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The origin of Metazoa: a unicellular perspective

Nature Reviews Genetics volume 18, pages 498–512 (2017)Cite this article

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Key Points

  • The origin of animal multicellularity is one of the major evolutionary transitions in the history of life.

  • The identification and phylogenetic classification of the closest unicellular relatives of animals initiated the study of this transition from a unicellular perspective.

  • Comparative genomics has revealed that many genes associated with animal multicellularity evolved in a unicellular context and has enabled the rich gene repertoire of the unicellular ancestor of animals to be reconstructed.

  • The presence of highly regulated temporal cell types in animal relatives suggests the existence of cell differentiation in the unicellular ancestor of animals.

  • Initial studies suggest important differences between the genome regulatory mechanisms of animals and those of their closest unicellular relatives.

  • These innovations in genome regulation would have been key to the spatial integration of pre-existing cell types at the onset of Metazoa.

Abstract

The first animals evolved from an unknown single-celled ancestor in the Precambrian period. Recently, the identification and characterization of the genomic and cellular traits of the protists most closely related to animals have shed light on the origin of animals. Comparisons of animals with these unicellular relatives allow us to reconstruct the first evolutionary steps towards animal multicellularity. Here, we review the results of these investigations and discuss their implications for understanding the earliest stages of animal evolution, including the origin of metazoan genes and genome function.

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Figure 1: The multiple origins of multicellularity.
Figure 2: Phylogenetic relationships of animals and unicellular Holozoa.
Figure 3: Comparative genomics of Holozoa.
Figure 4: Unicellular holozoan life cycles.
Figure 5: A model of the origin of multicellularity: a transition from temporal to spatiotemporal cell differentiation.

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Change history

  • 10 May 2017

    In Figure 1a of the original version of this article, the Choanoflagellatea branch was missing a yellow-black split circle symbolizing that clonal multicellularity occurs in some Choanoflagellatea species. The symbol inadvertently dropped out prior to publication and has now been reinstated in the corrected article. The editors apologize for this error.

References

  1. Hyman, L. H. The Invertebrates: Protozoa Through Ctenophora (McGraw-Hill, 1940).

    Google Scholar 

  2. Grosberg, R. K. & Strathmann, R. R. The evolution of multicellularity: a minor major transition? Annu. Rev. Ecol. Evol. Syst. 38, 621–654 (2007).

    Article  Google Scholar 

  3. King, N. The unicellular ancestry of animal development. Dev. Cell 7, 313–325 (2004).

    Article  CAS  PubMed  Google Scholar 

  4. Knoll, A. H. The multiple origins of complex multicellularity. Annu. Rev. Earth Planet. Sci. 39, 217–239 (2011).

    Article  CAS  Google Scholar 

  5. Putnam, N. H. et al. Sea anemone genome reveals ancestral eumetazoan gene repertoire and genomic organization. Science 317, 86–94 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Moroz, L. L. et al. The ctenophore genome and the evolutionary origins of neural systems. Nature 510, 109–114 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ryan, J. F. et al. The genome of the ctenophore Mnemiopsis leidyi and its implications for cell type evolution. Science 342, 1242592 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Srivastava, M. et al. The Amphimedon queenslandica genome and the evolution of animal complexity. Nature 466, 720–726 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Srivastava, M. et al. The Trichoplax genome and the nature of placozoans. Nature 454, 955–960 (2008). References 5–9 report the genome sequencing and analysis of early animal lineages (Cnidaria, Placozoa, Ctenophora and Porifera). These studies reveal the existence of an extensive gene toolkit that is shared by all animals, and is involved in signalling, adhesion and transcriptional control.

    Article  CAS  PubMed  Google Scholar 

  10. Leininger, S. et al. Developmental gene expression provides clues to relationships between sponge and eumetazoan body plans. Nat. Commun. 5, 3905 (2014).

    Article  CAS  PubMed  Google Scholar 

  11. Zakhvatkin, A. A. The Comparative Embryology of the Low Invertebrates. Sources and Method of the Origin of Metazoan Development (Soviet Science, 1949).

    Google Scholar 

  12. Mikhailov, K. V. et al. The origin of Metazoa: a transition from temporal to spatial cell differentiation. Bioessays 31, 758–768 (2009). In this seminal review, the authors provide a broad historical perspective on hypotheses about animal origins and, in particular, they support and further extend Zakhvatkin's original Synzoospore hypothesis.

    Article  CAS  PubMed  Google Scholar 

  13. James-Clark, H. Note on the Infusoria flagellata and the Spongiae ciliatae. Am. J. Sci. 1, 113–114 (1866).

    Google Scholar 

  14. Saville-Kent, W. A Manual of the Infusoria, Including a Description of All Known Flagellate, Ciliate, and Tentaculiferous Protozoa, British and Foreign and an Account of the Organization and Affinities of the Sponges Vol. 1–3 (David Bogue, 1880).

