Fractal gene losses and concomitant genesis of novel clades sculpt the metazoan Gα gene repertoire

Gα proteins are integral components of cellular signaling, with an ancient evolutionary origin. Within animals, Gα proteins have been categorized into five canonical classes: Gαs, Gαi, Gαq, Gα12, and Gαv, with few unclassified genes outside of these groups. Here we have performed comprehensive phylogenetic analyses of nearly one thousand metazoan species, focusing on two species-rich phyla, arthropods and nematodes. Our analysis reveals a fractal pattern of gene loss in all five canonical classes, with Gαs and Gαv most prone to gene loss. On the other hand, gene gains are common in all five classes, most pronounced in Gαq and Gα12. Unexpectedly, we observe the emergence of thirteen novel clades, the majority specific to single phyla (arthropods, nematodes, tardigrades) and some even specific to lower taxonomic classifications. Those new clades exhibit all G box and switch region motifs, characteristic for the five canonical classes. For all of the new clades we observe many representatives in transcriptome assemblies, validating their expression and suggesting a functional role for them. Our results show a highly dynamic evolutionary landscape for Gα proteins, including extensive gene losses and frequent gains in the five canonical classes and recurrent genesis of new clades—unexpected in such a highly conserved and ancient family of proteins with central importance in cellular signalling. Our findings advance the understanding of Gα protein evolution, and lay the foundation for deciphering the functional role of the novel Gα clades.