIS) to assess change in effort of the trawl fishery from 2001–2009 and to quantify the exposure of 70 reef, non-reef and deep water bioregions to trawl fishing. The number of trawlers and the number of days fished almost halved between 2001 and 2009 and new spatial closures introduced in 2004 reduced the area zoned available for trawl fishing by 33%. However, we found that there was only a relatively minor change in the spatial footprint of the fishery as a result of new spatial closures. Non-reef bioregions benefited the most from new spatial closures followed by deep and reef bioregions. Conclusions/Significance Although the catch of non target species remains an issue of concern for fisheries management, the small spatial footprint of the ECOTF relative to the size of the GBRWHA means that the impact on benthic habitats is likely to be negligible. The decline in effort as a result of fishing industry structural adjustment, increasing variable costs and business decisions of fishers is likely to continue a trend to fish only in the most productive areas. This will provide protection for most benthic habitats without any further legislative or management intervention. PMID:21695155

Parasites and deleterious mutations: interactions influencing the evolutionary maintenance of sex.

PubMed

Park, A W; Jokela, J; Michalakis, Y

2010-05-01

The restrictive assumptions associated with purely genetic and purely ecological mechanisms suggest that neither of the two forces, in isolation, can offer a general explanation for the evolutionary maintenance of sex. Consequently, attention has turned to pluralistic models (i.e. models that apply both ecological and genetic mechanisms). Existing research has shown that combining mutation accumulation and parasitism allows restrictive assumptions about genetic and parasite parameter values to be relaxed while still predicting the maintenance of sex. However, several empirical studies have shown that deleterious mutations and parasitism can reduce fitness to a greater extent than would be expected if the two acted independently. We show how interactions between these genetic and ecological forces can completely reverse predictions about the evolution of reproductive modes. Moreover, we demonstrate that synergistic interactions between infection and deleterious mutations can render sex evolutionarily stable even when there is antagonistic epistasis among deleterious mutations, thereby widening the conditions for the evolutionary maintenance of sex.

Conserved molecular interactions in centriole-to-centrosome conversion.

PubMed

Fu, Jingyan; Lipinszki, Zoltan; Rangone, Hélène; Min, Mingwei; Mykura, Charlotte; Chao-Chu, Jennifer; Schneider, Sandra; Dzhindzhev, Nikola S; Gottardo, Marco; Riparbelli, Maria Giovanna; Callaini, Giuliano; Glover, David M

2016-01-01

Centrioles are required to assemble centrosomes for cell division and cilia for motility and signalling. New centrioles assemble perpendicularly to pre-existing ones in G1-S and elongate throughout S and G2. Fully elongated daughter centrioles are converted into centrosomes during mitosis to be able to duplicate and organize pericentriolar material in the next cell cycle. Here we show that centriole-to-centrosome conversion requires sequential loading of Cep135, Ana1 (Cep295) and Asterless (Cep152) onto daughter centrioles during mitotic progression in both Drosophila melanogaster and human. This generates a molecular network spanning from the inner- to outermost parts of the centriole. Ana1 forms a molecular strut within the network, and its essential role can be substituted by an engineered fragment providing an alternative linkage between Asterless and Cep135. This conserved architectural framework is essential for loading Asterless or Cep152, the partner of the master regulator of centriole duplication, Plk4. Our study thus uncovers the molecular basis for centriole-to-centrosome conversion that renders daughter centrioles competent for motherhood.

Right-handed neutrinos and T-violating, P-conserving interactions

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

El-Menoufi, Basem Kamal; Ramsey-Musolf, Michael J.; Seng, Chien -Yeah

We show that experimental probes of the P-conserving, T-violating triple correlation in polarized neutron or nuclear β-decay provide a unique probe of possible T-violation at the TeV scale in the presence of right-handed neutrinos. In contrast to other possible sources of semileptonic T-violation involving only left-handed neutrinos, those involving right-handed neutrinos are relatively unconstrained by present limits on the permanent electric dipole moments of the electron, neutral atoms, and the neutron. On the other hand, LHC results for pp→e+ missing transverse energy imply that an order of magnitude of improvement in D-coefficient sensitivity would be needed for discovery. Lastly, wemore » discuss the interplay with the scale of neutrino mass and naturalness considerations.« less

Right-handed neutrinos and T-violating, P-conserving interactions

DOE PAGES

El-Menoufi, Basem Kamal; Ramsey-Musolf, Michael J.; Seng, Chien -Yeah

2016-12-02

We show that experimental probes of the P-conserving, T-violating triple correlation in polarized neutron or nuclear β-decay provide a unique probe of possible T-violation at the TeV scale in the presence of right-handed neutrinos. In contrast to other possible sources of semileptonic T-violation involving only left-handed neutrinos, those involving right-handed neutrinos are relatively unconstrained by present limits on the permanent electric dipole moments of the electron, neutral atoms, and the neutron. On the other hand, LHC results for pp→e+ missing transverse energy imply that an order of magnitude of improvement in D-coefficient sensitivity would be needed for discovery. Lastly, wemore » discuss the interplay with the scale of neutrino mass and naturalness considerations.« less

Conservation of the sequence of the Alzheimer's disease amyloid peptide in dog, polar bear and five other mammals by cross-species polymerase chain reaction analysis.

PubMed

Johnstone, E M; Chaney, M O; Norris, F H; Pascual, R; Little, S P

1991-07-01

Neuritic plaque and cerebrovascular amyloid deposits have been detected in the aged monkey, dog, and polar bear and have rarely been found in aged rodents (Biochem. Biophy. Res. Commun., 12 (1984) 885-890; Proc. Natl. Acad. Sci. U.S.A., 82 (1985) 4245-4249). To determine if the primary structure of the 42-43 residue amyloid peptide is conserved in species that accumulate plaques, the region of the amyloid precursor protein (APP) cDNA that encodes the peptide region was amplified by the polymerase chain reaction and sequenced. The deduced amino acid sequence was compared to those species where amyloid accumulation has not been detected. The DNA sequences of dog, polar bear, rabbit, cow, sheep, pig and guinea pig were compared and a phylogenetic tree was generated. We conclude that the amino acid sequence of dog and polar bear and other mammals which may form amyloid plaques is conserved and the species where amyloid has not been detected (mouse, rat) may be evolutionarily a distinct group. In addition, the predicted secondary structure of mouse and rat amyloid that differs from that of amyloid bearing species is its lack of propensity to form a beta sheeted structure. Thus, a cross-species examination of the amyloid peptide may suggest what is essential for amyloid deposition.

State of the interface between conservation and physiology: a bibliometric analysis

PubMed Central

Lennox, Robert; Cooke, Steven J.

2014-01-01

Contemporary conservation science benefits from the perspectives of a variety of different disciplines, including a recent synergy with physiology, an interface known as ‘conservation physiology’. To evaluate the degree of interaction between conservation and animal/plant physiology, we conducted three bibliometric analyses. We first pursued the use of the term ‘conservation physiology’ since its first definition in 2006 to determine how frequently it has been used and in which publications. Secondly, we evaluated the occurrence of conservation terms in animal and plant physiology journals, physiological terms in conservation journals, and a combination of terms in ecology journals. Thirdly, we explored trends in a subset of conservation physiology articles published between 2006 and 2012. We identified a surge in the use of the term ‘conservation physiology’ in 2012, after only a slow increase in usage between 2006 and 2011. Conservation journals tend to have been significantly more active in publishing conservation physiology than animal physiology, plant physiology or ecology journals. However, we found evidence that ecology and animal physiology journals began to incorporate more conservation physiology after 2006, while conservation- and plant physiology-themed journals did not. Among 299 conservation physiology articles that we identified, vertebrate taxa have been over-represented in conservation physiology compared with their relative taxonomic abundance, invertebrate taxa have been under-represented, and plants have been represented in proportion to their relative taxonomic abundance; however, those findings are reasonably consistent with publication trends in conservation biology. Diffuse distribution of conservation physiology papers throughout the literature may have been a barrier to the growth of the subdiscipline when the interface was emerging. The introduction of the focused journal Conservation Physiology in 2013 may address that

State of the interface between conservation and physiology: a bibliometric analysis.

PubMed

Lennox, Robert; Cooke, Steven J

2014-01-01

Contemporary conservation science benefits from the perspectives of a variety of different disciplines, including a recent synergy with physiology, an interface known as 'conservation physiology'. To evaluate the degree of interaction between conservation and animal/plant physiology, we conducted three bibliometric analyses. We first pursued the use of the term 'conservation physiology' since its first definition in 2006 to determine how frequently it has been used and in which publications. Secondly, we evaluated the occurrence of conservation terms in animal and plant physiology journals, physiological terms in conservation journals, and a combination of terms in ecology journals. Thirdly, we explored trends in a subset of conservation physiology articles published between 2006 and 2012. We identified a surge in the use of the term 'conservation physiology' in 2012, after only a slow increase in usage between 2006 and 2011. Conservation journals tend to have been significantly more active in publishing conservation physiology than animal physiology, plant physiology or ecology journals. However, we found evidence that ecology and animal physiology journals began to incorporate more conservation physiology after 2006, while conservation- and plant physiology-themed journals did not. Among 299 conservation physiology articles that we identified, vertebrate taxa have been over-represented in conservation physiology compared with their relative taxonomic abundance, invertebrate taxa have been under-represented, and plants have been represented in proportion to their relative taxonomic abundance; however, those findings are reasonably consistent with publication trends in conservation biology. Diffuse distribution of conservation physiology papers throughout the literature may have been a barrier to the growth of the subdiscipline when the interface was emerging. The introduction of the focused journal Conservation Physiology in 2013 may address that deficiency