Modularity in Protein Evolution: Modular Organization and de Novo Domain Evolution in Mollusk Metallothioneins

Sara Calatayud, Mario Garcia-Risco, Veronika Pedrini-Martha, Douglas J. Eernisse, Reinhard Dallinger, Òscar Palacios, Mercè Capdevila, Ricard Albalat*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)


Metallothioneins (MTs) are proteins devoted to the control of metal homeostasis and detoxification, and therefore, MTs have been crucial for the adaptation of the living beings to variable situations of metal bioavailability. The evolution of MTs is, however, not yet fully understood, and to provide new insights into it, we have investigated the MTs in the diverse classes of Mollusks. We have shown that most molluskan MTs are bimodular proteins that combine six domains - α, β1, β2, β3, γ, and δ- in a lineage-specific manner. We have functionally characterized the Neritimorpha β3β1 and the Patellogastropoda γβ1 MTs, demonstrating the metal-binding capacity of the new γdomain. Our results have revealed a modular organization of mollusk MT, whose evolution has been impacted by duplication, loss, and de novo emergence of domains. MTs represent a paradigmatic example of modular evolution probably driven by the structural and functional requirements of metal binding.

Original languageEnglish
Pages (from-to)424-436
Number of pages13
JournalMolecular Biology and Evolution
Issue number2
Publication statusPublished - 1 Feb 2021


  • bi- and multimodular metallothioneins
  • cysteine motifs
  • de novo evolution
  • domains
  • metal-binding capacity and preference
  • α
  • β1
  • β2
  • β3
  • γ
  • δ


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