Multiple human D5 dopamine receptor genes: A functional receptor and two pseudogenes

David K. Grandy, Yuan Zhang, Claudia Bouvier, Qun Yong Zhou, Robert A. Johnson, Lee Allen, Kari Buck, James R. Bunzow, John Salon, Olivier Civelli

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

Abstract

Three genes closely related to the D1 dopamine receptor were identified in the human genome. One of the genes lacks introns and encodes a functional human dopamine receptor, D5, whose deduced amino acid sequence is 49% identical to that of the human D1 receptor. Compared with the human D1 dopamine receptor, the D5 receptor displayed a higher affinity for dopamine and was able to stimulate a hiphasic rather than a monophasic intracellular accumulation of cAMP. Neither of the other two genes was able to direct the synthesis of a receptor. Nucleotide sequence analysis revealed that these two genes are 98% identical to each other and 95% identical to the D5 sequence. Relative to the D5 sequence, both contain insertions and deletions that result in several in-frame termination codons. Premature termination of translation is the most likely explanation for the failure of these genes to produce receptors in COS-7 and 293 cells even though their messages are transcribed. We conclude that the two are pseudogenes. Blot hybridization experiments performed on rat genomic DNA suggest that there is one D5 gene in this species and that the pseudogenes may be the result of a relatively recent evolutionary event.

Original languageEnglish (US)
Pages (from-to)9175-9179
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number20
DOIs
StatePublished - Oct 15 1991

Keywords

  • Adenylyl cyclase
  • Gene amplification
  • Guanine nucleotide-binding protein-coupled receptor
  • Termination codon
  • Transient expression

ASJC Scopus subject areas

  • General

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