  15. Mah, J. L., Christensen-Dalsgaard, K. K. & Leys, S. P. Choanoflagellate and choanocyte collar-flagellar systems and the assumption of homology. Evol. Dev. 16, 25–37 (2014).

    Article  CAS  PubMed  Google Scholar 

  16. Ruiz-Trillo, I., Roger, A. J., Burger, G., Gray, M. W. & Lang, B. F. Phylogenomic investigation into the origin of Metazoa. Mol. Biol. Evol. 25, 664–672 (2008).

    Article  CAS  PubMed  Google Scholar 

  17. Shalchian-Tabrizi, K. et al. Multigene phylogeny of Choanozoa and the origin of animals. PLoS ONE 3, e2098 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Torruella, G. et al. Phylogenetic relationships within the Opisthokonta based on phylogenomic analyses of conserved single-copy protein domains. Mol. Biol. Evol. 29, 531–544 (2012).

    Article  CAS  PubMed  Google Scholar 

  19. Torruella, G. et al. Phylogenomics reveals convergent evolution of lifestyles in close relatives of animals and fungi. Curr. Biol. 25, 2404–2410 (2015). This is the most comprehensive phylogenomic study on the holozoan clade published to date, both in terms of taxon sampling and the amount of data generated. It provides strong support for the scenario of three independent unicellular lineages close to Metazoa.

    Article  CAS  PubMed  Google Scholar 

  20. 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).

    Article  CAS  PubMed  Google Scholar 

  21. Zettler, L. A., Nerad, T. A., O'Kelly, C. J. & Sogin, M. L. The nucleariid amoebae: more protists at the animal–fungal boundary. J. Eukaryot. Microbiol. 48, 293–297 (2001).

    Article  PubMed  Google Scholar 

  22. Paps, J., Medina-Chacón, L. A., Marshall, W., Suga, H. & Ruiz-Trillo, I. Molecular phylogeny of unikonts: new insights into the position of apusomonads and ancyromonads and the internal relationships of opisthokonts. Protist 164, 2–12 (2013).

    Article  PubMed  Google Scholar 

  23. Carr, M. & Leadbeater, B. Molecular phylogeny of choanoflagellates, the sister group to Metazoa. Proc. Natl Acad. Sci. USA 105, 16641–16646 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Steenkamp, E. T., Wright, J. & Baldauf, S. L. The protistan origins of animals and fungi. Mol. Biol. Evol. 23, 93–106 (2006).

    Article  CAS  PubMed  Google Scholar 

  25. Leadbeater, B. S. C. The Choanoflagellates: Evolution, Biology and Ecology (Cambridge Univ. Press, 2015).

    Book  Google Scholar 

  26. Tong, S. M. Heterotrophic flagellates and other protists from Southampton Water, UK. Ophelia 47, 71–131 (1997).

    Article  Google Scholar 

  27. Hertel, L. A., Bayne, C. J. & Loker, E. S. The symbiont Capsaspora owczarzaki, nov. gen. nov. sp., isolated from three strains of the pulmonate snail Biomphalaria glabrata is related to members of the Mesomycetozoea. Int. J. Parasitol. 32, 1183–1191 (2002).

    Article  CAS  PubMed  Google Scholar 

  28. Stibbs, H. H., Owczarzak, A., Bayne, C. J. & DeWan, P. Schistosome sporocyst-killing amoebae isolated from Biomphalaria glabrata. J. Invertebr. Pathol. 33, 159–170 (1979).

    Article  CAS  PubMed  Google Scholar 

  29. Owczarzak, A., Stibbs, H. H. & Bayne, C. J. The destruction of Schistosoma mansoni mother sporocysts in vitro by amoebae isolated from Biomphalaria glabrata: an ultrastructural study. J. Invertebr. Pathol. 35, 26–33 (1980).

    Article  CAS  PubMed  Google Scholar 

  30. Hertel, L. A., Barbosa, C. S., Santos, R. A. & Loker, E. S. Molecular identification of symbionts from the pulmonate snail Biomphalaria glabrata in Brazil. J. Parasitol. 90, 759–763 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. Glockling, S. L., Marshall, W. L. & Gleason, F. H. Phylogenetic interpretations and ecological potentials of the Mesomycetozoea (Ichthyosporea). Fungal Ecol. 6, 237–247 (2013).

    Article  Google Scholar 

  32. Mendoza, L., Taylor, J. W. & Ajello, L. The class mesomycetozoea: a heterogeneous group of microorganisms at the animal–fungal boundary. Annu. Rev. Microbiol. 56, 315–344 (2002).

    Article  CAS  PubMed  Google Scholar 

  33. Del Campo, J. & Ruiz-Trillo, I. Environmental survey meta-analysis reveals hidden diversity among unicellular opisthokonts. Mol. Biol. Evol. 30, 802–805 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Marshall, W. L. & Berbee, M. L. Facing unknowns: living cultures (Pirum gemmata gen. nov., sp. nov., and Abeoforma whisleri, gen. nov., sp. nov.) from invertebrate digestive tracts represent an undescribed clade within the unicellular Opisthokont lineage Ichthyosporea (Mesomycetozoea). Protist 162, 33–57 (2011).

    Article  PubMed  Google Scholar 

  35. Marshall, W. L., Celio, G., McLaughlin, D. J. & Berbee, M. L. Multiple isolations of a culturable, motile Ichthyosporean (Mesomycetozoa, Opisthokonta), Creolimax fragrantissima n. gen., n. sp., from marine invertebrate digestive tracts. Protist 159, 415–433 (2008).

    Article  CAS  PubMed  Google Scholar 

  36. King, N. et al. The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. Nature 451, 783–788 (2008). This paper represents the foundation of comparative genomics approaches to animal origins. It reports the sequencing of the first genome of a unicellular holozoan species: the choanoflagellate M. brevicollis. It is the first study to extensively show that many genes that were previously considered to be animal-specific and tightly related to multicellularity evolved in a unicellular context.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Fairclough, S. R. et al. Premetazoan genome evolution and the regulation of cell differentiation in the choanoflagellate Salpingoeca rosetta. Genome Biol. 14, R15 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. de Mendoza, A., Suga, H., Permanyer, J., Irimia, M. & Ruiz-Trillo, I. Complex transcriptional regulation and independent evolution of fungal-like traits in a relative of animals. eLife 4, e08904 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Suga, H. et al. The Capsaspora genome reveals a complex unicellular prehistory of animals. Nat. Commun. 4, 2325 (2013).

    Article  CAS  PubMed  Google Scholar 

  40. Nichols, S. A., Roberts, B. W., Richter, D. J., Fairclough, S. R. & King, N. Origin of metazoan cadherin diversity and the antiquity of the classical cadherin/β-catenin complex. Proc. Natl Acad. Sci. USA 109, 13046–13051 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Sebé-Pedrós, A., Roger, A., Lang, B., King, N. & Ruiz-Trillo, I. Ancient origin of the integrin-mediated adhesion and signaling machinery. Proc. Natl Acad. Sci. USA 107, 10142–10147 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Richards, G. S. & Degnan, B. M. The dawn of developmental signaling in the Metazoa. Cold Spring Harb. Symp. Quant. Biol. 74, 81–90 (2009).

    Article  CAS  PubMed  Google Scholar 

  43. Suga, H. et al. Genomic survey of premetazoans shows deep conservation of cytoplasmic tyrosine kinases and multiple radiations of receptor tyrosine kinases. Sci. Signal. 5, ra35 (2012).

    Article  PubMed  Google Scholar 

  44. Suga, H., Torruella, G., Burger, G., Brown, M. W. & Ruiz-Trillo, I. Earliest holozoan expansion of phosphotyrosine signaling. Mol. Biol. Evol. 31, 517–528 (2014).

    Article  CAS  PubMed  Google Scholar 

  45. Manning, G., Young, S. L., Miller, W. T. & Zhai, Y. The protist, Monosiga brevicollis, has a tyrosine kinase signaling network more elaborate and diverse than found in any known metazoan. Proc. Natl Acad. Sci. USA 105, 9674–9679 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Sebé-Pedrós, A., Zheng, Y., Ruiz-Trillo, I. & Pan, D. Premetazoan origin of the Hippo signaling pathway. Cell Rep. 1, 13–20 (2012).

    Article  CAS  PubMed  Google Scholar 

  47. Sebé-Pedrós, A., de Mendoza, A., Lang, B. F., Degnan, B. M. & Ruiz-Trillo, I. Unexpected repertoire of metazoan transcription factors in the unicellular holozoan Capsaspora owczarzaki. Mol. Biol. Evol. 28, 1241–1254 (2011).

    Article  CAS  PubMed  Google Scholar 

  48. Sebé-Pedrós, A. et al. Early evolution of the T-box transcription factor family. Proc. Natl Acad. Sci. USA 110, 16050–16055 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Sebé-Pedrós, A. & de Mendoza, A. in Evolutionary Transitions to Multicellular Life Vol. 2 (eds Ruiz-Trillo, I. & Nedelcu, A. M.) 379–394 (Springer, 2015).

    Google Scholar 

  50. Fairclough, S., Dayel, M. & King, N. Multicellular development in a choanoflagellate. Curr. Biol. 20, 875–876 (2010).

    Article  CAS  Google Scholar 

  51. Dayel, M. J. et al. Cell differentiation and morphogenesis in the colony-forming choanoflagellate Salpingoeca rosetta. Dev. Biol. 357, 73–82 (2011). References 37, 50 and 51 describe for the first time in detail the life cycle of a choanoflagellate species and the associated transcriptional regulation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Alegado, R. A. et al. A bacterial sulfonolipid triggers multicellular development in the closest living relatives of animals. eLife 1, e00013 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Levin, T. C. & King, N. Evidence for sex and recombination in the choanoflagellate Salpingoeca rosetta. Curr. Biol. 23, 2176–2180 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Levin, T. C., Greaney, A. J., Wetzel, L. & King, N. The rosetteless gene controls development in the choanoflagellate S. rosetta. eLife 3, e04070 (2014). This is a careful study that, through a forward-genetics screen, provides the first direct evidence of the function of a gene (which encodes a C-type lectin) in a unicellular holozoan.

    Article  CAS  PubMed Central  Google Scholar 

  55. Abedin, M. & King, N. The premetazoan ancestry of cadherins. Science 319, 946–948 (2008).

    Article  CAS  PubMed  Google Scholar 

  56. Suga, H. & Ruiz-Trillo, I. Development of ichthyosporeans sheds light on the origin of metazoan multicellularity. Dev. Biol. 377, 284–292 (2013). This is the first report of the genetic transformation of a unicellular holozoan. It also provides a detailed description of the life cycle of an ichthyosporean species, for which the associated transcriptional regulation is described in reference 38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Sebé-Pedrós, A. et al. Regulated aggregative multicellularity in a close unicellular relative of Metazoa. eLife 2, e01287 (2013). This paper provides the first description of the life cycle of a filasterean and the associated transcriptional regulation, which involves multiple genes that are related to animal multicellularity.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sebé-Pedrós, A. et al. Insights into the origin of metazoan filopodia and microvilli. Mol. Biol. Evol. 30, 2013–2023 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Sebé-Pedrós, A. et al. High-throughput proteomics reveals the unicellular roots of animal phosphosignaling and cell differentiation. Dev. Cell 39, 186–197 (2016).

    Article  CAS  PubMed  Google Scholar 

  60. Arendt, D. et al. The origin and evolution of cell types. Nat. Rev. Genet. 17, 744–757 (2016).

    Article  CAS  PubMed  Google Scholar 

  61. Davidson, E. The Regulatory Genome (Academic Press, 2006).

    Google Scholar 

  62. Aguirre, J., Ríos-Momberg, M., Hewitt, D. & Hansberg, W. Reactive oxygen species and development in microbial eukaryotes. Trends Microbiol. 13, 111–118 (2005).

    Article  CAS  PubMed  Google Scholar 

  63. Loenarz, C. et al. The hypoxia-inducible transcription factor pathway regulates oxygen sensing in the simplest animal, Trichoplax adhaerens. EMBO Rep. 12, 63–70 (2011).

    Article  CAS  PubMed  Google Scholar 

  64. Adamska, M., Degnan, B. M., Green, K. & Zwafink, C. What sponges can tell us about the evolution of developmental processes. Zoology (Jena) 114, 1–10 (2011).

    Article  Google Scholar 

  65. Najafabadi, H. S. et al. C2H2 zinc finger proteins greatly expand the human regulatory lexicon. Nat. Biotechnol. 33, 555–562 (2015).

    Article  CAS  PubMed  Google Scholar 

  66. Jolma, A. et al. DNA-binding specificities of human transcription factors. Cell 152, 327–339 (2013).

    Article  CAS  PubMed  Google Scholar 

  67. de Mendoza, A. et al. Transcription factor evolution in eukaryotes and the assembly of the regulatory toolkit in multicellular lineages. Proc. Natl Acad. Sci. USA 110, E4858–E4866 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Reinke, A. W., Baek, J., Ashenberg, O. & Keating, A. E. Networks of bZIP protein–protein interactions diversified over a billion years of evolution. Science 340, 730–734 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Stergachis, A. B. et al. Conservation of trans-acting circuitry during mammalian regulatory evolution. Nature 515, 365–370 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sebé-Pedrós, A. et al. The dynamic regulatory genome of Capsaspora and the origin of animal multicellularity. Cell 165, 1224–1237 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Young, S. L. et al. Premetazoan ancestry of the Myc–Max network. Mol. Biol. Evol. 28, 2961–2971 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Heintzman, N. D. et al. Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459, 108–112 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Rada-Iglesias, A. et al. A unique chromatin signature uncovers early developmental enhancers in humans. Nature 470, 279–283 (2011).

