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Myosin domain evolution and the primary divergence of eukaryotes


Eukaryotic cells have two contrasting cytoskeletal and ciliary organizations. The simplest involves a single cilium-bearing centriole, nucleating a cone of individual microtubules (probably ancestral for unikonts: animals, fungi, Choanozoa and Amoebozoa). In contrast, bikonts (plants, chromists and all other protozoa) were ancestrally biciliate with a younger anterior cilium, converted every cell cycle into a dissimilar posterior cilium and multiple ciliary roots of microtubule bands. Here we show by comparative genomic analysis that this fundamental cellular dichotomy also involves different myosin molecular motors. We found 37 different protein domain combinations, often lineage-specific, and many previously unidentified. The sequence phylogeny and taxonomic distribution of myosin domain combinations identified five innovations that strongly support unikont monophyly and the primary bikont/unikont bifurcation. We conclude that the eukaryotic cenancestor (last common ancestor) had a cilium, mitochondria, pseudopodia, and myosins with three contrasting domain combinations and putative functions.

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Figure 1: Taxonomic distribution and evolutionary history of myosin paralogues.
Figure 2: Myosin head domain phylogeny (bayesian consensus: 118 myosins; 357 characters).
Figure 3: Section from a myosin sequence alignment, including a representative selection of myosin types.


  1. 1

    Sellers, J. R. Myosins (Oxford Univ. Press, Oxford, 1999)

    Google Scholar 

  2. 2

    Bahler, M. Are class III and class IX myosins motorized signalling molecules? Biochim. Biophys. Acta 1496, 52–59 (2000)

    CAS  Article  Google Scholar 

  3. 3

    Cavalier-Smith, T. The phagotrophic origin of eukaryotes and phylogenetic classification of Protozoa. Int. J. Syst. Evol. Microbiol. 52, 297–354 (2002)

    CAS  Article  Google Scholar 

  4. 4

    Thompson, R. F. & Langford, G. M. Myosin superfamily evolutionary history. Anat. Rec. 268, 276–289 (2002)

    CAS  Article  Google Scholar 

  5. 5

    Furusawa, T., Ikawa, S., Yanai, N. & Obinata, M. Isolation of a novel PDZ-containing myosin from hematopoietic supportive bone marrow stromal cell lines. Biochem. Biophys. Res. Commun. 270, 67–75 (2000)

    CAS  Article  Google Scholar 

  6. 6

    Goodson, H. V. & Spudich, J. A. Molecular evolution of the myosin family: relationships derived from comparisons of amino acid sequences. Proc. Natl Acad. Sci. USA 90, 659–663 (1993)

    ADS  CAS  Article  Google Scholar 

  7. 7

    Hodge, T. & Cope, M. J. A myosin family tree. J. Cell Sci. 113, 3353–3354 (2000)

    CAS  PubMed  Google Scholar 

  8. 8

    Berg, J. S., Powell, B. C. & Cheney, R. E. A millennial myosin census. Mol. Biol. Cell 12, 780–794 (2001)

    CAS  Article  Google Scholar 

  9. 9

    Kull, F. J., Vale, R. D. & Fletterick, R. J. The case for a common ancestor: kinesin and myosin motor proteins and G proteins. J. Muscle Res. Cell Motil. 19, 877–886 (1998)

    CAS  Article  Google Scholar 

  10. 10

    Leipe, D. D., Wolf, Y. I., Koonin, E. V. & Aravind, L. Classification and evolution of P-loop GTPases and related ATPases. J. Mol. Biol. 317, 41–72 (2002)

    CAS  Article  Google Scholar 

  11. 11

    Stechmann, A. & Cavalier-Smith, T. Rooting the eukaryote tree by using a derived gene fusion. Science 297, 89–91 (2002)

    ADS  CAS  Article  Google Scholar 

  12. 12

    Stechmann, A. & Cavalier-Smith, T. The root of the eukaryote tree pinpointed. Curr. Biol. 13, R665–R666 (2003)

    CAS  Article  Google Scholar 

  13. 13

    Cavalier-Smith, T. Protist phylogeny and the high-level classification of Protozoa. Eur. J. Protistol. 39, 338–348 (2003)

    Article  Google Scholar 

  14. 14

    Matsuzaki, M. et al. Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D. Nature 428, 653–657 (2004)

