, Volume 54, Issue 2, pp 69–86 | Cite as

Origin of eukaryotic cells: 40 years on



The year 1970 saw the publication of Origin of Eukaryotic Cells by Lynn Margulis. This influential book brought the exciting and weighty problems of cellular evolution to the scientific mainstream, simultaneously breaking new ground and ‘re-discovering’ the decades-old ideas of German and Russian biologists. In this commemorative review, I discuss the 40 years that have elapsed since this landmark publication, with a focus on the ‘molecular era’: how DNA sequencing and comparative genomics have proven beyond all doubt the central tenets of the endosymbiont hypothesis for the origin of mitochondria and plastids, and, at the same time, revealed a genetic and genomic complexity in modern-day eukaryotes that could not have been imagined in decades past.


Lynn Margulis Symbiosis Endosymbiosis Cell evolution Mitochondria Plastids 


  1. Allsopp A (1969) Phylogenetic relationships of the procaryotes and the origin of the eucaryotic cell. New Phytol 68:591–612CrossRefGoogle Scholar
  2. Andersson SG (2006) Genetics. The bacterial world gets smaller. Science 314:259–260PubMedCrossRefGoogle Scholar
  3. Archibald JM (2007) Nucleomorph genomes: structure, function, origin and evolution. Bioessays 29:392–402PubMedCrossRefGoogle Scholar
  4. Archibald JM (2009) The puzzle of plastid evolution. Curr Biol 19:R81–R88PubMedCrossRefGoogle Scholar
  5. Baldauf SL, Roger AJ, Wenk-Siefert I, Doolittle WF (2000) A kingdom-level phylogeny of eukaryotes based on combined protein data. Science 290:972–977PubMedCrossRefGoogle Scholar
  6. Barberà MJ, Ruiz-Trillo I, Leigh J, Hug LA, Roger AJ (2007) The diversity of mitochondrion-related organelles amongst eukaryotic microbes. In: Martin WF, Müller M (eds) Origin of mitochondria and hydrogenosomes. Springer, Berlin, pp 239–275CrossRefGoogle Scholar
  7. Belanger AS, Brouard JS, Charlebois P, Otis C, Lemieux C, Turmel M (2006) Distinctive architecture of the chloroplast genome in the chlorophycean green alga Stigeoclonium helveticum. Mol Gen and Genom 276:464–477CrossRefGoogle Scholar
  8. Bhattacharya D, Schmidt HA (1997) Division glaucocystophyta. In: Bhattacharya D (ed) Origin of algae and their plastids. Springer, Wein, pp 139–148Google Scholar
  9. Bhattacharya D, Yoon HS, Hackett JD (2003) Photosynthetic eukaryotes unite: endosymbiosis connects the dots. Bioessays 26:50–60CrossRefGoogle Scholar
  10. Bodyl A (2005) Do plastid-related characters support the chromalveolate hypothesis? J Phycol 41:712–719CrossRefGoogle Scholar
  11. Bodyl A, Mackiewicz P, Stiller JW (2010) Comparative genomic studies suggest that the cyanobacterial endosymbionts of the amoeba Paulinella chromatophora possess an import apparatus for nuclear-encoded proteins. Plant Biol (Stuttg) 12:639–649Google Scholar
  12. Bonen L, Doolittle WF (1975) On the prokaryotic nature of red algal chloroplasts. Proc Natl Acad Sci USA 72:2310–2314PubMedCrossRefGoogle Scholar
  13. Bonen L, Doolittle WF (1976) Partial sequences of 16S rRNA and the phylogeny of blue-green algae and chloroplasts. Nature 261:669–673PubMedCrossRefGoogle Scholar
  14. Bonen L, Cunningham RS, Gray MW, Doolittle WF (1977) Wheat embryo mitochondrial 18S ribosomal RNA: evidence for its prokaryotic nature. Nucleic Acids Res 4:663–671PubMedCrossRefGoogle Scholar
  15. Boxma B, de Graaf RM, van der Staay GW, van Alen TA, Ricard G, Gabaldon T, van Hoek AH, Moon-van der Staay SY, Koopman WJ, van Hellemond JJ, Tielens AG, Friedrich T, Veenhuis M, Huynen MA, Hackstein JH (2005) An anaerobic mitochondrion that produces hydrogen. Nature 434:74–79PubMedCrossRefGoogle Scholar
  16. Burki F, Shalchian-Tabrizi K, Pawlowski J (2008) Phylogenomics reveals a new 'megagroup' including most photosynthetic eukaryotes. Biol Lett 4:366–369. doi:10.1098/rsbl.2008.0224 PubMedCrossRefGoogle Scholar
  17. Burki F, Inagaki Y, Brate J, Archibald JM, Keeling PJ, Cavalier-Smith T, Sakaguchi M, Hashimoto T, Horak A, Kuma K, Klaveness D, Jakobsen KS, Pawlowski J, Shalchian-Tabrizi K (2009) Large-scale phylogenomic analyses reveal that two enigmatic protist lineages, Telonemia and Centroheliozoa, are related to photosynthetic chromalveolates. Genome Biol Evol 1:231–238PubMedCrossRefGoogle Scholar
  18. Cavalier-Smith T (1975) The origin of nuclei and of eukaryotic cells. Nature 256:463–467CrossRefGoogle Scholar
  19. Cavalier-Smith T (1983a) A 6-kingdom classification and a unified phylogeny. In: Schwemmler W, Schenk JEA (eds) Endocytobiology. de Gruyter, Berlin, pp 1027–1034Google Scholar
  20. Cavalier-Smith T (1983b) Endosymbiotic origin of the mitochondrial envelope. In: Schwemmler W, Schenk HEA (eds) Endocytobiology II. de Gruyter, Berlin, pp 265–279Google Scholar
  21. Cavalier-Smith T (1987) Origin of eukaryote and archaebacterial cells. Ann NY Acad Sci 504:17–54CrossRefGoogle Scholar
  22. Cavalier-Smith T (1999) Principles of protein and lipid targeting in secondary symbiogenesis: euglenoid, dinoflagellate, and sporozoan plastid origins and the eukaryote family tree. J Eukaryot Microbiol 46:347–366PubMedCrossRefGoogle Scholar
