Mu opioid receptor-like sequences are present throughout vertebrate evolution

Area of Science:

• Evolutionary biology
• Molecular biology
• Neuroscience

Background:

• The mu opioid receptor (MOR) is crucial for pain modulation and reward pathways.
• Its evolutionary history across diverse species remains incompletely understood.

Purpose of the Study:

• To investigate the evolutionary origins and conservation of the mu opioid receptor.
• To identify the earliest appearance of mu opioid receptor-like sequences in the metazoan phylogenetic tree.

Main Methods:

• Polymerase chain reaction (PCR) was employed to screen genomic DNA from various species.
• Degenerate oligonucleotides targeting conserved MOR regions were used for DNA screening.
• Rapid amplification of cDNA ends (RACE) was utilized to obtain full-length sequences from Pacific hagfish brain mRNA.

Main Results:

• Mu opioid receptor-like sequences were detected in all analyzed vertebrate species, including bovine, chicken, bullfrog, striped bass, thresher shark, and Pacific hagfish.
• No mu opioid receptor-like sequences were found in protostomes or any invertebrates.
• The region between the first intracellular loop and the third transmembrane domain (TM3) of the MOR gene shows high evolutionary conservation.
• The Pacific hagfish MOR sequence exhibited significant homology to human MOR (72% amino acid identity in specific domains) and other opioid receptor subtypes.

Conclusions:

• Mu opioid receptor-like sequences are ancient, present from the early stages of vertebrate evolution.
• The high conservation of specific MOR gene regions underscores their functional importance.
• Comparative analysis reveals evolutionary relationships between hagfish and mammalian opioid receptors.