Publications of P. Bork in the journal "Science".
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2022 1 publication(s).
33.
Cryptic and abundant marine viruses at the evolutionary origins of Earth's RNA virome.
Zayed AA, Wainaina JM, Dominguez-Huerta G, Pelletier E, Guo J, Mohssen M, Tian F, Pratama AA, Bolduc B, Zablocki O, Cronin D, Solden L, Delage E, Alberti A, Aury JM, Carradec Q, Da Silva C, Labadie K, Poulain J, Ruscheweyh HJ, Salazar G, Shatoff E, Tara Oceans coordinators , Bundschuh R, Fredrick K, Kubatko LS, Chaffron S, Culley AI, Sunagawa S, Kuhn JH, Wincker P, Sullivan MB, Acinas S, Babin M, Bork P, Boss E, Bowler C, Cochrane G, De Vargas C, Gorsky G, Guidi L, Grimsley N, Hingamp P, Iudicone PD, Jaillon O, Kandels S, Karp-Boss L, Karsenti E, Not F, Ogata H, Poulton N, Pesant S, Sardet C, Speich S, Stemmann L, Sullivan MB, Sungawa S, Wincker P
Science.
2022 Apr 8; 376(6589): 156-162. PubMed: 35389782.
AbstractWhereas DNA viruses are known to be abundant, diverse, and commonly key ecosystem players, RNA viruses are insufficiently studied outside disease settings. In this study, we analyzed ≈28 terabases of Global Ocean RNA sequences to expand Earth's RNA virus catalogs and their taxonomy, investigate their evolutionary origins, and assess their marine biogeography from pole to pole. Using new approaches to optimize discovery and classification, we identified RNA viruses that necessitate substantive revisions of taxonomy (doubling phyla and adding >50% new classes) and evolutionary understanding. "Species"-rank abundance determination revealed that viruses of the new phyla "," a missing link in early RNA virus evolution, and "" are widespread and dominant in the oceans. These efforts provide foundational knowledge critical to integrating RNA viruses into ecological and epidemiological models.
2021 1 publication(s).
32.
Profiling cellular diversity in sponges informs animal cell type and nervous system evolution.
Musser JM, Schippers KJ, Nickel M, Mizzon G, Kohn AB, Pape C, Ronchi P, Papadopoulos N, Tarashansky AJ, Hammel JU, Wolf F, Liang C, Hernández-Plaza A, Cantalapiedra CP, Achim K, Schieber NL, Pan L, Ruperti F, Francis WR, Vargas S, Kling S, Renkert M, Polikarpov M, Bourenkov G, Feuda R, Gaspar I, Burkhardt P, Wang B, Bork P, Beck M, Schneider TR, Kreshuk A, Wörheide G, Huerta-Cepas J, Schwab Y, Moroz LL, Arendt D
Science.
2021 Nov 5; 374(6568): 717-723. PubMed: 34735222.Abstract + PDFThe evolutionary origin of metazoan cell types such as neurons and muscles is not known. Using whole-body single-cell RNA sequencing in a sponge, an animal without nervous system and musculature, we identified 18 distinct cell types. These include nitric oxide–sensitive contractile pinacocytes, amoeboid phagocytes, and secretory neuroid cells that reside in close contact with digestive choanocytes that express scaffolding and receptor proteins. Visualizing neuroid cells by correlative x-ray and electron microscopy revealed secretory vesicles and cellular projections enwrapping choanocyte microvilli and cilia. Our data show a communication system that is organized around sponge digestive chambers, using conserved modules that became incorporated into the pre- and postsynapse in the nervous systems of other animals.
2019 2 publication(s).
31.
Consent insufficient for data release-Response.
Amann RI, Baichoo S, Blencowe BJ, Bork P, Borodovsky M, Brooksbank C, Chain PSG, Colwell RR, Daffonchio DG, Danchin A, de Lorenzo V, Dorrestein PC, Finn RD, Fraser CM, Gilbert JA, Hallam SJ, Hugenholtz P, Ioannidis JPA, Jansson JK, Kim JF, Klenk HP, Klotz MG, Knight R, Konstantinidis KT, Kyrpides NC, Mason CE, McHardy AC, Meyer F, Ouzounis CA, Patrinos AAN, Podar M, Pollard KS, Ravel J, Muñoz AR, Roberts RJ, Rosselló-Móra R, Sansone SA, Schloss PD, Schriml LM, Setubal JC, Sorek R, Stevens RL, Tiedje JM, Turjanski A, Tyson GW, Ussery DW, Weinstock GM, White O, Whitman WB, Xenarios I
Science.
2019 May 3; 364(6439): 446. PubMed: 31048484.PDF30.
Toward unrestricted use of public genomic data.
Amann RI, Baichoo S, Blencowe BJ, Bork P, Borodovsky M, Brooksbank C, Chain PSG, Colwell RR, Daffonchio DG, Danchin A, de Lorenzo V, Dorrestein PC, Finn RD, Fraser CM, Gilbert JA, Hallam SJ, Hugenholtz P, Ioannidis JPA, Jansson JK, Kim JF, Klenk HP, Klotz MG, Knight R, Konstantinidis KT, Kyrpides NC, Mason CE, McHardy AC, Meyer F, Ouzounis CA, Patrinos AAN, Podar M, Pollard KS, Ravel J, Muñoz AR, Roberts RJ, Rosselló-Móra R, Sansone SA, Schloss PD, Schriml LM, Setubal JC, Sorek R, Stevens RL, Tiedje JM, Turjanski A, Tyson GW, Ussery DW, Weinstock GM, White O, Whitman WB, Xenarios I
Science.
2019 Jan 25; 363(6425): 350-352. PubMed: 30679363.PDF2016 1 publication(s).
29.
Durable coexistence of donor and recipient strains after fecal microbiota transplantation.
Li SS, Zhu A, Benes V, Costea PI, Hercog R, Hildebrand F, Huerta-Cepas J, Nieuwdorp M, Salojärvi J, Voigt AY, Zeller G, Sunagawa S, de Vos WM, Bork P
Science.
2016 Apr 29; 352(6285): 586-9. PubMed: 27126044.Abstract + PDFFecal microbiota transplantation (FMT) has shown efficacy in treating recurrent Clostridium difficile infection and is increasingly being applied to other gastrointestinal disorders, yet the fate of native and introduced microbial strains remains largely unknown. To quantify the extent of donor microbiota colonization, we monitored strain populations in fecal samples from a recent FMT study on metabolic syndrome patients using single-nucleotide variants in metagenomes. We found extensive coexistence of donor and recipient strains, persisting 3 months after treatment. Colonization success was greater for conspecific strains than for new species, the latter falling within fluctuation levels observed in healthy individuals over a similar time frame. Furthermore, same-donor recipients displayed varying degrees of microbiota transfer, indicating individual patterns of microbiome resistance and donor-recipient compatibilities.
2015 7 publication(s).
28.
Tara Oceans studies plankton at planetary scale. Introduction.
Bork P, Bowler C, De Vargas C, Gorsky G, Karsenti E, Wincker P
Science.
2015 May 22; 348(6237): 873. Epub 2015 May 21; PubMed: 25999501.Abstract + PDFThe ocean is the largest ecosystem on Earth, and yet we know very little about it. This is particularly true for the plankton that inhabit the ocean. Although these organisms are at least as important for the Earth system as the rainforests and form the base of marine food webs, most plankton are invisible to the naked eye and thus are largely uncharacterized. To study this invisible world, the multinational Tara Oceans consortium, with use of the 110-foot research schooner Tara, sampled microscopic plankton at 210 sites and depths up to 2000 m in all the major oceanic regions during expeditions from 2009 through 2013.
27.
Patterns and ecological drivers of ocean viral communities.
Brum JR, Ignacio-Espinoza JC, Roux S, Doulcier G, Acinas SG, Alberti A, Chaffron S, Cruaud C, De Vargas C, Gasol JM, Gorsky G, Gregory AC, Guidi L, Hingamp P, Iudicone D, Not F, Ogata H, Pesant S, Poulos BT, Schwenck SM, Speich S, Dimier C, Kandels-Lewis S, Picheral M, Searson S, Bork P, Bowler C, Sunagawa S, Wincker P, Karsenti E, Sullivan MB
Science.
2015 May 22; 348(6237): 1261498. PubMed: 25999515.Abstract + PDFViruses influence ecosystems by modulating microbial population size, diversity, metabolic outputs, and gene flow. Here, we use quantitative double-stranded DNA (dsDNA) viral-fraction metagenomes (viromes) and whole viral community morphological data sets from 43 Tara Oceans expedition samples to assess viral community patterns and structure in the upper ocean. Protein cluster cataloging defined pelagic upper-ocean viral community pan and core gene sets and suggested that this sequence space is well-sampled. Analyses of viral protein clusters, populations, and morphology revealed biogeographic patterns whereby viral communities were passively transported on oceanic currents and locally structured by environmental conditions that affect host community structure. Together, these investigations establish a global ocean dsDNA viromic data set with analyses supporting the seed-bank hypothesis to explain how oceanic viral communities maintain high local diversity.
26.
Eukaryotic plankton diversity in the sunlit ocean.
De Vargas C, Audic S, Henry N, Decelle J, Mahé F, Logares R, Lara E, Berney C, Le Bescot N, Probert I, Carmichael M, Poulain J, Romac S, Colin S, Aury JM, Bittner L, Chaffron S, Dunthorn M, Engelen S, Flegontova O, Guidi L, Horák A, Jaillon O, Lima-Mendez G, Lukeš J, Malviya S, Morard R, Mulot M, Scalco E, Siano R, Vincent F, Zingone A, Dimier C, Picheral M, Searson S, Kandels-Lewis S, Acinas SG, Bork P, Bowler C, Gorsky G, Grimsley N, Hingamp P, Iudicone D, Not F, Ogata H, Pesant S, Raes J, Sieracki ME, Speich S, Stemmann L, Sunagawa S, Weissenbach J, Wincker P, Karsenti E.
Science.
2015 May 22; 348(6237): 1261605. PubMed: 25999516.Abstract + PDFMarine plankton support global biological and geochemical processes. Surveys of their biodiversity have hitherto been geographically restricted and have not accounted for the full range of plankton size. We assessed eukaryotic diversity from 334 size-fractionated photic-zone plankton communities collected across tropical and temperate oceans during the circumglobal Tara Oceans expedition. We analyzed 18S ribosomal DNA sequences across the intermediate plankton-size spectrum from the smallest unicellular eukaryotes (protists, >0.8 micrometers) to small animals of a few millimeters. Eukaryotic ribosomal diversity saturated at ~150,000 operational taxonomic units, about one-third of which could not be assigned to known eukaryotic groups. Diversity emerged at all taxonomic levels, both within the groups comprising the ~11,200 cataloged morphospecies of eukaryotic plankton and among twice as many other deep-branching lineages of unappreciated importance in plankton ecology studies. Most eukaryotic plankton biodiversity belonged to heterotrophic protistan groups, particularly those known to be parasites or symbiotic hosts.
25.
Determinants of community structure in the global plankton interactome.
Lima-Mendez G, Faust K, Henry N, Decelle J, Colin S, Carcillo F, Chaffron S, Ignacio-Espinosa JC, Roux S, Vincent F, Bittner L, Darzi Y, Wang J, Audic S, Berline L, Bontempi G, Cabello AM, Coppola L, Cornejo-Castillo FM, d'Ovidio F, De Meester L, Ferrera I, Garet-Delmas MJ, Guidi L, Lara E, Pesant S, Royo-Llonch M, Salazar G, Sánchez P, Sebastian M, Souffreau C, Dimier C, Picheral M, Searson S, Kandels-Lewis S, Gorsky G, Not F, Ogata H, Speich S, Stemmann L, Weissenbach J, Wincker P, Acinas SG, Sunagawa S, Bork P, Sullivan MB, Karsenti E, Bowler C, De Vargas C, Raes J
Science.
2015 May 22; 348(6237): 1262073. PubMed: 25999517.Abstract + PDFSpecies interaction networks are shaped by abiotic and biotic factors. Here, as part of the Tara Oceans project, we studied the photic zone interactome using environmental factors and organismal abundance profiles and found that environmental factors are incomplete predictors of community structure. We found associations across plankton functional types and phylogenetic groups to be nonrandomly distributed on the network and driven by both local and global patterns. We identified interactions among grazers, primary producers, viruses, and (mainly parasitic) symbionts and validated network-generated hypotheses using microscopy to confirm symbiotic relationships. We have thus provided a resource to support further research on ocean food webs and integrating biological components into ocean models.
24.
Operon structure and cotranslational subunit association direct protein assembly in bacteria.
Shieh YW, Minguez P, Bork P, Auburger JJ, Guilbride DL, Kramer G, Bukau B
Science.
2015 Nov 6; 350(6261): 678-80. Epub 2015 Sep 24; PubMed: 26405228.Abstract + PDFAssembly of protein complexes is considered a post-translational process involving random collision of subunits. We show that within the Escherichia coli cytosol, bacterial luciferase subunits LuxA and LuxB assemble into complexes close to the site of subunit synthesis. Assembly efficiency decreases markedly if subunits are synthesized on separate mRNAs from genes integrated at distant chromosomal sites. Subunit assembly initiates cotranslationally on nascent LuxB in vivo. The ribosome-associated chaperone Trigger Factor delays the onset of cotranslational interactions until the LuxB dimer interface is fully exposed. Protein assembly thus is directly coupled to the translation process, and involves spatially confined, actively chaperoned cotranslational subunit interactions. Bacterial gene organization into operons therefore reflects a fundamental mechanism for spatiotemporal regulation vital to effective cotranslational protein complex assembly.
23.
Structure and function of the global ocean microbiome.
Sunagawa S, Coelho LP, Chaffron S, Kultima JR, Labadie K, Salazar G, Djahanschiri B, Zeller G, Mende DR, Alberti A, Cornejo-Castillo FM, Costea PI, Cruaud C, d'Ovidio F, Engelen S, Ferrera I, Gasol JM, Guidi L, Hildebrand F, Kokoszka F, Lepoivre C, Lima-Mendez G, Poulain J, Poulos BT, Royo-Llonch M, Sarmento H, Vieira-Silva S, Dimier C, Picheral M, Searson S, Kandels-Lewis S, Bowler C, De Vargas C, Gorsky G, Grimsley N, Hingamp P, Iudicone D, Jaillon O, Not F, Ogata H, Pesant S, Speich S, Stemmann L, Sullivan MB, Weissenbach J, Wincker P, Karsenti E, Raes J, Acinas SG, Bork P
Science.