    Article  CAS  PubMed  Google Scholar 

  74. Corces, M. R. et al. Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution. Nat. Genet. 48, 1193–1203 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Thurman, R. E. et al. The accessible chromatin landscape of the human genome. Nature 489, 75–82 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Andersson, R. et al. An atlas of active enhancers across human cell types and tissues. Nature 507, 455–461 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Visel, A. et al. ChIP–seq accurately predicts tissue-specific activity of enhancers. Nature 457, 854–858 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Jin, F. et al. A high-resolution map of the three-dimensional chromatin interactome in human cells. Nature 503, 290–294 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Deng, W. et al. Controlling long-range genomic interactions at a native locus by targeted tethering of a looping factor. Cell 149, 1233–1244 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Shlyueva, D., Stampfel, G. & Stark, A. Transcriptional enhancers: from properties to genome-wide predictions. Nat. Rev. Genet. 15, 272–286 (2014).

    Article  CAS  PubMed  Google Scholar 

  81. Phillips-Cremins, J. E. et al. Architectural protein subclasses shape 3D organization of genomes during lineage commitment. Cell 153, 1281–1295 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Schmidt, D. et al. A CTCF-independent role for cohesin in tissue-specific transcription. Genome Res. 20, 578–588 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kvon, E. Z. et al. Genome-scale functional characterization of Drosophila developmental enhancers in vivo. Nature 512, 91–95 (2014).

    Article  CAS  PubMed  Google Scholar 

  84. Bonn, S. et al. Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development. Nat. Genet. 44, 148–156 (2012).

    Article  CAS  PubMed  Google Scholar 

  85. Schwarzer, W. & Spitz, F. The architecture of gene expression: integrating dispersed cis-regulatory modules into coherent regulatory domains. Curr. Opin. Genet. Dev. 27, 74–82 (2014).

    Article  CAS  PubMed  Google Scholar 

  86. Levine, M. Transcriptional enhancers in animal development and evolution. Curr. Biol. 20, R754–R763 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Ernst, J. et al. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473, 43–49 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Villar, D. et al. Enhancer evolution across 20 mammalian species. Cell 160, 554–566 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Irimia, M. et al. Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints. Genome Res. 22, 2356–2367 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Irimia, M., Maeso, I., Roy, S. W. & Fraser, H. B. Ancient cis-regulatory constraints and the evolution of genome architecture. Trends Genet. 29, 521–528 (2013).

    Article  CAS  PubMed  Google Scholar 

  91. Schwaiger, M. et al. Evolutionary conservation of the eumetazoan gene regulatory landscape. Genome Res. 24, 639–650 (2014). References 70 and 91 are the pioneering studies of the genome regulatory biology of unicellular Holozoa and early Metazoa, respectively. They reveal extensive conservation of epigenomic features within the animal lineages, and important differences between animals and their unicellular relatives.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Heger, P., Marin, B., Bartkuhn, M., Schierenberg, E. & Wiehe, T. The chromatin insulator CTCF and the emergence of metazoan diversity. Proc. Natl Acad. Sci. USA 109, 17507–17512 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Eagen, K. P., Lieberman Aiden, E. & Kornberg, R. D. Polycomb-mediated chromatin loops revealed by a sub-kilobase resolution chromatin interaction map. Preprint at bioRxiv http://dx.doi.org/10.1101/099804 (2017).

  94. Cubeñas-Potts, C. et al. Different enhancer classes in Drosophila bind distinct architectural proteins and mediate unique chromatin interactions and 3D architecture. Nucleic Acids Res. 45, 39–53 (2016).

    Google Scholar 

  95. Nora, E. P. et al. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485, 381–385 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Sexton, T. et al. Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148, 458–472 (2012).

    Article  CAS  PubMed  Google Scholar 

  97. Dixon, J. R. et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376–380 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Bonev, B. & Cavalli, G. Organization and function of the 3D genome. Nat. Rev. Genet. 17, 661–678 (2016).

    Article  CAS  PubMed  Google Scholar 

  99. Dixon, J. R., Gorkin, D. U. & Ren, B. Chromatin domains: the unit of chromosome organization. Mol. Cell 62, 668–680 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Tanay, A. & Cavalli, G. Chromosomal domains: epigenetic contexts and functional implications of genomic compartmentalization. Curr. Opin. Genet. Dev. 23, 197–203 (2013).