    ADS  CAS  Article  Google Scholar 

  15. 15

    Altschul, S. F. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402 (1997)

    CAS  Article  Google Scholar 

  16. 16

    Cavalier-Smith, T. Only six kingdoms of life. Proc. R. Soc. Lond. B 271, 1251–1262 (2004)

    CAS  Article  Google Scholar 

  17. 17

    Simpson, A. G. & Roger, A. J. The real ‘kingdoms’ of eukaryotes. Curr. Biol. 14, R693–R696 (2004)

    CAS  Article  Google Scholar 

  18. 18

    D'Aquino, J. A. & Ringe, D. Determinants of the SRC homology domain 3-like fold. J. Bacteriol. 185, 4081–4086 (2003)

    CAS  Article  Google Scholar 

  19. 19

    Bapteste, E. & Philippe, H. The potential value of indels as phylogenetic markers: position of trichomonads as a case study. Mol. Biol. Evol. 19, 972–977 (2002)

    CAS  Article  Google Scholar 

  20. 20

    Hirt, R. P. et al. Microsporidia are related to Fungi: evidence from the largest subunit of RNA polymerase II and other proteins. Proc. Natl Acad. Sci. USA 96, 580–585 (1999)

    ADS  CAS  Article  Google Scholar 

  21. 21

    Cavalier-Smith, T. Archamoebae: the ancestral eukaryotes? BioSystems 25, 25–38 (1991)

    CAS  Article  Google Scholar 

  22. 22

    Cavalier-Smith, T., Chao, E. E. & Oates, B. Molecular phylogeny of Amoebozoa and the evolutionary significance of the unikont Phalansterium. Eur. J. Protistol. 40, 21–48 (2004)

    Article  Google Scholar 

  23. 23

    Bolivar, I., Fahrni, J. F., Smirnov, A. & Pawlowski, J. SSU rRNA-based phylogenetic position of the genera Amoeba and Chaos (Lobosea, Gymnamoebia): the origin of gymnamoebae revisited. Mol. Biol. Evol. 18, 2306–2314 (2001)

    CAS  Article  Google Scholar 

  24. 24

    Kudryavtsev, A. A., Bernhardt, D., Schlegel, M., Chao, E. E. & Cavalier-Smith, T. 18S ribosomal RNA gene sequences of Cochliopodium (Himatismenida) and the phylogeny of Amoebozoa. Protist 156, 215–224 (2005)

    CAS  Article  Google Scholar 

  25. 25

    Milyutina, I. A., Aleshin, V. V., Mikrjukov, K. A., Kedrova, O. S. & Petrov, N. B. The unusually long small subunit ribosomal RNA gene found in amitochondriate amoeboflagellate Pelomyxa palustris: its rRNA predicted secondary structure and phylogenetic implication. Gene 272, 131–139 (2001)

    CAS  Article  Google Scholar 

  26. 26

    Dacks, J. B., Marinets, A., Doolittle, W. F., Cavalier-Smith, T. & Logsdon, J. M. Jr Analyses of RNA polymerase II genes from free-living protists: phylogeny, long branch attraction, and the eukaryotic big bang. Mol. Biol. Evol. 19, 830–840 (2002)

    CAS  Article  Google Scholar 

  27. 27

    Bapteste, E. et al. The analysis of 100 genes supports the grouping of three highly divergent amoebae: Dictyostelium, Entamoeba, and Mastigamoeba. Proc. Natl Acad. Sci. USA 99, 1414–1419 (2002)

    ADS  CAS  Article  Google Scholar 

  28. 28

    Lang, B. F., O'Kelly, C., Nerad, T., Gray, M. W. & Burger, G. The closest unicellular relatives of animals. Curr. Biol. 12, 1773–1778 (2002)

    CAS  Article  Google Scholar 

  29. 29

    Berney, C., Fahrni, J. & Pawlowski, J. How many novel eukaryotic ‘kingdoms’? Pitfalls and limitations of environmental DNA surveys. BMC Biol. 2, 13 (2004)

    Article  Google Scholar 

  30. 30

    Bass, D. et al. Polyubiquitin insertions and the phylogeny of Cercozoa and Rhizaria. Protist 156, 149–161 (2005)

