Enormous diversity of heterotrimeric complexes can be assembled from a limited PI-3065 repertoire of G protein subunits which are then activated by different receptors. Most receptors also are able to activate more than one type of G protein. Moreover, several Gbc complexes can interact with the same Ga suggesting that differential expression or subcellular localization are important in the regulation of downstream signaling. Ciona intestinalis is a Toceranib protochordate belonging to the ascidian class of chordates that diverged from the vertebrate lineage about 520 million years ago. An out-group to the vertebrates, this ascidian has the smallest genome of any experimentally manipulable chordate. A translucent morphology, availability of developmental mutants, quickly spawning embryos, established transgenic, morpholino-based gene knockdown, in situhybridization experimental procedures and extensive EST data are some of the many advantages that make Ciona an excellent model organism to study developmental and evolutionary biology of the vertebrate-invertebrate split. Moreover, Ciona possesses organ systems that are homologous to vertebrate heart, thyroid, blood, digestive and neural complex systems. In an earlier study, a genome wide survey of the repertoire of GPCRs in Ciona reported the presence of 169 putative receptors. A comparative analysis of the repertoire revealed a high level of orthology with that of human GPCRs. Here we extend the previous study and report the identification of the repertoire of the heterotrimeric G proteins and the RGS proteins in Ciona and present a comparative analysis with that in human. The analyses could provide insights into the origin and evolution of the GPCR signaling system in a protochordate and its further diversification into the vertebrate lineage. Our results thus could serve as a basis for carrying out experimental studies to address functional and regulatory aspects of GPCR mediated signaling. The repertoire of human RGS family includes at least 37 members that are broadly classified into eight subfamilies.