    Article  CAS  PubMed  Google Scholar 

  101. Haeckel, E. Die Gastraea-Theorie, die phylogenetische Klassifikation des Thierreichs und die Homologie der Keimblatter. Jenaische Z. Naturwiss. 8, 1–55 (in German) (1874).

    Google Scholar 

  102. Nielsen, C. Six major steps in animal evolution: are we derived sponge larvae? Evol. Dev. 10, 241–257 (2008).

    Article  PubMed  Google Scholar 

  103. Hashimshony, T., Feder, M., Levin, M., Hall, B. K. & Yanai, I. Spatiotemporal transcriptomics reveals the evolutionary history of the endoderm germ layer. Nature 519, 219–222 (2015).

    Article  CAS  PubMed  Google Scholar 

  104. Arendt, D., Benito-Gutierrez, E., Brunet, T. & Marlow, H. Gastric pouches and the mucociliary sole: setting the stage for nervous system evolution. Phil. Trans. R. Soc. B Biol. Sci. 370, 20150286 (2015).

    Article  CAS  Google Scholar 

  105. Richter, D. J. & King, N. The genomic and cellular foundations of animal origins. Annu. Rev. Genet. 47, 509–537 (2013).

    Article  PubMed  Google Scholar 

  106. Adamska, M. Sponges as models to study emergence of complex animals. Curr. Opin. Genet. Dev. 39, 21–28 (2016).

    Article  CAS  PubMed  Google Scholar 

  107. Nakanishi, N., Sogabe, S. & Degnan, B. M. Evolutionary origin of gastrulation: insights from sponge development. BMC Biol. 12, 26 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Arenas-Mena, C. The origins of developmental gene regulation. Evol. Dev. 19, 96–107 (2017).

    Article  PubMed  Google Scholar 

  109. Arendt, D. The evolution of cell types in animals: emerging principles from molecular studies. Nat. Rev. Genet. 9, 868–882 (2008).

    Article  CAS  PubMed  Google Scholar 

  110. Achim, K. & Arendt, D. Structural evolution of cell types by step-wise assembly of cellular modules. Curr. Opin. Genet. Dev. 27, 102–108 (2014).

    Article  CAS  PubMed  Google Scholar 

  111. Schwartzman, O. & Tanay, A. Single-cell epigenomics: techniques and emerging applications. Nat. Rev. Genet. 16, 716–726 (2015).

    Article  CAS  PubMed  Google Scholar 

  112. Tanay, A. & Regev, A. Scaling single-cell genomics from phenomenology to mechanism. Nature 541, 331–338 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Neph, S. et al. An expansive human regulatory lexicon encoded in transcription factor footprints. Nature 489, 83–90 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Newman, S. A. Physico-genetic determinants in the evolution of development. Science 338, 217–219 (2012).

    Article  CAS  PubMed  Google Scholar 

  115. Mshigeni, K. & Lorri, W. Spore germination and early stages of development in Hypnea musciformis (Rhodophyta, Gigartinales). Mar. Biol. 42, 161–164 (1977).

    Article  Google Scholar 

  116. Bouget, F. Y., Berger, F. & Brownlee, C. Position dependent control of cell fate in the Fucus embryo: role of intercellular communication. Development 125, 1999–2008 (1998).

    CAS  PubMed  Google Scholar 

  117. Xie, X., Wang, G., Pan, G. & Gao, S. Variations in morphology and PSII photosynthetic capabilities during the early development of tetraspores of Gracilaria vermiculophylla (Ohmi) Papenfuss (Gracilariales, Rhodophyta). BMC Dev. Biol. 10, 43 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. El Albani, A. et al. Large colonial organisms with coordinated growth in oxygenated environments 2.1 Gyr ago. Science 466, 100–104 (2010).

    CAS  Google Scholar 

  119. Butterfield, N. J. Modes of pre-Ediacaran multicellularity. Precambrian Res. 173, 201–211 (2009).

    Article  CAS  Google Scholar 

  120. Becker, B. Snow ball earth and the split of Streptophyta and Chlorophyta. Trends Plant Sci. 18, 180–183 (2013).

    Article  CAS  PubMed  Google Scholar 

  121. Laurin-Lemay, S., Brinkmann, H. & Philippe, H. Origin of land plants revisited in the light of sequence contamination and missing data. Curr. Biol. 22, R593–R594 (2012).

    Article  CAS  PubMed  Google Scholar 

  122. Love, G. D. et al. Fossil steroids record the appearance of Demospongiae during the Cryogenian period. Nature 457, 718–721 (2009).

    Article  CAS  PubMed  Google Scholar 

  123. Maloof, A. C. et al. Possible animal-body fossils in pre-Marinoan limestones from South Australia. Nat. Geosci. 3, 653–659 (2010).