2015 May 22; 348(6237): 1261359. PubMed: 25999513.Abstract + PDFMicrobes are dominant drivers of biogeochemical processes, yet drawing a global picture of functional diversity, microbial community structure, and their ecological determinants remains a grand challenge. We analyzed 7.2 terabases of metagenomic data from 243 Tara Oceans samples from 68 locations in epipelagic and mesopelagic waters across the globe to generate an ocean microbial reference gene catalog with >40 million nonredundant, mostly novel sequences from viruses, prokaryotes, and picoeukaryotes. Using 139 prokaryote-enriched samples, containing >35,000 species, we show vertical stratification with epipelagic community composition mostly driven by temperature rather than other environmental factors or geography. We identify ocean microbial core functionality and reveal that >73% of its abundance is shared with the human gut microbiome despite the physicochemical differences between these two ecosystems.
22.
Environmental characteristics of Agulhas rings affect interocean plankton transport.
Villar E, Farrant GK, Follows M, Garczarek L, Speich S, Audic S, Bittner L, Blanke B, Brum JR, Brunet C, Casotti R, Chase A, Dolan JR, d'Ortenzio F, Gattuso JP, Grima N, Guidi L, Hill CN, Jahn O, Jamet JL, Le Goff H, Lepoivre C, Malviya S, Pelletier E, Romagnan JB, Roux S, Santini S, Scalco E, Schwenck SM, Tanaka A, Testor P, Vannier T, Vincent F, Zingone A, Dimier C, Picheral M, Searson S, Kandels-Lewis S, Acinas SG, Bork P, Boss E, De Vargas C, Gorsky G, Ogata H, Pesant S, Sullivan MB, Sunagawa S, Wincker P, Karsenti E, Bowler C, Not F, Hingamp P, Iudicone D
Science.
2015 May 22; 348(6237): 1261447. PubMed: 25999514.Abstract + PDFAgulhas rings provide the principal route for ocean waters to circulate from the Indo-Pacific to the Atlantic basin. Their influence on global ocean circulation is well known, but their role in plankton transport is largely unexplored. We show that, although the coarse taxonomic structure of plankton communities is continuous across the Agulhas choke point, South Atlantic plankton diversity is altered compared with Indian Ocean source populations. Modeling and in situ sampling of a young Agulhas ring indicate that strong vertical mixing drives complex nitrogen cycling, shaping community metabolism and biogeochemical signatures as the ring and associated plankton transit westward. The peculiar local environment inside Agulhas rings may provide a selective mechanism contributing to the limited dispersal of Indian Ocean plankton populations into the Atlantic.
2011 1 publication(s).
21.
The ecoresponsive genome of Daphnia pulex.
Colbourne JK, Pfrender ME, Gilbert D, Thomas WK, Tucker A, Oakley TH, Tokishita S, Aerts A, Arnold GJ, Basu MK, Bauer DJ, Cáceres CE, Carmel L, Casola C, Choi JH, Detter JC, Dong Q, Dusheyko S, Eads BD, Fröhlich T, Geiler-Samerotte KA, Gerlach D, Hatcher P, Jogdeo S, Krijgsveld J, Kriventseva EV, Kültz D, Laforsch C, Lindquist E, Lopez J, Manak JR, Muller J, Pangilinan J, Patwardhan RP, Pitluck S, Pritham EJ, Rechtsteiner A, Rho M, Rogozin IB, Sakarya O, Salamov A, Schaack S, Shapiro H, Shiga Y, Skalitzky C, Smith Z, Souvorov A, Sung W, Tang Z, Tsuchiya D, Tu H, Vos H, Wang M, Wolf YI, Yamagata H, Yamada T, Ye Y, Shaw JR, Andrews J, Crease TJ, Tang H, Lucas SM, Robertson HM, Bork P, Koonin EV, Zdobnov EM, Grigoriev IV, Lynch M, Boore JL
Science.
2011 Feb 4; 331(6017): 555-61. PubMed: 21292972.Abstract + PDFWe describe the draft genome of the microcrustacean Daphnia pulex, which is only 200 megabases and contains at least 30,907 genes. The high gene count is a consequence of an elevated rate of gene duplication resulting in tandem gene clusters. More than a third of Daphnia's genes have no detectable homologs in any other available proteome, and the most amplified gene families are specific to the Daphnia lineage. The coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random, and the analysis of gene expression under different environmental conditions reveals that numerous paralogs acquire divergent expression patterns soon after duplication. Daphnia-specific genes, including many additional loci within sequenced regions that are otherwise devoid of annotations, are the most responsive genes to ecological challenges.
2010 1 publication(s).
20.
Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.
Nasonia Genome Working Group , Werren JH, Richards S, Desjardins CA, Niehuis O, Gadau J, Colbourne JK, Beukeboom LW, Desplan C, Elsik CG, Grimmelikhuijzen CJ, Kitts P, Lynch JA, Murphy T, Oliveira DC, Smith CD, van de Zande L, Worley KC, Zdobnov EM, Aerts M, Albert S, Anaya VH, Anzola JM, Barchuk AR, Behura SK, Bera AN, Berenbaum MR, Bertossa RC, Bitondi MM, Bordenstein SR, Bork P, Bornberg-Bauer E, Brunain M, Cazzamali G, Chaboub L, Chacko J, Chavez D, Childers CP, Choi JH, Clark ME, Claudianos C, Clinton RA, Cree AG, Cristino AS, Dang PM, Darby AC, de Graaf DC, Devreese B, Dinh HH, Edwards R, Elango N, Elhaik E, Ermolaeva O, Evans JD, Foret S, Fowler GR, Gerlach D, Gibson JD, Gilbert DG, Graur D, Gründer S, Hagen DE, Han Y, Hauser F, Hultmark D, Hunter HC, Hurst GD, Jhangian SN, Jiang H, Johnson RM, Jones AK, Junier T, Kadowaki T, Kamping A, Kapustin Y, Kechavarzi B, Kim J, Kim J, Kiryutin B, Koevoets T, Kovar CL, Kriventseva EV, Kucharski R, Lee H, Lee SL, Lees K, Lewis LR, Loehlin DW, Logsdon JM, Lopez JA, Lozado RJ, Maglott D, Maleszka R, Mayampurath A, Mazur DJ, McClure MA, Moore AD, Morgan MB, Muller J, Munoz-Torres MC, Muzny DM, Nazareth LV, Neupert S, Nguyen NB, Nunes FM, Oakeshott JG, Okwuonu GO, Pannebakker BA, Pejaver VR, Peng Z, Pratt SC, Predel R, Pu LL, Ranson H, Raychoudhury R, Rechtsteiner A, Reese JT, Reid JG, Riddle M, Robertson HM, Romero-Severson J, Rosenberg M, Sackton TB, Sattelle DB, Schlüns H, Schmitt T, Schneider M, Schüler A, Schurko AM, Shuker DM, Simões ZL, Sinha S, Smith Z, Solovyev V, Souvorov A, Springauf A, Stafflinger E, Stage DE, Stanke M, Tanaka Y, Telschow A, Trent C, Vattathil S, Verhulst EC, Viljakainen L, Wanner KW, Waterhouse RM, Whitfield JB, Wilkes TE, Williamson M, Willis JH, Wolschin F, Wyder S, Yamada T, Yi SV, Zecher CN, Zhang L, Gibbs RA
Science.
2010 Jan 15; 327(5963): 343-8. PubMed: 20075255.Abstract + PDFWe report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.
2009 3 publication(s).
19.
Transcriptome complexity in a genome-reduced bacterium.
Güell M, van Noort V, Yus E, Chen WH, Leigh-Bell J, Michalodimitrakis K, Yamada T, Arumugam M, Doerks T, Kühner S, Rode M, Suyama M, Schmidt S, Gavin AC, Bork P, Serrano L
Science.
2009 Nov 27; 326(5957): 1268-71. PubMed: 19965477.Abstract + PDFTo study basic principles of transcriptome organization in bacteria, we analyzed one of the smallest self-replicating organisms, Mycoplasma pneumoniae. We combined strand-specific tiling arrays, complemented by transcriptome sequencing, with more than 252 spotted arrays. We detected 117 previously undescribed, mostly noncoding transcripts, 89 of them in antisense configuration to known genes. We identified 341 operons, of which 139 are polycistronic; almost half of the latter show decaying expression in a staircase-like manner. Under various conditions, operons could be divided into 447 smaller transcriptional units, resulting in many alternative transcripts. Frequent antisense transcripts, alternative transcripts, and multiple regulators per gene imply a highly dynamic transcriptome, more similar to that of eukaryotes than previously thought.
18.
Proteome organization in a genome-reduced bacterium.
Kühner S, van Noort V, Betts MJ, Leo-Macias A, Batisse C, Rode M, Yamada T, Maier T, Bader S, Beltran-Alvarez P, Castaño-Diez D, Chen WH, Devos DP, Güell M, Norambuena T, Racke I, Rybin V, Schmidt A, Yus E, Aebersold R, Herrmann R, Böttcher B, Frangakis AS, Russell RB, Serrano L, Bork P, Gavin AC
Science.
2009 Nov 27; 326(5957): 1235-40. PubMed: 19965468.Abstract + PDFThe genome of Mycoplasma pneumoniae is among the smallest found in self-replicating organisms. To study the basic principles of bacterial proteome organization, we used tandem affinity purification-mass spectrometry (TAP-MS) in a proteome-wide screen. The analysis revealed 62 homomultimeric and 116 heteromultimeric soluble protein complexes, of which the majority are novel. About a third of the heteromultimeric complexes show higher levels of proteome organization, including assembly into larger, multiprotein complex entities, suggesting sequential steps in biological processes, and extensive sharing of components, implying protein multifunctionality. Incorporation of structural models for 484 proteins, single-particle electron microscopy, and cellular electron tomograms provided supporting structural details for this proteome organization. The data set provides a blueprint of the minimal cellular machinery required for life.
17.
Impact of genome reduction on bacterial metabolism and its regulation.
