The eukaryotic phylum Apicomplexa encompasses thousands of obligate intracellular parasites of humans and animals with immense socio-economic and health impacts. We sequenced nuclear genomes of Chromera velia and Vitrella brassicaformis, free-living non-parasitic photosynthetic algae closely related to apicomplexans. Proteins from key metabolic pathways and from the endomembrane trafficking systems associated with a free-living lifestyle have been progressively and non-randomly lost during adaptation to parasitism. The free-living ancestor contained a broad repertoire of genes many of which were repurposed for parasitic processes, such as extracellular proteins, components of a motility apparatus, and DNA- and RNA-binding protein families. Based on transcriptome analyses across 36 environmental conditions, Chromera orthologs of apicomplexan invasion-related motility genes were co-regulated with genes encoding the flagellar apparatus, supporting the functional contribution of flagella to the evolution of invasion machinery. This study provides insights into how obligate parasites with diverse life strategies arose from a once free-living phototrophic marine alga.

Biochemical Sciences Division CSIR National Chemical Laboratory Pune India

Bioscience Core Laboratory King Abdullah University of Science and Technology Thuwal Saudi Arabia

Broad Genome Sequencing and Analysis Program Broad Institute of MIT and Harvard Cambridge United States

Canadian Institute for Advanced Research Department of Botany University of British Columbia Vancouver Canada

Centre for GeoGenetics Natural History Museum of Denmark University of Copenhagen Copenhagen Denmark

Centro de Biología Molecular Severo Ochoa CSIC Universidad Autónoma de Madrid Madrid Spain

Department of Biology University of Pennsylvania Philadelphia United States

Department of Cell Biology University of Alberta Edmonton Canada

Department of Microbiology and Immunology Weill Cornell Medical College New York United States

Department of Microbiology Monash University Clayton Australia

Ecology and Evolutionary Biology Section Institut de Biologie de l'Ecole Normale Supérieure CNRS UMR8197 INSERM U1024 Paris France

European Bioinformatics Institute Wellcome Genome Campus Hinxton Cambridge United Kingdom

Institute of Parasitology Biology Centre Czech Academy of Sciences České Budějovice Czech Republic

Parasite Genomics Wellcome Trust Sanger Institute Wellcome Trust Genome Campus Cambridge United Kingdom

Pathogen Genomics Laboratory Biological and Environmental Sciences and Engineering Division King Abdullah University of Science and Technology Thuwal Saudi Arabia

School of Botany University of Melbourne Parkville Australia

Seattle Biomedical Research Institute Seattle United States

Wellcome Trust Centre For Molecular Parasitology Institute of Infection Immunity and Inflammation College of Medical Veterinary and Life Sciences University of Glasgow Glasgow United Kingdom

Komentář v

Nat Rev Microbiol. 2015 Oct;13(10):603. doi: 10.1038/nrmicro3551. PubMed

Zobrazit více v PubMed

Abrahamsen MS, Templeton TJ, Enomoto S, Abrahante JE, Zhu G, Lancto CA, Deng M, Liu C, Widmer G, Tzipori S, Buck GA, Xu P, Bankier AT, Dear PH, Konfortov BA, Spriggs HF, Iyer L, Anantharaman V, Aravind L, Kapur V. Complete genome sequence of the apicomplexan, Cryptosporidium parvum. Science. 2004;304:441–445. doi: 10.1126/science.1094786. PubMed DOI

Adl SM, Leander BS, Simpson AG, Archibald JM, Anderson OR, Bass D, Bowser SS, Brugerolle G, Farmer MA, Karpov S, Kolisko M, Lane CE, Lodge DJ, Mann DG, Meisterfeld R, Mendoza L, Moestrup O, Mozley-Standridge SE, Smirnov AV, Spiegel F. Diversity, nomenclature, and taxonomy of protists. Systematic Biology. 2007;56:684–689. doi: 10.1080/10635150701494127. PubMed DOI

Allen AE, Dupont CL, Oborník M, Horak A, Nunes-Nesi A, Mccrow JP, Zheng H, Johnson DA, Hu H, Fernie AR, Bowler C. Evolution and metabolic significance of the urea cycle in photosynthetic diatoms. Nature. 2011;473:203–207. doi: 10.1038/nature10074. PubMed DOI

Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. Journal of Molecular Biology. 1990;215:403–410. doi: 10.1016/S0022-2836(05)80360-2. PubMed DOI

Anantharaman V, Iyer LM, Balaji S, Aravind L. Adhesion molecules and other secreted host-interaction determinants in Apicomplexa: insights from comparative genomics. International Review of Cytology. 2007;262:1–74. doi: 10.1016/S0074-7696(07)62001-4. PubMed DOI

Aurrecoechea C, Barreto A, Brestelli J, Brunk BP, Cade S, Doherty R, Fischer S, Gajria B, Gao X, Gingle A, Grant G, Harb OS, Heiges M, Hu S, Iodice J, Kissinger JC, Kraemer ET, Li W, Pinney DF, Pitts B, Roos DS, Srinivasamoorthy G, Stoeckert CJ, Jr, Wang H, Warrenfeltz S. EuPathDB: the eukaryotic pathogen database. Nucleic Acids Research. 2013;41:D684–D691. doi: 10.1093/nar/gks1113. PubMed DOI PMC

Bahl A, Brunk B, Crabtree J, Fraunholz MJ, Gajria B, Grant GR, Ginsburg H, Gupta D, Kissinger JC, Labo P, Li L, Mailman MD, Milgram AJ, Pearson DS, Roos DS, Schug J, Stoeckert CJ, Jr, Whetzel P. PlasmoDB: the Plasmodium genome resource. A database integrating experimental and computational data. Nucleic Acids Research. 2003;31:212–215. doi: 10.1093/nar/gkg081. PubMed DOI PMC

Balaji S, Babu MM, Iyer LM, Aravind L. Discovery of the principal specific transcription factors of Apicomplexa and their implication for the evolution of the AP2-integrase DNA binding domains. Nucleic Acids Research. 2005;33:3994–4006. doi: 10.1093/nar/gki709. PubMed DOI PMC

Bannai H, Tamada Y, Maruyama O, Nakai K, Miyano S. Extensive feature detection of N-terminal protein sorting signals. Bioinformatics. 2002;18:298–305. doi: 10.1093/bioinformatics/18.2.298. PubMed DOI

Bao Z, Eddy SR. Automated de novo identification of repeat sequence families in sequenced genomes. Genome Research. 2002;12:1269–1276. doi: 10.1101/gr.88502. PubMed DOI PMC

Baum J, Gilberger TW, Frischknecht F, Meissner M. Host-cell invasion by malaria parasites: insights from Plasmodium and Toxoplasma. Trends in Parasitology. 2008;24:557–563. doi: 10.1016/j.pt.2008.08.006. PubMed DOI

Baum J, Papenfuss AT, Baum B, Speed TP, Cowman AF. Regulation of apicomplexan actin-based motility. Nature Reviews. Microbiology. 2006;4:621–628. doi: 10.1038/nrmicro1465. PubMed DOI

Bendtsen JD, Nielsen H, von Heijne G, Brunak S. Improved prediction of signal peptides: SignalP 3.0. Journal of Molecular Biology. 2004;340:783–795. doi: 10.1016/j.jmb.2004.05.028. PubMed DOI

Benson G. Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Research. 1999;27:573–580. doi: 10.1093/nar/27.2.573. PubMed DOI PMC

Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, Hall KP, Evers DJ, Barnes CL, Bignell HR, Boutell JM, Bryant J, Carter RJ, Keira Cheetham R, Cox AJ, Ellis DJ, Flatbush MR, Gormley NA, Humphray SJ, Irving LJ, Karbelashvili MS, Kirk SM, Li H, Liu X, Maisinger KS, Murray LJ, Obradovic B, Ost T, Parkinson ML, Pratt MR, Rasolonjatovo IM, Reed MT, Rigatti R, Rodighiero C, Ross MT, Sabot A, Sankar SV, Scally A, Schroth GP, Smith ME, Smith VP, Spiridou A, Torrance PE, Tzonev SS, Vermaas EH, Walter K, Wu X, Zhang L, Alam MD, Anastasi C, Aniebo IC, Bailey DM, Bancarz IR, Banerjee S, Barbour SG, Baybayan PA, Benoit VA, Benson KF, Bevis C, Black PJ, Boodhun A, Brennan JS, Bridgham JA, Brown RC, Brown AA, Buermann DH, Bundu AA, Burrows JC, Carter NP, Castillo N, Catenazzi E, Chiara M, Chang S, Neil Cooley R, Crake NR, Dada OO, Diakoumakos KD, Dominguez-Fernandez B, Earnshaw DJ, Egbujor UC, Elmore DW, Etchin SS, Ewan MR, Fedurco M, Fraser LJ, Fuentes Fajardo KV, Scott Furey W, George D, Gietzen KJ, Goddard CP, Golda GS, Granieri PA, Green DE, Gustafson DL, Hansen NF, Harnish K, Haudenschild CD, Heyer NI, Hims MM, Ho JT, Horgan AM, Hoschler K, Hurwitz S, Ivanov DV, Johnson MQ, James T, Huw Jones TA, Kang GD, Kerelska TH, Kersey AD, Khrebtukova I, Kindwall AP, Kingsbury Z, Kokko-Gonzales PI, Kumar A, Laurent MA, Lawley CT, Lee SE, Lee X, Liao AK, Loch JA, Lok M, Luo S, Mammen RM, Martin JW, McCauley PG, McNitt P, Mehta P, Moon KW, Mullens JW, Newington T, Ning Z, Ling Ng B, Novo SM, O'Neill MJ, Osborne MA, Osnowski A, Ostadan O, Paraschos LL, Pickering L, Pike AC, Pike AC, Chris Pinkard D, Pliskin DP, Podhasky J, Quijano VJ, Raczy C, Rae VH, Rawlings SR, Chiva Rodriguez A, Roe PM, Rogers J, Rogert Bacigalupo MC, Romanov N, Romieu A, Roth RK, Rourke NJ, Ruediger ST, Rusman E, Sanches-Kuiper RM, Schenker MR, Seoane JM, Shaw RJ, Shiver MK, Short SW, Sizto NL, Sluis JP, Smith MA, Ernest Sohna Sohna J, Spence EJ, Stevens K, Sutton N, Szajkowski L, Tregidgo CL, Turcatti G, Vandevondele S, Verhovsky Y, Virk SM, Wakelin S, Walcott GC, Wang J, Worsley GJ, Yan J, Yau L, Zuerlein M, Rogers J, Mullikin JC, Hurles ME, McCooke NJ, West JS, Oaks FL, Lundberg PL, Klenerman D, Durbin R, Smith AJ. Accurate whole human genome sequencing using reversible terminator chemistry. Nature. 2008;456:53–59. doi: 10.1038/nature07517. PubMed DOI PMC

Bernal A, Crammer K, Hatzigeorgiou A, Pereira F. Global discriminative learning for higher-accuracy computational gene prediction. PLOS Computational Biology. 2007;3:e54. doi: 10.1371/journal.pcbi.0030054. PubMed DOI PMC

Boetzer M, Henkel CV, Jansen HJ, Butler D, Pirovano W. Scaffolding pre-assembled contigs using SSPACE. Bioinformatics. 2011;27:578–579. doi: 10.1093/bioinformatics/btq683. PubMed DOI

Boetzer M, Pirovano W. Toward almost closed genomes with GapFiller. Genome Biology. 2012;13:R56. doi: 10.1186/gb-2012-13-6-r56. PubMed DOI PMC

Bolstad BM, Irizarry RA, Astrand M, Speed TP. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics. 2003;19:185–193. doi: 10.1093/bioinformatics/19.2.185. PubMed DOI

Bougdour A, Tardieux I, Hakimi MA. Toxoplasma exports dense granule proteins beyond the vacuole to the host cell nucleus and rewires the host genome expression. Cellular Microbiology. 2014;16:334–343. doi: 10.1111/cmi.12255. PubMed DOI

Box GE, Stuart Hunter J, Hunter WG. Statistics for experimenters: design, innovation, and discovery. 2nd ed., Wiley series in probability and statistics. Hoboken: Wiley-Interscience; 2005.

Bullen HE, Tonkin CJ, O'Donnell RA, Tham WH, Papenfuss AT, Gould S, Cowman AF, Crabb BS, Gilson PR. A novel family of Apicomplexan glideosome-associated proteins with an inner membrane-anchoring role. The Journal of Biological Chemistry. 2009;284:25353–25363. doi: 10.1074/jbc.M109.036772. PubMed DOI PMC

Campbell TL, de Silva EK, Olszewski KL, Elemento O, Llinas M. Identification and genome-wide prediction of DNA binding specificities for the ApiAP2 family of regulators from the malaria parasite. PLOS Pathogens. 2010;6:e1001165. doi: 10.1371/journal.ppat.1001165. PubMed DOI PMC

Capella-Gutierrez S, Silla-Martinez JM, Gabaldon T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics. 2009;25:1972–1973. doi: 10.1093/bioinformatics/btp348. PubMed DOI PMC

Caron F, Meyer E. Molecular basis of surface antigen variation in paramecia. Annual Review of Microbiology. 1989;43:23–42. doi: 10.1146/annurev.mi.43.100189.000323. PubMed DOI

Chaudhry F, Little K, Talarico L, Quintero-Monzon O, Goode BL. A central role for the WH2 domain of Srv2/CAP in recharging actin monomers to drive actin turnover in vitro and in vivo. Cytoskeleton. 2010;67:120–133. doi: 10.1002/cm.20429. PubMed DOI PMC

Chen F, Mackey AJ, Stoeckert CJ, Jr, Roos DS. OrthoMCL-DB: querying a comprehensive multi-species collection of ortholog groups. Nucleic Acids Research. 2006;34:D363–D368. doi: 10.1093/nar/gkj123. PubMed DOI PMC

Claros MG, Vincens P. Computational method to predict mitochondrially imported proteins and their targeting sequences. European Journal of Biochemistry. 1996;241:779–786. doi: 10.1111/j.1432-1033.1996.00779.x. PubMed DOI

Coppens I, Sinai AP, Joiner KA. Toxoplasma gondii exploits host low-density lipoprotein receptor-mediated endocytosis for cholesterol acquisition. The Journal of Cell Biology. 2000;149:167–180. doi: 10.1083/jcb.149.1.167. PubMed DOI PMC

Csuros M. Count: evolutionary analysis of phylogenetic profiles with parsimony and likelihood. Bioinformatics. 2010;26:1910–1912. doi: 10.1093/bioinformatics/btq315. PubMed DOI

Cumbo VR, Baird AH, Moore RB, Negri AP, Neilan BA, Salih A, van Oppen MJ, Wang Y, Marquis CP. Chromera velia is endosymbiotic in larvae of the reef corals Acropora digitifera and A. tenuis. Protist. 2013;164:237–244. doi: 10.1016/j.protis.2012.08.003. PubMed DOI

Danne JC, Gornik SG, Macrae JI, McConville MJ, Waller RF. Alveolate mitochondrial metabolic evolution: dinoflagellates force reassessment of the role of parasitism as a driver of change in apicomplexans. Molecular Biology and Evolution. 2013;30:123–139. doi: 10.1093/molbev/mss205. PubMed DOI

