Grandy D K, Zhang Y A, Bouvier C, Zhou Q Y, Johnson R A, Allen L, Buck K, Bunzow J R, Salon J, Civelli O
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University.
Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9175-9. doi: 10.1073/pnas.88.20.9175.
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 biphasic 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.
在人类基因组中鉴定出了三个与D1多巴胺受体密切相关的基因。其中一个基因没有内含子，编码一种功能性人类多巴胺受体D5，其推导的氨基酸序列与人类D1受体的氨基酸序列有49%的同一性。与人类D1多巴胺受体相比，D5受体对多巴胺表现出更高的亲和力，并且能够刺激cAMP的双相而非单相细胞内积累。另外两个基因都不能指导受体的合成。核苷酸序列分析表明，这两个基因彼此间有98%的同一性，与D5序列有95%的同一性。相对于D5序列，两者都含有插入和缺失，导致几个读框内终止密码子。翻译提前终止是这些基因即使其信息被转录却仍无法在COS-7和293细胞中产生受体的最可能解释。我们得出结论，这两个是假基因。对大鼠基因组DNA进行的印迹杂交实验表明，该物种中有一个D5基因，这些假基因可能是相对近期进化事件的结果。