Yus E, Maier T, Michalodimitrakis K, van Noort V, Yamada T, Chen WH, Wodke JA, Güell M, Martínez S, Bourgeois R, Kühner S, Raineri E, Letunic I, Kalinina OV, Rode M, Herrmann R, Gutiérrez-Gallego R, Russell RB, Gavin AC, Bork P, Serrano L
Science.
2009 Nov 27; 326(5957): 1263-8. PubMed: 19965476.Abstract + PDFTo understand basic principles of bacterial metabolism organization and regulation, but also the impact of genome size, we systematically studied one of the smallest bacteria, Mycoplasma pneumoniae. A manually curated metabolic network of 189 reactions catalyzed by 129 enzymes allowed the design of a defined, minimal medium with 19 essential nutrients. More than 1300 growth curves were recorded in the presence of various nutrient concentrations. Measurements of biomass indicators, metabolites, and (13)C-glucose experiments provided information on directionality, fluxes, and energetics; integration with transcription profiling enabled the global analysis of metabolic regulation. Compared with more complex bacteria, the M. pneumoniae metabolic network has a more linear topology and contains a higher fraction of multifunctional enzymes; general features such as metabolite concentrations, cellular energetics, adaptability, and global gene expression responses are similar, however.
2008 2 publication(s).
16.
Drug target identification using side-effect similarity.
Abstract + PDFTargets for drugs have so far been predicted on the basis of molecular or cellular features, for example, by exploiting similarity in chemical structure or in activity across cell lines. We used phenotypic side-effect similarities to infer whether two drugs share a target. Applied to 746 marketed drugs, a network of 1018 side effect-driven drug-drug relations became apparent, 261 of which are formed by chemically dissimilar drugs from different therapeutic indications. We experimentally tested 20 of these unexpected drug-drug relations and validated 13 implied drug-target relations by in vitro binding assays, of which 11 reveal inhibition constants equal to less than 10 micromolar. Nine of these were tested and confirmed in cell assays, documenting the feasibility of using phenotypic information to infer molecular interactions and hinting at new uses of marketed drugs.
2007 2 publication(s).
14.
Genome-Wide Experimental Determination of Barriers to Horizontal Gene Transfer.
Sorek R, Zhu Y, Creevey CJ, Francino MP, Bork P, Rubin EM
Science.
2007 Nov 30; 318(5855): 1449-52. Epub 2007 Oct 18; PubMed: 17947550.Abstract + PDFHorizontal gene transfer, in which genetic material is transferred from the genome of one organism to another, has been investigated in microbial species mainly through computational sequence analyses. To address the lack of experimental data, we studied the attempted movement of 246,045 genes from 79 prokaryotic genomes into Escherichia coli and identified genes that consistently fail to transfer. We studied the mechanisms underlying transfer inhibition by placing coding regions from different species under the control of inducible promoters. Our data suggest that toxicity to the host inhibited transfer regardless of the species of origin and that increased gene dosage and associated increased expression may be a predominant cause for transfer failure. While these experimental studies examined transfer solely into E. coli, a computational analysis of gene transfer rates across available bacterial and archaeal genomes supports that the barriers observed in our study are general across the tree of life.
13.
Quantitative Phylogenetic Assessment of Microbial Communities in Diverse Environments.
Abstract + PDFThe taxonomic composition of environmental communities is an important indicator of their ecology and function. Here, we use a set of protein-coding marker genes, extracted from large-scale environmental shotgun sequencing data, to provide a more direct, quantitative and accurate picture of community composition than traditional rRNA-based approaches using polymerase chain reaction (PCR). By mapping marker genes from four diverse environmental data sets onto a reference species phylogeny, we show that certain communities evolve faster than others, determine preferred habitats for entire microbial clades, and provide evidence that such habitat preferences are often remarkably stable over time.
2006 1 publication(s).
12.
Toward automatic reconstruction of a highly resolved tree of life.
Abstract + PDFWe have developed an automatable procedure for reconstructing the tree of life with branch lengths comparable across all three domains. The tree has its basis in a concatenation of 31 orthologs occurring in 191 species with sequenced genomes. It revealed interdomain discrepancies in taxonomic classification. Systematic detection and subsequent exclusion of products of horizontal gene transfer increased phylogenetic resolution, allowing us to confirm accepted relationships and resolve disputed and preliminary classifications. For example, we place the phylum Acidobacteria as a sister group of delta-Proteobacteria, support a Gram-positive origin of Bacteria, and suggest a thermophilic last universal common ancestor.
2005 3 publication(s).
11.
Dynamic complex formation during the yeast cell cycle.
de Lichtenberg U, Jensen LJ, Brunak S, Bork P
Abstract + PDFTo analyze the dynamics of protein complexes during the yeast cell cycle, we integrated data on protein interactions and gene expression. The resulting time-dependent interaction network places both periodically and constitutively expressed proteins in a temporal cell cycle context, thereby revealing previously unknown components and modules. We discovered that most complexes consist of both periodically and constitutively expressed subunits, which suggests that the former control complex activity by a mechanism of just-in-time assembly. Consistent with this, we show that additional regulation through targeted degradation and phosphorylation by Cdc28p (Cdk1) specifically affects the periodically expressed proteins.
