title: Deducing the origin of soluble adenylyl cyclase, a gene lost in multiple lineages.
abstract: The family of eukaryotic adenylyl cyclases consists of a very large group of 12 transmembrane adenylyl cyclases and a very small group of soluble adenylyl cyclase (sAC). Orthologs of human sAC are present in rat Dictyostelium and bacteria but absent from the completely sequenced genomes of Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, and Saccharomyces cereviciae. sAC consists of two cyclase domains and a long approximately 1,000 amino acid C-terminal (sCKH) region. This sCKH region and one cyclase domain have been found in only four bacterial genes; the sCKH region was also detected in bacterial Lux-transcription factors and in complex bacterial and fungal kinases. The phylogenies of the kinase and cyclase domains are identical to the phylogeny of the corresponding sCKH domain, suggesting that the sCKH region fused with the other domains early during evolution in bacteria. The amino acid sequences of sAC proteins yield divergence times from the human lineage for rat and Dictyostelium that are close to the reported divergence times of many other proteins in these species. The combined results suggest that the sCKH region was fused with one cyclase domain in bacteria, and a second cyclase domain was added in bacteria or early eukaryotes. The sAC was retained in a few bacteria and throughout the entire evolution of the human lineage but lost independently from many bacteria and from the lineages of plants, yeast, worms, and flies. We conclude that within the family of adenylyl cyclases, soluble AC was poorly fixed during evolution, whereas membrane-bound AC has expanded to form the subgroups of prevailing adenylyl and guanylyl cyclases.
authors.affiliation: GBB, Department of Biochemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Roelofs
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Van Haastert
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics*; D000818:Animals; D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics; D006801:Humans; D010802:Phylogeny; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics
chemical_list: D000262:Adenylyl Cyclases