Genes for two homologous G-protein alpha subunits map to different human chromosomes

Signal transduction across biological membranes is modulated by a family of related GTP-binding proteins termed G proteins. These G proteins have a heterotrimeric structure composed of alpha, beta, and gamma subunits. The alpha subunits of the G proteins bind GTP and appear to determine the biochemical specificity of the protein. We have recently cloned and characterized cDNA encoding two G-protein alpha subunits, alpha i and alpha h. The former is a substrate for ADP-ribosylation by pertussis toxin. The protein corresponding to alpha h has not yet been identified. These cDNAs encode proteins, which demonstrate 90% sequence identity to one another and also show marked similarity to other G proteins. The present studies were designed to determine whether the genes for these related proteins are clustered on a single human chromosome. Genomic DNA isolated from a panel of mouse-human hybrid cell lines was analyzed by hybridization to cDNAs for alpha i and alpha h. Based on the distribution patterns of alpha i and alpha h in cell hybrids, the gene for alpha i was assigned to human chromosome 7, and the gene for alpha h assigned to chromosome 12. These data suggest that the G-protein gene family may be distributed over at least two human chromosomes.