title: Evolution of multiple phosphodiesterase isoforms in stickleback involved in cAMP signal transduction pathway.
abstract: BACKGROUND
  Duplicate genes are considered to have evolved through the partitioning of ancestral functions among duplicates (subfunctionalization) and/or the acquisition of novel functions from a beneficial mutation (neofunctionalization). Additionally, an increase in gene dosage resulting from duplication may also confer an advantageous effect, as has been suggested for histone, tRNA, and rRNA genes. Currently, there is little understanding of the effect of increased gene dosage on subcellular networks like signal transduction pathways. Addressing this issue may provide further insights into the evolution by gene duplication.
  
  
  RESULTS
  We analyzed the evolution of multiple stickleback phosphodiesterase (PDE, EC: 3.1.4.17) 1C genes involved in the cyclic nucleotide signaling pathway. Stickleback has 8-9 copies of this gene, whereas only one or two loci exist in other model vertebrates. Our phylogenetic and synteny analyses suggested that the multiple PDE1C genes in stickleback were generated by repeated duplications of >100-kbp chromosome segments. Sequence evolution analysis did not provide strong evidence for neofunctionalization in the coding sequences of stickleback PDE1C isoforms. On the other hand, gene expression analysis suggested that the derived isoforms acquired expression in new organs, implying their neofunctionalization in terms of expression patterns. In addition, at least seven isoforms of the stickleback PDE1C were co-expressed with olfactory-type G-proteins in the nose, suggesting that PDE1C dosage is increased in the stickleback olfactory transduction (OT) pathway. In silico simulations of OT implied that the increased PDE1C dosage extends the longevity of the depolarization signals of the olfactory receptor neuron.
  
  
  CONCLUSIONS
  The predicted effect of the increase in PDE1C products on the OT pathway may play an important role in stickleback behavior and ecology. However, this possibility should be empirically examined. Our analyses imply that an increase in gene product sometimes has a significant, yet unexpected, effect on the functions of subcellular networks.
authors.affiliation: Division of Molecular Marine Biology, Ocean Research Institute, The University of Tokyo, Tokyo, Japan. ysato@ori.u-tokyo.ac.jp
authors.forename: Yukuto
authors.initials: Y
authors.lastname: Sato
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Hashiguchi
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Nishida
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001499:Bayes Theorem; D000242:Cyclic AMP / Q000378:metabolism*; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D007527:Isoenzymes / Q000235:genetics; D016013:Likelihood Functions; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010727:Phosphoric Diester Hydrolases / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics*; D023701:Smegmamorpha / Q000378:metabolism*; D012903:Smell / Q000502:physiology; D026801:Synteny / Q000235:genetics
chemical_list: D007527:Isoenzymes; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases