35 research outputs found

    The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics

    Get PDF
    The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIVPle), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA ΦST = 0.92; nDNA FST = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIVPle subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIVPle variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently

    Topology analysis and visualization of Potyvirus protein-protein interaction network

    Get PDF
    Background: One of the central interests of Virology is the identification of host factors that contribute to virus infection. Despite tremendous efforts, the list of factors identified remains limited. With omics techniques, the focus has changed from identifying and thoroughly characterizing individual host factors to the simultaneous analysis of thousands of interactions, framing them on the context of protein-protein interaction networks and of transcriptional regulatory networks. This new perspective is allowing the identification of direct and indirect viral targets. Such information is available for several members of the Potyviridae family, one of the largest and more important families of plant viruses. Results: After collecting information on virus protein-protein interactions from different potyviruses, we have processed it and used it for inferring a protein-protein interaction network. All proteins are connected into a single network component. Some proteins show a high degree and are highly connected while others are much less connected, with the network showing a significant degree of dissortativeness. We have attempted to integrate this virus protein-protein interaction network into the largest protein-protein interaction network of Arabidopsis thaliana, a susceptible laboratory host. To make the interpretation of data and results easier, we have developed a new approach for visualizing and analyzing the dynamic spread on the host network of the local perturbations induced by viral proteins. We found that local perturbations can reach the entire host protein-protein interaction network, although the efficiency of this spread depends on the particular viral proteins. By comparing the spread dynamics among viral proteins, we found that some proteins spread their effects fast and efficiently by attacking hubs in the host network while other proteins exert more local effects. Conclusions: Our findings confirm that potyvirus protein-protein interaction networks are highly connected, with some proteins playing the role of hubs. Several topological parameters depend linearly on the protein degree. Some viral proteins focus their effect in only host hubs while others diversify its effect among several proteins at the first step. Future new data will help to refine our model and to improve our predictions.This work was supported by the Spanish Ministerio de Economia y Competitividad grants BFU2012-30805 (to SFE), DPI2011-28112-C04-02 (to AF) and DPI2011-28112-C04-01 (to JP). The first two authors are recipients of fellowships from the Spanish Ministerio de Economia y Competitividad: BES-2012-053772 (to GB) and BES-2012-057812 (to AF-F).Bosque, G.; Folch Fortuny, A.; Picó Marco, JA.; Ferrer, A.; Elena Fito, SF. (2014). Topology analysis and visualization of Potyvirus protein-protein interaction network. BMC Systems Biology. 129(8):1-15. doi:10.1186/s12918-014-0129-8S1151298Gibbs A, Ohshima K: Potyviruses and the digital revolution. Annu Rev Phytopathol. 2010, 48: 205-223. 10.1146/annurev-phyto-073009-114404.Spence NJ, Phiri NA, Hughes SL, Mwaniki A, Simons S, Oduor G, Chacha D, Kuria A, Ndirangu S, Kibata GN, Marris GC: Economic impact of turnip mosaic virus, cauliflower mosaic virus and beet mosaic virus in three Kenyan vegetables. Plant Pathol. 2007, 56: 317-323. 10.1111/j.1365-3059.2006.01498.x.Ward CW, Shukla DD: Taxonomy of potyviruses: current problems and some solutions. Intervirology. 1991, 32: 269-296.Riechmann JL, Laín S, García JA: Highlights and prospects of potyvirus molecular biology. J Gen Virol. 1992, 73 (Pt 1): 1-16. 10.1099/0022-1317-73-1-1.Elena SF, Rodrigo G: Towards an integrated molecular model of plant-virus interactions. Curr Opin Virol. 2012, 2: 719-724. 10.1016/j.coviro.2012.09.004.Wei T, Zhang C, Hong J, Xiong R, Kasschau KD, Zhou X, Carrington JC, Wang A: Formation of complexes at plasmodesmata for potyvirus intercellular movement is mediated by the viral protein P3N-PIPO. PLoS Pathog. 2010, 6: e1000962-10.1371/journal.ppat.1000962.Chung BY-W, Miller WA, Atkins JF, Firth AE: An overlapping essential gene in the Potyviridae. Proc Natl Acad Sci. 2008, 105: 5897-5902. 10.1073/pnas.0800468105.Allison R, Johnston RE, Dougherty WG: The nucleotide sequence of the coding region of tobacco etch virus genomic RNA: evidence for the synthesis of a single polyprotein. Virology. 1986, 154: 9-20. 10.1016/0042-6822(86)90425-3.Domier LL, Franklin KM, Shahabuddin M, Hellmann GM, Overmeyer JH, Hiremath ST, Siaw MF, Lomonossoff GP, Shaw JG, Rhoads RE: The nucleotide sequence of tobacco vein mottling virus RNA. Nucleic Acids Res. 1986, 14: 5417-5430. 10.1093/nar/14.13.5417.Revers F, Le Gall O, Candresse T, Maule AJ: New advances in understanding the molecular biology of plant/potyvirus interactions. Mol Plant Microbe Interact. 1999, 12: 367-376. 10.1094/MPMI.1999.12.5.367.Urcuqui-Inchima S, Haenni AL, Bernardi F: Potyvirus proteins: a wealth of functions. Virus Res. 2001, 74: 157-175. 10.1016/S0168-1702(01)00220-9.Merits A, Rajamäki M-L, Lindholm P, Runeberg-Roos P, Kekarainen T, Puustinen P, Mäkeläinen K, Valkonen JPT, Saarma M: Proteolytic processing of potyviral proteins and polyprotein processing intermediates in insect and plant cells. J Gen Virol. 2002, 83: 1211-1221.Adams MJ, Antoniw JF, Beaudoin F: Overview and analysis of the polyprotein cleavage sites in the family Potyviridae. Mol Plant Pathol. 2005, 6: 471-487. 10.1111/j.1364-3703.2005.00296.x.Zheng H, Yan F, Lu Y, Sun L, Lin L, Cai L, Hou M, Chen J: Mapping the self-interacting domains of TuMV HC-Pro and the subcellular localization of the protein. Virus Genes. 2011, 42: 110-116. 10.1007/s11262-010-0538-8.Culver JN, Padmanabhan MS: Virus-induced disease: altering host physiology one interaction at a time. Annu Rev Phytopathol. 2007, 45: 221-243. 10.1146/annurev.phyto.45.062806.094422.De Las Rivas J, Fontanillo C: Protein-protein interactions essentials: key concepts to building and analyzing interactome networks. PLoS Comput Biol. 2010, 6: e1000807-10.1371/journal.pcbi.1000807.Bornke F: Protein Interaction Networks. Anal Biol Netw. Edited by: Junker BH, Schreiber F. 2008, John Wiley & Sons, Inc, Hoboken, NJ, USA, 207-232. 10.1002/9780470253489.ch9.Phizicky EM, Fields S: Protein-protein interactions: methods for detection and analysis. Microbiol Rev. 1995, 59: 94-123.Brückner A, Polge C, Lentze N, Auerbach D, Schlattner U: Yeast two-hybrid, a powerful tool for systems biology. Int J Mol Sci. 2009, 10: 2763-2788. 10.3390/ijms10062763.Fields S, Song O: A novel genetic system to detect protein-protein interactions. Nature. 1989, 340: 245-246. 10.1038/340245a0.Ho Y, Gruhler A, Heilbut A, Bader GD, Moore L, Adams S-L, Millar A, Taylor P, Bennett K, Boutilier K, Yang L, Wolting C, Donaldson I, Schandorff S, Shewnarane J, Vo M, Taggart J, Goudreault M, Muskat B, Alfarano C, Dewar D, Lin Z, Michalickova K, Willems AR, Sassi H, Nielsen PA, Rasmussen KJ, Andersen JR, Johansen LE, Hansen LH, et al: Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature. 2002, 415: 180-183. 10.1038/415180a.Hu C-D, Chinenov Y, Kerppola TK: Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation. Mol Cell. 2002, 9: 789-798. 10.1016/S1097-2765(02)00496-3.Kodama Y, Hu C-D: An improved bimolecular fluorescence complementation assay with a high signal-to-noise ratio. Biotechniques. 2010, 49: 793-805. 10.2144/000113519.Rual J-F, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, et al: Towards a proteome-scale map of the human protein-protein interaction network. Nature. 2005, 437: 1173-1178. 10.1038/nature04209.Venkatesan K, Rual J-F, Vazquez A, Stelzl U, Lemmens I, Hirozane-Kishikawa T, Hao T, Zenkner M, Xin X, Goh K-I, Yildirim MA, Simonis N, Heinzmann K, Gebreab F, Sahalie JM, Cevik S, Simon C, de Smet A-S, Dann E, Smolyar A, Vinayagam A, Yu H, Szeto D, Borick H, Dricot A, Klitgord N, Murray RR, Lin C, Lalowski M, Timm J, et al: An empirical framework for binary interactome mapping. Nat Methods. 2008, 6: 83-90. 10.1038/nmeth.1280.Uetz P, Giot L, Cagney G, Mansfield TA, Judson RS, Knight JR, Lockshon D, Narayan V, Srinivasan M, Pochart P, Qureshi-Emili A, Li Y, Godwin B, Conover D, Kalbfleisch T, Vijayadamodar G, Yang M, Johnston M, Fields S, Rothberg JM: A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature. 2000, 403: 623-627. 10.1038/35001009.Ito T, Chiba T, Ozawa R, Yoshida M, Hattori M, Sakaki Y: A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc Natl Acad Sci. 2001, 98: 4569-4574. 10.1073/pnas.061034498.Uetz P, Dong Y-A, Zeretzke C, Atzler C, Baiker A, Berger B, Rajagopala SV, Roupelieva M, Rose D, Fossum E, Haas J: Herpesviral protein networks and their interaction with the human proteome. Science. 2006, 311: 239-242. 10.1126/science.1116804.Fossum E, Friedel CC, Rajagopala SV, Titz B, Baiker A, Schmidt T, Kraus T, Stellberger T, Rutenberg C, Suthram S, Bandyopadhyay S, Rose D, von Brunn A, Uhlmann M, Zeretzke C, Dong Y-A, Boulet H, Koegl M, Bailer SM, Koszinowski U, Ideker T, Uetz P, Zimmer R, Haas J: Evolutionarily conserved herpesviral protein interaction networks. PLoS Pathog. 2009, 5: e1000570-10.1371/journal.ppat.1000570.Rodrigo G, Carrera J, Ruiz-Ferrer V, del Toro FJ, Llave C, Voinnet O, Elena SF: A meta-analysis reveals the commonalities and differences in Arabidopsis thaliana response to different viral pathogens. PLoS One. 2012, 7: e40526-10.1371/journal.pone.0040526.Newman MEJ: The structure and function of complex networks. SIAM Rev. 2003, 45: 167-256. 10.1137/S003614450342480.Watts DJ, Strogatz SH: Collective dynamics of "small-world" networks. Nature. 1998, 393: 440-442. 10.1038/30918.Albert R, Barabási A-L: Statistical mechanics of complex networks. Rev Mod Phys. 2002, 74: 47-97. 10.1103/RevModPhys.74.47.Boccaletti S, Latora V, Moreno Y, Chávez M, Hwang D: Complex networks: structure and dynamics. Phys Rep. 2006, 424: 175-308. 