MOLECULAR EVOLUTION OF GPCRS: Kisspeptin/kisspeptin receptors

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   Figure 1

   Kiss gene transcription, translation, and post-translational processing. CDS, coding sequence; SP, signal peptide. The minimal bioactive sequence, composed by ten amino acids, Kp(10), is represented by a hatched square.
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   Figure 2

   (A) Amino acid sequences of various vertebrate kisspeptin-10 (Kp10). Amino acids are colored according to their physicochemical properties. (B) Schematic helical top view of the human biological active kisspeptin Kp1(10). Conserved residues in Kp(10) vertebrate species are circled. Diagram reworked from http://bioweb2.pasteur.fr/docs/EMBOSS/pepwheel.html.
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   Figure 3

   Current status and proposed evolutionary history of Kiss genes among deuterostomes. The common names of representative species of each lineage are given at the extremity of the final branches, together with the symbols for the Kiss genes they possess. These hypotheses assume the presence of a single Kiss gene ancestor in early chordates leading to four Kiss paralogous genes after the 1R and 2R in early vertebrates. Multiple pseudogenization processes and gene loss events shaped the current vertebrate Kiss gene diversity.
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   Figure 4

   Proposed origin and evolution of vertebrate Kiss tetra-paralogons. The paralogous genes of several identified families, illustrated here by NAV, KCNC, and PLEKHA, delineate a tetra-paralogon in vertebrate (such as spotted gar and human) genomes that originated from 1R and 2R. In humans, a pseudo-Kiss2 gene has been predicted on chromosome 10 (Osugi et al. 2013), indicating a translocation and pseudogenization. A duplicated tetra-paralogon is present in teleost (such as zebrafish) genomes, as a result of the 3R. Due to multiple Kiss gene loss, there is no effect of the 3R on the number of Kiss genes in the extant teleost species.
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   Figure 5

   Current status and proposed evolutionary history of Kisspeptin receptor (KissR) genes among deuterostomes. The common names of representative species of each lineage are given at the extremity of the final branches, together with the symbols for the KissR genes they possess. These hypotheses assume the presence of a single KissR gene ancestor in early chordates leading to four KissR paralogous genes after the 1R and 2R in early vertebrates. Multiple pseudogenization processes and gene loss events shaped the current vertebrate KissR gene diversity.
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   Figure 6

   Proposed origin and evolution of vertebrate KissR tetra-paralogons. The paralogous genes of several identified families, illustrated here by PALM, PTBP, and LPAR, delineate a tetra-paralogon in vertebrate (such as spotted gar and human) genomes that originated from 1R and 2R. A duplicated tetra-paralogon is present in teleost (such as zebrafish) genomes, as a result of the 3R. Due to multiple KissR gene loss, there is no effect of the 3R on the number of kissr genes in the extant teleost species.
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   Figure 7

   Schematic representation of the Kiss/KissR signaling pathways. Kisspeptin (K) is translocated along the phospholipid bilayer toward its receptor (KissR), a seven-transmembrane-domain G-protein-coupled receptor. The main signaling pathway involves Gq protein and activation of phospholipase C (PLC). PLC is a crossroads of two activation pathways: one leading to MAP kinase phosphorylation (MAPKP) via protein kinase C (PKC) and the other leading to endoplasmic reticulum (ER) calcium mobilization via phosphatidylinositol-3-kinase (IP3) activation. In teleosts, which possess more than one KissR, the adenylate cylcase (AC)/ protein kinase A (PKA) signaling pathway can also be activated, leading to a rise in extracellular Ca^{2 +} influx.

• © 2014 Society for Endocrinology