    Article  CAS  Google Scholar 

  124. Erwin, D. H. et al. The Cambrian conundrum: early divergence and later ecological success in the early history of animals. Science 3, 1091–1097 (2011).

    Article  CAS  Google Scholar 

  125. Sanderson, M. Molecular data from 27 proteins do not support a Precambrian origin of land plants. Am. J. Bot. 90, 954–956 (2003).

    Article  CAS  PubMed  Google Scholar 

  126. Taylor, J. W. & Berbee, M. L. Dating divergences in the Fungal Tree of Life: review and new analyses. Mycologia 98, 838–849 (2006).

    Article  PubMed  Google Scholar 

  127. Silberfeld, T. et al. A multi-locus time-calibrated phylogeny of the brown algae (Heterokonta, Ochrophyta, Phaeophyceae): investigating the evolutionary nature of the 'brown algal crown radiation'. Mol. Phylogenet. Evol. 56, 659–674 (2010).

    Article  CAS  PubMed  Google Scholar 

  128. Abedin, M. & King, N. Diverse evolutionary paths to cell adhesion. Trends Cell Biol. 20, 734–742 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Niklas, K. J. The evolutionary-developmental origins of multicellularity. Am. J. Bot. 101, 6–25 (2014).

    Article  CAS  PubMed  Google Scholar 

  130. Burki, F., Okamoto, N., Pombert, J.-F. & Keeling, P. J. The evolutionary history of haptophytes and cryptophytes: phylogenomic evidence for separate origins. Proc. Biol. Sci. 279, 2246–2254 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  131. Burki, F. The eukaryotic tree of life from a global phylogenomic perspective. Cold Spring Harb. Perspect. Biol. 6, a016147 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Derelle, R., Lopez-Garcia, P., Timpano, H. & Moreira, D. A phylogenomic framework to study the diversity and evolution of stramenopiles (= heterokonts). Mol. Biol. Evol. 33, 2890–2898 (2016).

    Article  CAS  PubMed  Google Scholar 

  133. He, D., Sierra, R., Pawlowski, J. & Baldauf, S. L. Reducing long-branch effects in multi-protein data uncovers a close relationship between Alveolata and Rhizaria. Mol. Phylogenet. Evol. 101, 1–7 (2016).

    Article  CAS  PubMed  Google Scholar 

  134. Sierra, R. et al. Deep relationships of Rhizaria revealed by phylogenomics: a farewell to Haeckel's Radiolaria. Mol. Phylogenet. Evol. 67, 53–59 (2012).

    Article  PubMed  Google Scholar 

  135. Zhao, S. et al. Collodictyon — an ancient lineage in the tree of eukaryotes. Mol. Biol. Evol. 29, 1557–1568 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Derelle, R. & Lang, B. F. Rooting the eukaryotic tree with mitochondrial and bacterial proteins. Mol. Biol. Evol. 29, 1277–1289 (2012).

    Article  CAS  PubMed  Google Scholar 

  137. Brown, M. W. et al. Phylogenomics demonstrates that breviate flagellates are related to opisthokonts and apusomonads. Proc. Biol. Sci. 280, 20131755 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Finet, C., Timme, R. E., Delwiche, C. F. & Marlétaz, F. Multigene phylogeny of the green lineage reveals the origin and diversification of land plants. Curr. Biol. 20, 2217–2222 (2010).

    Article  CAS  PubMed  Google Scholar 

  139. Peterson, K. J., Cotton, J. A., Gehling, J. G. & Pisani, D. The Ediacaran emergence of bilaterians: congruence between the genetic and the geological fossil records. Phil. Trans. R. Soc. 363, 1435–1443 (2008).

    Article  Google Scholar 

  140. Whelan, N. V., Kocot, K. M., Moroz, L. L. & Halanych, K. M. Error, signal, and the placement of Ctenophora sister to all other animals. Proc. Natl Acad. Sci. USA 112, 5773–5778 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Simion, P. et al. A large and consistent phylogenomic dataset supports sponges as the sister group to all other animals. Curr Biol. 27, 958–967 (2017).

    Article  CAS  PubMed  Google Scholar 

  142. Fernandez-Valverde, S. L., Calcino, A. D. & Degnan, B. M. Deep developmental transcriptome sequencing uncovers numerous new genes and enhances gene annotation in the sponge Amphimedon queenslandica. BMC Genomics 16, 387 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Dunham, I. et al. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012).

    Article  CAS  Google Scholar 

  144. Moran, Y. et al. Cnidarian microRNAs frequently regulate targets by cleavage. Genome Res. 24, 651–663 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Grimson, A. et al. Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals. Nature 455, 1193–1197 (2008).

    Article  CAS  PubMed  Google Scholar 

  146. Cabili, M. N. et al. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 25, 1915–1927 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Young, R. S. et al. Identification and properties of 1,119 candidate lincRNA loci in the Drosophila melanogaster genome. Genome Biol. Evol. 4, 427–442 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Xie, C. et al. NONCODEv4: exploring the world of long non-coding RNA genes. Nucleic Acids Res. 42, D98–D103 (2014).

    Article  CAS  PubMed  Google Scholar 

  149. Lee, K. et al. Genetic landscape of open chromatin in yeast. PLoS Genet. 9, e1003229 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Thomas, S. et al. Dynamic reprogramming of chromatin accessibility during Drosophila embryo development. Genome Biol. 12, R43 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Davie, K. et al. Discovery of transcription factors and regulatory regions driving in vivo tumor development by ATAC-seq and FAIRE–seq open chromatin profiling. PLOS Genet. 11, e1004994 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank X. Grau-Bové and D. Lara-Astiaso for critical comments on the manuscript, and G. Torruella and A. de Mendoza for discussion and ideas. A.S.-P. is supported by a European Molecular Biology Organization Long-Term Fellowship (ALTF 841-2014). Research by B.M.D. is supported by an Australian Research Council grant. Research by I.R.-T. is supported by an Institució Catalana de Recerca i Estudis Avançats (ICREA) contract, a European Research Council Starting Grant (ERC-2007-StG-206883), a European Research Council Consolidator Grant (ERC-2012-Co -616960) grant, and a grant (BFU2014-57779-P) from Ministerio de Economía y Competitividad (MINECO); his latest research is co-funded by the European Regional Development Fund (fondos FEDER). I.R-T. also acknowledges financial support from Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement de la Generalitat de Catalunya (project 2014 SGR 619).

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Authors and Affiliations

  1. Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Herzl Street 234, 7610001, Rehovot, Israel

    Arnau Sebé-Pedrós

  2. School of Biological Sciences, University of Queensland, Brisbane, 4072, QLD, Australia

    Bernard M. Degnan

  3. Institut de Biologia Evolutiva (Consejo Superior de Investigaciones Científicas–Universitat Pompeu Fabra), Passeig Marítim de la Barceloneta 37–49, 08003, Barcelona, Spain

    Iñaki Ruiz-Trillo

  4. ICREA, Pg Lluís Companys 23, 08010, Barcelona, Spain

    Iñaki Ruiz-Trillo

  5. Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Avinguda Diagonal 643, 08028, Barcelona, Spain

    Iñaki Ruiz-Trillo

Authors
  1. Arnau Sebé-Pedrós
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Correspondence to Arnau Sebé-Pedrós or Iñaki Ruiz-Trillo.

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PowerPoint slides

Glossary

Protist

An informal name that is given to eukaryotes (usually unicellular eukaryotes) that are not included in the fungal, animal or plant lineages. Protists do not form a monophyletic clade.

Bilaterian animals

A monophyletic group that is defined by bilateral symmetry of the body plan and three germ layers, and that comprises most animal phyla.

Choanocyte

A specialized filter-feeding cell type that is characteristic of sponges. The basic cell structure, with a central flagellum surrounded by a microvilli collar, to some extent resembles that of choanoflagellate cells.

Filopodia

Thin, actin-based cellular projections that are used in environmental sensing and cell motility.

Metabarcoding

Analysis of species or lineage diversity in pooled environmental samples by sequencing of a standardized, common region of DNA, usually the gene encoding the 18S ribosomal RNA.

Coenocyte

A multinucleated cell resulting from successive nuclear divisions (karyokinesis) without associated cytokinesis.

Orthologues

Genes in different species that are descended from a common ancestral gene through a speciation divergence event.

Effector gene

A gene that is related to structural and metabolic cellular functions (for example, enzymes or cytoskeletal proteins), as opposed to a regulatory gene.

Cis-regulatory element

A genomic segment that regulates the transcription of (usually neighbouring) genes on the same chromosome.

Chromatin looping

Physical folding of the chromatin nucleoprotein fibre. It is often associated with regulatory events that involve physical proximity between distal enhancer elements and gene promoters.

Microsyntenic

Describes small genomic regions in which the physical colocalization of loci is conserved between different species.

Chromatin states

Unique combinations of histone post-translational modifications and chromatin-associated proteins that define different biochemical activities of the genome.

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Sebé-Pedrós, A., Degnan, B. & Ruiz-Trillo, I. The origin of Metazoa: a unicellular perspective. Nat Rev Genet 18, 498–512 (2017). https://doi.org/10.1038/nrg.2017.21

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