PUBLICATION
Adenylyl cyclase 9: Fundamental change of regulation in vertebrates and gene sub-functionalization after teleost-specific whole-genome duplication
- Authors
- Antoni, F.A., Mazzolini, J., McClafferty, H., Chen, Z., Szalai, L., Xia, C., Iqbal, S., Denvir, M., Balla, A., Sieger, D., Shipston, M.J., Skehel, P.
- ID
- ZDB-PUB-260713-4
- Date
- 2026
- Source
- iScience 29: 116562 (Journal)
- Registered Authors
- Sieger, Dirk
- Keywords
- G protein coupled receptors, adenylyl cyclase, auto-inhibition, medaka, whole genome duplication, zebrafish
- MeSH Terms
- none
- PubMed
- 42438824 Full text @ iScience
Citation
Antoni, F.A., Mazzolini, J., McClafferty, H., Chen, Z., Szalai, L., Xia, C., Iqbal, S., Denvir, M., Balla, A., Sieger, D., Shipston, M.J., Skehel, P. (2026) Adenylyl cyclase 9: Fundamental change of regulation in vertebrates and gene sub-functionalization after teleost-specific whole-genome duplication. iScience. 29:116562.
Abstract
In mammals, transmembrane adenylyl cyclase 9 (AC9) is resistant to regulation by cell surface receptors coupled to heterotrimeric G proteins. A major facet of this resistance is auto-inhibition-in the presence of activated Gsa, AC9 is inhibited by its C-terminal domain. Here, we examined the evolution of this seemingly paradoxical control mechanism. The hallmarks of auto-inhibition are apparent in all vertebrates; none are found in invertebrates. Teleost-specific whole genome duplication (TGD) resulted in adcy9 ohnologs, one of which lacked the hallmarks of auto-inhibition, which was confirmed in functional assays. The tissue distributions of the adcy9 ohnologs in teleost species pointed to their sub-functionalization. Auto-inhibited adcy9 was largely restricted to the brain, indicating a significant role in brain function. We document a fundamental change in the regulation of the enzymatic activity of AC9 and the potency of TGD to meet an adaptational challenge through functionally diversified ohnologs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping