The phylum Apicomplexa (Alveolates) comprises a group of host-associated protists, predominately intracellular parasites, including devastating parasites like Plasmodium falciparum, the causative agent of malaria. One of the more fascinating characteristics of Apicomplexa is their highly reduced (and occasionally lost) remnant plastid, termed the apicoplast. Four core metabolic pathways are retained in the apicoplast: heme synthesis, iron-sulfur cluster synthesis, isoprenoid synthesis, and fatty acid synthesis. It has been suggested that one or more of these pathways are essential for plastid and plastid genome retention. The past decade has witnessed the discovery of several apicomplexan relatives, and next-generation sequencing efforts are revealing that they retain variable plastid metabolic capacities. These data are providing clues about the core genes and pathways of reduced plastids, while at the same time further confounding our view on the evolutionary history of the apicoplast. Here, we examine the evolutionary history of the apicoplast, explore plastid metabolism in Apicomplexa and their close relatives, and propose that the differences among reduced plastids result from a game of endosymbiotic roulette. Continued exploration of the Apicomplexa and their relatives is sure to provide new insights into the evolution of the apicoplast and apicomplexans as a whole.

Institute of Parasitology Biology Centre Czech Acad Sci České Budějovice 370 05 Czech Republic

Zobrazit více v PubMed

Adl S.M., Leander B.S., Simpson A.G.B., Archibald J.M., Anderson O.R., Bass D., Bowser S.S., Brugerolle G., Farmer M.A., Karpov S., et al. Diversity, nomenclature, and taxonomy of protists. Syst. Biol. 2007;56:684–689. doi: 10.1080/10635150701494127. PubMed DOI

Leander B., Clopton R., Keeling P. Phylogeny of gregarines (Apicomplexa) as inferred from small-subunit rDNA and beta-tubulin. Int. J. Syst. Evol. Microbiol. 2003;53:345–354. doi: 10.1099/ijs.0.02284-0. PubMed DOI

Gentil J., Hempel F., Moog D., Zauner S., Maier U.G. Review: Origin of complex algae by secondary endosymbiosis: A journey through time. Protoplasma. 2017;254:1835–1843. doi: 10.1007/s00709-017-1098-8. PubMed DOI

Archibald J.M. Endosymbiosis and Eukaryotic Cell Evolution. Curr. Biol. 2015;25:R911–R921. doi: 10.1016/j.cub.2015.07.055. PubMed DOI

Fussy Z., Obornik M. Chromerids and their plastids. In: Hirakawa Y., editor. Advances in Botanical Research. Volume 84. Academic Press; Cambridge, MA, USA: 2017. pp. 187–218.

Waller R.F., Kořený L. Chapter Four—Plastid complexity in dinoflagellates: A picture of gains, losses, replacements and revisions. In: Hirakawa Y., editor. Advances in Botanical Research. Volume 84. Academic Press; Cambridge, MA, USA: 2017. pp. 105–143.

Wetherbee R., Jackson C.J., Repetti S.I., Clementson L.A., Costa J.F., van de Meene A., Crawford S., Verbruggen H. The golden paradox—A new heterokont lineage with chloroplasts surrounded by two membranes. J. Phycol. 2019;55:257–278. doi: 10.1111/jpy.12822. PubMed DOI

Lemgruber L., Kudryashev M., Dekiwadia C., Riglar D.T., Baum J., Stahlberg H., Ralph S.A., Frischknecht F. Cryo-electron tomography reveals four-membrane architecture of the Plasmodium apicoplast. Malaria J. 2013;12:25. doi: 10.1186/1475-2875-12-25. PubMed DOI PMC

Köhler S., Delwiche C.F., Denny P.W., Tilney L.G., Webster P., Wilson R.J.M., Palmer J.D., Roos D.S. A plastid of probable green algal origin in apicomplexan parasites. Science. 1997;275:1485–1489. doi: 10.1126/science.275.5305.1485. PubMed DOI