10.
Vertebrate-type intron-rich genes in the marine annelid Platynereis dumerilii.
Raible F, Tessmar-Raible K, Osoegawa K, Wincker P, Jubin C, Balavoine G, Ferrier D, Benes V, de Jong P, Weissenbach J, Bork P, Arendt D
Abstract + PDFPrevious genome comparisons have suggested that one important trend in vertebrate evolution has been a sharp rise in intron abundance. By using genomic data and expressed sequence tags from the marine annelid Platynereis dumerilii, we provide direct evidence that about two-thirds of human introns predate the bilaterian radiation but were lost from insect and nematode genomes to a large extent. A comparison of coding exon sequences confirms the ancestral nature of Platynereis and human genes. Thus, the urbilaterian ancestor had complex, intron-rich genes that have been retained in Platynereis and human.
9.
Comparative metagenomics of microbial communities.
Tringe SG, von Mering C, Kobayashi A, Salamov AA, Chen K, Chang HW, Podar M, Short JM, Mathur EJ, Detter JC, Bork P, Hugenholtz P, Rubin EM
Abstract + PDFThe species complexity of microbial communities and challenges in culturing representative isolates make it difficult to obtain assembled genomes. Here we characterize and compare the metabolic capabilities of terrestrial and marine microbial communities using largely unassembled sequence data obtained by shotgun sequencing DNA isolated from the various environments. Quantitative gene content analysis reveals habitat-specific fingerprints that reflect known characteristics of the sampled environments. The identification of environment-specific genes through a gene-centric comparative analysis presents new opportunities for interpreting and diagnosing environments.
2004 1 publication(s).
8.
Structure-based assembly of protein complexes in yeast.
Aloy P, Böttcher B, Ceulemans H, Leutwein C, Mellwig C, Fischer S, Gavin AC, Bork P, Superti-Furga G, Serrano L, Russell RB
Science.
2004 Mar 26; 303(5666): 2026-9. PubMed: 15044803.Abstract + PDFImages of entire cells are preceding atomic structures of the separate molecular machines that they contain. The resulting gap in knowledge can be partly bridged by protein-protein interactions, bioinformatics, and electron microscopy. Here we use interactions of known three-dimensional structure to model a large set of yeast complexes, which we also screen by electron microscopy. For 54 of 102 complexes, we obtain at least partial models of interacting subunits. For 29, including the exosome, the chaperonin containing TCP-1, a 3'-messenger RNA degradation complex, and RNA polymerase II, the process suggests atomic details not easily seen by homology, involving the combination of two or more known structures. We also consider interactions between complexes (cross-talk) and use these to construct a structure-based network of molecular machines in the cell.
2002 3 publication(s).
7.
Immunity-related genes and gene families in Anopheles gambiae.
Christophides GK, Zdobnov EM, Barillas-Mury C, Birney E, Blandin S, Blass C, Brey PT, Collins FH, Danielli A, Dimopoulos G, Hetru C, Hoa NT, Hoffmann JA, Kanzok SM, Letunic I, Levashina EA, Loukeris TG, Lycett G, Meister S, Michel K, Moita LF, Müller HM, Osta MA, Paskewitz SM, Reichhart JM, Rzhetsky A, Troxler L, Vernick KD, Vlachou D, Volz J, von Mering C, Xu J, Zheng L, Bork P, Kafatos FC
Science.
2002 Oct 4; 298(5591): 159-65. PubMed: 12364793.Abstract + PDFWe have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire.
6.
The genome sequence of the malaria mosquito Anopheles gambiae.
Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, Wincker P, Clark AG, Ribeiro JM, Wides R, Salzberg SL, Loftus B, Yandell M, Majoros WH, Rusch DB, Lai Z, Kraft CL, Abril JF, Anthouard V, Arensburger P, Atkinson PW, Baden H, de Berardinis V, Baldwin D, Benes V, Biedler J, Blass C, Bolanos R, Boscus D, Barnstead M, Cai S, Center A, Chaturverdi K, Christophides GK, Chrystal MA, Clamp M, Cravchik A, Curwen V, Dana A, Delcher A, Dew I, Evans CA, Flanigan M, Grundschober-Freimoser A, Friedli L, Gu Z, Guan P, Guigo R, Hillenmeyer ME, Hladun SL, Hogan JR, Hong YS, Hoover J, Jaillon O, Ke Z, Kodira C, Kokoza E, Koutsos A, Letunic I, Levitsky A, Liang Y, Lin JJ, Lobo NF, Lopez JR, Malek JA, McIntosh TC, Meister S, Miller J, Mobarry C, Mongin E, Murphy SD, O'Brochta DA, Pfannkoch C, Qi R, Regier MA, Remington K, Shao H, Sharakhova MV, Sitter CD, Shetty J, Smith TJ, Strong R, Sun J, Thomasova D, Ton LQ, Topalis P, Tu Z, Unger MF, Walenz B, Wang A, Wang J, Wang M, Wang X, Woodford KJ, Wortman JR, Wu M, Yao A, Zdobnov EM, Zhang H, Zhao Q, Zhao S, Zhu SC, Zhimulev I, Coluzzi M, della Torre A, Roth CW, Louis C, Kalush F, Mural RJ, Myers EW, Adams MD, Smith HO, Broder S, Gardner MJ, Fraser CM, Birney E, Bork P, Brey PT, Venter JC, Weissenbach J, Kafatos FC, Collins FH, Hoffman SL
Science.