  23. Cavalier-Smith T (2007) The chimaeric origin of mitochondria: photosynthetic cell enslavement, gene-transfer pressure, and compartmentation efficiency. In: Martin WF, Müller M (eds) Origin of mitochondria and hydrogenosomes. Springer, Berlin, pp 161–199CrossRefGoogle Scholar
  24. Cavalier-Smith T (2010) Origin of the cell nucleus, mitosis and sex: roles of intracellular coevolution. Biol Direct 5:7PubMedCrossRefGoogle Scholar
  25. Cavalier-Smith T, Lee JJ (1985) Protozoa as hosts for endosymbioses and the conversion of symbionts into organelles. J Protozool 32:376–379Google Scholar
  26. Chan CX, Yang EC, Banerjee T, Yoon HS, Martone PT, Estevez JM, Bhattacharya D (2011) Red and green algal monophyly and extensive gene sharing found in a rich repertoire of red algal genes. Curr Biol 21:328–333PubMedCrossRefGoogle Scholar
  27. Clark CG, Roger AJ (1995) Direct evidence for secondary loss of mitochondria in Entamoeba histolytica. Proc Natl Acad Sci USA 92:6518–6521PubMedCrossRefGoogle Scholar
  28. Curtis BA, Archibald JM (2010) Problems and progress in understanding the origins of mitochondria and plastids. In: Seckbach J, Grube M (eds) Symbioses and stress. Springer, Germany, pp 41–62Google Scholar
  29. Dacks JB, Doolittle WF (2001) Reconstructing/deconstructing the earliest eukaryotes: how comparative genomics can help. Cell 107:419–425PubMedCrossRefGoogle Scholar
  30. Dagan T, Martin W (2007) Testing hypotheses without considering predictions. Bioessays 29:500–503PubMedCrossRefGoogle Scholar
  31. de Duve C (1969) Evolution of the peroxisome. Ann NY Acad Sci USA 168:369–381CrossRefGoogle Scholar
  32. Delwiche CF (1999) Tracing the thread of plastid diversity through the tapestry of life. Am Nat 154(Supplement):S164–S177PubMedCrossRefGoogle Scholar
  33. Delwiche CF, Kuhsel M, Palmer JD (1995) Phylogenetic analysis of tufA sequences indicates a cyanobacterial origin of all plastids. Mol Phylogenet Evol 4:110–128PubMedCrossRefGoogle Scholar
  34. Delwiche C, Andersen RA, Bhattacharya D, Mishler BD (2004) Algal evolution and the early radiation of green plants. In: Cracraft J, Donoghue MJ (eds) Assembling the tree of life. Oxford University Press, New York, pp 121–137Google Scholar
  35. Doolittle WF (1980) Revolutionary concepts in evolutionary biology. Trends Biochem Sci 5:146–149CrossRefGoogle Scholar
  36. Douglas SE, Penny SL (1999) The plastid genome of the cryptophyte alga, Guillardia theta: complete sequence and conserved synteny groups confirm its common ancestry with red algae. J Mol Evol 48:236–244PubMedCrossRefGoogle Scholar
  37. Douglas SE, Zauner S, Fraunholz M, Beaton M, Penny S, Deng L, Wu X, Reith M, Cavalier-Smith T, Maier U-G (2001) The highly reduced genome of an enslaved algal nucleus. Nature 410:1091–1096PubMedCrossRefGoogle Scholar
  38. Drum RW, Pankratz S (1965) Fine structure of an unusual cytoplasmic inclusion in the diatom genus Rhopalodia. Protoplasma 60:141–149CrossRefGoogle Scholar
  39. Durnford DG, Deane JA, Tan S, McFadden GI, Gantt E, Green BR (1999) A phylogenetic assessment of the eukaryotic light-harvesting antenna proteins, with implications for plastid evolution. J Mol Evol 48:59–68PubMedCrossRefGoogle Scholar
  40. Edlind TD, Li J, Visvesvara GS, Vodkin MH, McLaughlin GL, Katiyar SK (1996) Phylogenetic analysis of beta-tubulin sequences from amitochondrial protozoa. Mol Phylogenet Evol 5:359–367PubMedCrossRefGoogle Scholar
  41. Embley TM, Martin W (2006) Eukaryotic evolution, changes and challenges. Nature 440:623–630PubMedCrossRefGoogle Scholar
  42. Embley TM, van der Giezen M, Horner DS, Dyal PL, Foster PG (2002) Mitochondria and hydrogenosomes are two forms of the same fundamental organelle. Royal Soc London Series B 358:191–203CrossRefGoogle Scholar
  43. Embley TM, van der Giezen M, Horner DS, Dyal PL, Bell S, Foster PG (2003) Hydrogenosomes, mitochondria and early eukaryotic evolution. IUBMB Life 55:387–395PubMedCrossRefGoogle Scholar
  44. Geitler L (1977) Life history of the Epithemiaceae Epithemia, Rhopalodia and Denticula (Diatomophyceae) and their presumable symbiotic spheroid bodies. Plant Syst Evol 128:259–275CrossRefGoogle Scholar
  45. Gibbs SP (1978) The chloroplasts of Euglena may have evolved from symbiotic green algae. Can J Bot 56:2883–2889CrossRefGoogle Scholar
  46. Gibbs SP (2006) Looking at life: from binoculars to the electron microscope. Annu Rev Plant Biol 57:1–17PubMedCrossRefGoogle Scholar
  47. Gillott MA, Gibbs SP (1980) The cryptomonad nucleomorph: its ultrastructure and evolutionary significance. J Phycol 16:558–568CrossRefGoogle Scholar
  48. Gilson P, McFadden GI (1995) The chlorarachniophyte: a cell with two different nuclei and two different telomeres. Chromosoma 103:635–641PubMedCrossRefGoogle Scholar
  49. Gilson PR, Su V, Slamovits CH, Reith ME, Keeling PJ, McFadden GI (2006) Complete nucleotide sequence of the chlorarachniophyte nucleomorph: nature's smallest nucleus. Proc Natl Acad Sci USA 103:9566–9571PubMedCrossRefGoogle Scholar
  50. Glockner G, Rosenthal A, Valentin K (2000) The structure and gene repertoire of an ancient red algal plastid genome. J Mol Evol 51:382–390PubMedGoogle Scholar