Diniz J.A.P., Silva E.O., Lainson R., de Souza W. The fine structure of Garnia gonadati and its association with the host cell. Parasitol. Res. 2000;86:971–977. doi: 10.1007/PL00008528. PubMed DOI

Tomova C., Geerts W.J.C., Müller-Reichert T., Entzeroth R., Humbel B.M. New comprehension of the apicoplast of Sarcocystis by transmission electron tomography. Biol. Cell. 2006;98:535–545. doi: 10.1042/BC20060028. PubMed DOI

Boucher M.J., Yeh E. Plastid–endomembrane connections in apicomplexan parasites. PLoS Pathog. 2019;15:1–9. doi: 10.1371/journal.ppat.1007661. PubMed DOI PMC

Waller R., McFadden G. The Apicoplast: A review of the derived plastid of apicomplexan parasites. Curr. Issues Mol. Biol. 2005;7:57–80. PubMed

Striepen B., Crawford M.J., Shaw M.K., Tilney L.G., Seeber F., Roos D.S. The plastid of Toxoplasma gondii is divided by association with the centrosomes. J. Cell Biol. 2000;151:1423–1434. doi: 10.1083/jcb.151.7.1423. PubMed DOI PMC

Janouskovec J., Horak A., Obornik M., Lukes J., Keeling P.J. A common red algal origin of the apicomplexan, dinoflagellate, and heterokont plastids. Proc. Natl. Acad. Sci. USA. 2010;107:10949–10954. doi: 10.1073/pnas.1003335107. PubMed DOI PMC

Fussy Z., Obornik M. Complex Endosymbioses I: From Primary to Complex Plastids, Multiple Independent Events. In: Marechal E., editor. Plastids. Volume 1829. Humana Press; New York, NY, USA: 2018. pp. 17–35. PubMed

Fichera M.E., Roos D.S. A plastid organelle as a drug target in apicomplexan parasites. Nature. 1997;390:407–409. doi: 10.1038/37132. PubMed DOI

McFadden G., Reith M., Munholland J., LangUnnasch N. Plastid in human parasites. Nature. 1996;381:482. doi: 10.1038/381482a0. PubMed DOI

Moore R.B., Obornik M., Janouskovec J., Chrudimsky T., Vancova M., Green D.H., Wright S.W., Davies N.W., Bolch C.J.S., Heimann K., et al. A photosynthetic alveolate closely related to apicomplexan parasites. Nature. 2008;451:959–963. doi: 10.1038/nature06635. PubMed DOI

Kwong W.K., del Campo J., Mathur V., Vermeij M.J.A., Keeling P.J. A widespread coral-infecting apicomplexan with chlorophyll biosynthesis genes. Nature. 2019;568:103–107. doi: 10.1038/s41586-019-1072-z. PubMed DOI

Mathur V., del Campo J., Kolisko M., Keeling P.J. Global diversity and distribution of close relatives of apicomplexan parasites. Environ. Microbiol. 2018;20:2824–2833. doi: 10.1111/1462-2920.14134. PubMed DOI

Hepler P., Huff C., Sprinz H. Fine structure of exoerythrocytic stages of Plasmodium fallax. J. Cell Biol. 1966;30:333–358. doi: 10.1083/jcb.30.2.333. PubMed DOI PMC

Gardner M., Feagin J., Moore D., Spencer D., Gray M., Williamson D., Wilson R. Organization and expression of small subunit ribosomal-RNA genes encoded by a 35-kilobase circular DNA in Plasmodium falciparum. Mol. Biochem. Parasitol. 1991;48:77–88. doi: 10.1016/0166-6851(91)90166-4. PubMed DOI

Palmer J.D. Green ancestry of malarial parasites? Curr. Biol. 1992;2:318–320. doi: 10.1016/0960-9822(92)90887-G. PubMed DOI

Vaidya A.B., Akella R., Suplick K. Sequences similar to genes for two mitochondrial proteins and portions of ribosomal RNA in tandemly arrayed 6-kilobase-pair DNA of a malarial parasite. Mol. Biol. Parasitol. 1989;35:97–107. doi: 10.1016/0166-6851(89)90112-6. PubMed DOI