2002 Oct 4; 298(5591): 129-49. PubMed: 12364791.Abstract + PDFAnopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency ("dual haplotypes") in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in cell adhesion and immunity were noted. An expressed sequence tag analysis of genes regulated by blood feeding provided insights into the physiological adaptations of a hematophagous insect.
5.
Comparative genome and proteome analysis of Anopheles gambiae and Drosophila melanogaster.
Zdobnov EM, von Mering C, Letunic I, Torrents D, Suyama M, Copley RR, Christophides GK, Thomasova D, Holt RA, Subramanian GM, Mueller HM, Dimopoulos G, Law JH, Wells MA, Birney E, Charlab R, Halpern AL, Kokoza E, Kraft CL, Lai Z, Lewis S, Louis C, Barillas-Mury C, Nusskern D, Rubin GM, Salzberg SL, Sutton GG, Topalis P, Wides R, Wincker P, Yandell M, Collins FH, Ribeiro J, Gelbart WM, Kafatos FC, Bork P
Science.
2002 Oct 4; 298(5591): 149-59. PubMed: 12364792.Abstract + PDFComparison of the genomes and proteomes of the two diptera Anopheles gambiae and Drosophila melanogaster, which diverged about 250 million years ago, reveals considerable similarities. However, numerous differences are also observed; some of these must reflect the selection and subsequent adaptation associated with different ecologies and life strategies. Almost half of the genes in both genomes are interpreted as orthologs and show an average sequence identity of about 56%, which is slightly lower than that observed between the orthologs of the pufferfish and human (diverged about 450 million years ago). This indicates that these two insects diverged considerably faster than vertebrates. Aligned sequences reveal that orthologous genes have retained only half of their intron/exon structure, indicating that intron gains or losses have occurred at a rate of about one per gene per 125 million years. Chromosomal arms exhibit significant remnants of homology between the two species, although only 34% of the genes colocalize in small "microsyntenic" clusters, and major interarm transfers as well as intra-arm shuffling of gene order are detected.
1999 1 publication(s).
4.
Lateral Gene Transfer, Genome Surveys and the Phylogeny of Prokaryotes.
Science.
1999 Nov 19; 286(5444): 1443. PID: 293.Abstract + PDFDoolittle argued that to construct phylogenies, an organism should be regarded as either less or more than the sum of its genes (1). The argument is based on the observation that gene phylogenies are rarely consistent with one another because, among others, of lateral gene transfer (LGT). Creating phylogenies from sequence data in which an organism is described exactly as the sum of its genes is not, however, the only approach (2). Rather than creating phylogenies based on sequence identity for separate genes, this alternative creates a distance-based phylogeny at the genome level by comparing the fraction of genes shared between genomes (2). The resulting phylogeny (Fig. 1) of completely sequenced genomes (for an overview, see http://www.tigr.org/tdb/tdb.html) is remarkably similar to the phylogenies that are based on 16S ribosomal RNA (3). Not only is the trichotomy between Eukarya, Bacteria, and Archaea present, but within each of these taxa the clusters generally recognized as being monophyletic and for which multiple genomes are available, all have high bootstrap values (the Proteobacteria and their branching order, the Spirochaetales, the low (G+C) Gram-positive bacteria, and the Euryarchaeota). This method does not resolve the major branchings of the Bacteria, but neither do the phylogenies based on sequences that do not show LGT resolve this part of Bacterial phylogeny with a high degree of confidence.
1997 2 publication(s).
3.
Genome maps 8. Building gene families. Wall chart.
Green EA, Pietrokovski S, Henikoff S, Bork P, Attwood T, Hood L, Bairoch A
Science.
1997 Oct 24; 278(5338): 615-30. PubMed: 9381172.2.
Gene families: the taxonomy of protein paralogs and chimeras.
Henikoff S, Greene EA, Pietrokovski S, Bork P, Attwood TK, Hood L
Science.
1997 Oct 24; 278(5338): 609-14. PubMed: 9381171.Abstract + PDFAncient duplications and rearrangements of protein-coding segments have resulted in complex gene family relationships. Duplications can be tandem or dispersed and can involve entire coding regions or modules that correspond to folded protein domains. As a result, gene products may acquire new specificities, altered recognition properties, or modified functions. Extreme proliferation of some families within an organism, perhaps at the expense of other families, may correspond to functional innovations during evolution. The underlying processes are still at work, and the large fraction of human and other genomes consisting of transposable elements may be a manifestation of the evolutionary benefits of genomic flexibility.