Modularity in protein evolution: modular organization and de novo domain evolution in mollusc metallothioneins.

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 Molluscs. We have shown that most molluscan MTs are bi-modular 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 γ domain. Our results have revealed a modular organization of mollusc 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.