The fifth element in animal Galpha protein evolution

Abstract

Heterotrimeric G proteins are key molecules regulating cellular responses to extracellular stimuli, and are composed of alpha, beta and gamma subunits. All alpha 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 Galpha 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 Galpha proteins. The discovery of a novel major class of Galpha proteins provides new insights in the evolution of the Galpha protein family and opens new possibilities in G protein signaling research.

Keywords: GPCR; birth-and-death mode; heterotrimeric G protein; metazoan evolution; negative selection.

Figure 1

Evolution of Gv. (A) The phylogenetic tree of Gα proteins. The class Gv (red) does not cluster with any of the other four classes (Gs, light blue; Gi, blue; Gq, yellow and G12, brown) collected from human, zebrafish, fruit fly, nor any Gα proteins of nematode (orange). Plant Gα proteins (grey) are included as outgroup. Scale bar indicates amino acid substitution rate. (B) Gene gain and loss events of Gv in animal evolution. Species in red contain at least one Gv ortholog; species in black, no Gv orthologs found; blue crosses, inferred gene loss event; red circle, gene gain event.