The evolution of metazoan aα-carbonic anhydrases and their roles in calcium carbonate biomineralization

Abstract

The carbonic anhydrase (CA; EC 4.2.1.1) superfamily is a class of ubiquitous metallo-enzymes that catalyse the reversible hydration of carbon dioxide. The aα-CA family, present in all metazoan clades, is a key enzyme involved in a wide range of physiological functions including pH regulation, respiration, photosynthesis, and biocalcification. This paper reviews the evolution of the aα-CA family, with an emphasis on metazoan aα-CA members involved in biocalcification. Phylogenetic analyses reveal a complex evolutionary history of aα-CAs, and suggest aα-CA was independently co-opted into a variety of skeleton forming roles (e.g. as a provider of HCO 3 - ions, a structural protein, a nucleation activator, etc.) in multiple metazoan lineages. This evolutionary history is most likely the result of multiple gene duplications coupled with the insertion of repetitive or non-repetitive low-complexity domains (RLCDs/LCDs). These domains, of largely unknown function, appear to be lineage-specific, and provide further support for the hypothesis of independent recruitment of aα-CAs to diverse metazoan biocalcification processes. An analysis of aα-CA sequences associated with biocalcification processes indicates that the domains involved in the activity and conformation of the active site are extremely conserved among metazoans.