The evolutionary conservation of eukaryotic membrane-bound adenylyl cyclase isoforms

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Biochemistry

Background:

• Eukaryotic adenylyl cyclases (mACs) are pseudoheterodimers with conserved domain structures.
• These enzymes play crucial roles in cellular signaling pathways.

Approach:

• Bioinformatic analysis was employed to trace the evolutionary history of mACs.
• The study investigated the divergence and conservation patterns of mAC subdomains.

Key Points:

• mACs evolved from monomeric bacterial proteins through gene duplication and fusion approximately 1.5 billion years ago.
• Nine distinct mAC isoforms diverged over a billion years, with diversification ceasing around 0.5 billion years ago.
• While catalytic domains (C1, C2) show divergence, other subdomains like membrane domains (TM1, TM2) and linkers exhibit high conservation within isoforms.

Conclusions:

• The conserved membrane anchor domains, previously overlooked for regulation, likely possess isoform-specific regulatory functions.
• Understanding these regulatory roles is key to deciphering adenylyl cyclase signaling diversity.