Blanchard J., Hicks J. The non-photosynthetic plastid in malarial parasites and other apicomplexans is derived from outside the green plastid lineage. J. Eukaryot. Microbiol. 1999;46:367–375. doi: 10.1111/j.1550-7408.1999.tb04615.x. PubMed DOI

Fast N., Kissinger J., Roos D., Keeling P. Nuclear-encoded, plastid-targeted genes suggest a single common origin for apicomplexan and dinoflagellate plastids. Mol. Biol. Evol. 2001;18:418–426. doi: 10.1093/oxfordjournals.molbev.a003818. PubMed DOI

Funes S., Reyes-Prieto A., Perez-Martinez X., Gonzalez-Halphen D. On the evolutionary origins of apicoplasts: Revisiting the rhodophyte vs. chlorophyte controversy. Microbes Infect. 2004;6:305–311. doi: 10.1016/j.micinf.2003.11.011. PubMed DOI

Funes S., Davidson E., Reyes-Prieto A., Magallon S., Herion P., King M., Gonzalez-Halphen D. A green algal apicoplast ancestor. Science. 2002;298:2155. doi: 10.1126/science.1076003. PubMed DOI

Huang Y., He L., Hu J., He P., He J., Yu L., Malobi N., Zhou Y., Shen B., Zhao J. Characterization and annotation of Babesia orientalis apicoplast genome. Parasite Vector. 2015;8:543. doi: 10.1186/s13071-015-1158-x. PubMed DOI PMC

Cai X., Fuller A.L., McDougald L.R., Zhu G. Apicoplast genome of the coccidian Eimeria tenella. Gene. 2003;321:39–46. doi: 10.1016/j.gene.2003.08.008. PubMed DOI

Arisue N., Hashimoto T., Mitsui H., Palacpac N.M.Q., Kaneko A., Kawai S., Hasegawa M., Tanabe K., Horii T. The Plasmodium apicoplast genome: Conserved structure and close relationship of P. ovale to rodent malaria parasites. Mol. Biol. Evol. 2012;29:2095–2099. doi: 10.1093/molbev/mss082. PubMed DOI

Waller R., Keeling P., Donald R., Striepen B., Handman E., Lang-Unnasch N., Cowman A., Besra G., Roos D., McFadden G. Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum. Proc. Natl. Acad. Sci. USA. 1998;95:12352–12357. doi: 10.1073/pnas.95.21.12352. PubMed DOI PMC

Ralph S.A., van Dooren G.G., Waller R.F., Crawford M.J., Fraunholz M.J., Foth B.J., Tonkin C.J., Roos D.S., McFadden G.I. Metabolic maps and functions of the Plasmodium falciparum apicoplast. Nat. Rev. Microbiol. 2004;2:203–216. doi: 10.1038/nrmicro843. PubMed DOI

Lim L., McFadden G.I. The evolution, metabolism and functions of the apicoplast. Philos. Trans. R. Soc. B. 2010;365:749–763. doi: 10.1098/rstb.2009.0273. PubMed DOI PMC

Zhu G., Marchewka M.J., Keithly J.S. Cryptosporidium parvum appears to lack a plastid genome. Microbiology. 2000;146:315–321. doi: 10.1099/00221287-146-2-315. PubMed DOI

Toso M.A., Omoto C.K. Gregarina niphandroides may lack both a plastid genome and organelle. J. Eukaryot. Microbiol. 2007;54:66–72. doi: 10.1111/j.1550-7408.2006.00229.x. PubMed DOI

Schrevel J. Observations biologiques et ultrastructurales sur les selenidiidaeet leurs consequences sur la systematique des gregarinomorphes. J. Protozool. 1971;18:448–470. doi: 10.1111/j.1550-7408.1971.tb03355.x. DOI

Cumbo V.R., Baird A.H., Moore R.B., Negri A.P., Neilan B.A., Salih A., van Oppen M.J.H., Wang Y., Marquis C.P. 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

