Convergent Evolution of Two Dopamine Receptor Genes: Repeated Evolution of Exon 6 Skipping in Drd2, and Repeated Deletion of Exon 6 in Drd3.

ABSTRACT: Drd2 dopamine receptor mRNAs are alternatively spliced in rodents and primates by skipping exon 6 to produce the D2_S protein, or including exon 6 to produce the D2_L protein. These protein isoforms have differing roles in pre- vs. post-synaptic signaling, cytoplasmic vesicle processing, and calcium-mediated desensitization. Genetic alteration in the D2_S/D2_L ratio affects human behavior and cognition at multiple levels, including working memory. Here we show that exon 6 originated early in vertebrate evolution, after the duplication and divergence of D2 and D4 dopamine receptor genes, but before the duplication and divergence of D2 and D3 dopamine receptor genes. Exon 6 encodes a relatively conserved sequence in the third cytoplasmic loop of the D2

SUBMITTER: Peglar MT 

PROVIDER: S-EPMC12198306 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature