Ryanodine receptor calcium release channels: An evolutionary perspective

Ryanodine receptors (RyRs), along with the related inositol 1,4,5-trisphosphate receptors (IP ₃Rs), mediate the release of Ca ²⁺ from intracellular organelles of eukaryotes. As discussed in other chapters, such increases in intracellular Ca ²⁺ levels act a fundamental second messenger, regulating a diverse array of cellular processes. For over two decades, it has been reported that vertebrates express multiple RYR genes, whereas non-vertebrate multicellular organisms possess a single homologue within their genomes. Recently, the existence of RyR-like channels in unicellular organisms has also been reported. This chapter exploits recent expansions in available genome data to generate an overview of the expression of RyR-like genes in organisms representing a broad range of viral, archaeal, bacterial and eukaryotic taxa. Analyses of the multidomain structures and phylogenetic relationships of these proteins has lead to a model in which, early during eukaryotic evolution, IP ₃R-like ancestral Ca ²⁺ release channels were converted to RyR proteins via the addition of promiscuous protein domains, possibly via horizontal gene transfer mechanisms.