Foster C., Portman N., Chen M., Šlapeta J. Increased growth and pigment content of Chromera velia in mixotrophic culture. FEMS Microbiol. Ecol. 2014;88:121–128. doi: 10.1111/1574-6941.12275. PubMed DOI

Mohamed A.R., Cumbo V.R., Harii S., Shinzato C., Chan C.X., Ragan M.A., Satoh N., Ball E.E., Miller D.J. Deciphering the nature of the coral—Chromera association. ISME J. 2018;12:776–790. doi: 10.1038/s41396-017-0005-9. PubMed DOI PMC

Voolstra C.R., Schwarz J.A., Schnetzer J., Sunagawa S., Desalvo M.K., Szmant A.M., Coffroth M.A., Medina M. The host transcriptome remains unaltered during the establishment of coral–algal symbioses. Mol. Ecol. 2009;18:1823–1833. doi: 10.1111/j.1365-294X.2009.04167.x. PubMed DOI

Obornik M., Modry D., Lukes M., Cernotikova-Stribrna E., Cihlar J., Tesarova M., Kotabova E., Vancova M., Prasil O., Lukes 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

Woo Y.H., Ansari H., Otto T.D., Klinger C.M., Kolisko M., Michalek J., Saxena A., Shanmugam D., Tayyrov A., Veluchamy A., et al. Chromerid genomes reveal the evolutionary path from photosynthetic algae to obligate intracellular parasites. eLife. 2015;4:e06974. doi: 10.7554/eLife.06974. PubMed DOI PMC

Sevcikova T., Horak A., Klimes V., Zbrankova V., Demir-Hilton E., Sudek S., Jenkins J., Schmutz J., Pribyl P., Fousek J., et al. Updating algal evolutionary relationships through plastid genome sequencing: Did alveolate plastids emerge through endosymbiosis of an ochrophyte? Sci. Rep. 2015;5:10134. doi: 10.1038/srep10134. PubMed DOI PMC

Janouskovec J., Horak A., Barott K.L., Rohwer F.L., Keeling P.J. Global analysis of plastid diversity reveals apicomplexan-related lineages in coral reefs. Curr. Biol. 2012;22:R518–R519. doi: 10.1016/j.cub.2012.04.047. PubMed DOI

Brugerolle G., Mignot J.P. Observations sur le cycle l’ultrastructure et la position systématique de. Spiromonas perforans. 1938;15:183–196.

Cavalier-Smith T., Chao E.E. Protalveolate phylogeny and systematics and the origins of Sporozoa and dinoflagellates (phylum Myzozoa nom. nov.) Eur. J. Protistol. 2004;40:185–212. doi: 10.1016/j.ejop.2004.01.002. DOI

Kuvardina O., Leander B., Aleshin V., Myl’nikov A., Keeling P., Simdyanov T. The phylogeny of colpodellids (alveolata) using small subunit rRNA gene sequences suggests they are the free-living sister group to apicomplexans. J. Eucariot. Microbiol. 2002;49:498–504. doi: 10.1111/j.1550-7408.2002.tb00235.x. PubMed DOI

Gile G.H., Slamovits C.H. Transcriptomic analysis reveals evidence for a cryptic plastid in the colpodellid Voromonas pontica, a close relative of chromerids and apicomplexan parasites. PLoS ONE. 2014;9:e96258. doi: 10.1371/journal.pone.0096258. PubMed DOI PMC

Janouskovec J., Tikhonenkov D.V., Burki F., Howe A.T., Kolisko M., Mylnikov A.P., Keeling P.J. Factors mediating plastid dependency and the origins of parasitism in apicomplexans and their close relatives. Proc. Natl. Acad. Sci. USA. 2015;112:10200–10207. doi: 10.1073/pnas.1423790112. PubMed DOI PMC

Janouskovec J., Horak A., Barott K.L., Rohwer F.L., Keeling P.J. Environmental distribution of coral-associated relatives of apicomplexan parasites. ISME J. 2013;7:444–447. doi: 10.1038/ismej.2012.129. PubMed DOI PMC

Toller W., Rowan R., Knowlton N. Genetic evidence for a protozoan (phylum Apicomplexa) associated with corals of the Montastraea annularis species complex. Coral Reefs. 2002;21:143–146.