  51. Gokøsyr J (1967) Evolution of eucaryotic cells. Nature 214:1161CrossRefGoogle Scholar
  52. Goldberg AV, Molik S, Tsaousis AD, Neumann K, Kuhnke G, Delbac F, Vivares CP, Hirt RP, Lill R, Embley TM (2008) Localization and functionality of microsporidian iron-sulphur cluster assembly proteins. Nature 452:624–629PubMedCrossRefGoogle Scholar
  53. Gould SB, Waller RF, McFadden GI (2008) Plastid evolution. Annu Rev Plant Biol 59:491–517PubMedCrossRefGoogle Scholar
  54. Gray MW (1992) The endosymbiont hypothesis revisited. Int Rev Cytol 141:233–357PubMedCrossRefGoogle Scholar
  55. Gray MW, Doolittle WF (1982) Has the endosymbiont hypothesis been proven? Microbiol Rev 46:1–42PubMedGoogle Scholar
  56. Gray MW, Burger G, Lang BF (1999) Mitochondrial evolution. Science 283:1476–1481PubMedCrossRefGoogle Scholar
  57. Greenwood AD (1974) The Cryptophyta in relation to phylogeny and photosynthesis. Proc 8th Int Congr Electron Microsc 2:566–567Google Scholar
  58. Greenwood AD, Griffiths HB, Santore UJ (1977) Chloroplasts and cell compartments in Cryptophyceae. Brit Phycol J 12:119Google Scholar
  59. Hackett JD, Anderson DM, Erdner DL, Bhattacharya D (2004) Dinoflagellates: a remarkable evolutionary experiment. Am J Bot 91:1523–1534PubMedCrossRefGoogle Scholar
  60. Hampl V, Hug L, Leigh JW, Dacks JB, Lang BF, Simpson AG, Roger AJ (2009) Phylogenomic analyses support the monophyly of Excavata and resolve relationships among eukaryotic "supergroups". Proc Natl Acad Sci USA 106:3859–3864PubMedCrossRefGoogle Scholar
  61. Hansmann P, Eschbach S (1991) Isolation and preliminary characterization of the nucleus and the nucleomorph of a cryptomonad, Pyrenomonas salina. Europ J Cell Biol 52:373–378Google Scholar
  62. Hansmann P, Falk H, Sitte P (1985) DNA in the nucleomorph of Cryptomonas demonstrated by DAPI fluorescence. Zeitschrift fur Naturforschung 40c:933–935Google Scholar
  63. Hashimoto T, Nakamura Y, Kamaishi T, Hasegawa M (1997) Early evolution of eukaryotes inferred from the amino acid sequences of elongation factors 1a and 2. Arch Protistenkd 148:287–295Google Scholar
  64. Helmchen TA, Bhattacharya D, Melkonian M (1995) Analyses of ribosomal RNA sequences from glaucocystophyte cyanelles provide new insights into the evolutionary relationships of plastids. J Mol Evol 41:203–210PubMedCrossRefGoogle Scholar
  65. Hibberd DJ, Norris RE (1984) Cytology and ultrastructure of Chlorarachnion reptans (Chlorarachniophyta divisio nova, Chlorarachniophyceae classis nova). J Phycol 20:310–330CrossRefGoogle Scholar
  66. Hirt RP, Healy B, Vossbrinck CR, Canning EU, Embley TM (1997) A mitochondrial Hsp70 orthologue in Vairimorpha necatrix: molecular evidence that microsporidia once contained mitochondria. Curr Biol 7:995–998PubMedCrossRefGoogle Scholar
  67. Hirt RP, Logsdon JM Jr, Healy B, Dorey MW, Doolittle WF, Embley TM (1999) Microsporidia are related to Fungi: evidence from the largest subunit of RNA polymerase II and other proteins. Proc Natl Acad Sci USA 96:580–585PubMedCrossRefGoogle Scholar
  68. Hjort K, Goldberg AV, Tsaousis AD, Hirt RP, Embley TM (2010) Diversity and reductive evolution of mitochondria among microbial eukaryotes. Phil Trans R Soc B 365:713–727PubMedCrossRefGoogle Scholar
  69. Hoogenraad HR (1927) Zur Kenntnis der Fortpflanzung von Paulinella chromatophora Lauterb. Zool Anz 72:140–150Google Scholar
  70. Hug LA, Stechmann A, Roger AJ (2010) Phylogenetic distributions and histories of proteins involved in anaerobic pyruvate metabolism in eukaryotes. Mol Biol Evol 27:311–324PubMedCrossRefGoogle Scholar
  71. John P, Whatley FR (1975) Paracoccus denitrificans and the evolutionary origin of the mitochondrion. Nature 254:495–498PubMedCrossRefGoogle Scholar
  72. Johnson PW, Hargraves PE, Sieburth JM (1988) Ultrastructure and ecology of Calycomonas ovalis Wulff, 1919, (Chrysophyceae) and its redescription as a testate rhizopod, Paulinella ovalis n. comb. (Filosea: Euglyphina). J Protozool 35:618–626Google Scholar
  73. Karakashian SJ, Karakashian M, Rudzinska M (1968) Electron microscopic observations on the symbiosis of Paramecium bursaria and its intracellular algae. J Protozool 15:113–128Google Scholar
  74. 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 (2001) Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. Nature 414:450–453PubMedCrossRefGoogle Scholar
  75. Keeling PJ (2009) Chromalveolates and the evolution of plastids by secondary endosymbiosis. J Eukaryot Microbiol 56:1–8PubMedCrossRefGoogle Scholar
  76. Keeling PJ (2010) The endosymbiotic origin, diversification and fate of plastids. Philos Trans R Soc Lond B Biol Sci 365:729–748PubMedCrossRefGoogle Scholar
  77. Keeling PJ, Doolittle WF (1996) Alpha-tubulin from early-diverging eukaryotic lineages and the evolution of the tubulin family. Mol Biol Evol 13:1297–1305PubMedGoogle Scholar
  78. Keeling PJ, Slamovits CH (2004) Simplicity and complexity of microsporidian genomes. Eukaryot Cell 3:1363–1369PubMedCrossRefGoogle Scholar
  79. Keeling PJ, Luker MA, Palmer JD (2000) Evidence from beta-tubulin phylogeny that microsporidia evolved from within the fungi. Mol Biol Evol 17:23–31PubMedGoogle Scholar