10.1016/j.physrep.2005.10.009.Barabási A-L, Oltvai ZN: Network biology: understanding the cell's functional organization. Nat Rev Genet. 2004, 5: 101-113. 10.1038/nrg1272.Albert R, DasGupta B, Hegde R, Sivanathan GS, Gitter A, Gürsoy G, Paul P, Sontag E: Computationally efficient measure of topological redundancy of biological and social networks. Phys Rev E. 2011, 84: 036117-10.1103/PhysRevE.84.036117.Cho D-Y, Kim Y-A, Przytycka TM: Chapter 5: network biology approach to complex diseases. PLoS Comput Biol. 2012, 8: e1002820-10.1371/journal.pcbi.1002820.Russell RB, Aloy P: Targeting and tinkering with interaction networks. Nat Chem Biol. 2008, 4: 666-673. 10.1038/nchembio.119.Winterbach W, Mieghem PV, Reinders M, Wang H, de Ridder D: Topology of molecular interaction networks. BMC Syst Biol. 2013, 7: 90-10.1186/1752-0509-7-90.Pržulj N: Protein-protein interactions: making sense of networks via graph-theoretic modeling. Bioessays. 2011, 33: 115-123. 10.1002/bies.201000044.Yook S-H, Oltvai ZN, Barabási A-L: Functional and topological characterization of protein interaction networks. Proteomics. 2004, 4: 928-942. 10.1002/pmic.200300636.Pržulj N, Wigle DA, Jurisica I: Functional topology in a network of protein interactions. Bioinformatics. 2004, 20: 340-348. 10.1093/bioinformatics/btg415.Elena SF, Carrera J, Rodrigo G: A systems biology approach to the evolution of plant-virus interactions. Curr Opin Plant Biol. 2011, 14: 372-377. 10.1016/j.pbi.2011.03.013.Zilian E, Maiss E: Detection of plum pox potyviral protein-protein interactions in planta using an optimized mRFP-based bimolecular fluorescence complementation system. J Gen Virol. 2011, 92: 2711-2723. 10.1099/vir.0.033811-0.Lin L, Shi Y, Luo Z, Lu Y, Zheng H, Yan F, Chen J, Chen J, Adams MJ, Wu Y: Protein-protein interactions in two potyviruses using the yeast two-hybrid system. Virus Res. 2009, 142: 36-40. 10.1016/j.virusres.2009.01.006.Guo D, Rajamäki M-L, Saarma M, Valkonen JPT: Towards a protein interaction map of potyviruses: protein interaction matrixes of two potyviruses based on the yeast two-hybrid system. J Gen Virol. 2001, 82: 935-939.Shen WT, Wang MQ, Yan P, Gao L, Zhou P: Protein interaction matrix of papaya ringspot virus type P based on a yeast two-hybrid system. Acta Virol. 2010, 54: 49-54. 10.4149/av_2010_01_49.Kang S, Ws L, Kh K: A protein interaction map of soybean mosaic virus strain G7H based on the yeast two-hybrid system. Mol Cells. 2004, 18: 122-126.Yambao MLM, Masuta C, Nakahara K, Uyeda I: The central and C-terminal domains of VPg of Clover yellow vein virus are important for VPg-HCPro and VPg-VPg interactions. J Gen Virol. 2003, 84: 2861-2869. 10.1099/vir.0.19312-0.Evidence for network evolution in an Arabidopsis interactome map. Science. 2011, 333: 601-607. 10.1126/science.1203877.Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T: Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003, 13: 2498-2504. 10.1101/gr.1239303.Fouss F, Francoisse K, Yen L, Pirotte A, Saerens M: An experimental investigation of kernels on graphs for collaborative recommendation and semisupervised classification. Neural Netw Off J Int Neural Netw Soc. 2012, 31: 53-72. 10.1016/j.neunet.2012.03.001.Bass JIF, Diallo A, Nelson J, Soto JM, Myers CL, Walhout AJM: Using networks to measure similarity between genes: association index selection. Nat Methods. 2013, 10: 1169-1176. 10.1038/nmeth.2728.Newman MEJ: Assortative mixing in networks. Phys Rev Lett. 2002, 89: 208701-10.1103/PhysRevLett.89.208701

    Flux-dependent graphs for metabolic networks

    Get PDF
    Cells adapt their metabolic fluxes in response to changes in the environment. We present a framework for the systematic construction of flux-based graphs derived from organism-wide metabolic networks. Our graphs encode the directionality of metabolic fluxes via edges that represent the flow of metabolites from source to target reactions. The methodology can be applied in the absence of a specific biological context by modelling fluxes probabilistically, or can be tailored to different environmental conditions by incorporating flux distributions computed through constraint-based approaches such as Flux Balance Analysis. We illustrate our approach on the central carbon metabolism of Escherichia coli and on a metabolic model of human hepatocytes. The flux-dependent graphs under various environmental conditions and genetic perturbations exhibit systemic changes in their topological and community structure, which capture the re-routing of metabolic fluxes and the varying importance of specific reactions and pathways. By integrating constraint-based models and tools from network science, our framework allows the study of context-specific metabolic responses at a system level beyond standard pathway descriptions

    Metabolic network destruction: Relating topology to robustness

    No full text
    Biological networks exhibit intriguing topological properties such as small-worldness. In this paper, we investigate whether the topology of a metabolic network is related to its robustness. We do so by perturbing a metabolic system in silico, one reaction at a time and studying the correlations between growth, as predicted by flux balance analysis, and a number of topological metrics, as computed from three network representations of the metabolic system. We find that a small number of metrics correlate with growth and that only one of the network representations stands out in terms of correlated metrics. The most correlated metrics point to the importance of hub nodes in this network: so-called "currency metabolites". Since they are responsible for interconnecting distant functional modules in the network, they are important points in the networks for predicting if reaction removal affects growth. Source code and data are available upon request.Network Architectures and ServicesElectrical Engineering, Mathematics and Computer Scienc

    Correlating the topology of a metabolic network with its growth capacity

    No full text
    Network Architectures & Services (NAS)Electrical Engineering, Mathematics and Computer Scienc

    Topology of molecular interaction networks

    Get PDF
    Molecular interactions are often represented as network models which have become the common language of many areas of biology. Graphs serve as convenient mathematical representations of network models and have themselves become objects of study. Their topology has been intensively researched over the last decade after evidence was found that they share underlying design principles with many other types of networks. Initial studies suggested that molecular interaction network topology is related to biological function and evolution. However, further whole-network analyses did not lead to a unified view on what this relation may look like, with conclusions highly dependent on the type of molecular interactions considered and the metrics used to study them. It is unclear whether global network topology drives function, as suggested by some researchers, or whether it is simply a byproduct of evolution or even an artefact of representing complex molecular interaction networks as graphs. Nevertheless, network biology has progressed significantly over the last years. We review the literature, focusing on two major developments. First, realizing that molecular interaction networks can be naturally decomposed into subsystems (such as modules and pathways), topology is increasingly studied locally rather than globally. Second, there is a move from a descriptive approach to a predictive one: rather than correlating biological network 1 topology to generic properties such as robustness, it is used to predict specific functions or phenotypes. Taken together, this change in focus from globally descriptive to locally predictive points to new avenues of research. In particular, multi-scale approaches are developments promising to drive the study of molecular interaction networks further.Network Architectures and Services Group (NAS)Electrical Engineering, Mathematics and Computer Scienc

    Aging traits and sustainable trophy hunting of African lions

    Get PDF
    Trophy hunting plays a significant role in wildlife conservation in some contexts in various parts of the world. Yet excessive hunting is contributing to species declines, especially for large carnivores. Simulation models suggest that sustainable hunting of African lions may be achieved by restricting offtakes to males old enough to have reared a cohort of offspring. We tested and expanded criteria for an age-based approach for sustainably regulating lion hunting. Using photos of 228 known-age males from ten sites across Africa, we measured change in ten phenotypic traits with age and found four age classes with distinct characteristics: 1-2.9 years, 3-4.9 years, 5-6.9 years, and ≥7 years. We tested the aging accuracy of professional hunters and inexperienced observers before and after training on aging. Before training, hunters accurately aged more lion photos (63%) than inexperienced observers (48%); after training, both groups improved (67-69%). Hunters overestimated 22% of lions <5 years as 5-6.9 years (unsustainable) but only 4% of lions <5 years as ≥7 years (sustainable). Due to the lower aging error for males ≥7 years, we recommend 7 years as a practical minimum age for hunting male lions. Results indicate that age-based hunting is feasible for sustainably managing threatened and economically significant species such as the lion, but must be guided by rigorous training, strict monitoring of compliance and error, and conservative quotas. Our study furthermore demonstrates methods for identifying traits to age individuals, information that is critical for estimating demographic parameters underlying management and conservation of age-structured species
    corecore