Patten R. Notes on a new protozoon, Piridium sociabile n.gen., n.sp., from the foot of Buccinum undatum. Parasitology. 1936;28:502–516. doi: 10.1017/S003118200002268X. DOI

Adl S.M., Simpson A.G.B., Lane C.E., Lukes J., Bass D., Bowser S.S., Brown M.W., Burki F., Dunthorn M., Hampl V., et al. The revised classification of eukaryotes. J. Eukaryot. Mikrobiol. 2012;59:429–493. doi: 10.1111/j.1550-7408.2012.00644.x. PubMed DOI PMC

Cavalier-Smith T. Gregarine site-heterogeneous 18S rDNA trees, revision of gregarine higher classification, and the evolutionary diversification of Sporozoa. Eur. J. Protistol. 2014;50:472–495. doi: 10.1016/j.ejop.2014.07.002. PubMed DOI

Mathur V., Kolisko M., Hehenberger E., Irwin N.A., Leander B.S., Kristmundsson Á., Freeman M.A., Keeling P.J. Multiple independent origins of apicomplexan-like parasites. Biorxiv. 2019 doi: 10.1016/j.cub.2019.07.019. PubMed DOI

Barbrook A.C., Voolstra C.R., Howe C.J. The chloroplast genome of a Symbiodinium sp. clade c3 isolate. Protist. 2014;165:1–13. doi: 10.1016/j.protis.2013.09.006. PubMed DOI

Smith D.R., Keeling P.J. Mitochondrial and plastid genome architecture: Reoccurring themes, but significant differences at the extremes. Proc. Natl. Acad. Sci. USA. 2015;112:10177–10184. doi: 10.1073/pnas.1422049112. PubMed DOI PMC

Garg A., Stein A., Zhao W., Dwivedi A., Frutos R., Cornillot E., Ben Mamoun C. Sequence and annotation of the apicoplast genome of the human pathogen Babesia microti. PLoS ONE. 2014;9:e107939. doi: 10.1371/journal.pone.0107939. PubMed DOI PMC

Sato S. The apicomplexan plastid and its evolution. Cell Mol. Life Sci. 2011;68:1285–1296. doi: 10.1007/s00018-011-0646-1. PubMed DOI PMC

de Vries J., Archibald J.M. Plastid genomes. Curr. Biol. 2018;28:R336–R337. doi: 10.1016/j.cub.2018.01.027. PubMed DOI

Salomaki E.D., Nickles K.R., Lane C.E. The ghost plastid of Choreocolax polysiphoniae. J. Phycol. 2015;51:217–221. doi: 10.1111/jpy.12283. PubMed DOI

Salomaki E.D., Lane C.E. Molecular phylogenetics supports a clade of red algal parasites retaining native plastids: Taxonomy and terminology revised. J. Phycol. 2019;55:279–288. doi: 10.1111/jpy.12823. PubMed DOI

Evans J.R., Amour N.S., Verbruggen H., Salomaki E.D., Vis M.L. Chloroplast and mitochondrial genomes of Balbiania investiens (Balbianiales, Nemaliophycidae) Phycologia. 2019;58:310–318. doi: 10.1080/00318884.2019.1573349. DOI

McFadden G.I. The apicoplast. Protoplasma. 2011;248:641–650. doi: 10.1007/s00709-010-0250-5. PubMed DOI

Glaser S., van Dooren G.G., Agrawal S., Brooks C.F., McFadden G.I., Striepen B., Higgins M.K. Tic22 is an essential chaperone required for protein import into the apicoplast. J. Biol. Chem. 2012;287:39505–39512. doi: 10.1074/jbc.M112.405100. PubMed DOI PMC

Soll J., Schleiff E. Protein import into chloroplasts. Nat. Rev. Mol. Cell Biol. 2004;5:198–208. doi: 10.1038/nrm1333. PubMed DOI

