Convergent Evolution of Two Dopamine Receptor Genes: Repeated Evolution of Exon 6 Skipping in Drd2, and Repeated Deletion of Exon 6 in Drd3.
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| Title: | Convergent Evolution of Two Dopamine Receptor Genes: Repeated Evolution of Exon 6 Skipping in Drd2, and Repeated Deletion of Exon 6 in Drd3. |
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| Authors: | Peglar, Michael T.1,2 (AUTHOR) mtpeglar@gmail.com, Fryxell, Karl J.3 (AUTHOR) kfryxell@gmu.edu |
| Source: | Journal of Molecular Evolution. Jun2025, Vol. 93 Issue 3, p441-464. 24p. |
| Subjects: | Dopamine receptors, Convergent evolution, Tetrapods, Alternative RNA splicing, Genetic engineering |
| Abstract: | Drd2 dopamine receptor mRNAs are alternatively spliced in rodents and primates by skipping exon 6 to produce the D2S protein, or including exon 6 to produce the D2L protein. These protein isoforms have differing roles in pre- vs. post-synaptic signaling, cytoplasmic vesicle processing, and calcium-mediated desensitization. Genetic alteration in the D2S/D2L 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–D3 receptor. Its amino acid sequence is relatively short (24–33 amino acids), and is not strictly necessary for dopamine signal transduction. Exon skipping of Drd2 exon 6 was not detectable in the brains of cyclostomes, sharks, fish, relatively primitive amphibians (Xenopus, Notophthalmus), relatively primitive reptiles (turtles), relatively primitive birds (ostrich), or relatively primitive mammals (monotremes and marsupials). However, exon skipping of Drd2 exon 6 did occur at significant levels in the brains of more derived amphibians, reptiles, birds and mammals. Thus, skipping of Drd2 exon 6 arose convergently and specifically in the more derived tetrapod lineages, none of which deleted this exon. In contrast, exon 6 was convergently deleted during Drd3 evolution in an apparently random subset of the species of sharks, fish, amphibians, reptiles, birds, and mammals. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Molecular Evolution is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
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| Header | DbId: egs DbLabel: Engineering Source An: 186156870 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Convergent Evolution of Two Dopamine Receptor Genes: Repeated Evolution of Exon 6 Skipping in Drd2, and Repeated Deletion of Exon 6 in Drd3. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Peglar%2C+Michael+T%2E%22">Peglar, Michael T.</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<i> mtpeglar@gmail.com</i><br /><searchLink fieldCode="AR" term="%22Fryxell%2C+Karl+J%2E%22">Fryxell, Karl J.</searchLink><relatesTo>3</relatesTo> (AUTHOR)<i> kfryxell@gmu.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Molecular+Evolution%22">Journal of Molecular Evolution</searchLink>. Jun2025, Vol. 93 Issue 3, p441-464. 24p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Dopamine+receptors%22">Dopamine receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Convergent+evolution%22">Convergent evolution</searchLink><br /><searchLink fieldCode="DE" term="%22Tetrapods%22">Tetrapods</searchLink><br /><searchLink fieldCode="DE" term="%22Alternative+RNA+splicing%22">Alternative RNA splicing</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+engineering%22">Genetic engineering</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Drd2 dopamine receptor mRNAs are alternatively spliced in rodents and primates by skipping exon 6 to produce the D2S protein, or including exon 6 to produce the D2L protein. These protein isoforms have differing roles in pre- vs. post-synaptic signaling, cytoplasmic vesicle processing, and calcium-mediated desensitization. Genetic alteration in the D2S/D2L 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–D3 receptor. Its amino acid sequence is relatively short (24–33 amino acids), and is not strictly necessary for dopamine signal transduction. Exon skipping of Drd2 exon 6 was not detectable in the brains of cyclostomes, sharks, fish, relatively primitive amphibians (Xenopus, Notophthalmus), relatively primitive reptiles (turtles), relatively primitive birds (ostrich), or relatively primitive mammals (monotremes and marsupials). However, exon skipping of Drd2 exon 6 did occur at significant levels in the brains of more derived amphibians, reptiles, birds and mammals. Thus, skipping of Drd2 exon 6 arose convergently and specifically in the more derived tetrapod lineages, none of which deleted this exon. In contrast, exon 6 was convergently deleted during Drd3 evolution in an apparently random subset of the species of sharks, fish, amphibians, reptiles, birds, and mammals. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Molecular Evolution is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1007/s00239-025-10255-7 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 24 StartPage: 441 Subjects: – SubjectFull: Dopamine receptors Type: general – SubjectFull: Convergent evolution Type: general – SubjectFull: Tetrapods Type: general – SubjectFull: Alternative RNA splicing Type: general – SubjectFull: Genetic engineering Type: general Titles: – TitleFull: Convergent Evolution of Two Dopamine Receptor Genes: Repeated Evolution of Exon 6 Skipping in Drd2, and Repeated Deletion of Exon 6 in Drd3. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Peglar, Michael T. – PersonEntity: Name: NameFull: Fryxell, Karl J. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 06 Text: Jun2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 00222844 Numbering: – Type: volume Value: 93 – Type: issue Value: 3 Titles: – TitleFull: Journal of Molecular Evolution Type: main |
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