Comments on the evolution of TRPV6

It is well known that not all biological findings derived from animals can be directly applied to humans. The TRPV6 protein may serve as an example which highlights these inter-species differences as an example of parallel evolutionary pathways. TRPV6 (and TRPV5) belong to a family of ion channels from the transient receptor potential group but are selectively permeable for Ca2+ , in contrast to other members of the family. Sequences with recognizable similarity to TRPV6 can already be found in archaebacteria. These ancient sequences show clear similarity to the ion-conducting pore of TRPV6. Over the course of evolution, the duplication of the TRPV6 gene gave rise to TRPV5. Duplications of the complete genome as well as subsequent loss of genetic material have led to a variety of different TRPV5/6 combinations. In addition, there is an N-terminal extension of the protein in placental animals. This extension causes translation of TRPV6 to be initiated from an ACG codon. Inactivation of one TRPV6 allele can be correlated with alcohol-independent pancreatitis in humans while inactivation of both alleles leads to skeletal dysplasia of newborn babies. The latter effect is not observed in mice, implying that the effects due to perturbations in TRPV6 levels are much more pronounced in humans. (C) 2021 Elsevier GmbH. All rights reserved.

Automated summary

TRPV6 and TRPV5 are part of an ion channel family that selectively permeable for Ca2+ as part of the transient receptor potential group. The duplication of the TRPV6 gene gave rise to TRPV5 and a variety of different TRPV5/6 combinations have evolved over time. Effects due to perturbations in TRPV6 levels are much more pronounced in humans.