Sommer M.S., Gould S.B., Lehmann P., Gruber A., Przyborski J.M., Maier U.-G. Der1-mediated preprotein import into the periplastid compartment of chromalveolates? Mol. Biol. Evol. 2007;24:918–928. doi: 10.1093/molbev/msm008. PubMed DOI

Hempel F., Bullmann L., Lau J., Zauner S., Maier U.G. ERAD-derived preprotein transport across the second outermost plastid membrane of diatoms. Mol. Biol. Evol. 2009;26:1781–1790. doi: 10.1093/molbev/msp079. PubMed DOI

Spork S., Hiss J.A., Mandel K., Sommer M., Kooij T.W.A., Chu T., Schneider G., Maier U.G., Przyborski J.M. An unusual ERAD-like complex is targeted to the apicoplast of Plasmodium falciparum. Eukaryot. Cell. 2009;8:1134–1145. doi: 10.1128/EC.00083-09. PubMed DOI PMC

Nagaraj V.A., Arumugam R., Prasad D., Rangarajan P.N., Padmanaban G. Protoporphyrinogen IX oxidase from Plasmodium falciparum is anaerobic and is localized to the mitochondrion. Mol. Biochem. Parasitol. 2010;174:44–52. doi: 10.1016/j.molbiopara.2010.06.012. PubMed DOI

Nagaraj V.A., Prasad D., Arumugam R., Rangarajan P.N., Padmanaban G. Characterization of coproporphyrinogen III oxidase in Plasmodium falciparum cytosol. Parasitol. Int. 2010;59:121–127. doi: 10.1016/j.parint.2009.12.001. PubMed DOI

Sato S., Clough B., Coates L., Wilson R.J.M. Enzymes for heme biosynthesis are found in both the mitochondrion and plastid of the malaria parasite Plasmodium falciparum. Protist. 2004;155:117–125. doi: 10.1078/1434461000169. PubMed DOI

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

Nagaraj V.A., Sundaram B., Varadarajan N.M., Subramani P.A., Kalappa D.M., Ghosh S.K., Padmanaban G. Malaria parasite-synthesized heme is essential in the mosquito and liver stages and complements host heme in the blood stages of infection. PLoS Pathogens. 2013;9:1–13. doi: 10.1371/journal.ppat.1003522. PubMed DOI PMC

Botte C.Y., Yamaryo-Botte Y. Complex Endosymbioses II: The nonphotosynthetic plastid of apicomplexa parasites (the apicoplast) and its integrated metabolism. In: Marechal E., editor. Plastids. Volume 1829. Humana Press; New York, NY, USA: 2018. pp. 37–54. PubMed

Gornicki P. Apicoplast fatty acid biosynthesis as a target for medical intervention in Apicomplexan parasites. Int. J. Parasitol. 2003;33:885–896. doi: 10.1016/S0020-7519(03)00133-4. PubMed DOI

Goodman C.D., McFadden G.I. Fatty acid biosynthesis as a drug target in apicomplexan parasites. Curr. Drug Targets. 2007;8:15–30. doi: 10.2174/138945007779315579. PubMed DOI

Gardner M.J., Bishop R., Shah T., de Villiers E.P., Carlton J.M., Hall N., Ren Q., Paulsen I.T., Pain A., Berriman M., et al. Genome sequence of Theileria parva, a bovine pathogen that transforms lymphocytes. Science. 2005;309:134–137. doi: 10.1126/science.1110439. PubMed DOI

Vaughan A.M., O’Neill M.T., Tarun A.S., Camargo N., Phuong T.M., Aly A.S.I., Cowman A.F., Kappe S.H.I. Type II fatty acid synthesis is essential only for malaria parasite late liver stage development. Cell. Microbiol. 2009;11:506–520. doi: 10.1111/j.1462-5822.2008.01270.x. PubMed DOI PMC

van Schaijk B.C.L., Kumar T.R.S., Vos M.W., Richman A., van Gemert G.-J., Li T., Eappen A.G., Williamson K.C., Morahan B.J., Fishbaugher M., et al. Type II fatty acid biosynthesis is essential for Plasmodium falciparum sporozoite development in the midgut of Anopheles mosquitoes. Eukaryot. Cell. 2014;13:550–559. doi: 10.1128/EC.00264-13. 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

