RT Journal Article SR Electronic T1 Evolutionary analyses reveal independent origins of gene repertoires and structural motifs associated to fast inactivation in calcium-selective TRPV channels JF bioRxiv FD Cold Spring Harbor Laboratory SP 564997 DO 10.1101/564997 A1 Lisandra Flores-Aldama A1 Michael W. Vandewege A1 Kattina Zavala A1 Charlotte K. Colenso A1 Wendy Gonzalez A1 Sebastian E. Brauchi A1 Juan C. Opazo YR 2019 UL http://biorxiv.org/content/early/2019/10/17/564997.abstract AB Important for calcium homeostasis, TRPV5 and TRPV6 are calcium-selective channels belonging to the transient receptor potential (TRP) gene family. In this study, we investigated the evolutionary history of these channels to add an evolutionary context to the already available physiological information. Phylogenetic analyses revealed that paralogs found in mammals, sauropsids, amphibians, and chondrichthyans, are the product of independent duplication events in the ancestor of each group. Within amniotes, we identified a traceable signature of three amino acids located at the amino-terminal intracellular region (HLH domain). The signature correlates well with both the duplication events and the phenotype of fast inactivation observed in mammalian TRPV6 channels. Electrophysiological recordings and mutagenesis suggest that calcium-induced fast inactivation represents an evolutionary innovation that emerged independently after gene duplication.