    CAS  Article  Google Scholar 

  31. 31

    Cavalier-Smith, T. & Chao, E. E. Phylogeny and classification of phylum Cercozoa (Protozoa). Protist 154, 341–358 (2003)

    Article  Google Scholar 

  32. 32

    Titus, M. A. A class VII unconventional myosin is required for phagocytosis. Curr. Biol. 9, 1297–1303 (1999)

    CAS  Article  Google Scholar 

  33. 33

    Tuxworth, R. I. et al. A role for myosin VII in dynamic cell adhesion. Curr. Biol. 11, 318–329 (2001)

    CAS  Article  Google Scholar 

  34. 34

    Marchler-Bauer, A. et al. CDD: a curated Entrez database of conserved domain alignments. Nucleic Acids Res. 31, 383–387 (2003)

    CAS  Article  Google Scholar 

  35. 35

    Bateman, A. et al. The Pfam protein families database. Nucleic Acids Res. 32, D138–D141 (2004)

    CAS  Article  Google Scholar 

  36. 36

    Thompson, J. D., Gibson, T. J., Plewniak, F., Jeanmougin, F. & Higgins, D. G. The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res. 25, 4876–4882 (1997)

    CAS  Article  Google Scholar 

  37. 37

    Ronquist, F. & Huelsenbeck, J. P. MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 19, 1572–1574 (2003)

    CAS  Article  Google Scholar 

  38. 38

    Schmidt, H. A., Strimmer, K., Vingron, M. & von Haeseler, A. TREE-PUZZLE: maximum likelihood phylogenetic analysis using quartets and parallel computing. Bioinformatics 18, 502–504 (2002)

    CAS  Article  Google Scholar 

  39. 39

    Felsenstein, J. Phylip (Department of Genetics, University of Washington, Seattle, 1995)

    Google Scholar 

  40. 40

    Minotto, L., Edwards, M. R. & Bagnara, A. S. Trichomonas vaginalis: Characterization, expression, and phylogenetic analysis of a carbamate kinase gene sequence. Exp. Parasitol. 95, 54–62 (2000)

    CAS  Article  Google Scholar 

  41. 41

    Baldauf, S. L. & Palmer, J. D. Animals and fungi are each other's closest relatives: congruent evidence from multiple proteins. Proc. Natl Acad. Sci. USA 90, 11558–11562 (1993)

    ADS  CAS  Article  Google Scholar 

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Preliminary sequence data were obtained from The Institute for Genomic Research website ( and the Department of Energy Joint Genome Institute (JGI) website ( We thank TIGR and DOE JGI for making data publicly available, A. A. Davies for comments and assistance with data management, and D. Soanes for PSI BLAST assistance. T.A.R. was supported by a BBSRC studentship. T.C.-S. thanks NERC for research grants and NERC and the Canadian Institute for Advanced Research Evolutionary Biology Program for Fellowship support.

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Corresponding author

Correspondence to Thomas A. Richards.

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Reprints and permissions information is available at The authors declare no competing financial interests.

Supplementary information

Supplementary Table S1.

Comparative genome survey of myosin genes. Full details of comparative genomic analyses of the myosin gene family displayed as a table with footnotes and an additional table listing details about domain names, definitions and abbreviations. (DOC 185 kb)

Supplementary Figure S1.

Alignment of representatives of myosin class II, V and XI. Annotated amino acid alignment that illustrates sequence synapomorphies and details about protein domain evolution. (PDF 1803 kb)

Supplementary Figure S2.

Alignment of myosins with either MYTH4 and/or FERM domains. Annotated amino acid alignment that illustrates sequence synapomorphies and details about protein domain evolution. (PDF 2115 kb)

Supplementary Figure S3.

Alignment of representatives of myosin class I. Annotated amino acid alignment that illustrates sequence synapomorphies and details about protein domain evolution. (PDF 2638 kb)

Supplementary Figure S4.

Phylogeny of myosin head domains; this is the same tree as in Fig. 2 of the main text of the paper, except that accession numbers replace species names and exact support values are shown. The details of the phylogenetic methods are explained in the figure legend. (PDF 82 kb)

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Richards, T., Cavalier-Smith, T. Myosin domain evolution and the primary divergence of eukaryotes. Nature 436, 1113–1118 (2005).

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