Heterotrimeric G proteins are key molecules regulating cellular responses to extracellular stimuli, and are composed of α, β and γ subunits. All α subunits in vertebrates belong to four major classes, Gs, Gi, Gq and G12, which are conserved throughout the animal kingdom. Unexpectedly, now a fifth class of Gα protein, Gv, has been discovered. Gv is conserved across the animal kingdom and present in vertebrates, arthropods, mollusks, annelids and even sponges. Presumably, Gv has been missed so far, because it has been lost in many lineages in the major model organisms such as nematodes, fruit fly and mammals. On the other hand, gene gains are also observed for Gv, with at least two independent gene duplications, one in sponges and the other in the teleost lineage. Such frequent gene gains and losses fit to a birth-and-death mode of evolution, which is unusual for a well-conserved and ancient gene family like the Gα proteins. The discovery of a novel major class of Gα proteins provides new insights in the evolution of the Gα protein family and opens new possibilities in G protein signaling research.
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