  80. Khakhina L (1979) Concepts of symbiogenesis: a historical and critical study of the research of Russian Botanists (trans: Merkel S, Coalson R). Yale University PressGoogle Scholar
  81. Kies L (1974) Electron microscopical investigations on Paulinella chromatophora Lauterborn, a thecamoeba containing blue-green endosymbionts (Cyanelles) (author's transl). Protoplasma 80:69–89PubMedCrossRefGoogle Scholar
  82. Kim E, Archibald JM (2009) Diversity and evolution of plastids and their genomes. In: Aronsson H, Sandelius AS (eds) The chloroplast-interactions with the environment. Plant cell monographs. Springer, Berlin, pp 1–39Google Scholar
  83. Kim E, Graham LE (2008) EEF2 analysis challenges the monophyly of Archaeplastida and Chromalveolata. PLoS One 3:e2621PubMedCrossRefGoogle Scholar
  84. Klein RM (1970) Relationships between blue-green and red algae. Ann NY Acad Sci 175:623–632CrossRefGoogle Scholar
  85. Klein R, Cronquist A (1967) A consideration of the evolutionary and taxonomic significance of some biochemical, micromorphological and physiological characters in the Thallophytes. Quart Rev Biol 42:105–296PubMedGoogle Scholar
  86. Kleine T, Maier UG, Leister D (2009) DNA transfer from organelles to the nucleus: the idiosyncratic genetics of endosymbiosis. Annu Rev Plant Biol 60:115–138PubMedCrossRefGoogle Scholar
  87. Kneip C, Voss C, Lockhart PJ, Maier UG (2008) The cyanobacterial endosymbiont of the unicellular algae Rhopalodia gibba shows reductive genome evolution. BMC Evol Biol 8:30PubMedCrossRefGoogle Scholar
  88. Koonin EV (2010a) The origin and early evolution of eukaryotes in the light of phylogenomics. Genome Biol 11:209PubMedCrossRefGoogle Scholar
  89. Koonin EV (2010b) Preview. The incredible expanding ancestor of eukaryotes. Cell 140:606–608PubMedCrossRefGoogle Scholar
  90. Kozo-Polyansky B (1924) Symbiogenesis: a new principle of evolution (trans: Fet V). Harvard University Press, Cambridge MassachusettsGoogle Scholar
  91. Lane N, Martin W (2010) The energetics of genome complexity. Nature 467:929–934PubMedCrossRefGoogle Scholar
  92. Lane CE, van den Heuvel K, Kozera C, Curtis BA, Parsons B, Bowman S, Archibald JM (2007) Nucleomorph genome of Hemiselmis andersenii reveals complete intron loss and compaction as a driver of protein structure and function. Proc Natl Acad Sci USA 104:19908–19913PubMedCrossRefGoogle Scholar
  93. Larkum AW, Lockhart PJ, Howe CJ (2007) Shopping for plastids. Trends Plant Sci 12:189–195PubMedCrossRefGoogle Scholar
  94. Lauterborn R (1895) Protozoenstudien II. Paulinella chromatophora nov. gen., nov. spec., ein beschalter Rhizopode des Süßwassers mit blaugrünen chromatophorenartigen Einschlüssen. Z Wiss Zool 59:537–544Google Scholar
  95. Lee RE (1977) Evolution of algal flagellates with chloroplast endoplasmic reticulum from the ciliates. South Afr J Sci 73:179–182Google Scholar
  96. Leipe DD, Gunderson JH, Nerad TA, Sogin ML (1993) Small subunit ribosomal RNA+ of Hexamita inflata and the quest for the first branch in the eukaryotic tree. Mol Biochem Parasitol 59:41–48PubMedCrossRefGoogle Scholar
  97. Lewis LA, McCourt RM (2004) Green algae and the origin of land plants. Am J Bot 91:1535–1556PubMedCrossRefGoogle Scholar
  98. Li J, Katiyar SK, Hamelin A, Visvesvara GS (1996) Tubulin genes from AIDS-associated microsporidia and implications for phylogeny and benzimidazole sensitivity. Mol Biochem Parasitol 78:289–295PubMedCrossRefGoogle Scholar
  99. Lindmark DG, Müller M (1973) Hydrogenosome, a cytoplasmic organelle of the anaerobic flagellate Tritrichomonas foetus, and its role in pyruvate metabolism. J Biol Chem 248:7724–7728PubMedGoogle Scholar
  100. Löffelhardt W, Bohnert HJ, Bryant DA (1997) The complete sequence of the Cyanophora paradoxa cyanelle genome. In: Bhattacharya D (ed) Origins of Algae and their Plastids. Springer, Wein, pp 142–162Google Scholar
  101. Ludwig M, Gibbs SP (1985) DNA is present in the nucleomorph of cryptomonads: further evidence that the chloroplast evolved from a eukaryotic endosymbiont. Protoplasma 127:9–20CrossRefGoogle Scholar
  102. Mackiewicz P, Bodyl A (2010) A hypothesis for import of the nuclear-encoded PsaE protein of Paulinella chromatophora (Cercozoa, Rhizaria) into its cyanobacterial endosymbionts/plastids via the endomembrane system. J Phycol 46:847–859CrossRefGoogle Scholar
  103. Maier UG, Hofmann CJ, Eschbach S, Wolters J, Igloi GL (1991) Demonstration of nucleomorph-encoded eukaryotic small subunit ribosomal RNA in cryptomonads. Mol Gen Genet 230:155–160PubMedCrossRefGoogle Scholar
  104. Margulis L (1970) Origin of eukaryotic cells. Yale University Press, New HavenGoogle Scholar
  105. Margulis L (1981) Symbiosis in cell evolution. W. H. Freeman and Company, San FranciscoGoogle Scholar
  106. Margulis L (1998) Symbiotic planet. Basic Books, New YorkGoogle Scholar
  107. Margulis L (2004) Serial endosymbiotic theory (SET) and composite individuality: transition from bacterial to eukaryotic genomes. Microbiol Today 31:172–174Google Scholar
