Identification of duplicated fourth {alpha}2-adrenergic receptor subtype by cloning and mapping of five receptor genes in zebrafish

Ruuskanen, J., Xhaard, H., Marjamäki, A., Salaneck, E., Salminen, T., Yan, Y.-L., Postlethwait, J.H., Johnson, M.S., Larhammar, D., and Scheinin, M.
Mol. Biol. Evol.   10: 14-28 (Journal)
Registered Authors
Larhammar, Dan, Postlethwait, John H., Ruuskanen, Jori, Salaneck, Erik, Yan, Yi-Lin
genome duplication, synteny, fish, 2-adrenergic receptor
MeSH Terms
  • Animals
  • Base Sequence
  • Blotting, Southern
  • Chromosome Mapping
  • Evolution, Molecular*
  • Gene Duplication*
  • Gene Library
  • Molecular Sequence Data
  • Phylogeny*
  • Polymerase Chain Reaction
  • Receptors, Adrenergic, alpha-2/genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Sequence Homology
  • Zebrafish/genetics*
12949138 Full text @ Mol. Biol. Evol.
The alpha2-adrenergic receptors (alpha2-ARs) belong to the large family of rhodopsin-like G-protein coupled receptors that share a common structure of 7 transmembrane (TM) alpha-helices. The aims of this study were (1) to determine the number of alpha2-AR genes in a teleost fish, the zebrafish (Danio rerio); (2) to study the gene duplication events that generated the alpha2-AR subtypes; and (3) to study changes in receptor structure that have occurred since the divergence of the mammalian and fish lineages. Here we report the cloning and chromosomal mapping of fish orthologs for all three mammalian alpha2-ARs. In addition, we identified a fourth alpha2-AR subtype with two duplicates in zebrafish. Chromosomal mapping showed that the zebrafish alpha2-AR genes are located within conserved chromosomal segments, consistent with the origin of the four alpha2-AR subtypes by two rounds of chromosome or block duplication prior to the divergence of the ray fin fish and tetrapod lineages. Thus, the fourth subtype has apparently been present in the common ancestor of vertebrates, but has been deleted or is yet to be identified in mammals. The overall percentage identity between the fish and mammalian orthologs is 53-67%, and in the TM regions 80-87%. These values are clearly lower than what is observed between mammalian orthologs. Still, all of the residues thought to be important for alpha2-adrenergic ligand binding are conserved across species and subtypes, and even the most divergent regions of the fish receptors show clear 'molecular fingerprints' typical for orthologs of a given subtype.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes