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Fig. 17 Model of vertebrate two-pore domain potassium (K2P) gene evolution. Based on our phylogenetic and syntenic analysis, we proposed this model for this two-pore potassium channel. (A) In invertebrates, the six subtypes of K2P have already evolved. At least there is one gene for each subtype. Some species, such as lancelets and tunicates, may get multiple copies of K2P genes through independent duplication events. (B) Two consecutive whole-genome duplications (WGDs) happened at the dawn of vertebrates. Then, all the K2P genes were doubled twice in the vertebrate ancestor. Some of the genes were lost after the two rounds of WGDs (2R). Lost genes are in gray boxes. It is worth noting that the KCNK19 and KCNK20 were lost in tetrapods. (C) The 3rd round teleost-specific WGD (3R) further reshaped the gene numbers in this group of animals. Some gene duplicates were maintained, whereas others were lost. In zebrafish, the kcnk15a and kcnk16 were lost independently (gray-colored boxes) but retained in other teleost fish. The horizontal black arrows indicate the WGD events. TALK, TWIK-related alkaline pH-activated K+; TASK, TWIK-related acid-sensitive K+; THIK, tandem pore domain halothane-inhibited K+; TREK, TWIK-related K+; TRESK, TWIK-related spinal cord K+; TWIK, tandem of pore domains in a weak inward rectifying K+.