Du P, Li T, Wang X. Recent progress in predicting protein sub-subcellular locations. Expert Review of Proteomics. 2011;8:391–404. doi: 10.1586/epr.11.20. PubMed DOI

Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Research. 2004;32:1792–1797. doi: 10.1093/nar/gkh340. PubMed DOI PMC

Edgar RC, Myers EW. PILER: identification and classification of genomic repeats. Bioinformatics. 2005;21(Suppl 1):i152–i158. doi: 10.1093/bioinformatics/bti1003. PubMed DOI

Eisen JA, Coyne RS, Wu M, Wu D, Thiagarajan M, Wortman JR, Badger JH, Ren Q, Amedeo P, Jones KM, Tallon LJ, Delcher AL, Salzberg SL, Silva JC, Haas BJ, Majoros WH, Farzad M, Carlton JM, Smith RK, Jr, Garg J, Pearlman RE, Karrer KM, Sun L, Manning G, Elde NC, Turkewitz AP, Asai DJ, Wilkes DE, Wang Y, Cai H, Collins K, Stewart BA, Lee SR, Wilamowska K, Weinberg Z, Ruzzo WL, Wloga D, Gaertig J, Frankel J, Tsao CC, Gorovsky MA, Keeling PJ, Waller RF, Patron NJ, Cherry JM, Stover NA, Krieger CJ, del Toro C, Ryder HF, Williamson SC, Barbeau RA, Hamilton EP, Orias E. Macronuclear genome sequence of the ciliate Tetrahymena thermophila, a model eukaryote. PLOS Biology. 2006;4:e286. doi: 10.1371/journal.pbio.0040286. PubMed DOI PMC

Ellinghaus D, Kurtz S, Willhoeft U. LTRharvest, an efficient and flexible software for de novo detection of LTR retrotransposons. BMC Bioinformatics. 2008;9:18. doi: 10.1186/1471-2105-9-18. PubMed DOI PMC

Emanuelsson O, Brunak S, von Heijne G, Nielsen H. Locating proteins in the cell using TargetP, SignalP and related tools. Nature Protocols. 2007;2:953–971. doi: 10.1038/nprot.2007.131. PubMed DOI

Emanuelsson O, Nielsen H, Brunak S, von Heijne G. Predicting subcellular localization of proteins based on their N-terminal amino acid sequence. Journal of Molecular Biology. 2000;300:1005–1016. doi: 10.1006/jmbi.2000.3903. PubMed DOI

Faith JJ, Hayete B, Thaden JT, Mogno I, Wierzbowski J, Cottarel G, Kasif S, Collins JJ, Gardner TS. Large-scale mapping and validation of Escherichia coli transcriptional regulation from a compendium of expression profiles. PLOS Biology. 2007;5:e8. doi: 10.1371/journal.pbio.0050008. PubMed DOI PMC

Fedoroff NV. Presidential address. Transposable elements, epigenetics, and genome evolution. Science. 2012;338:758–767. doi: 10.1126/science.338.6108.758. PubMed DOI

Fehrenbacher K, Huckaba T, Yang HC, Boldogh I, Pon L. Actin comet tails, endosomes and endosymbionts. The Journal of Experimental Biology. 2003;206:1977–1984. doi: 10.1242/jeb.00240. PubMed DOI

Ferguson DJ, Sahoo N, Pinches RA, Bumstead JM, Tomley FM, Gubbels MJ. MORN1 has a conserved role in asexual and sexual development across the Apicomplexa. Eukaryot Cell. 2008;7:698–711. doi: 10.1128/EC.00021-08. PubMed DOI PMC

Field HI, Coulson RMR, Field MC. An automated graphics tool for comparative genomics: the Coulson plot generator. BMC Bioinformatics. 2013;14:141. doi: 10.1186/1471-2105-14-141. PubMed DOI PMC

Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, Sonnhammer EL, Tate J, Punta M. Pfam: the protein families database. Nucleic Acids Research. 2014;42:D222–D230. doi: 10.1093/nar/gkt1223. PubMed DOI PMC

Finn RD, Clements J, Eddy SR. HMMER web server: interactive sequence similarity searching. Nucleic Acids Research. 2011;39:W29–W37. doi: 10.1093/nar/gkr367. PubMed DOI PMC

Flegontov P, Michalek J, Janouskovec J, Lai DH, Jirku M, Hajduskova E, Tomcala A, Otto TD, Keeling PJ, Pain A, Oborník M, Lukeš J. Divergent mitochondrial respiratory chains in phototrophic relatives of apicomplexan parasites. Molecular Biology and Evolution. 2015;32:1115–1131. doi: 10.1093/molbev/msv021. PubMed DOI

Flueck C, Bartfai R, Niederwieser I, Witmer K, Alako BT, Moes S, Bozdech Z, Jenoe P, Stunnenberg HG, Voss TS. A major role for the Plasmodium falciparum ApiAP2 protein PfSIP2 in chromosome end biology. PLOS Pathogens. 2010;6:e1000784. doi: 10.1371/journal.ppat.1000784. PubMed DOI PMC

Flutre T, Duprat E, Feuillet C, Quesneville H. Considering transposable element diversification in de novo annotation approaches. PLOS ONE. 2011;6:e16526. doi: 10.1371/journal.pone.0016526. PubMed DOI PMC

Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. The Journal of Biological Chemistry. 1957;226:497–509. PubMed

Foth BJ, Goedecke MC, Soldati D. New insights into myosin evolution and classification. Proceedings of the National Academy of Sciences of USA. 2006;103:3681–3686. doi: 10.1073/pnas.0506307103. PubMed DOI PMC

Francia ME, Jordan CN, Patel JD, Sheiner L, Demerly JL, Fellows JD, de Leon JC, Morrissette NS, Dubremetz JF, Striepen B. Cell division in Apicomplexan parasites is organized by a homolog of the striated rootlet fiber of algal flagella. PLOS Biology. 2012;10:e1001444. doi: 10.1371/journal.pbio.1001444. PubMed DOI PMC

Frenal K, Polonais V, Marq JB, Stratmann R, Limenitakis J, Soldati-Favre D. Functional dissection of the apicomplexan glideosome molecular architecture. Cell Host & Microbe. 2010;8:343–357. doi: 10.1016/j.chom.2010.09.002. PubMed DOI

Frenal K, Soldati-Favre D. Role of the parasite and host cytoskeleton in Apicomplexa parasitism. Cell Host & Microbe. 2009;5:602–611. doi: 10.1016/j.chom.2009.05.013. PubMed DOI

Gajria B, Bahl A, Brestelli J, Dommer J, Fischer S, Gao X, Heiges M, Iodice J, Kissinger JC, Mackey AJ, Pinney DF, Roos DS, Stoeckert CJ, Jr, Wang H, Brunk BP. ToxoDB: an integrated Toxoplasma gondii database resource. Nucleic Acids Research. 2008;36:D553–D556. doi: 10.1093/nar/gkm981. PubMed DOI PMC

Gandhi M, Jangi M, Goode BL. Functional surfaces on the actin-binding protein coronin revealed by systematic mutagenesis. The Journal of Biological Chemistry. 2010;285:34899–34908. doi: 10.1074/jbc.M110.171496. PubMed DOI PMC

Gerstein MB, Rozowsky J, Yan KK, Wang D, Cheng C, Brown JB, Davis CA, Hillier L, Sisu C, Li JJ, Pei B, Harmanci AO, Duff MO, Djebali S, Alexander RP, Alver BH, Auerbach R, Bell K, Bickel PJ, Boeck ME, Boley NP, Booth BW, Cherbas L, Cherbas P, Di C, Dobin A, Drenkow J, Ewing B, Fang G, Fastuca M, Feingold EA, Frankish A, Gao G, Good PJ, Guigo R, Hammonds A, Harrow J, Hoskins RA, Howald C, Hu L, Huang H, Hubbard TJ, Huynh C, Jha S, Kasper D, Kato M, Kaufman TC, Kitchen RR, Ladewig E, Lagarde J, Lai E, Leng J, Lu Z, MacCoss M, May G, McWhirter R, Merrihew G, Miller DM, Mortazavi A, Murad R, Oliver B, Olson S, Park PJ, Pazin MJ, Perrimon N, Pervouchine D, Reinke V, Reymond A, Robinson G, Samsonova A, Saunders GI, Schlesinger F, Sethi A, Slack FJ, Spencer WC, Stoiber MH, Strasbourger P, Tanzer A, Thompson OA, Wan KH, Wang G, Wang H, Watkins KL, Wen J, Wen K, Xue C, Yang L, Yip K, Zaleski C, Zhang Y, Zheng H, Brenner SE, Graveley BR, Celniker SE, Gingeras TR, Waterston R. Comparative analysis of the transcriptome across distant species. Nature. 2014;512:445–448. doi: 10.1038/nature13424. PubMed DOI PMC

Gordon JL, Sibley LD. Comparative genome analysis reveals a conserved family of actin-like proteins in apicomplexan parasites. BMC Genomics. 2005;6:179. doi: 10.1186/1471-2164-6-179. PubMed DOI PMC

Gournier H, Goley ED, Niederstrasser H, Trinh T, Welch MD. Reconstitution of human Arp2/3 complex reveals critical roles of individual subunits in complex structure and activity. Molecular Cell. 2001;8:1041–1052. doi: 10.1016/S1097-2765(01)00393-8. PubMed DOI

Gouy M, Guindon S, Gascuel O. SeaView version 4: a multiplatform graphical user interface for sequence alignment and phylogenetic tree building. Molecular Biology and Evolution. 2010;27:221–224. doi: 10.1093/molbev/msp259. PubMed DOI

Gschloessl B, Guermeur Y, Cock JM. HECTAR: a method to predict subcellular targeting in heterokonts. BMC Bioinformatics. 2008;9:393. doi: 10.1186/1471-2105-9-393. PubMed DOI PMC

Hafner MS, Sudman PD, Villablanca FX, Spradling TA, Demastes JW, Nadler SA. Disparate rates of molecular evolution in cospeciating hosts and parasites. Science. 1994;265:1087–1090. doi: 10.1126/science.8066445. PubMed DOI

Hager KM, Striepen B, Tilney LG, Roos DS. The nuclear envelope serves as an intermediary between the ER and Golgi complex in the intracellular parasite Toxoplasma gondii. Journal of Cell Science. 1999;112:2631–2638. PubMed

Hintze JL, Nelson RD. Violin plots: a box plot-density trace synergism. American Statistician. 1998;52:181–184. doi: 10.2307/2685478. DOI

Hirst J, Barlow LD, Francisco GC, Sahlender DA, Seaman MNJ, Dacks JB, Robinson MS. The fifth adaptor protein complex. PLOS Biology. 2011;9:e1001170. doi: 10.1371/journal.pbio.1001170. PubMed DOI PMC

Hsiao CH, Luisa Hiller N, Haldar K, Knoll LJ. A HT/PEXEL motif in Toxoplasma dense granule proteins is a signal for protein cleavage but not export into the host cell. Traffic. 2013;14:519–531. doi: 10.1111/tra.12049. PubMed DOI PMC

Hu G, Cabrera A, Kono M, Mok S, Chaal BK, Haase S, Engelberg K, Cheemadan S, Spielmann T, Preiser PR, Gilberger TW, Bozdech Z. Transcriptional profiling of growth perturbations of the human malaria parasite Plasmodium falciparum. Nature Biotechnology. 2010;28:91–98. doi: 10.1038/nbt.1597. PubMed DOI

Hu K, Johnson J, Florens L, Fraunholz M, Suravajjala S, DiLullo C, Yates J, Roos DS, Murray JM. Cytoskeletal components of an invasion machine—the apical complex of Toxoplasma gondii. PLOS Pathogens. 2006;2:e13. doi: 10.1371/journal.ppat.0020013. PubMed DOI PMC

Hunt M, Kikuchi T, Sanders M, Newbold C, Berriman M, Otto TD. REAPR: a universal tool for genome assembly evaluation. Genome Biology. 2013;14:R47. doi: 10.1186/gb-2013-14-5-r47. PubMed DOI PMC

Janouškovec J, Horák A, Barott KL, Rohwer FL, Keeling PJ. Global analysis of plastid diversity reveals apicomplexan-related lineages in coral reefs. Current Biology. 2012;22:R518–R519. doi: 10.1016/j.cub.2012.04.047. PubMed DOI

Janouškovec J, Horák A, Barott KL, Rohwer FL, Keeling PJ. Environmental distribution of coral-associated relatives of apicomplexan parasites. The ISME Journal. 2013;7:444–447. doi: 10.1038/ismej.2012.129. PubMed DOI PMC

Janouškovec J, Horák A, Oborník M, Lukeš J, Keeling PJ. A common red algal origin of the apicomplexan, dinoflagellate, and heterokont plastids. Proceedings of the National Academy of Sciences of USA. 2010;107:10949–10954. doi: 10.1073/pnas.1003335107. PubMed DOI PMC

Janouškovec J, Tikhonenkov DV, Burki F, Howe AT, Kolisko M, Mylnikov AP, Keeling PJ. Factors mediating plastid dependency and the origins of parasitism in apicomplexans and their close relatives. Proceedings of the National Academy of Sciences of USA. 2015 doi: 10.1073/pnas.1423790112. PubMed DOI PMC

Johnson LS, Eddy SR, Portugaly E. Hidden Markov model speed heuristic and iterative HMM search procedure. BMC Bioinformatics. 2010;11:431. doi: 10.1186/1471-2105-11-431. PubMed DOI PMC

Jurka J, Kapitonov VV, Pavlicek A, Klonowski P, Kohany O, Walichiewicz J. Repbase update, a database of eukaryotic repetitive elements. Cytogenetic and Genome Research. 2005;110:462–467. doi: 10.1159/000084979. PubMed DOI

Jurka J, Klonowski P, Dagman V, Pelton P. CENSOR–a program for identification and elimination of repetitive elements from DNA sequences. Computers and Chemistry. 1996;20:119–121. doi: 10.1016/S0097-8485(96)80013-1. PubMed DOI

Kafsack BF, Rovira-Graells N, Clark TG, Bancells C, Crowley VM, Campino SG, Williams AE, Drought LG, Kwiatkowski DP, Baker DA, Cortes A, Llinas M. A transcriptional switch underlies commitment to sexual development in malaria parasites. Nature. 2014;507:248–252. doi: 10.1038/nature12920. PubMed DOI PMC

Kanehisa M, Goto S, Sato Y, Kawashima M, Furumichi M, Tanabe M. Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Research. 2014;42:D199–D205. doi: 10.1093/nar/gkt1076. PubMed DOI PMC

Kaneko I, Iwanaga S, Kato T, Kobayashi I, Yuda M. Genome-wide identification of the target genes of AP2-O, a plasmodium AP2-family transcription factor. PLOS Pathogens. 2015;11:e1004905. doi: 10.1371/journal.ppat.1004905. PubMed DOI PMC

Katinka MD, Duprat S, Cornillot E, Metenier G, Thomarat F, Prensier G, Barbe V, Peyretaillade E, Brottier P, Wincker P, Delbac F, El Alaoui H, Peyret P, Saurin W, Gouy M, Weissenbach J, Vivares CP. Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. Nature. 2001;414:450–453. doi: 10.1038/35106579. PubMed DOI

Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Molecular Biology and Evolution. 2013;30:772–780. doi: 10.1093/molbev/mst010. PubMed DOI PMC

Kawase O, Nishikawa Y, Bannai H, Zhang H, Zhang G, Jin S, Lee EG, Xuan X. Proteomic analysis of calcium-dependent secretion in Toxoplasma gondii. Proteomics. 2007;7:3718–3725. doi: 10.1002/pmic.200700362. PubMed DOI

Keeling PJ. Reduction and compaction in the genome of the apicomplexan parasite Cryptosporidium parvum. Developmental Cell. 2004;6:614–616. PubMed

Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biology. 2013;14:R36. doi: 10.1186/gb-2013-14-4-r36. PubMed DOI PMC

Klinger CM, Klute MJ, Dacks JB. Comparative genomic analysis of multi-subunit tethering complexes demonstrates an ancient pan-eukaryotic complement and sculpting in Apicomplexa. PLOS ONE. 2013a;8:e76278. doi: 10.1371/journal.pone.0076278. PubMed DOI PMC

Klinger CM, Nisbet RE, Ouologuem DT, Roos DS, Dacks JB. Cryptic organelle homology in apicomplexan parasites: insights from evolutionary cell biology. Current Opinion in Microbiology. 2013b;16:424–431. doi: 10.1016/j.mib.2013.07.015. PubMed DOI PMC

Kolpakov R, Bana G, Kucherov G. mreps: efficient and flexible detection of tandem repeats in DNA. Nucleic Acids Research. 2003;31:3672–3678. doi: 10.1093/nar/gkg617. PubMed DOI PMC

Kono M, Herrmann S, Loughran NB, Cabrera A, Engelberg K, Lehmann C, Sinha D, Prinz B, Ruch U, Heussler V, Spielmann T, Parkinson J, Gilberger TW. Evolution and architecture of the inner membrane complex in asexual and sexual stages of the malaria parasite. Molecular Biology and Evolution. 2012;29:2113–2132. doi: 10.1093/molbev/mss081. PubMed DOI

Kořený L, Oborník M. Sequence evidence for the presence of two tetrapyrrole pathways in Euglena gracilis. Genome Biology and Evolution. 2011;3:359–364. doi: 10.1093/gbe/evr029. PubMed DOI PMC

Kořený L, Sobotka R, Janouskovec J, Keeling PJ, Oborník M. Tetrapyrrole synthesis of photosynthetic chromerids is likely homologous to the unusual pathway of apicomplexan parasites. The Plant Cell. 2011;23:3454–3462. doi: 10.1105/tpc.111.089102. PubMed DOI PMC

Koumandou VL, Dacks JB, Coulson RM, Field MC. Control systems for membrane fusion in the ancestral eukaryote; evolution of tethering complexes and SM proteins. BMC Evolutionary Biology. 2007;7:29. doi: 10.1186/1471-2148-7-29. PubMed DOI PMC

Kozarewa I, Ning Z, Quail MA, Sanders MJ, Berriman M, Turner DJ. Amplification-free Illumina sequencing-library preparation facilitates improved mapping and assembly of (G+C)-biased genomes. Nature Methods. 2009;6:291–295. doi: 10.1038/nmeth.1311. PubMed DOI PMC

Krogh A, Larsson B, von Heijne G, Sonnhammer EL. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. Journal of Molecular Biology. 2001;305:567–580. doi: 10.1006/jmbi.2000.4315. PubMed DOI

Kucera K, Koblansky AA, Saunders LP, Frederick KB, De La Cruz EM, Ghosh S, Modis Y. Structure-based analysis of Toxoplasma gondii profilin: a parasite-specific motif is required for recognition by Toll-like receptor 11. Journal of Molecular Biology. 2010;403:616–629. doi: 10.1016/j.jmb.2010.09.022. PubMed DOI PMC

Kursula I, Kursula P, Ganter M, Panjikar S, Matuschewski K, Schuler H. Structural basis for parasite-specific functions of the divergent profilin of Plasmodium falciparum. Structure. 2008;16:1638–1648. doi: 10.1016/j.str.2008.09.008. PubMed DOI

Lartillot N, Philippe H. A Bayesian mixture model for across-site heterogeneities in the amino-acid replacement process. Molecular Biology and Evolution. 2004;21:1095–1109. doi: 10.1093/molbev/msh112. PubMed DOI

Le SQ, Dang CC, Gascuel O. Modeling protein evolution with several amino acid replacement matrices depending on site rates. Molecular Biology and Evolution. 2012;29:2921–2936. doi: 10.1093/molbev/mss112. PubMed DOI

Lee I, Hong W. RAP–a putative RNA-binding domain. Trends in Biochemical Sciences. 2004;29:567–570. doi: 10.1016/j.tibs.2004.09.005. PubMed DOI

Leonardi R, Zhang YM, Rock CO, Jackowski S. Coenzyme A: back in action. Progress in Lipid Research. 2005;44:125–153. doi: 10.1016/j.plipres.2005.04.001. PubMed DOI

Leung KF, Dacks JB, Field MC. Evolution of the multivesicular body ESCRT machinery; retention across the eukaryotic lineage. Traffic. 2008;9:1698–1716. doi: 10.1111/j.1600-0854.2008.00797.x. PubMed DOI

Li H, Child MA, Bogyo M. Proteases as regulators of pathogenesis: examples from the Apicomplexa. Biochimica et Biophysica Acta. 2012;1824:177–185. doi: 10.1016/j.bbapap.2011.06.002. PubMed DOI PMC

Li L, Stoeckert CJ, Jr, Roos DS. OrthoMCL: identification of ortholog groups for eukaryotic genomes. Genome Research. 2003;13:2178–2189. doi: 10.1101/gr.1224503. PubMed DOI PMC

Lim L, McFadden GI. The evolution, metabolism and functions of the apicoplast. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 2010;365:749–763. doi: 10.1098/rstb.2009.0273. PubMed DOI PMC

Liu J, Guo W. The exocyst complex in exocytosis and cell migration. Protoplasma. 2012;249:587–597. doi: 10.1007/s00709-011-0330-1. PubMed DOI

Logan-Klumpler FJ, de Silva N, Boehme U, Rogers MB, Velarde G, McQuillan JA, Carver T, Aslett M, Olsen C, Subramanian S, Phan I, Farris C, Mitra S, Ramasamy G, Wang H, Tivey A, Jackson A, Houston R, Parkhill J, Holden M, Harb OS, Brunk BP, Myler PJ, Roos D, Carrington M, Smith DF, Hertz-Fowler C, Berriman M. GeneDB–an annotation database for pathogens. Nucleic Acids Research. 2012;40:D98–D108. doi: 10.1093/nar/gkr1032. PubMed DOI PMC

Machesky LM, Atkinson SJ, Ampe C, Vandekerckhove J, Pollard TD. Purification of a cortical complex containing two unconventional actins from Acanthamoeba by affinity chromatography on profilin-agarose. The Journal of Cell Biology. 1994;127:107–115. doi: 10.1083/jcb.127.1.107. PubMed DOI PMC

Magnani E, Sjolander K, Hake S. From endonucleases to transcription factors: evolution of the AP2 DNA binding domain in plants. The Plant Cell. 2004;16:2265–2277. doi: 10.1105/tpc.104.023135. PubMed DOI PMC

Mazumdar J, Striepen B. Make it or take it: fatty acid metabolism of apicomplexan parasites. Eukaryot Cell. 2007;6:1727–1735. doi: 10.1128/EC.00255-07. PubMed DOI PMC

McFadden GI, Reith ME, Munholland J, Lang-Unnasch N. Plastid in human parasites. Nature. 1996;381:482. doi: 10.1038/381482a0. PubMed DOI

Meyer PE, Lafitte F, Bontempi G. minet: a R/Bioconductor package for inferring large transcriptional networks using mutual information. BMC Bioinformatics. 2008;9:461. doi: 10.1186/1471-2105-9-461. PubMed DOI PMC

Miranda K, Pace DA, Cintron R, Rodrigues JCF, Fang J, Smith A, Rohloff P, Coelho E, de Haas F, de Souza W, Coppens I, Sibley LD, Moreno SNJ. Characterization of a novel organelle in Toxoplasma gondii with similar composition and function to the plant vacuole. Molecular Microbiology. 2010;76:1358–1375. doi: 10.1111/j.1365-2958.2010.07165.x. PubMed DOI PMC

Moore RB, Oborník M, Janouškovec J, Chrudimský T, Vancová M, Green DH, Wright SW, Davies NW, Bolch CJ, Heimann K, Slapeta J, Hoegh-Guldberg O, Logsdon JM, Carter DA. A photosynthetic alveolate closely related to apicomplexan parasites. Nature. 2008;451:959–963. doi: 10.1038/nature06635. PubMed DOI

Moriya Y, Itoh M, Okuda S, Yoshizawa AC, Kanehisa M. KAAS: an automatic genome annotation and pathway reconstruction server. Nucleic Acids Research. 2007;35:W182–W185. doi: 10.1093/nar/gkm321. PubMed DOI PMC

Morrison HG, McArthur AG, Gillin FD, Aley SB, Adam RD, Olsen GJ, Best AA, Cande WZ, Chen F, Cipriano MJ, Davids BJ, Dawson SC, Elmendorf HG, Hehl AB, Holder ME, Huse SM, Kim UU, Lasek-Nesselquist E, Manning G, Nigam A, Nixon JE, Palm D, Passamaneck NE, Prabhu A, Reich CI, Reiner DS, Samuelson J, Svard SG, Sogin ML. Genomic minimalism in the early diverging intestinal parasite Giardia lamblia. Science. 2007;317:1921–1926. doi: 10.1126/science.1143837. PubMed DOI

Morrissette NS, Sibley LD. Cytoskeleton of apicomplexan parasites. Microbiology and Molecular Biology Reviews. 2002;66:21–38. doi: 10.1128/MMBR.66.1.21-38.2002. PubMed DOI PMC

Mullins RD, Stafford WF, Pollard TD. Structure, subunit topology, and actin-binding activity of the Arp2/3 complex from Acanthamoeba. The Journal of Cell Biology. 1997;136:331–343. doi: 10.1083/jcb.136.2.331. PubMed DOI PMC

Mundwiler-Pachlatko E, Beck HP. Maurer's clefts, the enigma of Plasmodium falciparum. Proceedings of the National Academy of Sciences of USA. 2013;110:19987–19994. doi: 10.1073/pnas.1309247110. PubMed DOI PMC

Mutwil M, Klie S, Tohge T, Giorgi FM, Wilkins O, Campbell MM, Fernie AR, Usadel B, Nikoloski Z, Persson S. PlaNet: combined sequence and expression comparisons across plant networks derived from seven species. The Plant Cell. 2011;23:895–910. doi: 10.1105/tpc.111.083667. PubMed DOI PMC

Nevin WD, Dacks JB. Repeated secondary loss of adaptin complex genes in the Apicomplexa. Parasitology International. 2009;58:86–94. doi: 10.1016/j.parint.2008.12.002. PubMed DOI

Oborník M, Modrý D, Lukeš M, Cernotíková-Stříbrná E, Cihlář J, Tesařová M, Kotabová E, Vancová M, Prášil O, Lukeš J. Morphology, ultrastructure and life cycle of Vitrella brassicaformis n. sp., n. gen., a novel chromerid from the Great Barrier Reef. Protist. 2012;163:306–323. doi: 10.1016/j.protis.2011.09.001. PubMed DOI

Oborník M, Vancová M, Lai DH, Janouškovec J, Keeling PJ, Lukeš J. Morphology and ultrastructure of multiple life cycle stages of the photosynthetic relative of Apicomplexa, Chromera velia. Protist. 2011;162:115–130. doi: 10.1016/j.protis.2010.02.004. PubMed DOI

Okamoto N, Keeling PJ. The 3D structure of the apical complex and association with the flagellar apparatus revealed by serial TEM tomography in Psammosa pacifica, a distant relative of the Apicomplexa. PLOS ONE. 2014;9:e84653. doi: 10.1371/journal.pone.0084653. PubMed DOI PMC

Otto TD, Sanders M, Berriman M, Newbold C. Iterative Correction of Reference Nucleotides (iCORN) using second generation sequencing technology. Bioinformatics. 2010;26:1704–1707. doi: 10.1093/bioinformatics/btq269. PubMed DOI PMC

Pawlowski J, Audic S, Adl S, Bass D, Belbahri L, Berney C, Bowser SS, Cepicka I, Decelle J, Dunthorn M, Fiore-Donno AM, Gile GH, Holzmann M, Jahn R, Jirku M, Keeling PJ, Kostka M, Kudryavtsev A, Lara E, Lukeš J, Mann DG, Mitchell EA, Nitsche F, Romeralo M, Saunders GW, Simpson AG, Smirnov AV, Spouge JL, Stern RF, Stoeck T, Zimmermann J, Schindel D, de Vargas C. CBOL protist working group: barcoding eukaryotic richness beyond the animal, plant, and fungal kingdoms. PLOS Biology. 2012;10:e1001419. doi: 10.1371/journal.pbio.1001419. PubMed DOI PMC

Pelletier L, Stern C, Pypaert M, Sheff D. Golgi biogenesis in Toxoplasma gondii. Nature. 2002;418:1–5. doi: 10.1038/nature00946. PubMed DOI

Petersen TN, Brunak S, von Heijne G, Nielsen H. SignalP 4.0: discriminating signal peptides from transmembrane regions. Nature Methods. 2011;8:785–786. doi: 10.1038/nmeth.1701. PubMed DOI

Petsalaki EI, Bagos PG, Litou ZI, Hamodrakas SJ. PredSL: a tool for the N-terminal sequence-based prediction of protein subcellular localization. Genomics, Proteomics & Bioinformatics. 2006;4:48–55. doi: 10.1016/S1672-0229(06)60016-8. PubMed DOI PMC

Pieperhoff MS, Schmitt M, Ferguson DJ, Meissner M. The role of clathrin in post-Golgi trafficking in Toxoplasma gondii. PLOS ONE. 2013;8:e77620. doi: 10.1371/journal.pone.0077620. PubMed DOI PMC

Pombert JF, Blouin NA, Lane C, Boucias D, Keeling PJ. A lack of parasitic reduction in the obligate parasitic green alga Helicosporidium. PLOS Genetics. 2014;10:e1004355. doi: 10.1371/journal.pgen.1004355. PubMed DOI PMC

Pollard TD, Borisy GG. Cellular motility driven by assembly and disassembly of actin filaments. Cell. 2003;112:453–465. doi: 10.1016/S0092-8674(03)00120-X. PubMed DOI

Portman N, Foster C, Walker G, Slapeta J. Evidence of intraflagellar transport and apical complex formation in a free-living relative of the Apicomplexa. Eukaryot Cell. 2014;13:10–20. doi: 10.1128/EC.00155-13. PubMed DOI PMC

Poulin B, Patzewitz EM, Brady D, Silvie O, Wright MH, Ferguson DJ, Wall RJ, Whipple S, Guttery DS, Tate EW, Wickstead B, Holder AA, Tewari R. Unique apicomplexan IMC sub-compartment proteins are early markers for apical polarity in the malaria parasite. Biology Open. 2013;2:1160–1170. doi: 10.1242/bio.20136163. PubMed DOI PMC

Quail MA, Smith M, Coupland P, Otto TD, Harris SR, Connor TR, Bertoni A, Swerdlow HP, Gu Y. A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers. BMC Genomics. 2012;13:341. doi: 10.1186/1471-2164-13-341. PubMed DOI PMC

Quesneville H, Nouaud D, Anxolabehere D. Detection of new transposable element families in Drosophila melanogaster and Anopheles gambiae genomes. Journal of Molecular Evolution. 2003;57(Suppl 1):S50–S59. doi: 10.1007/s00239-003-0007-2. PubMed DOI

Quigg A, Kotabova E, Jaresova J, Kana R, Setlik J, Sediva B, Komarek O, Prasil O. Photosynthesis in Chromera velia represents a simple system with high efficiency. PLOS ONE. 2012;7:e47036. doi: 10.1371/journal.pone.0047036. PubMed DOI PMC

Radke JB, Lucas O, de Silva EK, Ma Y, Sullivan WJ, Jr, Weiss LM, Llinas M, White MW. ApiAP2 transcription factor restricts development of the Toxoplasma tissue cyst. Proceedings of the National Academy of Sciences of USA. 2013;110:6871–6876. doi: 10.1073/pnas.1300059110. PubMed DOI PMC

Raffaele S, Kamoun S. Genome evolution in filamentous plant pathogens: why bigger can be better. Nature Reviews. Microbiology. 2012;10:417–430. doi: 10.1038/nrmicro2790. PubMed DOI

Ravindran S, Boothroyd JC. Secretion of proteins into host cells by Apicomplexan parasites. Traffic. 2008;9:647–656. doi: 10.1111/j.1600-0854.2008.00723.x. PubMed DOI

Reid AJ, Blake DP, Ansari HR, Billington K, Browne HP, Bryant J, Dunn M, Hung SS, Kawahara F, Miranda-Saavedra D, Malas TB, Mourier T, Naghra H, Nair M, Otto TD, Rawlings ND, Rivailler P, Sanchez-Flores A, Sanders M, Subramaniam C, Tay YL, Woo Y, Wu X, Barrell B, Dear PH, Doerig C, Gruber A, Ivens AC, Parkinson J, Rajandream MA, Shirley MW, Wan KL, Berriman M, Tomley FM, Pain A. Genomic analysis of the causative agents of coccidiosis in domestic chickens. Genome Research. 2014;24:1676–1685. doi: 10.1101/gr.168955.113. PubMed DOI PMC

Roiko MS, Carruthers VB. New roles for perforins and proteases in apicomplexan egress. Cellular Microbiology. 2009;11:1444–1452. doi: 10.1111/j.1462-5822.2009.01357.x. PubMed DOI PMC

Roos DS. Genetics. Themes and variations in apicomplexan parasite biology. Science. 2005;309:72–73. doi: 10.1126/science.1115252. PubMed DOI

Russell K, Hasenkamp S, Emes R, Horrocks P. Analysis of the spatial and temporal arrangement of transcripts over intergenic regions in the human malarial parasite Plasmodium falciparum. BMC Genomics. 2013;14:267. doi: 10.1186/1471-2164-14-267. PubMed DOI PMC

Rybakin V, Clemen CS. Coronin proteins as multifunctional regulators of the cytoskeleton and membrane trafficking. Bioessays. 2005;27:625–632. doi: 10.1002/bies.20235. PubMed DOI

Sakharkar KR, Dhar PK, Chow VT. Genome reduction in prokaryotic obligatory intracellular parasites of humans: a comparative analysis. International Journal of Systematic and Evolutionary Microbiology. 2004;54:1937–1941. doi: 10.1099/ijs.0.63090-0. PubMed DOI

Shoguchi E, Shinzato C, Kawashima T, Gyoja F, Mungpakdee S, Koyanagi R, Takeuchi T, Hisata K, Tanaka M, Fujiwara M, Hamada M, Seidi A, Fujie M, Usami T, Goto H, Yamasaki S, Arakaki N, Suzuki Y, Sugano S, Toyoda A, Kuroki Y, Fujiyama A, Medina M, Coffroth MA, Bhattacharya D, Satoh N. Draft assembly of the Symbiodinium minutum nuclear genome reveals dinoflagellate gene structure. Current Biology. 2013;23:1399–1408. doi: 10.1016/j.cub.2013.05.062. PubMed DOI

Silflow CD, Lefebvre PA. Assembly and motility of eukaryotic cilia and flagella. Lessons from Chlamydomonas reinhardtii. Plant Physiology. 2001;127:1500–1507. doi: 10.1104/pp.010807. PubMed DOI PMC

Simpson JT, Durbin R. Efficient de novo assembly of large genomes using compressed data structures. Genome Research. 2012;22:549–556. doi: 10.1101/gr.126953.111. PubMed DOI PMC

Singh BK, Sattler JM, Chatterjee M, Huttu J, Schuler H, Kursula I. Crystal structures explain functional differences in the two actin depolymerization factors of the malaria parasite. The Journal of Biological Chemistry. 2011;286:28256–28264. doi: 10.1074/jbc.M111.211730. PubMed DOI PMC

Sinha A, Hughes KR, Modrzynska KK, Otto TD, Pfander C, Dickens NJ, Religa AA, Bushell E, Graham AL, Cameron R, Kafsack BF, Williams AE, Llinas M, Berriman M, Billker O, Waters AP. A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium. Nature. 2014;507:253–257. doi: 10.1038/nature12970. PubMed DOI PMC

Skillman KM, Diraviyam K, Khan A, Tang K, Sept D, Sibley LD. Evolutionarily divergent, unstable filamentous actin is essential for gliding motility in apicomplexan parasites. PLOS Pathogens. 2011;7:e1002280. doi: 10.1371/journal.ppat.1002280. PubMed DOI PMC

Soldati-Favre D. Molecular dissection of host cell invasion by the apicomplexans: the glideosome. Parasite. 2008;15:197–205. PubMed

Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics. 2014;30:1312–1313. doi: 10.1093/bioinformatics/btu033. PubMed DOI PMC

Stanke M, Keller O, Gunduz I, Hayes A, Waack S, Morgenstern B. AUGUSTUS: ab initio prediction of alternative transcripts. Nucleic Acids Research. 2006;34:W435–W439. doi: 10.1093/nar/gkl200. PubMed DOI PMC

Stevens JM, Galyov EE, Stevens MP. Actin-dependent movement of bacterial pathogens. Nature Reviews. Microbiology. 2006;4:91–101. doi: 10.1038/nrmicro1320. PubMed DOI

Struck NS, Herrmann S, Schmuck-Barkmann I, de Souza Dias S, Haase S, Cabrera AL, Treeck M, Bruns C, Langer C, Cowman AF, Marti M, Spielmann T, Gilberger TW. Spatial dissection of the cis- and trans-Golgi compartments in the malaria parasite Plasmodium falciparum. Molecular Microbiology. 2008;67:1320–1330. doi: 10.1111/j.1365-2958.2008.06125.x. PubMed DOI

Stuart JM, Segal E, Koller D, Kim SK. A gene-coexpression network for global discovery of conserved genetic modules. Science. 2003;302:249–255. doi: 10.1126/science.1087447. PubMed DOI

Sutak R, Slapeta J, San Roman M, Camadro JM, Lesuisse E. Nonreductive iron uptake mechanism in the marine alveolate Chromera velia. Plant Physiology. 2010;154:991–1000. doi: 10.1104/pp.110.159947. PubMed DOI PMC