Zhu G., Marchewka M.J., Woods K.M., Upton S.J., Keithly J.S. Molecular analysis of a Type I fatty acid synthase in Cryptosporidium parvum. Mol. Biochem. Parasitol. 2000;105:253–260. doi: 10.1016/S0166-6851(99)00183-8. PubMed DOI

Abrahamsen M.S., Templeton T.J., Enomoto S., Abrahante J.E., Zhu G., Lancto C.A., Deng M., Liu C., Widmer G., Tzipori S., et al. Complete genome sequence of the apicomplexan, Cryptosporidium parvum. Science. 2004;304:441. doi: 10.1126/science.1094786. PubMed DOI

Caballero M.C., Pedroni M.J., Palmer G.H., Suarez C.E., Davitt C., Lau A.O.T. Characterization of acyl carrier protein and LytB in Babesia bovis apicoplast. Mol. Biochem. Parasit. 2012;181:125–133. doi: 10.1016/j.molbiopara.2011.10.009. PubMed DOI PMC

Cassera M., Gozzo F., D’Alexandri F., Merino E., del Portillo H., Peres V., Almeida I., Eberlin M., Wunderlich G., Wiesner J., et al. The methylerythritol phosphate pathway is functionally active in all intraerythrocytic stages of Plasmodium falciparum. J. Biol. Chem. 2004;279:51749–51759. doi: 10.1074/jbc.M408360200. PubMed DOI

Yeh E., DeRisi J.L. Chemical rescue of malaria parasites lacking an apicoplast defines organelle function in blood-stage Plasmodium falciparum. PLoS Biol. 2011;9:e1001138. doi: 10.1371/journal.pbio.1001138. PubMed DOI PMC

Suazo K.F., Schaber C., Palsuledesai C.C., Odom John A.R., Distefano M.D. Global proteomic analysis of prenylated proteins in Plasmodium falciparum using an alkyne-modified isoprenoid analogue. Sci. Rep. 2016;6:38615. doi: 10.1038/srep38615. PubMed DOI PMC

Gisselberg J.E., Zhang L., Elias J.E., Yeh E. The prenylated proteome of Plasmodium falciparum reveals pathogen-specific prenylation activity and drug mechanism-of-action. Mol. Cell. Proteom. 2017;16:S54. doi: 10.1074/mcp.M116.064550. PubMed DOI PMC

Johnson D., Dean D., Smith A., Johnson M. Structure, function, and formation of biological iron-sulfur clusters. Annu. Rev. Biochem. 2005;74:247–281. doi: 10.1146/annurev.biochem.74.082803.133518. PubMed DOI

Gisselberg J.E., Dellibovi-Ragheb T.A., Matthews K.A., Bosch G., Prigge S.T. The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites. PLoS Pathogens. 2013;9:e1003655. doi: 10.1371/journal.ppat.1003655. PubMed DOI PMC

Strassert J.F.H., Karnkowska A., Hehenberger E., del Campo J., Kolisko M., Okamoto N., Burki F., Janouskovec J., Poirier C., Leonard G., et al. Single cell genomics of uncultured marine alveolates shows paraphyly of basal dinoflagellates. ISME J. 2018;12:304–308. doi: 10.1038/ismej.2017.167. PubMed DOI PMC

Gawryluk R.M.R., del Campo J., Okamoto N., Strassert J.F.H., Lukeš J., Richards T.A., Worden A.Z., Santoro A.E., Keeling P.J. Morphological identification and single-cell genomics of marine diplonemids. Curr. Biol. 2016;26:3053–3059. doi: 10.1016/j.cub.2016.09.013. PubMed DOI

Kolisko M., Boscaro V., Burki F., Lynn D.H., Keeling P.J. Single-cell transcriptomics for microbial eukaryotes. Curr. Biol. 2014;24:R1081–R1082. doi: 10.1016/j.cub.2014.10.026. PubMed DOI