  108. Margulis L, Dolan MF, Guerrero R (2000) The chimeric eukaryote: origin of the nucleus from the karyomastigont in amitochondriate protists. Proc Natl Acad Sci USA 97:6954–6959PubMedCrossRefGoogle Scholar
  109. Margulis L, Dolan MF, Whiteside JH (2005) "Imprefections and oddities" in the origin of the nucleus. Paleobiology 31:175–191CrossRefGoogle Scholar
  110. Margulis L, Chapman M, Guerrero R, Hall J (2006) The last eukaryotic common ancestor (LECA): acquisition of cytoskeletal motility from aerotolerant spirochetes in the Proterozoic Eon. Proc Natl Acad Sci USA 103:13080–13085PubMedCrossRefGoogle Scholar
  111. Marin B, Nowack ECM, Melkonian M (2005) A plastid in the making: evidence for a second primary endosymbiosis. Protist 156:425–432PubMedCrossRefGoogle Scholar
  112. Martin W (2008) Anaerobic eukaryotes in pursuit of phylogenetic normality: the evolution of hydrogenosomes and mitosomes. In: Tachezy J (ed) Hydrogenosomes and mitosomes: mitochondria of anaerobic eukaryotes, vol 9. Microbiol Monogr Springer-Verlag, Berlin, pp 1–20CrossRefGoogle Scholar
  113. Martin W, Muller M (1998) The hydrogen hypothesis for the first eukaryote. Nature 392:37–41PubMedCrossRefGoogle Scholar
  114. Martin W, Hoffmeister M, Rotte C, Henze K (2001) An overview of endosymbiotic models for the origins of eukaryotes, their ATP-producing organelles (mitochondria and hydrogenosomes), and their heterotrophic lifestyle. Biol Chem 382:1521–1539PubMedCrossRefGoogle Scholar
  115. Matsuzaki M, Misumi O, Shin IT, Maruyama S, Takahara M, Miyagishima SY, Mori T, Nishida K, Yagisawa F, Nishida K, Yoshida Y, Nishimura Y, Nakao S, Kobayashi T, Momoyama Y, Higashiyama T, Minoda A, Sano M, Nomoto H, Oishi K, Hayashi H, Ohta F, Nishizaka S, Haga S, Miura S, Morishita T, Kabeya Y, Terasawa K, Suzuki Y, Ishii Y, Asakawa S, Takano H, Ohta N, Kuroiwa H, Tanaka K, Shimizu N, Sugano S, Sato N, Nozaki H, Ogasawara N, Kohara Y, Kuroiwa T (2004) Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D. Nature 428:653–657PubMedCrossRefGoogle Scholar
  116. Maxam AM, Gilbert W (1977) A new method for sequencing DNA. Proc Natl Acad Sci USA 74:560–564PubMedCrossRefGoogle Scholar
  117. McCutcheon JP (2010) The bacterial essence of tiny symbiont genomes. Curr Opin Microbiol 13:73–78PubMedCrossRefGoogle Scholar
  118. McCutcheon JP, McDonald BR, Moran NA (2009) Origin of an alternative genetic code in the extremely small and GC-rich genome of a bacterial symbiont. PLoS Genet 5:e1000565PubMedCrossRefGoogle Scholar
  119. McFadden GI (1999) Plastids and protein targeting. J Eukaryot Microbiol 46:339–346PubMedCrossRefGoogle Scholar
  120. McFadden GI, van Dooren GG (2004) Evolution: red algal genome affirms a common origin of all plastids. Curr Biol 14:R514–R516PubMedCrossRefGoogle Scholar
  121. Melkonian M, Mollenhauer D (2005) Robert Lauterborn (1869–1952) and his Paulinella chromatophora. Protist 156:253–262PubMedCrossRefGoogle Scholar
  122. Mereschkowsky C (1905) Über Natur und Ursprung der Chromatophoren im Pflanzenreiche. Biol Centralbl 25:593–604. English translation in Martin W, Kowallik, KV (1999) Annotated English translation of Mereschkowsky's paper Über Natur und Ursprung der Chromatophoren im Pflanzenreiche. Eur J Phycol 34:287–295Google Scholar
  123. Moore CE, Archibald JM (2009) Nucleomorph genomes. Annu Rev Genet 43:251–264PubMedCrossRefGoogle Scholar
  124. Moran NA (2002) Microbial minimalism: genome reduction in bacterial pathogens. Cell 108:583–586PubMedCrossRefGoogle Scholar
  125. Moran NA, McCutcheon JP, Nakabachi A (2008) Genomics and evolution of heritable bacterial symbionts. Annu Rev Genet 42:165–190PubMedCrossRefGoogle Scholar
  126. Moreira D, Le Guyader H, Phillippe H (2000) The origin of red algae and the evolution of chloroplasts. Nature 405:69–72PubMedCrossRefGoogle Scholar
  127. 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 (2007) Genomic minimalism in the early diverging intestinal parasite Giardia lamblia. Science 317:1921–1926PubMedCrossRefGoogle Scholar
  128. Müller M (1993) The hydrogenosome. J Gen Microbiol 139(Pt 12):2879–2889PubMedGoogle Scholar
  129. Nakabachi A, Yamashita A, Toh H, Ishikawa H, Dunbar HE, Moran NA, Hattori M (2006) The 160-kilobase genome of the bacterial endosymbiont Carsonella. Science 314:267PubMedCrossRefGoogle Scholar
  130. Nakayama T, Ishida K (2009) Another acquisition of a primary photosynthetic organelle is underway in Paulinella chromatophora. Curr Biol 19:R284–R285PubMedCrossRefGoogle Scholar
  131. Nass MMK, Nass S (1963) Intramitochondrial fibers with DNA characteristics. I. Fixation and electron staining reactions. J Cell Biol 19:593–611PubMedCrossRefGoogle Scholar
  132. Nelissen B, Van de Peer Y, Wilmotte A, De Wachter R (1995) An early origin of plastids within the cyanobacterial divergence is suggested by evolutionary trees based on complete 16S rRNA sequences. Mol Biol Evol 12:1166–1173PubMedGoogle Scholar
  133. Nikoh N, McCutcheon JP, Kudo T, Miyagishima SY, Moran NA, Nakabachi A (2010) Bacterial genes in the aphid genome: absence of functional gene transfer from buchnera to its host. PLoS Genet 6:e1000827PubMedCrossRefGoogle Scholar
  134. Nowack EC, Melkonian M (2010) Endosymbiotic associations within protists. Philos Trans R Soc Lond B Biol Sci 365:699–712PubMedCrossRefGoogle Scholar
  135. Nowack ECM, Melkonian M, Glöckner G (2008) Chromatophore genome sequence of Paulinella sheds light on acquisition of photosynthesis by eukaryotes. Curr Biol 18:410–418PubMedCrossRefGoogle Scholar
  136. Nowack EC, Vogel H, Groth M, Grossman AR, Melkonian M, Glockner G (2011) Endosymbiotic gene transfer and transcriptional regulation of transferred genes in Paulinella chromatophora. Mol Biol Evol 28:407–422PubMedCrossRefGoogle Scholar
  137. Nozaki H (2005) A new scenario of plastid evolution: plastid primary endosymbiosis before the divergence of the "Plantae," emended. J Plant Res 118:247–255PubMedCrossRefGoogle Scholar
  138. Nozaki H, Iseki M, Hasegawa M, Misawa K, Nakada T, Sasaki N, Watanabe M (2007) Phylogeny of primary photosynthetic eukaryotes as deduced from slowly evolving nuclear genes. Mol Biol Evol 24:1592–1595PubMedCrossRefGoogle Scholar
  139. Nozaki H, Maruyama S, Matsuzaki M, Nakada T, Kato S, Misawa K (2009) Phylogenetic positions of Glaucophyta, green plants (Archaeplastida) and Haptophyta (Chromalveolata) as deduced from slowly evolving nuclear genes. Mol Phylogenet Evol 53:872–880PubMedCrossRefGoogle Scholar
  140. O'Malley MA (2010) The first eukaryote cell: an unfinished history of contestation. Stud Hist Philos Biol Biomed Sci 41:212–224PubMedGoogle Scholar
  141. Palmer JD (2003) The symbiotic birth and spread of plastids: how many times and whodunnit? J Phycol 39:4–11CrossRefGoogle Scholar
  142. Parfrey LW, Barbero E, Lasser E, Dunthorn M, Bhattacharya D, Patterson DJ, Katz LA (2006) Evaluating support for the current classification of eukaryotic diversity. PLoS Genet 2:e220PubMedCrossRefGoogle Scholar
  143. Parfrey LW, Grant J, Tekle YI, Lasek-Nesselquist E, Morrison HG, Sogin ML, Patterson DJ, Katz LA (2010) Broadly sampled multigene analyses yield a well-resolved eukaryotic tree of life. Syst Biol 59:518–533PubMedCrossRefGoogle Scholar
  144. Patron NJ, Inagaki Y, Keeling PJ (2007) Multiple gene phylogenies support the monophyly of cryptomonad and haptophyte host lineages. Curr Biol 17:887–891PubMedCrossRefGoogle Scholar
  145. Perez-Brocal V, Clark AG (2008) Analysis of two genomes from the mitochondrion-like organelle of the intestinal parasite Blastocystis: complete sequences, gene content and genome organization. Mol Biol Evol 25:2475–2482PubMedCrossRefGoogle Scholar
  146. Philippe H, Germot A (2000) Phylogeny of eukaryotes based on ribosomal RNA: long-branch attraction and models of sequence evolution. Mol Biol Evol 17:830–834PubMedGoogle Scholar
  147. Philippe H, Zhou Y, Brinkmann H, Rodrigue N, Delsuc F (2005) Heterotachy and long-branch attraction in phylogenetics. BMC Evol Biol 5:50PubMedCrossRefGoogle Scholar
  148. Pierce SK, Curtis NE, Hanten JJ, Boerner SL, Schwarts JL (2007) Transfer, integration and expression of functional nuclear genes between multicellular species. Symbiosis 43:57–64Google Scholar
  149. Poole AM, Penny D (2007) Evaluating hypotheses for the origin of eukaryotes. Bioessays 29:74–84PubMedCrossRefGoogle Scholar
  150. Prechtl J, Kneip C, Lockhart P, Wenderoth K, Maier UG (2004) Intracellular spheroid bodies of Rhopalodia gibba have nitrogen-fixing apparatus of cyanobacterial origin. Mol Biol Evol 21:1477–1481PubMedCrossRefGoogle Scholar
  151. Raff RA, Mahler HR (1972) The non symbiotic origin of mitochondria. Science 177:575–582PubMedCrossRefGoogle Scholar
  152. Raven PH (1970) A multiple origin for plastids and mitochondria. Science 169:641–646PubMedCrossRefGoogle Scholar
  153. Reith M, Munholland J (1995) Complete nucleotide sequence of the Porphyra purpurea chloroplast genome. Plant Mol Biol Rep 13:333–335CrossRefGoogle Scholar
  154. Rensing SA, Goddemeier M, Hofmann CJ, Maier UG (1994) The presence of a nucleomorph hsp70 gene is a common feature of Cryptophyta and Chlorarachniophyta. Curr Genet 26:451–455PubMedCrossRefGoogle Scholar
  155. Reyes-Prieto A, Weber AP, Bhattacharya D (2007) The origin and establishment of the plastid in algae and plants. Annu Rev Genet 41:147–168PubMedCrossRefGoogle Scholar
  156. Reyes-Prieto A, Yoon HS, Moustafa A, Yang EC, Andersen RA, Boo SM, Nakayama T, Ishida K, Bhattacharya D (2010) Differential gene retention in plastids of common recent origin. Mol Biol Evol 27:1530–1537PubMedCrossRefGoogle Scholar
  157. Ris H (1961) Ultrastructure and molecular organization of genetic systems. Can J Genet Cytol 3:95–120PubMedGoogle Scholar
  158. Rodriguez-Ezpeleta N, Brinkmann H, Burey SC, Roure B, Burger G, Loffelhardt W, Bohnert HJ, Philippe H, Lang BF (2005) Monophyly of primary photosynthetic eukaryotes: green plants, red algae, and glaucophytes. Curr Biol 15:1325–1330PubMedCrossRefGoogle Scholar
  159. Roger AJ (1999) Reconstructing early events in eukaryotic evolution. Am Nat 154:S146–S163PubMedCrossRefGoogle Scholar
  160. Roger AJ, Clark CG, Doolittle WF (1996) A possible mitochondrial gene in the early-branching amitochondriate protist Trichomonas vaginalis. Proc Natl Acad Sci USA 93:14618–14622PubMedCrossRefGoogle Scholar
  161. Roger AJ, Svard SG, Tovar J, Clark CG, Smith MW, Gillin FD, Sogin ML (1998) A mitochondrial-like chaperonin 60 gene in Giardia lamblia: evidence that diplomonads once harbored an endosymbiont related to the progenitor of mitochondria. Proc Natl Acad Sci USA 95:229–234PubMedCrossRefGoogle Scholar
  162. Rogers MB, Gilson PR, Su V, McFadden GI, Keeling PJ (2007) The complete chloroplast genome of the chlorarachniophyte Bigelowiella natans: evidence for independent origins of chlorarachniophyte and euglenid secondary endosymbionts. Mol Biol Evol 24:54–62PubMedCrossRefGoogle Scholar
  163. Roos DS, Crawford MJ, Donald RGK, Kissinger JC, Klimczak LJ, Striepen B (1999) Origin, targeting, and function of the apicomplexan plastid. Curr Opin Microbiol 2:426–432PubMedCrossRefGoogle Scholar
  164. Rumpho ME, Worful JM, Lee J, Kannan K, Tyler MS, Bhattacharya D, Moustafa A, Manhart JR (2008) Horizontal gene transfer of the algal nuclear gene psbO to the photosynthetic sea slug Elysia chlorotica. Proc Natl Acad Sci USA 105:17867–17871PubMedCrossRefGoogle Scholar
  165. Rumpho ME, Pelletreau KN, Moustafa A, Bhattacharya D (2011) The making of a photosynthetic animal. J Exp Biol 214:303–311PubMedCrossRefGoogle Scholar
  166. Sagan L (1967) On the origin of mitosing cells. J Theoret Biol 14:225–274CrossRefGoogle Scholar
  167. Sanchez-Puerta MV, Delwiche CF (2008) A hypothesis for plastid evolution in chromalveolates. J Phycol 44:1097–1107CrossRefGoogle Scholar
  168. Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467PubMedCrossRefGoogle Scholar
  169. Sapp J (1990) Symbiosis in evolution: an origin story. Endocytobiosis and Cell Res 7:5–36Google Scholar
  170. Sapp J (1994) Evolution by association: a history of symbiosis. Oxford University Press, New YorkGoogle Scholar
  171. Sapp J (2009) The New foundations of evolution. Oxford University Press, New YorkGoogle Scholar
  172. Schimper AFW (1883) Ueber die Entwickelung der Chlorophyllkörner und Farbkörper. Bot Zeit 41:105–114, 121–131, 137–146, 153–162Google Scholar
  173. Schwartz JA, Curtis NE, Pierce SK (2010) Using algal transcriptome sequences to identify transferred genes in the sea slug, Elysia chlorotica. Evol Biol 37:29–37CrossRefGoogle Scholar
  174. Simon C, Daniel R (2011) Metagenomic analyses: past and future trends. Appl Environ Microbiol 77:1153–1161PubMedCrossRefGoogle Scholar
  175. Simpson AGB, Roger AJ (2004) The real 'kingdoms' of eukaryotes. Curr Biol 14:R693–R696PubMedCrossRefGoogle Scholar
  176. Sogin ML (1997) History assignment: when was the mitochondrion founded? Curr Opp Genet Dev 7:792–799CrossRefGoogle Scholar
  177. Sogin ML, Gunderson JH, Elwood HJ, Alonso RA, Peattie DA (1989) Phylogenetic meaning of the kingdom concept: an unusual ribosomal RNA from Giardia lamblia. Science 243:75–77PubMedCrossRefGoogle Scholar
  178. Stahl DA, Lane DJ, Olsen GJ, Pace NR (1985) Characterization of a Yellowstone hot spring microbial community by 5S rRNA sequences. Appl Environ Microbiol 49:1379–1384PubMedGoogle Scholar
  179. Stanier RY (1970) Some aspects of the biology of cells and their possible evolutionary significance. In: Charles HP, Knight BD (eds) Organization and control in prokaryotic and eukaryotic cells: 20th symposium of the Society for General Microbiology. Cambridge University Press, London, pp 1–38Google Scholar
  180. Stechmann A, Hamblin K, Perez-Brocal V, Gaston D, Richmond GS, van der Giezen M, Clark CG, Roger AJ (2008) Organelles in Blastocystis that blur the distinction between mitochondria and hydrogenosomes. Curr Biol 18:580–585PubMedCrossRefGoogle Scholar
  181. Stiller JW (2007) Plastid endosymbiosis, genome evolution and the origin of green plants. Trends Plant Sci 12:391–396PubMedCrossRefGoogle Scholar
  182. Stiller JW, Hall BD (1997) The origin of red algae: implications for plastid evolution. Proc Natl Acad Sci USA 94:4520–4525PubMedCrossRefGoogle Scholar
  183. Stiller JW, Reel DC, Johnson JC (2003) A single origin of plastids revisited: convergent evolution in organellar genome content. J Phycol 39:95–105CrossRefGoogle Scholar
  184. Stoebe B, Kowallik KV (1999) Gene-cluster analysis in chloroplast genomics. Trends Genet 15:344–347PubMedCrossRefGoogle Scholar
  185. Tachezy J, Dolezal P (2007) Iron-Sulfure proteins and iron-sulfur cluster assembly in organisms with hydrogenosomes and mitosomes. In: Martin WF, Müller M (eds) Origin of mitochondria and hydrogenosomes. Springer, Berlin, pp 105–133CrossRefGoogle Scholar
  186. Tanifuji G, Onodera NT, Wheeler TJ, Dlutek M, Donaher N, Archibald JM (2011) Complete nucleomorph genome sequence of the non-photosynthetic alga Cryptomonas paramecium reveals a core nucleomorph gene set. Genome Biol Evol 3:44–54PubMedCrossRefGoogle Scholar
  187. Taylor FJR (1974) Implications and extensions of the serial endosymbiosis theory of the origin of eukaryotes. Taxon 23:229–258CrossRefGoogle Scholar
  188. Taylor FJR (1976) Autogenous theories for the origin of eukaryotes. Taxon 23:377–390CrossRefGoogle Scholar
