Evolution of the Rho family of ras-like GTPases in eukaryotes

GTPases of the Rho family are molecular switches that play important roles in converting and amplifying external signals into cellular effects. Originally demonstrated to control the dynamics of the F-actin cytoskeleton, Rho GTPases have been implicated in many basic cellular processes that influence cell proliferation, differentiation, motility, adhesion, survival or secretion. To elucidate the evolutionary history of the Rho family, we have analyzed over twenty species covering major eukaryotic clades from unicellular organisms to mammals, including platypus and opossum, and have reconstructed the ontogeny and the chronology of emergence of the different subfamilies. Our data establish that the 20 mammalian Rho members are structured into eight subfamilies, among which Rac is the founder of the whole family. Rho, Cdc42, RhoUV and RhoBTB subfamilies appeared before Coelomates, and RhoJQ, RhoDF and Rnd emerged in Chordates. In Vertebrates, gene duplications and retrotranspositions increased the size of each chordate Rho subfamily, while RhoH, the last subfamily, arose probably by horizontal gene transfer. Rac1b, a Rac1 isoform generated by alternative splicing, emerged in amniotes, and RhoD, only in therians. Analysis of Rho mRNA expression patterns in mouse tissues shows that recent subfamilies have tissue-specific specific and low level expression, which supports their implication only in narrow time windows or in differentiated metabolic functions. These findings give a comprehensive view of the evolutionary canvas of the Rho family and provide guides for futur