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Emergence of a Thrombospondin Superfamily at the Origin of Metazoans

Research output: Contribution to journalArticle

Original languageEnglish
Article numbermsz060
Pages (from-to)1220-1238
Number of pages19
JournalMolecular Biology and Evolution
Issue number6
Early online date13 Mar 2019
DateAccepted/In press - 6 Mar 2019
DateE-pub ahead of print - 13 Mar 2019
DatePublished (current) - 1 Jun 2019


Extracellular matrix (ECM) is considered central to the evolution of metazoan multicellularity, however the repertoire of ECM proteins in non-bilaterians remains unclear. Thrombospondins (TSPs) are known to be well-conserved from cnidarians to vertebrates, yet to date have been considered a unique family, principally studied for matricellular functions in vertebrates. Through searches utilizing the highlyconserved C-terminal region of TSPs we identify undisclosed new families of thrombospondin-related proteins in metazoans, designated mega-thrombospondin, sushi-thrombospondin and poriferan-thrombospondin, each with a distinctive phylogenetic distribution. These proteins share the TSP C-terminal region domain architecture, as determined by domain composition and analysis of molecular models against known structures. Mega-thrombospondins, the only form identified in ctenophores, are typically >2700aa and are also characterized by N-terminal leucine-rich repeats and central cadherin/immunoglobulin domains. In cnidarians, which have a well-defined ECM, Mega-TSP was expressed throughout embryogenesis in Nematostella vectensis, with dynamic endodermal expression in larvae and primary polyps and widespread ectodermal expression in adult N. vectensis and Hydra magnipapillata polyps. Hydra Mega-TSP was also expressed during regeneration and siRNA-silencing of Mega-TSP in Hydra caused specific blockade of head regeneration. Molecular phylogenetic analyses based on the conserved TSP C-terminal region identified each of the TSP-related groups to form clades distinct from the canonical TSPs. We discuss models for the evolution of the newly-defined TSP superfamily by gene duplications, radiation and gene losses from a debut in the last metazoan common ancestor. Together, the data provide new insight into the evolution of ECM and tissue organization in metazoans.

Additional information

© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

    Research areas

  • multicellularity, metazoa, extracellular matrix, regeneration, protein domains

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