A functional two-pore-domain K + channel from a large DNA virus

The evolutionary history of proteins helps to understand their structure/function correlates and suggests on how functional complexity evolved from primitive precursors. In the superfamily of K + channels, functional features of complex eukaryotic inward rectifier (Kir) channels and voltage-dependent (Kv) channels could be understood in terms of an increase in structural complexity of their prokaryotic precursors. K2P channels, which are made from tandem repeats of two pore domains, are not found in prokaryotes and their evolutionary origin is still unknown. In searching for primitive K2P channel precursors, we screened the genomes of nucleocytoplasmic large DNA viruses (NCLDVs) for genes coding for K2P channels. This was motivated by two reasons: NCLDVs are already known for coding primitive Kir type channels, and they play important roles in the evolution of eukaryotes. Here, we report that the NCLDV Pyramimonas orientalis virus codes for K2P-like K + channels. With only 178 amino acids and no cytosolic domains, this Kpov protein is much smaller than any eukaryotic K2P channel, but still functional as K + selective channel in lipid bilayers. Phylogenetic analysis suggests that Kpov is not the product of molecular piracy from the host but may result from fusion of primitive viral K + channel pore domains.