Picelli S., Faridani O.R., Björklund Å.K., Winberg G., Sagasser S., Sandberg R. Full-length RNA-seq from single cells using Smart-seq2. Nat. Protocols. 2014;9:171. doi: 10.1038/nprot.2014.006. PubMed DOI

Leger M.M., Kolisko M., Kamikawa R., Stairs C.W., Kume K., Cepicka I., Silberman J.D., Andersson J.O., Xu F., Yabuki A., et al. Organelles that illuminate the origins of Trichomonas hydrogenosomes and Giardia mitosomes. Nat. Rvol. Evol. 2017;1:0092. doi: 10.1038/s41559-017-0092. PubMed DOI PMC

Vacek V., Novak L.V.F., Treitli S.C., Taborsky P., Cepicka I., Kolisko M., Keeling P.J., Hampl V. Fe-S cluster assembly in oxymonads and related protists. Mol. Biol. Evol. 2018;35:2712–2718. doi: 10.1093/molbev/msy168. PubMed DOI PMC

McFadden G.I., Yeh E. The apicoplast: Now you see it, now you don’t. Int. J. Parasitol. 2017;47:137–144. doi: 10.1016/j.ijpara.2016.08.005. PubMed DOI PMC

Tovar J., León-Avila G., Sánchez L.B., Sutak R., Tachezy J., van der Giezen M., Hernández M., Müller M., Lucocq J.M. Mitochondrial remnant organelles of Giardia function in iron-sulphur protein maturation. Nature. 2003;426:172–176. doi: 10.1038/nature01945. PubMed DOI

Lill R., Dutkiewicz R., Freibert S.A., Heidenreich T., Mascarenhas J., Netz D.J., Paul V.D., Pierik A.J., Richter N., Stümpfig M., et al. The role of mitochondria and the CIA machinery in the maturation of cytosolic and nuclear iron–sulfur proteins. Eur. J. Cell Biol. 2015;94:280–291. doi: 10.1016/j.ejcb.2015.05.002. PubMed DOI

Karnkowska A., Vacek V., Zubáčová Z., Treitli S.C., Petrželková R., Eme L., Novák L., Žárský V., Barlow L.D., Herman E.K., et al. A eukaryote without a mitochondrial organelle. Curr. Biol. 2016;26:1274–1284. doi: 10.1016/j.cub.2016.03.053. PubMed DOI

Wang X., Wang J., Liu J., Liu A., He X., Xu J., Li Z., Zhao S., Li Y., Yin H., et al. Comparative analysis of apicoplast genomes of Babesia infective to small ruminants in China. Parasites Vectors. 2019;12:312. doi: 10.1186/s13071-019-3581-x. PubMed DOI PMC

Barbrook A.C., Howe C.J., Purton S. Why are plastid genomes retained in non-photosynthetic organisms? Trends Plant Sci. 2006;11:101–108. doi: 10.1016/j.tplants.2005.12.004. PubMed DOI

Goodman C.D., McFadden G.I. Ycf93 (Orf105), a small Apicoplast-encoded membrane protein in the relict plastid of the malaria parasite Plasmodium falciparum that is conserved in apicomplexa. PLoS ONE. 2014;9:e91178. doi: 10.1371/journal.pone.0091178. PubMed DOI PMC

Reduced plastid genomes of colorless facultative pathogens Prototheca (Chlorophyta) are retained for membrane transport genes

Integrated overview of stramenopile ecology, taxonomy, and heterotrophic origin

Reconstruction of Plastid Proteomes of Apicomplexans and Close Relatives Reveals the Major Evolutionary Outcomes of Cryptic Plastids

Organellar Evolution: A Path from Benefit to Dependence

Evolutionary and Molecular Aspects of Plastid Endosymbioses

Gregarine single-cell transcriptomics reveals differential mitochondrial remodeling and adaptation in apicomplexans

Fatty Acid Biosynthesis in Chromerids