Tempel S. Using and understanding RepeatMasker. Methods in Molecular Biology. 2012;859:29–51. doi: 10.1007/978-1-61779-603-6_2. PubMed DOI

Templeton TJ, Iyer LM, Anantharaman V, Enomoto S, Abrahante JE, Subramanian GM, Hoffman SL, Abrahamsen MS, Aravind L. Comparative analysis of Apicomplexa and genomic diversity in eukaryotes. Genome Research. 2004a;14:1686–1695. doi: 10.1101/gr.2615304. PubMed DOI PMC

Templeton TJ, Lancto CA, Vigdorovich V, Liu C, London NR, Hadsall KZ, Abrahamsen MS. The Cryptosporidium oocyst wall protein is a member of a multigene family and has a homolog in Toxoplasma. Infection and Immunity. 2004b;72:980–987. doi: 10.1128/IAI.72.2.980-987.2004. PubMed DOI PMC

Tenter AM, Heckeroth AR, Weiss LM. Toxoplasma gondii: from animals to humans. International Journal for Parasitology. 2000;30:1217–1258. doi: 10.1016/S0020-7519(00)00124-7. PubMed DOI PMC

Tomavo S, Slomianny C, Meissner M, Carruthers VB. Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion. PLOS Pathogens. 2013;9:e1003629. doi: 10.1371/journal.ppat.1003629. PubMed DOI PMC

Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, Pimentel H, Salzberg SL, Rinn JL, Pachter L. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nature Protocols. 2012;7:562–578. doi: 10.1038/nprot.2012.016. PubMed DOI PMC

Treeck M, Sanders JL, Elias JE, Boothroyd JC. The phosphoproteomes of Plasmodium falciparum and Toxoplasma gondii reveal unusual adaptations within and beyond the parasites' boundaries. Cell Host & Microbe. 2011;10:410–419. doi: 10.1016/j.chom.2011.09.004. PubMed DOI PMC

Tsai IJ, Otto TD, Berriman M. Improving draft assemblies by iterative mapping and assembly of short reads to eliminate gaps. Genome Biology. 2010;11:R41. doi: 10.1186/gb-2010-11-4-r41. PubMed DOI PMC

Van de Peer Y, Frickey T, Taylor J, Meyer A. Dealing with saturation at the amino acid level: a case study based on anciently duplicated zebrafish genes. Gene. 2002;295:205–211. doi: 10.1016/S0378-1119(02)00689-3. PubMed DOI

van Dooren GG, Kennedy AT, McFadden GI. The use and abuse of heme in apicomplexan parasites. Antioxidants & Redox Signaling. 2012;17:634–656. doi: 10.1089/ars.2012.4539. PubMed DOI

Wilson D, Charoensawan V, Kummerfeld SK, Teichmann SA. DBD—taxonomically broad transcription factor predictions: new content and functionality. Nucleic Acids Research. 2008;36:D88–D92. PubMed PMC

Wong W, Webb AI, Olshina MA, Infusini G, Tan YH, Hanssen E, Catimel B, Suarez C, Condron M, Angrisano F, Nebi T, Kovar DR, Baum J. A mechanism for actin filament severing by malaria parasite actin depolymerizing factor 1 via a low affinity binding interface. The Journal of Biological Chemistry. 2014;289:4043–4054. doi: 10.1074/jbc.M113.523365. PubMed DOI PMC

Woo Y, Affourtit J, Daigle S, Viale A, Johnson K, Naggert J, Churchill G. A comparison of cDNA, oligonucleotide, and Affymetrix GeneChip gene expression microarray platforms. Journal of Biomolecular Techniques. 2004;15:276–284. PubMed PMC

Woo YH, Li WH. Gene clustering pattern, promoter architecture, and gene expression stability in eukaryotic genomes. Proceedings of the National Academy of Sciences of USA. 2011;108:3306–3311. doi: 10.1073/pnas.1100210108. PubMed DOI PMC

Wu TD, Nacu S. Fast and SNP-tolerant detection of complex variants and splicing in short reads. Bioinformatics. 2010;26:873–881. doi: 10.1093/bioinformatics/btq057. PubMed DOI PMC

Xu P, Widmer G, Wang Y, Ozaki LS, Alves JM, Serrano MG, Puiu D, Manque P, Akiyoshi D, Mackey AJ, Pearson WR, Dear PH, Bankier AT, Peterson DL, Abrahamsen MS, Kapur V, Tzipori S, Buck GA. The genome of Cryptosporidium hominis. Nature. 2004;431:1107–1112. doi: 10.1038/nature02977. PubMed DOI

Xu Z, Wang H. LTR_FINDER: an efficient tool for the prediction of full-length LTR retrotransposons. Nucleic Acids Research. 2007;35:W265–W268. doi: 10.1093/nar/gkm286. PubMed DOI PMC

Zahradnickova H, Tomcala A, Berkova P, Schneedorferova I, Okrouhlik J, Simek P, Hodkova M. Cost effective, robust, and reliable coupled separation techniques for the identification and quantification of phospholipids in complex biological matrices: application to insects. Journal of Separation Science. 2014;37:2062–2068. PubMed

Zdobnov EM, Apweiler R. InterProScan–an integration platform for the signature-recognition methods in InterPro. Bioinformatics. 2001;17:847–848. doi: 10.1093/bioinformatics/17.9.847. PubMed DOI

Zerbino DR, Birney E. Velvet: algorithms for de novo short read assembly using de Bruijn graphs. Genome Research. 2008;18:821–829. doi: 10.1101/gr.074492.107. PubMed DOI PMC

Expanded gene and taxon sampling of diplomonads shows multiple switches to parasitic and free-living lifestyle

Comparative genomics of Ascetosporea gives new insight into the evolutionary basis for animal parasitism in Rhizaria

Circadian rhythms and circadian clock gene homologs of complex alga Chromera velia

Lessons from the deep: mechanisms behind diversification of eukaryotic protein complexes

AAK1-like: A putative pseudokinase with potential roles in cargo uptake in bloodstream form Trypanosoma brucei parasites

Combined nanometric and phylogenetic analysis of unique endocytic compartments in Giardia lamblia sheds light on the evolution of endocytosis in Metamonada

A Phosphoinositide-Binding Protein Acts in the Trafficking Pathway of Hemoglobin in the Malaria Parasite Plasmodium falciparum

The cell wall polysaccharides of a photosynthetic relative of apicomplexans, Chromera velia

Heterotrophic euglenid Rhabdomonas costata resembles its phototrophic relatives in many aspects of molecular and cell biology

Using Diatom and Apicomplexan Models to Study the Heme Pathway of Chromera velia

The Mastigamoeba balamuthi Genome and the Nature of the Free-Living Ancestor of Entamoeba

Fatty Acid Biosynthesis in Chromerids

Evolution of late steps in exocytosis: conservation and specialization of the exocyst complex

Transcriptomic Analysis Reveals the Roles of Detoxification Systems in Response to Mercury in Chromera velia

There Is Treasure Everywhere: Reductive Plastid Evolution in Apicomplexa in Light of Their Close Relatives

Characterization of Aminoacyl-tRNA Synthetases in Chromerids

Endosymbiotic Evolution of Algae, Secondary Heterotrophy and Parasitism

Subcellular Compartments Interplay for Carbon and Nitrogen Allocation in Chromera velia and Vitrella brassicaformis

Archigregarines of the English Channel revisited: New molecular data on Selenidium species including early described and new species and the uncertainties of phylogenetic relationships

Extensive gain and loss of photosystem I subunits in chromerid algae, photosynthetic relatives of apicomplexans