  189. Theissen U, Martin W (2006) The difference between organelles and endosymbionts. Curr Biol 16:R1016–R1017, author reply R1017-1018PubMedCrossRefGoogle Scholar
  190. Timmis JN, Ayliffe MA, Huang CY, Martin W (2004) Endosymbiotic gene transfer: organelle genomes forge eukaryotic chromosomes. Nat Rev Genet 5:123–135PubMedCrossRefGoogle Scholar
  191. Tomas R, Cox E (1973) Observations on the symbiosis of Peridinium balticum and its intracellular alga. I. Ultrastructure. J Phycol 9:304–323Google Scholar
  192. Tovar J (2007) Mitosomes of parasitic protozoa: biology and evolutionary significance. In: Martin WF, Muller M (eds) Origin of mitochondria and hydrogenosomes. Springer, Berlin, pp 277–300CrossRefGoogle Scholar
  193. Tovar J, Fischer A, Clark CG (1999) The mitosome, a novel organelle related to mitochondria in the amitochondrial parasite Entamoeba histolytica. Mol Microbiol 32:1013–1021PubMedCrossRefGoogle Scholar
  194. Tovar J, Leon-Avila G, Sanchez LB, Sutak R, Tachezy J, van der Giezen M, Hernandez M, Muller M, Lucocq JM (2003) Mitochondrial remnant organelles of Giardia function in iron-sulphur protein maturation. Nature 426:172–176PubMedCrossRefGoogle Scholar
  195. Tringe SG, Rubin EM (2005) Metagenomics: DNA sequencing of environmental samples. Nat Rev Genet 6:805–814PubMedCrossRefGoogle Scholar
  196. Tsaousis AD, Kunji ERS, Goldberg AV, Lucocq JM, Hirt RP, Embley TM (2008) A novel route for ATP acquisition by the remnant mitochondria of Encephalitozoon cuniculi. Nature 453:553–557PubMedCrossRefGoogle Scholar
  197. Turner S (1997) Molecular systematics of oxygenic photosynthetic bacteria. Pl Syst Evol [Suppl] 11:13–52Google Scholar
  198. Turner S, Pryer KM, Miao VP, Palmer JD (1999) Investigating deep phylogenetic relationships among cyanobacteria and plastids by small subunit rRNA sequence analysis. J Eukaryot Microbiol 46:327–338PubMedCrossRefGoogle Scholar
  199. Tyson GW, Chapman J, Hugenholtz P, Allen EE, Ram RJ, Richardson PM, Solovyev VV, Rubin EM, Rokhsar DS, Banfield JF (2004) Community structure and metabolism through reconstruction of microbial genomes from the environment. Nature 428:37–43PubMedCrossRefGoogle Scholar
  200. Van de Peer Y, Ben Ali A, Meyer A (2000) Microsporidia: accumulating molecular evidence that a group of amitochondriate and suspectedly primitive eukaryotes are just curious fungi. Gene 246:1–8PubMedCrossRefGoogle Scholar
  201. Venter JC, Remington K, Heidelberg JF, Halpern AL, Rusch D, Eisen JA, Wu D, Paulsen I, Nelson KE, Nelson W, Fouts DE, Levy S, Knap AH, Lomas MW, Nealson K, White O, Peterson J, Hoffman J, Parsons R, Baden-Tillson H, Pfannkoch C, Rogers YH, Smith HO (2004) Environmental genome shotgun sequencing of the Sargasso Sea. Science 304:66–74PubMedCrossRefGoogle Scholar
  202. Wägele H, Deusch O, Handeler K, Martin R, Schmitt V, Christa G, Pinzger B, Gould SB, Dagan T, Klussmann-Kolb A, Martin W (2011) Transcriptomic evidence that longevity of acquired plastids in the photosynthetic slugs Elysia timida and Plakobranchus ocellatus does not entail lateral transfer of algal nuclear genes. Mol Biol Evol 28:699–706PubMedCrossRefGoogle Scholar
  203. Waller RF, McFadden GI (2005) The apicoplast: a review of the derived plastid of apicomplexan parasites. Curr Issues Mol Biol 7:57–79PubMedGoogle Scholar
  204. Whatley JM, John P, Whatley FR (1979) From extracellular to intracellular: the establishment of mitochondria and chloroplasts. Proc R Soc Lond B 204:165–187PubMedCrossRefGoogle Scholar
  205. Williams BA, Hirt RP, Lucocq JM, Embley TM (2002) A mitochondrial remnant in the microsporidian Trachipleistophora hominis. Nature 418:865–869PubMedCrossRefGoogle Scholar
  206. Woese CR, Fox GE (1977) Phylogenetic structure of the prokaryotic domain. The primary kingdoms. Proc Natl Acad Sci USA 74:5088–5090PubMedCrossRefGoogle Scholar
  207. Woese CR, Kandler O, Wheelis ML (1990) Towards a natural system of organisms, proposal for the domains Archaea, Bacteria, and Eucarya. Proc Natl Acad Sci USA 87:4576–4579PubMedCrossRefGoogle Scholar
  208. Wolfe GR, Cunningham FX, Durnford DG, Green BR, Gantt E (1995) Evidence for a common origin of chloroplasts with light-harvesting complexes of different pigmentation. Nature 367:566–568CrossRefGoogle Scholar
  209. Yoon HS, Reyes-Prieto A, Melkonian M, Bhattacharya D (2006) Minimal plastid genome evolution in the Paulinella endosymbiont. Curr Biol 16:R670–R672PubMedCrossRefGoogle Scholar
  210. Yoon HS, Zuccarello G, Bhattacharya D (2010) Evolutionary history and taxonomy of red algae. In: Seckback J, Chapman DJ (eds) Red algae in the genomic age, vol 13. Cellular origin, life in extreme habitats and astrobiology. Springer, New York, pp 25–42Google Scholar
  211. Zablen LB, Kissil MS, Woese CR, Buetow DE (1975) Phylogenetic origin of the chloroplast and prokaryotic nature of its ribosomal RNA. Proc Natl Acad Sci USA 72:2418–2422PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Canadian Institute for Advanced Research, Program in Integrated Microbial Biodiversity, Department of Biochemistry and Molecular Biology, Sir Charles Tupper Medical BuildingDalhousie UniversityHalifaxCanada

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