THE MULTIGENE FAMILIES OF GUANINE-NUCLEOTIDE-BINDING PROTEINS - EVOLUTIONARY AND COMPUTATIONAL ANALYSIS

The multigene families of guanine nucleotide-binding proteins (G prote ins) regulate numerous cell functions including transmembrane signal t ransduction and oncogenesis. These gene families have been intensively studied in a wide variety of eukaryotic systems, resulting in rich su bstrate for computational analysis in an evolutionary and developmenta l context. Signal transducing GTP-binding proteins are often considere d in three general categories: (1) the heterotrimeric G proteins e.g. G(s) and G(i), the stimulatory and inhibitory regulators of adenylyl c yclase that transmit signals from transmembrane receptors to intracell ular effectors and contain distinctive 40 kDa alpha subunits: (2) the family of smaller (approximately 20 kDa) monomeric proteins related to the oncogene product ras, including rab, rac, ypt, and sec4; and (3) the ADP-ribosylation factors (ARFs). Analysis of these multigene G pro tein families present instructive examples of the increasing sophistic ation in computational sequence analysis that will be necessary to kee p pace with the expanding number of gene families that will be charact erized in the course of the Human Genome Project. Convenient computati onal analysis is critical to multiple phases of the current work: (1) to design PCR primers for effective cross-species amplification; (2) t o analyze the gene structures of sequence obtained; (3) to identify fu nctional domains in protein coding exons and in untranslated regions ( UTRs); and (4) to discern evolutionary relationships between cloned se quences.